bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Genomic Risk Stratification Model for Primary Gastrointestinal Stromal Tumors (GIST) in the Adjuvant Therapy Era
Authors: Dermawan Josephine K. , Kelly Ciara , Gao Zhidong , Smith Shaleigh , Jadeja Bhumika , Singer Samuel , Tap William D. , Chi Ping , Antonescu Cristina R. 
Published: July 2023

Abstract

Purpose:
Traditional risk stratification schemes in gastrointestinal stromal tumors (GIST) were defined in the pre-imatinib era and rely solely on clinicopathologic metrics. We hypothesize that genomic-based risk stratification is prognostically relevant in the current era of tyrosine kinase inhibitor (TKI) therapeutics.

Experimental Design:
Comprehensive mutational and copy-number profiling using MSK-IMPACT was performed. We integrated clinicopathologic and genomic parameters and utilized an elastic-net penalized Cox proportional hazards machine learning model for outcome risk stratification.

Results:
A 3-tier genomic risk stratification model for recurrence-free survival (RFS) in 152 primary localized gastric and 80 small bowel GISTs was proposed. Gastric GISTs were classified as high risk if chr1p deletion or SDHB loss was present, and intermediate risk if chr14q deletion was present or KIT exon 11 mutation was absent. Small bowel GISTs were classified as high risk if MAX/MGA/MYC, CDKN2A, or RB1 alterations were present, and intermediate risk if chr1p deletion or chr5q amplification was present. Compared with conventional risk stratification, genomic risk stratification both upgrades and downgrades, suggesting that conventional risk stratification may underestimate or overtreat some high-risk and low-risk patients, respectively. Longitudinal sequencing detected most KIT-independent genomic alterations at baseline. Subanalysis in 26 SDH-deficient GISTs revealed that presence of TP53 mutations or chr1q amplifications portends worse RFS and disease-free survival.

Conclusions:
We developed a novel, next-generation genomic risk stratification model for primary gastric and small bowel GISTs, complementing traditional clinicopathologic models. Future independent validation of our model in external cohorts is essential.
EGFR/IGF1R Signaling Modulates Relaxation in Hypertrophic Cardiomyopathy
Authors: Algül Sila , Schuldt Maike , Manders Emmy , Jansen Valentijn , Schlossarek Saskia , de Goeij-de Haas Richard , Henneman Alex A. , Piersma Sander R. , Jimenez Connie R. , Michels Michelle , Carrier Lucie , Helmes Michiel , van der Velden Jolanda , Kuster Diederik W.D. 
Published: July 2023

BACKGROUND:
Diastolic dysfunction is central to diseases such as heart failure with preserved ejection fraction and hypertrophic cardiomyopathy (HCM). However, therapies that improve cardiac relaxation are scarce, partly due to a limited understanding of modulators of cardiomyocyte relaxation. We hypothesized that cardiac relaxation is regulated by multiple unidentified proteins and that dysregulation of kinases contributes to impaired relaxation in patients with HCM.

METHODS:

We optimized and increased the throughput of unloaded shortening measurements and screened a kinase inhibitor library in isolated adult cardiomyocytes from wild-type mice. One hundred fifty-seven kinase inhibitors were screened. To assess which kinases are dysregulated in patients with HCM and could contribute to impaired relaxation, we performed a tyrosine and global phosphoproteomics screen and integrative inferred kinase activity analysis using HCM patient myocardium. Identified hits from these 2 data sets were validated in cardiomyocytes from a homozygous
MYBPC3
c.2373insG
HCM mouse model.

RESULTS:
Screening of 157 kinase inhibitors in wild-type (N=33) cardiomyocytes (n=24 563) resulted in the identification of 17 positive inotropes and 21 positive lusitropes, almost all of them novel. The positive lusitropes formed 3 clusters: cell cycle, EGFR (epidermal growth factor receptor)/IGF1R (insulin-like growth factor 1 receptor), and a small Akt (α-serine/threonine protein kinase) signaling cluster. By performing phosphoproteomic profiling of HCM patient myocardium (N=24 HCM and N=8 donors), we demonstrated increased activation of 6 of 8 proteins from the EGFR/IGFR1 cluster in HCM. We validated compounds from this cluster in mouse HCM (N=12) cardiomyocytes (n=2023). Three compounds from this cluster were able to improve relaxation in HCM cardiomyocytes.

