bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reference Groups and Relative Effects on Well‐Being
Authors: Kudrna Laura 
Published: July 2023

AbstractEconomic growth may not improve society if people compare their achievements to others in relative ways that detract from well‐being. But who are these others and what economic dimensions matter? This research applied a p‐value ranking approach from genetics research to tackle the issue of reference group selection. Data from over 30,000 British and American adults were analyzed in nearly 800 multi‐level models. Over 300 measures of reference group socio‐economic status and eight measures of well‐being were used. The results showed that reference groups based on geography and age, perceptions of those in “society,” and rank wealth were most consistently associated with well‐being. Measures less consistently associated with well‐being used averages, medians, and proportions in states and local authorities without demographic sub‐groups. Future researchers should consider the consistently associated dimensions of reference groups when constructing relative measures.
Targeting the Nerve–Cancer Circuit
Authors: Ye Yi , Xie Tongxin , Amit Moran 
Published: July 2023

Abstract
The tumor microenvironment is innervated by sensory, sympathetic, and parasympathetic nerves that actively stimulate cancer growth and dissemination. The cross-talk among the peripheral nerves, cancer cells, and stromal cells is mediated by a diverse set of bioactive ligands and their corresponding receptors. Dissecting the specific neuronal subtypes and molecular signals that drive cancer–nerve interaction holds the hope of developing targeted therapies for cancer. A recent study by Restaino and colleagues demonstrated that regardless of tumor type, origin, or anatomic location, tumors are densely innervated, predominantly by transient receptor potential cation channel subfamily V member 1 positive (TRPV1+) sensory fibers. The intratumoral fibers likely have functional connectivity and contribute to increased electrical activity in the tumor bed. Importantly, the neuropeptide substance P produced by intratumoral fibers stimulates its neurokinin 1 receptor (NK1R) expressed on tumor cells to drive tumor proliferation and migration. The findings raised the intriguing possibility of a generalizable molecular pathway that mediates cancer–nerve interaction that can be targeted to inhibit tumor growth and metastasis across different tumor types.
A Phase II Study of Optimized Individualized Adaptive Radiotherapy for Hepatocellular Carcinoma
Authors: Herr Daniel J. , Wang Chang , Mendiratta-Lala Mishal , Matuszak Martha , Mayo Charles S. , Cao Yue , Parikh Neehar D. , Ten Haken Randy , Owen Dawn , Evans Joseph R. , Stanescu Teodor , Yan Michael , Dawson Laura A. , Schipper Matthew , Lawrence Theodore S. , Cuneo Kyle C. 
Published: July 2023

Abstract

Purpose:
We hypothesized that optimizing the utility of stereotactic body radiotherapy (SBRT) based on the individual patient's probability for tumor control and risk of liver injury would decrease toxicity without sacrificing local control in patients with impaired liver function or tumors not amenable to thermal ablation.

Patients and Methods:
Patients with Child-Pugh (CP) A to B7 liver function with aggregate tumor size &gt;3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an Institutional Review Board–approved phase II clinical trial to undergo SBRT with baseline and midtreatment dose optimization using a quantitative, individualized utility-based analysis. Primary endpoints were change in CP score of ≥2 points within 6 months and local control. Protocol-treated patients were compared with patients receiving conventional SBRT at another cancer center using overlap weighting.

Results:
A total of 56 patients with 80 treated tumors were analyzed with a median follow-up of 11.2 months. Two-year cumulative incidence of local progression was 6.4% [95% confidence interval (CI, 2.4–13.4)]. Twenty-one percent of patients experienced treatment-related toxicity within 6 months, which is similar to the rate for SBRT in patients with CP A liver function. An analysis using overlap weighting revealed similar local control [HR, 0.69; 95% CI (0.25–1.91); P = 0.48] and decreased toxicity [OR, 0.26; 95% CI (0.07–0.99); P = 0.048] compared with conventional SBRT.

