bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum CXCL8 Concentration Can Be Used as a Noninvasive Marker of Subclinical Rejection After Pediatric Liver Transplantation
Authors: Zhang Zhixin , Wang Zhenglu , Dong Chong , Sun Chao , Zheng Weiping , Wang Kai , Zhang Wei , Song Zhuolun , Zhao Shengqiao , Si Zhuyuan , Gao Wei , Shen ZhongYang 
Published: May 2023

Background.
This study aimed to explore whether serum CXCL8 concentration can be used as a noninvasive marker of subclinical rejection (SCR) after pediatric liver transplantation (pLT).

Methods.
Firstly, RNA sequencing (RNA-seq) was performed on 22 protocol liver biopsy samples. Secondly, several experimental methods were used to verify the RNA-seq results. Finally, the clinical data and serum samples of 520 LT patients in the Department of Pediatric Transplantation of Tianjin First Central Hospital from January 2018 to December 2019 were collected.

Results.
RNA-seq results indicated that CXCL8 was significantly increased in the SCR group. The results of the 3 experimental methods were consistent with RNA-seq results. According to the 1:2 propensity score matching, 138 patients were divided into the SCR (n = 46) and non-SCR (n = 92) groups. Serological test results indicated that there was no difference in preoperative CXCL8 concentration between the SCR and non-SCR groups (P > 0.05). However, during protocol biopsy, CXCL8 in the SCR group was significantly higher than in the non-SCR group (P < 0.001). In diagnosing SCR, receiver operating characteristic curve analysis showed that the area under the curve of CXCL8 was 0.966 (95% confidence interval, 0.938-0.995), sensitivity was 95%, and specificity was 94.6%. In differentiating nonborderline from borderline rejection, the area under the curve of CXCL8 was 0.853 (95% confidence interval, 0.718-0.988), sensitivity was 86.7%, and specificity was 94.6%.

Conclusions.
This study demonstrates that serum CXCL8 concentration has high accuracy for the diagnosis and disease stratification of SCR after pLT.
Contribution of central hemodynamics and end-tidal CO2to cerebrovascular dynamics during aerobic exercise
Authors: Aaron Stacey E. , Whitaker Alicen A. , Billinger Sandra A. 
Published: May 2023

AbstractDuring aerobic exercise, central hemodynamics and CO2 partial pressure are central to middle cerebral artery blood velocity (MCAv) response. Still, the extent of their contribution is unknown. The purpose of this study was to characterize and utilize statistical modeling to determine the contribution of heart rate (HR), mean arterial pressure (MAP), and end-tidal CO2(PETCO2) dynamics to MCAv dynamics. Three randomized exercise bouts were completed on a recumbent stepper at 30-40% (Low), 45-55% (Mod1), and 60-70% (Mod2) of estimated HRmax. A 90-s resting period was followed by 6-min of continuous exercise within the estimated HR ranges. HR, MAP, PETCO2, and MCAv exercise dynamics were modeled with a monoexponential curve. From this modeling, the baseline (BL), time delay (TD), time constant (τ), and steady-state (SS) responses were determined. Backward AIC linear regression models determined contributing dynamics. Seventeen healthy adults completed all exercise bouts (28 ± 6 yrs, 8 females). The time from initiation of exercise to an exponential increase in HR (HRTD) was significantly longer for Low than Mod2 (p=0.047). The time constant for the rise in HR (HRτ) was significantly shorter for Low than Mod1 and Mod2 (p=0.01). The absolute change in HR from baseline to steady-state (HRSS) was significantly lower for Low than Mod1 and Mod2 (p<0.001), and Mod1 was significantly lower than Mod2 (p<0.001). MAPSSwas significantly lower for Low than Mod1 (p=0.01) and Mod2 (p<0.001). Exercise intensity, HRTD, and MAPTDaccounted for 17% of variation for MCAvTD(p=0.01). HRTD, PETCO2TD, and MCAvTDaccounted for 21% of variation MCAvτ (p<0.01). MCAvτ, MAPSS, and PETCO2SSaccounted for 60% of variation for MCAvSS(p<0.001). Throughout the MCAv dynamic response pathway central hemodynamics and end-tidal CO2do not account for most MCAv response until the steady-state phase. Thus, other physiological factors should be considered with assessing cerebrovascular function during aerobic exercise.
The effects of oxygenation on acute vasodilator challenge in pulmonary arterial hypertension
Authors: Rockstrom Matthew D , Jin Ying , Peterson Ryan A , Hountras Peter , Badesch David , Gu Sue , Park Bryan , Messenger John , Forbes Lindsay M. , Cornwell William K. , Bull Todd M 
Published: May 2023