CONCLUSIONS:
We showed the feasibility of screening for functional modulators of cardiomyocyte relaxation and contraction, parameters that we observed to be modulated by kinases involved in EGFR/IGF1R, Akt, cell cycle signaling, and FoxO (forkhead box class O) signaling, respectively. Integrating the screening data with phosphoproteomics analysis in HCM patient tissue indicated that inhibition of EGFR/IGF1R signaling is a promising target for treating impaired relaxation in HCM.
“We’ll deal with it as it comes”: A qualitative analysis of romantic partners’ dyadic coping in cystic fibrosis
Authors: Lau Nancy , Ramos Kathleen J. , Aitken Moira L. , Goss Christopher H. , Barton Krysta S. , Kross Erin K. , Engelberg Ruth A. 
Published: July 2023

Background Although cystic fibrosis (CF) is a progressive, life-limiting, genetic disease, recent advances have extended survival, allowing persons with CF the time and physical and mental health to form romantic relationships. Previous studies have shown the importance of dyadic coping to positive psychosocial functioning and relationship satisfaction for people with serious chronic illness and their romantic partners, but little work has been done with persons with CF and their partners. The present study examines dyadic coping processes in persons with CF and their romantic partners. Methods 16 adults with moderate to severe CF (Mage = 42.3, 43.8% identified as cisgender male, 56.2% identified as cisgender female) and their romantic partners (Mage = 43.8, 56.3% identified as cisgender male, 43.7% identified as cisgender female) participated in individual semi-structured interviews focused on topics related to quality of life, communication, and palliative care. We conducted a directed content analysis utilizing Berg and Upchurch’s (2007) developmental-contextual theoretical model to examine dyadic coping processes in persons with CF and their romantic partners. Results Consistent with the developmental-contextual model of dyadic coping, couples described adapting to health and functional declines that occurred over time. Dyads were aligned in their appraisals of illness representation, illness ownership, and perspectives of illness as a shared stressor; they used shared coping mechanisms that included supportive and collaborative actions rather than uninvolved or controlling strategies. Conclusions We recommend family-based approaches to medical decision-making and goals of care conversations with persons with CF and their partners, aligning those approaches with supportive and collaborative coping configurations. This may improve psychosocial outcomes for patients and their partners.
Increased circulating levels of MIP-1α and CD14 are associated with the presence of severe stenosis and hypoechoic plaques in patients with carotid atherosclerosis
Authors: Profumo Elisabetta , Buttari Brigitta , Tosti Maria Elena , Salvati Bruno , Capoano Raffaele , Riganò Rachele 
Published: July 2023

Objective Carotid atherosclerosis, a major cause of ischemic cerebrovascular events, is characterized by a pro-inflammatory and pro-oxidant vascular microenvironment. The current risk score models based on traditional risk factors for cardiovascular risk assessment have some limitations. The identification of novel blood biomarkers could be useful to improve patient management. The aim of the study was to evaluate the association of selected inflammation- and oxidative stress-related markers with the presence of severe stenosis and/or vulnerable plaques. Methods Circulating levels of soluble CD40 ligand, interleukin-10, macrophage inflammatory protein (MIP)-1α, endoglin, CD163, CD14, E-selectin, tumor necrosis factor-α, monocyte chemoattractant protein-1, C-Reactive protein, CD40 L + T lymphocytes, total antioxidant capacity, glutathione reductase activity, and protein carbonyl content were determined in patients with carotid atherosclerosis. Results Multiparametric analysis showed significantly higher levels of MIP-1α in patients with stenosis ≥70% than in patients with stenosis <70%, and significantly higher levels of CD14 in patients with hypoechoic (vulnerable) lesions compared to those with hyperechoic (stable) ones. The area under the curve obtained by the receiver operating characteristic curve analysis was 0.7253 for MIP-1α and 0.6908 for CD14. Conclusions Our data suggest that circulating MIP-1α and CD14 levels are associated with the presence of advanced stenosis and of vulnerable carotid plaques.
Finite element analysis of the underslung carrier rocket effect on stress and strain distribution in a structure of the MiG-29 aircraft
Authors: Olejnik Aleksander , Kachel Stanisław , Zalewski Piotr , Rogólski Robert , Jędrak Michał , Szcześniak Michał 
Published: July 2023