Conclusions:
Treatment of individuals with impaired liver function or tumors not amenable to thermal ablation with a treatment paradigm designed to optimize utility may decrease treatment-related toxicity while maintaining tumor control.
Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment
Authors: Wrenn Emma D. , Apfelbaum April A. , Rudzinski Erin R. , Deng Xuemei , Jiang Wei , Sud Sudha , Van Noord Raelene A. , Newman Erika A. , Garcia Nicolas M. , Miyaki Aya , Hoglund Virginia J. , Bhise Shruti S. , Kanaan Sami B. , Waltner Olivia G. , Furlan Scott N. , Lawlor Elizabeth R. 
Published: July 2023

Abstract

Purpose:
Despite limited genetic and histologic heterogeneity, Ewing sarcoma (EwS) tumor cells are transcriptionally heterogeneous and display varying degrees of mesenchymal lineage specification in vitro. In this study, we investigated if and how transcriptional heterogeneity of EwS cells contributes to heterogeneity of tumor phenotypes in vivo.

Experimental Design:
Single-cell proteogenomic-sequencing of EwS cell lines was performed and integrated with patient tumor transcriptomic data. Cell subpopulations were isolated by FACS for assessment of gene expression and phenotype. Digital spatial profiling and human whole transcriptome analysis interrogated transcriptomic heterogeneity in EwS xenografts. Tumor cell subpopulations and matrix protein deposition were evaluated in xenografts and patient tumors using multiplex immunofluorescence staining.

Results:
We identified CD73 as a biomarker of highly mesenchymal EwS cell subpopulations in tumor models and patient biopsies. CD73+ tumor cells displayed distinct transcriptional and phenotypic properties, including selective upregulation of genes that are repressed by EWS::FLI1, and increased migratory potential. CD73+ cells were distinguished in vitro and in vivo by increased expression of matrisomal genes and abundant deposition of extracellular matrix (ECM) proteins. In epithelial-derived malignancies, ECM is largely deposited by cancer-associated fibroblasts (CAF), and we thus labeled CD73+ EwS cells, CAF-like tumor cells. Marked heterogeneity of CD73+ EwS cell frequency and distribution was detected in tumors in situ, and CAF-like tumor cells and associated ECM were observed in peri-necrotic regions and invasive foci.

Conclusions:
EwS tumor cells can adopt CAF-like properties, and these distinct cell subpopulations contribute to tumor heterogeneity by remodeling the tumor microenvironment.
See related commentary by Kuo and Amatruda, p. 5002
Identifying the skills requirements related to industrial symbiosis and energy efficiency for the European process industry
Authors: Akyazi Tugce , Goti Aitor , Bayón Felix , Kohlgrüber Michael , Schröder Antonius 
Published: July 2023

AbstractThe need for sustainable production, efficient use of resources, energy efficiency and reduction in CO2 emission are currently the main drivers that are transforming the European process industry besides Industry 4.0. Since the potential of industrial symbiosis (IS) and energy efficiency (EE) about environmental, economic and social issues has been discovered, the interest in them is gradually increasing. The funding and investments for IS and EE are highly encouraged by the European Commission, while more and more policies as well as research and innovation (R&I) activities are initiated to promote European industry’s advancement towards a circular economy and CO2 neutrality. The aim is to maintain the competitiveness and economic progress of the industry. The key to build a competitive and sustainable European manufacturing industry is to create a competent, highly qualified workforce that is capable of handling the new business models coming with IS and EE requirements and digital technologies. We can generate this by identifying the skills needs and upskilling and reskilling the current workforce accordingly by delivering the suitable training programmes. Therefore, this work identifies the most critical skills needs related to IS and EE for six different energy-intensive sectors (steel, ceramic, water, cement, chemical and minerals) in Europe. The effect of the digital transformation on the skills needs is as well discussed. The identified skills are aimed to be included in vocational education and training (VET), tertiary education and other kinds of training curricula. We also identify the cross-sectoral most representative job profiles linked with EE and IS in these sectors and demonstrate the methodology for the selection process. Furthermore, we present a key tool for identifying the most significant current and future skills requirements. Also, we define the critical skill gaps of the European process industry using this tool. Once the skill gaps are defined, they can be reduced by delivering well-developed continuous trainings. We also link our work to the respectable ESCO, the European Classification of skills, competences, qualifications and occupations, to attain a common ground with other studies and frameworks, minimise the complexity and contribute to their work. Our work is developed to be an academic and industrial guideline to prepare well-developed training programmes to deliver the needed skills.
Mapping the risk of respiratory infections using suburban district areas in a large city in Colombia
Authors: Cortes-Ramirez Javier , Gatton Michelle , Wilches-Vega Juan D. , Mayfield Helen J. , Wang Ning , Paris-Pineda Olga M. , Sly Peter D. 
Published: July 2023

