bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Spatial Structure of the Tumor Immune Microenvironment Can Explain and Predict Patient Response in High-Grade Serous Carcinoma
Authors: Van Kleunen Lucy B. , Ahmadian Mansooreh , Post Miriam D. , Wolsky Rebecca J. , Rickert Christian , Jordan Kimberly R. , Hu Junxiao , Richer Jennifer K. , Brubaker Lindsay W. , Marjon Nicole , Behbakht Kian , Sikora Matthew J. , Bitler Benjamin G. , Clauset Aaron 
Published: August 2024

Abstract
Ovarian cancer is the deadliest gynecologic malignancy, and therapeutic options and mortality rates over the last three decades have largely not changed. Recent studies indicate that the composition of the tumor immune microenvironment (TIME) influences patient outcomes. To improve spatial understanding of the TIME, we performed multiplexed ion beam imaging on 83 human high-grade serous carcinoma tumor samples, identifying approximately 160,000 cells across 23 cell types. From the 77 of these samples that met inclusion criteria, we generated composition features based on cell type proportions, spatial features based on the distances between cell types, and spatial network features representing cell interactions and cell clustering patterns, which we linked to traditional clinical and IHC variables and patient overall survival (OS) and progression-free survival (PFS) outcomes. Among these features, we found several significant univariate correlations, including B-cell contact with M1 macrophages (OS HR = 0.696; P = 0.011; PFS HR = 0.734; P = 0.039). We then used high-dimensional random forest models to evaluate out-of-sample predictive performance for OS and PFS outcomes and to derive relative feature importance scores for each feature. The top model for predicting low or high PFS used TIME composition and spatial features and achieved an average AUC score of 0.71. The results demonstrate the importance of spatial structure in understanding how the TIME contributes to treatment outcomes. Furthermore, the present study provides a generalizable roadmap for spatial analyses of the TIME in ovarian cancer research.
MYBL2 Drives Prostate Cancer Plasticity: Inhibiting Its Transcriptional Target CDK2 for RB1-Deficient Neuroendocrine Prostate Cancer
Authors: German Beatriz , Alaiwi Sarah A. , Ho Kun-Lin , Nanda Jagpreet S. , Fonseca Marcos A. , Burkhart Deborah L. , Sheahan Anjali V. , Bergom Hannah E. , Morel Katherine L. , Beltran Himisha , Hwang Justin H. , Freedman Matthew L. , Lawrenson Kate , Ellis Leigh 
Published: August 2024

Abstract

Phenotypic plasticity is a recognized mechanism driving therapeutic resistance in patients with prostate cancer. Although underlying molecular causations driving phenotypic plasticity have been identified, therapeutic success is yet to be achieved. To identify putative master regulator transcription factors (MR-TF) driving phenotypic plasticity in prostate cancer, this work utilized a multiomic approach using genetically engineered mouse models of prostate cancer combined with patient data to identify MYB proto-oncogene like 2 (MYBL2) as a significantly enriched transcription factor in prostate cancer exhibiting phenotypic plasticity. Genetic inhibition of Mybl2 using independent murine prostate cancer cell lines representing phenotypic plasticity demonstrated Mybl2 loss significantly decreased in vivo growth as well as cell fitness and repressed gene expression signatures involved in pluripotency and stemness. Because MYBL2 is currently not druggable, a MYBL2 gene signature was employed to identify cyclin-dependent kinase-2 (CDK2) as a potential therapeutic target. CDK2 inhibition phenocopied genetic loss of Mybl2 and significantly decreased in vivo tumor growth associated with enrichment of DNA damage. Together, this work demonstrates MYBL2 as an important MR-TF driving phenotypic plasticity in prostate cancer. Furthermore, high MYBL2 activity identifies prostate cancer that would be responsive to CDK2 inhibition.

Significance:
Prostate cancers that escape therapy targeting the androgen receptor signaling pathways via phenotypic plasticity are currently untreatable. Our study identifies MYBL2 as a MR-TF in phenotypic plastic prostate cancer and implicates CDK2 inhibition as a novel therapeutic target for this most lethal subtype of prostate cancer.
Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers—Brief Report
Authors: Witkowski Marco , Wilcox Jennifer , Province Valesha , Wang Zeneng , Nemet Ina , Tang W.H. Wilson , Hazen Stanley L. 
Published: August 2024

BACKGROUND:
Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease–relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined.