The paper presents selected aspect of the analytical-conceptual research project entitled: Airborne-Rocket Launch System for Delivering Satellite Payloads into Low Earth Orbit – Feasibility Study. The aim of the project is to conduct series of aerodynamic, strength, and aeroelastic simulations of Polish aging combat aircraft (Mig-29 and Su-22) to explore applicability of both fighters as an airborne platform for carrying out carrier rockets with a detachable satellite payload. This work presents exemplary analyses in the area of airframe loads and structural strength and deformability of MiG-29 for predicted operational variants with carrier rockets put to the hardpoints under fuselage. The numerical simulations were conducted for a structural discrete model of the aircraft prepared for finite element analysis in MSC Software. Model development involved such aspects as precise discretization of geometric model, declaration of material constants, identification of structural properties, introduction of suitable merging connections for included airframe assemblies, and final validation of model mass and stiffness. The model was analyzed in MSC Nastran software with application of linear “Statics” solution. External flight loads introduced into the model were calculated for specific points of the flight envelope—the highest values of load factor were taken into consideration ( n=9). The counterpart aerodynamic force distribution in a form of a set of equivalent lumped forces was calculated. Then, the aerodynamic and weight loads were added to the model as a set of forces applied to specific structural nodes. Additionally, weights of applicable carrier rockets were taken into account as concentrated forces applied to under-fuselage suspension hardpoints. Calculations were performed for several rockets of mass values between 250 and 1200 kg. Parametric dependencies were investigated as an effect of missile mass and size on stress and strain distribution over the whole structure. The areas of stress cumulations were identified. On the basis of static structural deformation, maximum wing tip displacements were assessed.
Fludarabine-induced bradycardia in allogeneic hematopoietic stem cell transplantation: A retrospective study
Authors: Çelik Serhat , Güven Zeynep Tuğba , Altınsoy Abdullah , Tubay Şaziye Esra , Keklik Muzaffer , Ünal Ali 
Published: July 2023

Introduction Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The side effect of bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in the conditioning regimen in allo-HSCT recipients and to increase awareness of this issue. Methods This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia. Results Fludarabine administration doses and days were higher in the bradycardia group, but no statistically significant difference was observed. In the multivariate analysis, age was the only independent predictor of fludarabine-induced bradycardia (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.89–0.98, p = 0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19–49) vs 53 (19–69), p = 0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients. Conclusion Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients.
Effect of Cognitive Training Programs Based on Computer Systems on Executive Functions in Children With ADHD: A Systematic Review
Authors: Robledo-Castro Carolina , Lerma-Castaño Piedad Rocio , Bonilla-Santos Gisella 
Published: July 2023

Background: The purpose of this systematic review is to synthesize the existing literature reporting the effects of computerized cognitive trainings on the executive functions of children with ADHD. Method: A systematic review was carried out following the PRISMA statement; the primary sources used were five electronic databases (Scopus, Science Direct, Pubmed, Springer, Taylor & Francis). Results: 20 articles met the eligibility criteria, data on the training characteristics and the effects on executive functions were extracted, followed by an analysis of bias and the methodological quality of the studies. The results of the studies were widely heterogeneous, largely associated with the variety of training programs and the measurement instruments used. The most studied executive functions were working memory and inhibitory control. Some of the studies reported that the intervention led to significant effects on working memory and attention ( N = 7), and improvements in inhibitory control ( N = 5) and planning ( N = 4) were also reported. At the same time, others did not report the effects of the intervention on these processes. The assessment of the quality of the evidence showed important risk biases among the reviewed studies. Conclusion: Some training based on computer systems showed positive effects on the executive functions of working memory, attention, and inhibitory control in children with ADHD. However, other training sessions did not show significant effects. In general, the evidence shows mixed results, a high diversity of measurement instruments, and high risks of bias between the studies. Therefore, the evidence has not been consistent about the general benefits of computerized training on the executive functions of children with ADHD.
Linkage of NAMPT promoter variants to eNAMPT secretion, plasma eNAMPT levels, and ARDS severity
Authors: Lynn Heather , Sun Xiaoguang , Casanova Nancy G. , Bime Christian , Reyes Hernon Vivian , Lanham Clayton , Oita Radu C. , Ramos Nikolas , Sun Belinda , Coletta Dawn K. , Camp Sara M. , Karnes Jason H. , Ellis Nathan A. , Garcia Joe G.N. 
Published: July 2023