AbstractBackgroundAcute respiratory infections (ARI) in Cúcuta -Colombia, have a comparatively high burden of disease associated with high public health costs. However, little is known about the epidemiology of these diseases in the city and its distribution within suburban areas. This study addresses this gap by estimating and mapping the risk of ARI in Cúcuta and identifying the most relevant risk factors.MethodsA spatial epidemiological analysis was designed to investigate the association of sociodemographic and environmental risk factors with the rate of ambulatory consultations of ARI in urban sections of Cúcuta, 2018. The ARI rate was calculated using a method for spatial estimation of disease rates. A Bayesian spatial model was implemented using the Integrated Nested Laplace Approximation approach and the Besag-York-Mollié specification. The risk of ARI per urban section and the hotspots of higher risk were also estimated and mapped.ResultsA higher risk of IRA was found in central, south, north and west areas of Cúcuta after adjusting for sociodemographic and environmental factors, and taking into consideration the spatial distribution of the city’s urban sections. An increase of one unit in the percentage of population younger than 15 years; the Index of Multidimensional Poverty and the rate of ARI in the migrant population was associated with a 1.08 (1.06—1.1); 1.04 (1.01—1.08) and 1.25 (1.22—1.27) increase of the ARI rate, respectively. Twenty-four urban sections were identified as hotspots of risk in central, south, north and west areas in Cucuta.ConclusionSociodemographic factors and their spatial patterns are determinants of acute respiratory infections in Cúcuta. Bayesian spatial hierarchical models can be used to estimate and map the risk of these infections in suburban areas of large cities in Colombia. The methods of this study can be used globally to identify suburban areas and or specific communities at risk to support the implementation of prevention strategies and decision-making in the public and private health sectors.
Pyruvate Dehydrogenase Kinase 1 inhibition mediated oxidative phosphorylation enhancement in cartilage promotes osteoarthritis progression
Authors: Yang Xian , Jiang Qingsong , Luan Tiankuo , Yu Chao , Liu Zhibo , Wang Ting , Wan Jingyuan , Huang Jiayu , Li Ke 
Published: July 2023

AbstractOsteoarthritis (OA) is a common disease characterized by cartilage degradation. Growing evidence showed that glucose metabolism impacts joint homeostasis and an imbalance between glycolysis and oxidative phosphorylation (OXPHOS) may exacerbate OA progression, however, a definitive link is yet to be established. Here, we report that pyruvate metabolism and oxidative phosphorylation pathway is enriched in OA cartilage through gene set enrichment analysis (GSEA) and expression of Pyruvate Dehydrogenase Kinase 1 (PDK1), an enzyme that can phosphorylate Pyruvate Dehydrogenase (PDH), and inhibit pyruvate fluxes into the tricarboxylic acid (TCA) cycle and to OXPHOS, in articular cartilage is notably reduced through destabilization of medial meniscus (DMM). Moreover, by inhibiting PDK1, cartilage loss is markedly accelerated in DMM-induced OA through extracellular matrix (ECM) degradation and apoptosis of chondrocytes. These results indicate that PDK1 is involved in the progression of OA through accelerating cartilage matrix degradation and synovium inflammation to ameliorate cartilage degeneration.
RDN for the treatment of influenza in children: a randomized, double-blinded, parallel-controlled clinical trial
Authors: Yang Shuo , Xie Yan-ming , Wang Lian-xin 
Published: July 2023

Abstract
Background
The morbidity of influenza in children increased rapidly in decade. Reduning injection (RDN), a small but fine Chinese herbal formula, has antipyretic, antiviral, anti-inflammatory effects. We intend to evaluate the efficacy and safety of RDN for the influenza in children versus Oseltamivir, explore the possible antiviral mechanism of RDN and provide evidence-based medical evidence for rational clinical drug usage.