BackgroundIdentification of long-term calcium channel blocker (CCB) responders with acute vasodilator challenge is critical in the evaluation of patients with pulmonary arterial hypertension. Currently there is no standardized approach for use of supplemental oxygen during acute vasodilator challenge.MethodsRetrospective analysis of patients identified as acute vasoresponders, treated with CCBs. All patients had hemodynamic measurements in three phases: 1) at baseline; 2) with 100% fractional inspired oxygen; and 3) with 100% fractional inspired oxygen plus inhaled nitric oxide (iNO). Patients were divided into two cohorts. Those meeting the definition of acute vasoresponsiveness from phase 2 to phase 3 were labeled “iNO Responders.” Those who did not reach the threshold of acute vasoresponsiveness from phase 2 to phase 3 but did meet the definition from phase 1 to phase 3 were labeled “Oxygen Responders.” Survival, hospitalization for decompensated right heart failure, duration of CCB monotherapy, and functional data were collected.ResultsiNO Responders, when compared to Oxygen Responders, had superior survival (100% vs 50.1% 5-year survival, respectively), fewer hospitalizations for acute decompensated right heart failure (0% vs 30.4% at 1 year, respectively), longer duration of CCB monotherapy (80% versus 52% at 1 year, respectively), and superior six-minute walk distance.ConclusionCurrent guidelines for acute vasodilator testing do not standardize oxygen coadministration with iNO. This study demonstrates that adjusting for the effects of supplemental oxygen before assessing for acute vasoresponsiveness identifies a cohort with superior functional status, tolerance of CCB monotherapy, and survival while on long-term CCB therapy.
Prognostic utility of rhythmic components in 24-hour ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity
Authors: Jamal Nadim El , Brooks Thomas G. , Cohen Jordana , Townsend Raymond R. , Rodriguez de Sosa Giselle , Shah Vallabh , Nelson Robert G. , Drawz Paul E. , Rao Panduranga , Bhat Zeenat , Chang Alexander , Yang Wei , FitzGerald Garret A. , Skarke Carsten ,   the CRIC Study Investigators
Published: May 2023

AbstractBackgroundChronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD.MethodsWe extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-hour profiles of ambulatory blood pressure monitoring (ABPM) in the African American Study for Kidney Disease and Hypertension (AASK) cohort and the Chronic Renal Insufficiency Cohort (CRIC) using Cox proportional hazards models.ResultsWe find that rhythmic profiling of BP through JTK_Cycle analysis identifies subgroups of CRIC participants at advanced risk of cardiovascular death. CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.38, 95% CI: 1.45-7.88,p=0.005). This substantially increased risk was independent of whether ABPM followed a dipping or non-dipping pattern whereby non-dipping or reverse dipping were not significantly associated with cardiovascular death in patients with prior CVD (p>0.1). In the AASK cohort, unadjusted models demonstrate a higher risk in reaching end stage renal disease among participants without rhythmic ABPM components (HR:1.80, 95% CI: 1.10-2.96); however, full adjustment abolished this association.ConclusionsThis study proposes rhythmic blood pressure components as a novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.
Comparing Providers for the Treatment of Early Childhood Caries with a Value-based Rating Methodology: A Cross-sectional study
Authors: Okuji David , Ben Dor Betty , Jivraj Ashiana , Wu Yinxiang 
Published: May 2023