Background and objectives: eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a novel DAMP and TLR4 ligand, is a druggable ARDS therapeutic target with NAMPT promoter SNPs associated with ARDS severity. This study assesses the previously unknown influence of NAMPT promoter SNPs on NAMPT transcription, eNAMPT secretion, and ARDS severity. Methods and design: Human lung endothelial cells (ECs) transfected with NAMPT promoter luciferase reporters harboring SNPs G-1535A, A-1001 C, and C-948A, were exposed to LPS or LPS/18% cyclic stretch (CS) and NAMPT promoter activity, NAMPT protein expression, and secretion assessed. NAMPT genotypes and eNAMPT plasma measurements (Days 0/7) were assessed in two ARDS cohorts (DISCOVERY n = 428; ALVEOLI n = 103). Results: Comparisons of minor allelic frequency (MAF) in both ARDS cohorts with the 1000 Human Genome Project revealed the G-1535A and C-948A SNPs to be significantly associated with ARDS in Blacks compared with controls and trended toward significance in non-Hispanic Whites. LPS-challenged and LPS/18% CS–challenged EC harboring the -1535G wild-type allele exhibited significantly increased NAMPT promoter activity (compared with -1535A) with the -1535G/-948A diplotype exhibiting significantly increased NAMPT promoter activity, NAMPT protein expression, and eNAMPT secretion compared with the -1535A/-948 C diplotype. Highly significant increases in Day 0 eNAMPT plasma values were observed in both DISCOVERY and ALVEOLI ARDS cohorts (compared with healthy controls). Among subjects surviving to Day 7, Day 7 eNAMPT values were significantly increased in Day 28 non-survivors versus survivors. The protective -1535A SNP allele drove -1535A/-1001A and -1535A/-948 C diplotypes that confer significantly reduced ARDS risk (compared with -1535G, -1535G/-1001 C, -1535G/-948A), particularly in Black ARDS subjects. NAMPT SNP comparisons within the two ARDS cohorts did not identify significant association with either APACHE III scores or plasma eNAMPT levels. Conclusion: NAMPT SNPs influence promoter activity, eNAMPT protein expression/secretion, plasma eNAMPT levels, and ARDS severity. NAMPT genotypes are a potential tool for stratification in eNAMPT-focused ARDS clinical trials.
Advanced technology in shoulder arthroplasty
Authors: Zhong Jack , Boin Michael , Zuckerman Joseph D. 
Published: July 2023

Background Glenoid component positioning is an important and challenging aspect of total shoulder arthroplasty. The use of freehand technique with standard instrumentation or preoperative planning based on 2-dimensional computed tomography (CT) scans provides an opportunity for improvement in terms of component accuracy, precision, and deformity correction. These techniques have produced varying outcomes. Methods Preoperative planning software (PPS), patient specific instrumentation (PSI), and intraoperative navigation (NAV) have been developed to improve the accuracy of implant placement and deformity correction with the ultimate goals of improved patient outcomes and implant longevity. Literature search was conducted on published and available studies comparing the accuracy of glenoid component placement and improvements in surgical and patient outcomes amongst the aforementioned techniques. Results PPS, PSI, and NAV have demonstrated improved accuracy over freehand techniques with standard instrumentation. However, data demonstrating the clinical benefit and cost effectiveness of these new technologies are lacking. Discussion In this paper, we reviewed the evidence available to answer the question of whether or not advanced shoulder arthroplasty technologies have been beneficial and reviewed future technologies in development such as virtual/mixed-reality and robotic assisted shoulder surgery. Level of Evidence 4.
Oral paclitaxel and encequidar in patients with breast cancer: a pharmacokinetic, safety, and antitumor activity study
Authors: Dai Ming-Shen , Chao Ta-Chung , Chiu Chang-Fang , Lu Yen-Shen , Shiah Her-Shyong , Jackson Christopher G. C. A. , Hung Noelyn , Zhi Jianguo , Cutler David L. , Kwan Rudolf , Kramer Douglas , Chan Wing-Kai , Qin Albert , Tseng Kuan-Chiao , Hung Cheung Tak , Chao Tsu-Yi 
Published: July 2023