Method
We design a randomized, double-blind, double-dummy, parallel control of positive drug, multi-centre clinical study. According to the formula of mean superiority test, a total of 240 patients with influenza in children will be randomized 1:1 into the experimental group and control group. The experimental group will take RDN and Oseltamivir phosphate granule simulants and the control group will take Oseltamivir phosphate granule and RDN simulants. Each group will be treated for 5 days. The primary outcome measure is temperature recovery time, and the secondary outcome measures include time when the fever begins to subside, time and degree of disease to alleviate, disappearance rate of individual symptoms and so on. We will measure before enrollment and each 24 h after treatment for comparison.

Discussion
The study is launched to evaluate the efficacy and safety of RDN for the treatment of influenza in children and to provide an alternative option for influenza in children.

Trial registration
This study is registered in ClinicalTrials.gov as NCT04183725, registered on 3 December, 2019.
An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway
Authors: Liu Yuqiang , Yang Han , Luo Nanbo , Fu Yifei , Qiu Fang , Pan Zhenglong , Li Xiongjuan , Jian Wenling , Yang Xinping , Xue Qingsheng , Luo Yan , Yu Buwei , Liu Zhiheng 
Published: July 2023

AbstractBackgroundSepsis-associated encephalopathy (SAE) is characterized by diffuse brain dysfunction, long-term cognitive impairment, and increased morbidity and mortality. The current treatment for SAE is mainly symptomatic; the lack of specific treatment options and a poor understanding of the underlying mechanism of disease are responsible for poor patient outcomes. Fgr is a member of the Src family of tyrosine kinases and is involved in the innate immune response, hematologic cancer, diet-induced obesity, and hemorrhage-induced thalamic pain. This study investigated the protection provided by an Fgr kinase inhibitor in SAE and the underlying mechanism(s) of action.MethodsA cecal ligation and puncture (CLP)-induced mouse sepsis model was established. Mice were treated with or without an Fgr inhibitor and a PGC-1α inhibitor/activator. An open field test, a novel object recognition test, and an elevated plus maze were used to assess neurobehavioral changes in the mice. Western blotting and immunofluorescence were used to measure protein expression, and mRNA levels were measured using quantitative PCR (qPCR). An enzyme-linked immunosorbent assay was performed to quantify inflammatory cytokines. Mitochondrial membrane potential and morphology were measured by JC-1, electron microscopy, and the MitoTracker Deep Red probe. Oxidative stress and mitochondrial dysfunction were analyzed. In addition, the regulatory effect of Fgr on sirtuin 1 (SIRT1) was assessed.ResultsCLP-induced sepsis increased the expression of Fgr in the hippocampal neurons. Pharmacological inhibition of Fgr attenuated CLP-induced neuroinflammation, the survival rate, cognitive and emotional dysfunction, oxidative stress, and mitochondrial dysfunction. Moreover, Fgr interacted with SIRT1 and reduced its activity and expression. In addition, activation of SIRT1/PGC-1α promoted the protective effects of the Fgr inhibitor on CLP-induced brain dysfunction, while inactivation of SIRT1/PGC-1α counteracted the benefits of the Fgr inhibitor.ConclusionsTo our knowledge, this is the first report of Fgr kinase inhibition markedly ameliorating SAE through activation of the SIRT1/PGC-1α pathway, and this may be a promising therapeutic target for SAE.Graphical Abstract
Protocol for a randomized controlled trial comparing a very low-carbohydrate diet or moderate-carbohydrate plate-method diet for type 2 diabetes: the LEGEND (Lifestyle Education about Nutrition for Diabetes) trial
Authors: Saslow Laura R. , Eslamian Adriana , Moran Patricia , Hartogensis Wendy , Mason Ashley E. , Kim Sarah , Bauer Douglas C. , Griauzde Dina Hafez , Goldman Veronica , Liu Vivian , Stephens Pam , Raymond Kate , Yeung George , Leung Cindy , Hecht Frederick M. 
Published: July 2023

Abstract
Background
Optimal carbohydrate intake is an important and controversial area in the nutritional management of type 2 diabetes. Some evidence indicates that reducing overall carbohydrate intake with a low- or very low-carbohydrate eating plan can improve glycemic control compared to following eating plans that involve greater carbohydrate intake. However, critical knowledge gaps currently prevent clear recommendations about carbohydrate intake levels.