ABSTRACTPurposeAn adapted Porter-Teisberg model of value-based health outcomes and cost was applied to comparatively rate providers who treat children with early childhood caries, by treatment modalities, facilities, and geographic location.MethodsQuality was measured by a Parental-Reported Symptom and Service Quality questionnaire, adapted from the Early Child Oral Health Impact Scale, Child-Oral Impacts on Daily Performance, and Dental Consumer Assessments of Healthcare Providers and Systems tools. Cost was measured by the labor cost for all providers involved in treatment and adjusted by dividing by total relative value units for the types and total number of procedures for all treatment visits. Value was calculated as the quotient of the weighted quality score and the adjusted cost, multiplied by a coefficient. To compare the value score by states and by facilities, Tukey’s multiple comparison test was used and a sensitivity analysis using the non-parametric Dunn’s Kruskal-Wallis multiple comparison test was conducted.ResultsFor surgical treatment with general anesthesia, Tennessee ranked the highest, followed by Arizona, Hawaii, and New York. These four states had significantly higher value metrics than Florida, Massachusetts, and Maryland. Maryland had a significantly higher value score for surgical treatment without general anesthesia. While patients were seen for non-surgical treatment only in Maryland and New York, Maryland also had a significantly higher value for this treatment modality.ConclusionA value-based rating system of providers, by geographic region and treatment facility, can assist patients to better compare and select providers; third-party payers, such as insurance companies and government programs, to better compare outcomes and costs for provider systems and clinic facilities; and providers to benchmark their comparative ratings on an internal and external basis for continuous quality improvement.HighlightsNon-surgical management of early childhood caries yields the most value.Surgical intervention with or without general anesthesia is less valued by patients.Ranking treatment modalities by value is a useful tool for patients.Using a parental-reported symptom and service quality questionnaire assesses quality.Provider value can be determined by dividing quality of care by the cost of delivery.
T cell activation via the CD40 ligand and transferrin receptor and deficits in T regulatory cells are associated with major depressive disorder and severity of depression
Authors: Rachayon Muanpetch , Jirakran Ketsupar , Sodsai Pimpayao , Sughondhabirom Atapol , Maes Michael 
Published: May 2023

AbstractMajor depressive disorder (MDD) is associated with T cell activation (Maes et al. 1990-1993), but no studies have examined the combined effects of T cell activation and deficits in T regulatory (Treg) cells on the severity of acute phase MDD. Using flow cytometry, we determined the percentage and median fluorescence intensity of CD69, CD71, CD40L, and HLADR-bearing CD3+, CD4+, and CD8+ cells, and cannabinoid type 1 receptor (CB1), CD152 and GARP-bearing CD25+FoxP3 T regulatory (Treg) cells in 30 MDD patients and 20 healthy controls in unstimulated and stimulated (anti-CD3/CD28) conditions. Based on cytokine levels, we assessed M1 macrophage, T helper (Th)-1, immune-inflammatory response system (IRS), T cell growth, and neurotoxicity immune profiles. We found that the immune profiles (including IRS and neurotoxicity) were significantly predicted by decreased numbers of CD152 or GARP-bearing CD25+FoxP3 cells or CD152 and GARP expression in combination with increases in activated T cells (especially CD8+CD40L+ percentage and expression). MDD patients showed significantly increased numbers of CD3+CD71+, CD3+CD40L+, CD4+CD71+, CD4+CD40L+, CD4+HLADR+, and CD8+HLADR+ T cells, increased CD3+CD71+, CD4+CD71+ and CD4+HLADR+ expression, and lowered CD25+FoxP3 expression and CD25+FoxP+CB1+ numbers as compared with controls. The Hamilton Depression Rating Scale score was strongly predicted (between 30-40% of its variance) by a lower number of CB1 or GARP-bearing Treg cells and one or more activated T cell subtypes (especially CD8+CD40L+). In conclusion, T helper and cytotoxic cell activation coupled with lowered Treg homeostatic defenses are key components of MDD and contribute towards greater immune responses and consequent neuroimmunotoxicity.
Accelerated Clonal Hematopoiesis in Pediatric and Young Adult Survivors of Childhood Cancer
Authors: Greer Chelsee D. , Kroger Benjamin R. , Hartshorne Taylor N. , Xu Jian , Chung Stephen S. , Dickerson Kathryn E. 
Published: May 2023

AbstractClonal hematopoiesis of indeterminate potential(CHIP) is a recognized consequence of aging and a precursor to myelodysplastic syndrome and acute myeloid leukemia which independently increases all-cause mortality in adults. Childhood cancer survivors experience a phenomenon of accelerated aging with increased all-cause mortality; however, the mechanism of this is not known and the prevalence of CHIP not well defined. We prospectively studied 305 pediatric and young adult childhood cancer survivors to determine the prevalence of clonal hematopoiesis(CH). Targeted next-generation sequencing analysis of peripheral blood mononuclear cells elucidated the prevalence of CH (VAF >1%) at a rate of ∼6%, approaching that of adults >50-70 years and much higher than previously reported. This is the first prospective study of CH in pediatric and young adult survivors of childhood cancer and highlights the importance of further investigation to better understand how CH may contribute to treatment-related myeloid neoplasms and other late effects.
Valid, invalid, or somewhere in between? Baseline ImPACT and stand-alone performance validity testing in collegiate athletes
Authors: Higgins Kate L. , Bouchard Heather C. , Maietta Julia E. , Laing-Young Julia M. , Schultz Douglas H. 
Published: May 2023

AbstractObjectiveBaseline cognitive testing is important for sport concussion management. Assessing baseline data for both the validity and reliability is vital to ensuring its utility. Stand-alone performance validity tests (PVT) and embedded validity indicators (EVI) (collectively called “validity measures” hereafter) are commonly used in neuropsychological testing and screening. This study further investigates efficient ways to assess validity of baseline cognitive testing.Methods231 NCAA athletes completed baseline assessment with ImPACT and one of two PVT’s: Medical Symptom Validity Test or Rey Dot Counting Test. The relationship between scores on validity measures and cognitive performance, symptoms, and sleep was assessed.ResultsAthletes who failed two or more validity measures performed worse on the Visual Motor Speed Composite while athletes failing three or more measures performed worse on the Reaction Time Composite. Those athletes who failed validity measures and also reported poor sleep performed worse on both composites. Self-reported symptoms and hours of sleep were not independently associated with failing validity measures. Lastly, athletes with self-reported ADHD and/or LD were more likely to fail two+ validity measures (46% versus 27% of neurotypical athletes).ConclusionsConsistent with previous research, ImPACT Baseline++ only identified 1.7% of the sample’s data as invalid despite 4.8% of the dataset failing a combination of PVT and EVI and an additional 42.9% failing at least EVI alone. Results suggest that assessing validity on a continuum and using multiple validity measures may be useful to identify data validity that falls in the middle of the continuum.Public Significance StatementBaseline concussion testing is common and often mandated prior to sport participation, however, a baseline only has utility if it is both a reliable and valid representation of the athlete’s healthy and optimal functioning. This study adds to the growing body of literature demonstrating that baseline testing may frequently have questionable validity. It also provides support to the value of conceptualizing validity as a spectrum, rather than dichotomy and is the first to apply the concept to baseline concussion testing data.
Drug Target Identification in Triple Negative Breast Cancer Stem Cell Pathways: a computational study of gene regulatory pathways using Boolean networks
Authors: Lahiri Aditya , Vundavilli Haswanth , Mondal Madhurima , Bhattacharjee Pranabesh , Decker Brian , Del Priore Giuseppe , Reeves N. Peter , Datta Aniruddha 
Published: May 2023