METHODS:
Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released.

RESULTS:

Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930–7300] versus 3.75 [3.35–3.87] μmol/L;
P
<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (
P
<0.0001 for TRAP6 [thrombin activator peptide 6] and
P
=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4;
P
<0.0001 for TRAP6 and
P
=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4.

CONCLUSIONS:
Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04731363.
Polygenic Risk and Coronary Artery Disease Severity
Authors: Sherafati Alborz , Norland Kristjan , Naderian Mohammadreza , Schaid Daniel J. , Kullo Iftikhar J. 
Published: August 2024

BACKGROUND:
Coronary atherosclerotic burden and adverse coronary heart disease events are related phenotypes with likely shared genetic cause.

METHODS:

We analyzed 6021 patients with available coronary angiography, genotyping, and exome sequencing data. We tested for associations of polygenic risk scores for coronary heart disease (PRS
CHD
) with multiple measures of coronary artery disease (CAD) severity. We assessed the joint associations of PRS
CHD
and pathogenic/likely pathogenic variants in 3 familial hypercholesterolemia genes, with CAD severity. We performed mediation analyses to explore whether CAD severity mediated the association of PRS
CHD
with prevalent coronary heart disease and incident myocardial infarction.

RESULTS:

A 1-SD increase in PRS
CHD
was associated with multiple measures of CAD severity, including the log Gensini score (β, 0.31 [95% CI, 0.28–0.33]). Carrying a pathogenic/likely pathogenic familial hypercholesterolemia variant was associated with a higher log Gensini score after adjustment for PRS
CHD
(β, 0.21 [95% CI, 0.03–0.38]). A 1-SD increase in PRS
CHD
was associated with incident myocardial infarction over a mean follow-up of 9.2 years (hazard ratio, 1.20 [95% CI, 1.13–1.27];
P
=5×10
−
10
), and the Gensini score mediated 90% of this association.

CONCLUSIONS:

PRS
CHD
was associated with multiple measures of CAD severity. The association of PRS
CHD
with incident myocardial infarction was almost fully mediated by CAD severity, indicating a considerable genetic overlap between the 2 phenotypes.
Determining the Authenticity of Dunhuang Colophons: Practical Procedures Derived from a Study of Three Colophons Employing Similar Templates
Authors: Chen Ruifeng 
Published: August 2024

Abstract
Addressing the perennial problem of forged colophons to Chinese Buddhist scriptures in Dunhuang manuscripts, I suggest some general procedures for identifying such items. Some of these approaches include comparing the date of the colophon with the time when the scripture was translated into Chinese, and comparing the script of a dubious colophon and the scripture title(s) enumerated in this colophon with the other colophons appended to the same set of scriptures. To ground these observations, I investigate the authenticity of three colophons that were composed based on similar templates. They are appended to scriptures in manuscripts BD15076, Nakamura51, and Nakamura65, respectively, which were purportedly found in the Dunhuang area. The colophons of BD15076 and Nakamura65 are probably forged, possibly produced by imitating the colophon of Nakamura51 or other similar colophons that are yet unknown to us. These approaches will help scholars avoid drawing faulty conclusions based on dubious colophons, and thus help to provide a more solid foundation for future research.
The Old Man and the Diamond Sūtra: A Case Study of the Production of Religious Manuscripts in Dunhuang during the Early Tenth Century
Authors: Feng Jing 
Published: August 2024

Abstract
This paper is a case study of the manuscripts of the Diamond Sūtra completed by an old man who lived in Dunhuang during the early tenth century. It investigates the textual and physical aspects of these manuscripts and reconstructs their production and use in an attempt to offer additional information on local religious life and the reproduction and transmission of the Diamond Sūtra during the medieval period. The first section focuses on a special version of the Diamond Sūtra which survives in the old man’s manuscripts and examines its textual and paratextual characteristics. This version, originating in Xichuan, provides valuable clues regarding the function and use of the Diamond Sūtra during the medieval period. The second section, based on the examination of paleographic and codicological features of the manuscripts, delineates the religious practices and motivations involved in their production and sheds light on medieval Buddhist manuscript culture.
Effect of spiritual intelligence and employment status on the association between education and depressive symptoms among adults in rural Puducherry, India: A mediation analysis
Authors: Rajan Vishnu , Marimuthu Yamini , Menon Vikas , Kumar Saya Ganesh , Raj Ruben 
Published: August 2024