Methods
The LEGEND (Lifestyle Education about Nutrition for Diabetes) Trial aims to compare a very low-carbohydrate diet to a moderate-carbohydrate plate-method diet for glycemic control in adults with type 2 diabetes. This two-site trial plans to recruit 180 adults with type 2 diabetes. We will randomize participants to either a 20-session group-based diet and lifestyle intervention that teaches either a very low-carbohydrate diet or a moderate-carbohydrate plate-method diet. We will assess participants at study entry and 4 and 12 months later. The primary outcome is HbA1c, and secondary outcomes include inflammation (high sensitivity C-reactive protein), body weight, changes in diabetes medications, lipids (small particle LDL, HDL, triglycerides), skeletal metabolism (bone mineral density from dual-energy x-ray absorptiometry and bone turnover markers serum procollagen type I N propeptide and serum C-terminal telopeptide of type I collagen), and body composition (percent body fat, percent lean body mass).

Discussion
The LEGEND trial is a randomized controlled trial to assess optimal carbohydrate intake in type 2 diabetes by evaluating the effects of a very low-carbohydrate diet vs. a moderate-carbohydrate plate-method diet over a year-long period. The research addresses important gaps in the evidence base for the nutritional management of type 2 diabetes by providing data on potential benefits and adverse effects of different levels of carbohydrate intake.

Trial registration
ClinicalTrials.gov NCT05237128. Registered on February 11, 2022
Mapping the poultry insectome in and around broiler breeder pullet farms identifies new potential Dipteran vectors of Histomonas meleagridis
Authors: Terra Maria Tereza , Macklin Kenneth S. , Burleson Mark , Jeon Alan , Beckmann John F. , Hauck Ruediger 
Published: July 2023

Abstract
Background
Histomonas meleagridis can infect chickens and turkeys. It uses the eggs of the cecal worm Heterakis gallinarum as a vector and reservoir. Litter beetles (Alphitobius diaperinus) and other arthropod species have been implicated as potential vectors, but little information about other arthropod species as potential vectors is known.

Methods
Four broiler breeder pullet farms were sampled every 4 months. On each farm, three types of traps were set inside and outside two houses. Trapped arthropod specimens were morphologically identified at order level and grouped into families/types when possible. Selected specimens from abundant types found both inside and outside barns were screened for H. meleagridis and H. gallinarum by qPCR.

Results
A total of 4743 arthropod specimens were trapped. The three most frequently encountered orders were Diptera (38%), Coleoptera (17%), and Hymenoptera (7%). Three hundred seventeen discrete types were differentiated. More arthropods were trapped outside than inside. Alpha diversity was greater outside than inside but not significantly influenced by season. The composition of the arthropod populations, including the insectome, varied significantly between trap location and seasons. Up to 50% of litter beetles tested positive for H. meleagridis DNA 4 months after an observed histomonosis outbreak. Sporadically litter beetles were positive for H. gallinarum DNA. Thirteen further arthropod types were tested, and specimens of four Dipteran families tested positive for either one or both parasites.

Conclusions
This study describes the insectome in and around broiler breeder pullet farms and identifies new potential vectors of H. meleagridis through qPCR. The results show a limited but present potential of arthropods, especially flies, to transmit histomonosis between farms.

Graphical Abstract
Determining the psychometric properties of safety attitudes questionnaire in NICUs
Authors: Sarhadi Arezo , Farahani Azam Shirinabadi , Rassouli Maryam , Nasiri Malihe , Babaie Mohadese , Khademi Fatemeh 
Published: July 2023

Abstract
Introduction
This study aimed to translate and assess the psychometric properties of the Persian version of the “Safety Attitude Questionnaire” in the NICUs.

Methods
In this psychometric study, the “Safety Attitude Questionnaire” was translated into Persian. Then this version was used for psychometric evaluation. For this purpose, the qualitative face, content validity and construct validity were performed by confirmatory factor analysis. Internal consistency and stability reliability were calculated. Data were analyzed using SPSS and AMOS software.

Results
Face validity was also performed with a slight change in four items. The factor structure of the tool was determined by confirmatory factor analysis. Fit indices were appropriate. Internal consistency reliability in the whole questionnaire was 0.65 and the stability reliability was calculated to be 0.64.

Discussion and conclusion
“Safety Attitude Questionnaire” has appropriate psychometric properties and can be used in NICUs.