Background: Paclitaxel is widely used for the treatment of metastatic breast cancer (MBC). However, it has a low oral bioavailability due to gut extrusion caused by P-glycoprotein (P-gp). Oral paclitaxel (oPAC) may be more convenient, less resource-intensive, and more tolerable than its intravenous form. Encequidar (E) is a first-in-class, minimally absorbed, gut-specific oral P-gp inhibitor that facilitates the oral absorption of paclitaxel. Objectives: To investigate the pharmacokinetics (PK), overall response rate (ORR), and safety of weekly oral paclitaxel with encequidar (oPAC + E) in patients with advanced breast cancer. Design: This is a multicenter, single-arm, open-label study in six medical centers in Taiwan. Methods: Patients with advanced breast cancer were administered 205 mg/m2 oPAC and 12.9 mg E for 3 consecutive days weekly for up to 16 weeks. Plasma samples were collected at weeks 1 and 4. PK, ORR, and safety were evaluated. Results: In all, 28 patients were enrolled; 27 had MBC; 23 had prior chemotherapy; and 14 had ⩾2 lines of prior chemotherapy. PK were evaluable in 25 patients. Plasma paclitaxel area under the curve (AUC)(0–52 h) at week 1 (3419 ± 1475 ng h/ml) and week 4 (3224 ± 1150 ng h/ml) were equivalent. Best overall response in 28 evaluable patients was partial response (PR) in 11 (39.3%), 13 (46.4%) stable disease (SD), and 1 (3.6%) with progressive disease (PD). No patient achieved complete response (CR). The clinical benefit rate (CR + PR + SD) was 85.7%. Major adverse events among the 28 treated patients were grade 3 neutropenia (25%), grade 4 neutropenia (18%), with febrile neutropenia in 4%, and grade 3 diarrhea (4%). No treatment-related deaths occurred. Grade 2 peripheral neuropathy occurred in 1 (4%) patient and grade 3 peripheral neuropathy in 1 (4%) patient. Conclusions: oPAC + E produced a consistent therapeutic plasma paclitaxel exposure during treatment. There was a high rate of radiologically assessed clinical benefit, and a low rate of neurotoxicity which may provide advantages over IV paclitaxel. Registration: ClinicalTrials.gov Identifier: NCT03165955
Association between home and community-based services and depressive symptoms in Chinese older adults: a multilevel analysis
Authors: Xu Tingke , Huang Zishuo , Huang Yucheng , Wang Shanshan , Zhang Xinxin , Hu Yaqi , Zhu Yue , Cheng Dayi , Fu Yating , Zhang Xiangyang , Chen Chun 
Published: July 2023

Abstract
Background
As the phenomenon of ageing continues to intensify, home and community-based services (HCBSs) have been increasingly important in China. However, the association between HCBSs utilization and depressive symptoms in older adults in China is unclear. Consequently, this study aimed to examine the association between HCBSs utilization and depressive symptoms in Chinese older adults.

Methods
This study included 7,787 older adults (≥ 60 years old) who were recruited within the framework of the 2018 China Health and Retirement Longitudinal Study (CHARLS). Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale (CES-D-10). HCBSs utilization was assessed via the question, “What kind of HCBSs were being utilized in their community?”. Data were analyzed using binary logistic regression models and generalized hierarchical linear models (GHLM).

Results
Of the 7,787 participants, 20.0% (n = 1,556) reported that they utilized HCBSs, and 36.7% (n = 2,859) were evaluated that they had depressive symptoms. After adjusting for individual- and province-level covariates, the HCBSs utilization was found to be associated with depressive symptoms (OR = 1.180, 95% CI: 1.035–1.346, p < 0.05). Additionally, the depressive symptoms were significantly associated with gender, residence, educational level, marital status, number of chronic diseases, self-rated health (SRH), smoking, and provincial Gross Domestic Product (GDP) per capita.

Conclusions
This study found HCBSs utilization might be a protective factor against depressive symptoms in Chinese older adults. It is of utmost significance for the government to provide targeted HCBSs at the community level to address the unmet care needs of older adults, which can reduce the occurrence of negative emotions, consequently contributing to less severe depressive symptoms.