Background: Depression is a major global health concern, particularly in India, where it significantly impacts the population’s well-being. The interplay of various factors, including education, employment status, and spiritual intelligence, contributes to the complex landscape of depressive symptoms among adults. Methodology: A community-based cross-sectional study was conducted in the rural service areas of a tertiary care medical institution in rural India from March 2021 to September 2022. The study employed structured questionnaires and validated scales to assess depressive symptoms, spiritual intelligence, educational status, and occupational status among participants. Structural equation modelling was used for mediation analysis to evaluate the effect of spiritual intelligence and employment status on the association between education and depressive symptoms. Results: The study included 381 participants, with a prevalence of depressive symptoms at 14.4%. Higher educational attainment was associated with lower odds of depressive symptoms (aOR = 0.34, 95% CI [0.17, 0.67]). Employment status mediated the relationship between education and depression, with employed individuals exhibiting lower odds of depressive symptoms (aOR = 0.42, 95% CI [0.22, 0.82]). While spiritual intelligence was higher among those with formal education, its direct impact on depression was not statistically significant. The mediation analysis revealed that a significant portion (77.5%) of the total effect of education on depression was mediated through employment status and spiritual intelligence. Conclusion: The study underscores the importance of education and employment opportunities in mitigating depressive symptoms among rural adults. It suggests targeted interventions that promote education and employment support to enhance mental health resilience. While spiritual intelligence may influence mental health outcomes, its exact role requires further investigation.
Lightweight plastic waste gypsum composites for sustainable and energy efficient buildings
Authors: Mourid Amina , El Alami Mustapha , Idrissi Kaitouni Samir , Saadani Rachid , Rahmoune Miloud 
Published: August 2024

The buildup of plastic waste (PW) in different ecosystems is a major environmental issue that has detrimental effects on people, wildlife, and their habitats. Our study aims to investigate specific plaster properties while reducing the rate at which end-of-life plastic is rejected in nature. This manuscript explores a gypsum composite reinforced with plastic waste (GPPS), with an emphasis on thermo-physical, chemical, and mechanical characteristics. Ten samples were produced, with varying addition rates (0%, 5%, 10%, and 15%) by weight of GPPS waste, incorporating three different sizes of GPPS aggregates (δ ≤ 1 mm; 1 mm < δ ≤ 1.25 mm; and 1.6 mm < δ ≤ 3 mm). The results demonstrate that the gradual increase in the quantity of GPPS aggregates incorporated into the plaster matrix produced a notable enhancement in thermal properties. However, this resulted in a slight decrease in mechanical performance due to a loss of workability. In general, the material evolution indicated that the inclusion of 15% size 2 GPPS was concluded to be the optimal arrangement for effectively reducing both thermal and mechanical qualities. Specifically, density, conductivity, and thermal diffusivity were decreased by approximately 20.73%, 42.47%, and 53.57%, respectively, while compressive strength decreased by 15.73% (6.64 MPa), a tolerable value according to the EN 13279 standard.
Less risk of patellofemoral degeneration without significant clinical and survivorship difference for distal tibial tuberosity high tibial osteotomy compared to biplanar high tibial osteotomy over a mid-term follow-up
Authors: Li Ke , Guo Hengbing , Sun Fenglong , Wang Hongqing 
Published: August 2024

Purpose This study aims to compare the mid-term radiographic, clinical results and survivorship between distal tibial tuberosity high tibial osteotomy (DTT-HTO) and conventional biplanar medial open-wedge high tibial osteotomy (cOW-HTO). Methods The weight-bearing line ratio (WBL%) and medial proximal tibial angle (MPTA) were evaluated using a standing anteroposterior view of lower extremity. The posterior tibial slope (PTS), Caton-Deschamps index (CDI), tilting angle (TT) and lateral shift ratio (LSR) were evaluated using the lateral views and Merchant views. The Knee Society (KS) knee and function score, Lysholm score, and Anterior Knee Pain Scale (Kujala score) were were used to evaluate the functional outcomes. All parameters were evaluated preoperatively and at the final follow-up. The postoperative complications and survivorship for both groups were also evaluated during the follow-up period. Results The WBL% and MPTA exhibited no significant differences between the two groups preoperatively and at the final follow-up. The postoperative CDI and TT in the cOW group decreased significantly compared with the DTT group ( p = .037 and .041, respectively). The PF grade showed a significant increase after DTT-HTO and cOW-HTO ( p = .036 and <0.001, respectively). Furthermore, the postoperative PF grade of cOW group was significantly higher than that of DTT group ( p = .039). The KS knee and function score, Lysholm score, and Kujala score for both groups improved similarly at the final follow-up. The survivorship free of revision was 92.7 % in the DTT group and 94.2% in the OW group. Conclusions Despite observing a lower risk of PF joint progression in DTT-HTO compared to cOW-HTO, the clinical outcomes and survivorship after DTT-HTO and cOWHTO were comparable over a mid-term follow-up.
Association between BMI and success of transaxillary venous port implantation: A retrospective cohort study
Authors: Shao Fei , Zhang Chunling , Jin Yang , Cai Hao , Pang Yunfeng , Wen Gehua , Ma Chong , Wang Guodong , Sun Ziqiang , Jin Song 
Published: August 2024