ABSTRACTTriple-negative breast cancer (TNBC) is an aggressive form of breast cancer associated with an early age of onset, greater propensity towards metastasis, and poorer clinical outcomes. It accounts for 10% to 20% of newly diagnosed breast cancer cases and disproportionately affects individuals from the African American race. While TNBC is sensitive to chemotherapy, it is also prone to relapse. This is because chemotherapy successfully targets the primary TNBC tumor cell but often fails to target the subpopulation of TNBC stem cells. TNBC stem cells display cancerous traits such as cell cycle progression, survival, proliferation, apoptosis inhibition, and epithelial-mesenchymal transition. To study the cancer initiating behavior of the TNBC stem cells, we studied their underlying signaling pathways using Boolean networks(BN). BNs are effective in capturing the causal interactions taking place in signaling pathways. We built the BN from the pathway literature and used it to evaluate the efficacies of eleven targeted inhibitory drugs in suppressing cancer-promoting genes. We simulated the BN when the pathways had single or multiple mutations, with a maximum of three mutations at a time. Our findings indicated thatSTAT3, GLI, andNF-κBare the most optimal targets for inhibition. These genes are known regulators of the cancer-promoting genes in the pathway,hence our model agrees with the existing biological literature. Therefore inhibiting these three genes has the potential to prevent TNBC relapse. Additionally, our studies found that drug efficacies decreased as mutations increased in the pathway. Furthermore, we noticed that combinations of drugs performed better than single drugs.
A comparative ultrastructure study of the tardigradeRamazzottius varieornatusin the hydrated state, after desiccation and during the process of rehydration
Authors: Galas Simon , Le Goff Emilie , Cazevieille Chantal , Tanaka Akihiro , Cuq Pierre , Baghdiguian Stephen , Kunieda Takekazu , Godefroy Nelly , Richaud Myriam 
Published: May 2023

AbstractTardigrades can survive hostile environments such as desiccation by adopting a state of anhydrobiosis. Numerous tardigrade species have been described thus far, and recent genome and transcriptome analyses revealed that several distinct strategies were employed to cope with harsh environments depending on the evolutionary lineages. Detailed analyses at the cellular and subcellular levels are essential to complete these data. In this work, we analyzed a tardigrade species that can withstand rapid dehydration,Ramazzottius varieornatus. Surprisingly, we noted an absence of the anhydrobiotic-specific extracellular structure previously described for theHypsibius exemplarisspecies. BothRamazzottius varieornatusandHypsibius exemplarisbelong to the same evolutionary class of Eutardigrada. Nevertheless, our observations reveal discrepancies in the anhydrobiosis mechanisms between these two species. Interestingly, these discrepancies are correlated with their variations in dehydration resistance.
Exploring disease-drug pairs in Clinical Trials information for personalized drug repurposing
Authors: Álvarez-Pérez Andrea , Prieto-Santamaría Lucía , Ugarte-Carro Esther , Otero-Carrasco Belén , Ayuso-Muñoz Adrián , Rodríguez-González Alejandro 
Published: May 2023

AbstractDrug repurposing, the process of finding new uses for existing drugs, has gained considerable attention due to its potential to reduce the time and costs associated with drug development. Personalized drug repurposing, in which drugs are selected based on the characteristics of individual patients, is an emerging approach that holds promise for improving clinical outcomes. In this context, exploring disease-drug pairs in already conducted clinical trials can provide valuable insights to identify promising patient populations for further study that may lead to personalized drug repositioning. Our analysis aims to shed a light into clinical outcomes by selecting the most appropriate repurposed drug based on clinical trials patient groups’ characteristics, such as age and gender. It also gives information about the state of the clinical trials studying these disease-drug pairs, gathering information about the study type, phase and statistical method used to calculate the p-value of the chosen outcome measurement, among others. Overall, this study highlights the importance of using existing knowledge as an initial framework to facilitate further research, particularly in providing patient-specific information. Furthermore, it underlines the importance of building on previous research to facilitate a comprehensive understanding of the research topic, which can eventually improve patient outcomes.