Purpose: Totally implanted venous access device are widely used for long-term chemotherapy in cancer patients. Previous studies have only focused on the analysis of complications associated with infusion port implantation, ignoring the causes of unsuccessful infusion port implantation. The purpose of this study was to investigate the association between body mass index (BMI) and the success rate of transaxillary intravenous port implantation in breast cancer patients. Materials and methods: To review 361 breast cancer patients who underwent intravenous port implantation from January 2021 to September 2021. Baseline data, and surgical data were collected from the patients, and the success rate of puncture of the axillary vein was recorded. The logistic regression analysis and smoothed curve fitting were used to assess the relationship between BMI and the success rate of axillary venipuncture. In addition, subgroup analyses were performed to explore potential interactions. Results: Under ultrasound guidance, 67.3% of patients (243/361) had an infusion port implanted by axillary vein puncture. There was a roughly linear relationship between BMI and the success rate of axillary venipuncture. In the multiple regression equation, BMI was significantly and negatively associated with the success rate of axillary venipuncture (OR = 0.83; 95% CI = 0.77–0.89; p < 0.001). Stratified analysis showed that the relationship between BMI and the success rate of axillary venipuncture was stable and unaffected by other variables. Conclusions: The higher the patient’s BMI, the higher the chance of difficult axillary venipuncture or failed cannulation.
Educational inequalities in blood pressure across the adult life course: Evidence from a 20-year follow-up study
Authors: Gebreslassie Mihretab , Warolén Marie , Lager Anton , Fors Stefan 
Published: August 2024

Aim: High blood pressure (BP) is a key contributor to the burden of disease. This study aimed to assess: a) educational differences across the entire BP distribution, and b) educational differences in the trajectories of BP across the adult life course. Method: Longitudinal data from the Stockholm Diabetes Prevention Program was analysed using quantile regression and linear mixed effects models. Models were adjusted for age, sex, lifestyle, and BP medication. Results: Lower educational level was associated with higher systolic BP (SBP) at all follow-up periods. Age and sex adjusted mean SBP was 2.49 (95% confidence interval (CI) 1.10, 3.87), 3.95 (95% CI 2.45, 5.45) and 2.61 (95% CI 1.09, 4.13) mmHg higher for people with pre-secondary education compared with post-secondary at baseline, 10 years and 20 years follow-up, respectively. Quantile regressions revealed that the inequalities could be observed across the entire BP continuum. Longitudinally analysed, people with pre-secondary education had 3.01 (95% CI 1.91–4.11) mmHg higher SBP than those with post-secondary education, age and sex adjusted. No significant convergence or divergence of the educational gaps in SBP was observed. Educational differences remained even after adjusting for lifestyle and BP medication. Conclusions: These results imply that public health interventions should aim to bring about distributional shifts in blood pressure, rather than exclusively focusing on hypertensive people, if they are to effectively minimize the educational disparities in blood pressure and its consequences.
Influence of Age, Gender and Body Mass Index on Intravenous Pharmacokinetics of Buprenorphine in Children Undergoing Orthopedic Surgery
Authors: Rivera-Espinosa Liliana , Vicencio-Rosas Eréndira , Flores-Pérez Carmen , Flores-Pérez Janett , Lares-Asseff Ismael , Gándara Mireles Jesús Alonso , Solorio-López Edelmira , Chávez-Pacheco Juan Luis 
Published: August 2024

Background Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug. Objective The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates. Methods Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 μg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson’s correlation and/or ANOVA were used for statistical analysis. Results Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance. Conclusions The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters.