bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting child welfare and protection workers' intention to quit: a cross-sectional study from Norway
Authors: Nilsen Kristel Høie , Lauritzen Camilla , Vis Svein Arild , Iversen Anita 
Published: June 2023

Abstract
Introduction
High turnover rates have been a problem for Norwegian child welfare and protection services for years. The main aim of this study was to identify which factors affect Norwegian child welfare and protection (CWP) workers intention to quit their job and whether there is a difference between experienced (< 3 years) and less experienced workers.

Methods
A cross-sectional survey was performed among 225 Norwegian child welfare and protection workers. Data were collected using a self-report questionnaire. Turnover intention was examined using a variety of job demands and resources as possible predictors. T tests were used to study mean differences in variable scores between experienced and less experienced workers and linear regression analysis was employed determining predictors of intention to quit.

Results
For the total sample (N = 225) the most important predictors for intention to quit were workload, burnout, engagement, and views on leadership. Higher emotional exhaustion and cynicism, and low professional efficacy predicted a higher score on the intention to quit scale. High engagement and leadership satisfaction predicted lower scores. The effect of workload was moderated, such that intention to quit among less experienced workers increased more with high workload than it did among more experienced child welfare workers.

Conclusions
The conclusions are that job demands affect experienced and less experienced CWP workers differently and that when designing preventive efforts to reduce turnover this must be considered.
Dental pulp stem cell-derived exosomes revitalize salivary gland epithelial cell function in NOD mice via the GPER-mediated cAMP/PKA/CREB signaling pathway
Authors: Hu Shilin , Chen Bo , Zhou Jiannan , Liu Fangqi , Mao Tianjiao , Pathak Janak L. , Watanabe Nobumoto , Li Jiang 
Published: June 2023

AbstractBackgroundRestoration of salivary gland function in Sjogren’s syndrome (SS) is still a challenge. Dental pulp stem cells (DPSCs) derived exosomes had shown anti-inflammatory, anti-oxidative, immunomodulatory, and tissue function restorative abilities. However, the salivary gland function restoration potential of DPSCs-derived exosomes (DPSC-Exos) during SS has not been investigated yet.MethodsDPSC-Exos was isolated by ultracentrifugation methods and characterized. Salivary gland epithelial cells (SGEC) were treated with interferon-gamma (IFN-γ) to mimic SS in vitro and cultured with or without DPSC-Exos. SGEC survival and aquaporin 5 (AQP5) expression were analyzed. mRNA sequencing and bioinformatics analysis were performed in IFN-γ vs. DPSC-Exos+ IFN-γ treated SGEC. Non-obese diabetic (NOD)/ltj female mice (SS model), were intravenously administered with DPSC-Exos, and salivary gland functions and SS pathogenicity were analyzed. Furthermore, the mRNA sequencing and bioinformatics predicted mechanism of the therapeutic effect of DPSC-Exos was further investigated both in vitro and in vivo using RT-qPCR, Western blot, immunohistochemistry, immunofluorescence, flowcytometry analysis.ResultsDPSC-Exos partially rescued IFN-γ triggered SGEC death. IFN-γ inhibited AQP5 expression in SGEC and DPSC-Exos reversed this effect. Transcriptome analysis showed GPER was the upregulated DEG in DPSC-Exos-treated SGEC with a positive correlation with salivary secretion-related DEGs. Pathway enrichment analysis revealed that DEGs were mainly attributed to estrogen 16 alpha-hydroxylase activity, extracellular exosome function, cAMP signaling, salivary secretion, and estrogen signaling. Intravenous injection of DPSC-Exos in NOD/ltj mice alleviated the SS syndrome as indicated by the increased salivary flow rate, attenuated glandular inflammation, and increased AQP5 expression. GPER was also upregulated in the salivary gland of DPSC-Exos-treated NOD/ltj mice compared with the PBS-treated NOD/ltj mice. IFN-γ+DPSC-Exos-treated SGEC showed higher expression of AQP5, p-PKA, cAMP, and intracellular Ca2+levels compared with IFN-γ-treated SGEC. These effects were reversed by the inhibition of GPER.ConclusionsOur results showed that DPSC-Exos revitalize salivary gland epithelial cell function during SS via the GPER-mediated cAMP/PKA/CREB pathway suggesting the possible therapeutic potential of DPSC-Exos in SS-treatment.
Group-specific cellular metabolism in Medulloblastoma
Authors: Funke Viktoria L. E. , Walter Carolin , Melcher Viktoria , Wei Lanying , Sandmann Sarah , Hotfilder Marc , Varghese Julian , Jäger Natalie , Kool Marcel , Jones David T. W. , Pfister Stefan M. , Milde Till , Mynarek Martin , Rutkowski Stefan , Seggewiss Jochen , Jeising Daniela , de Faria Flavia W. , Marquardt Thorsten , Albert Thomas K. , Schüller Ulrich , Kerl Kornelius 
Published: June 2023

Abstract
Background
Cancer metabolism influences multiple aspects of tumorigenesis and causes diversity across malignancies. Although comprehensive research has extended our knowledge of molecular subgroups in medulloblastoma (MB), discrete analysis of metabolic heterogeneity is currently lacking. This study seeks to improve our understanding of metabolic phenotypes in MB and their impact on patients’ outcomes.

Methods
Data from four independent MB cohorts encompassing 1,288 patients were analysed. We explored metabolic characteristics of 902 patients (ICGC and MAGIC cohorts) on bulk RNA level. Moreover, data from 491 patients (ICGC cohort) were searched for DNA alterations in genes regulating cell metabolism. To determine the role of intratumoral metabolic differences, we examined single-cell RNA-sequencing (scRNA-seq) data from 34 additional patients. Findings on metabolic heterogeneity were correlated to clinical data.

Results
Established MB groups exhibit substantial differences in metabolic gene expression. By employing unsupervised analyses, we identified three clusters of group 3 and 4 samples with distinct metabolic features in ICGC and MAGIC cohorts. Analysis of scRNA-seq data confirmed our results of intertumoral heterogeneity underlying the according differences in metabolic gene expression. On DNA level, we discovered clear associations between altered regulatory genes involved in MB development and lipid metabolism. Additionally, we determined the prognostic value of metabolic gene expression in MB and showed that expression of genes involved in metabolism of inositol phosphates and nucleotides correlates with patient survival.

Conclusion
Our research underlines the biological and clinical relevance of metabolic alterations in MB. Thus, distinct metabolic signatures presented here might be the first step towards future metabolism-targeted therapeutic options.

Graphical Abstract
Spatiotemporal parameters for energy efficient kilohertz-frequency nerve block with low onset response
Authors: Peña Edgar , Pelot Nicole A. , Grill Warren M. 
Published: June 2023

AbstractBackgroundElectrical nerve conduction block has great potential for treatment of disease through reversible and local inactivation of somatic and autonomic nerves. However, the relatively high energy requirements and the presence of undesired excitation at the onset of the kilohertz-frequency (KHF) signals used for block pose obstacles to effective translation. Frequency, electrode geometry, and waveform shape are known to influence block threshold and onset response, but available data provide a limited understanding of how to select these parameters to optimize nerve block.MethodsWe evaluated KHF nerve block in rat tibial nerve across frequencies (5–60 kHz), electrode geometries (monopolar, bipolar, and tripolar), and waveform shapes. We present a novel Fourier-based method for constructing composite signals that systematically sample the KHF waveform design space.ResultsThe lowest frequencies capable of blocking (5–16 kHz) were not the most energy-efficient among the tested frequencies. Further, bipolar cuffs required the largest current and power to block, monopolar cuffs required the lowest current, and both tripolar and monopolar cuffs required the lowest power. Tripolar cuffs produced the smallest onset response across frequencies. Composite signals comprised of a first harmonic sinusoid at fundamental frequency (f0) superposed on a second harmonic sinusoid at 2f0could block at lower threshold and lower onset response compared to the constituent sinusoids alone. This effect was strongly dependent on the phase of the second harmonic and on the relative amplitudes of the first and second harmonics. This effect was also dependent on electrode geometry: monopolar and tripolar cuffs showed clear composite signal effects in most experiments; bipolar cuffs showed no clear effects in most experiments.ConclusionsOur data provide novel information about block threshold and onset response at the boundary of frequencies that can block. Our results also show an interaction between spatial (cuff geometry) and temporal (frequency and waveform shape) parameters. Finally, while previous studies suggested that temporal parameters could reduce onset response only in exchange for increased block threshold (or vice versa), our results show that waveform shape influences KHF response in ways that can be exploited to reducebothenergy and onset responses.
Three-dimensional femur morphology analysis for the optimal location of subtrochanteric osteotomy with an implanted Wagner cone stem in total hip arthroplasty for Crowe type IV developmental dysplasia of the hip
Authors: Tao Kun , Wang Shi-Cheng , Ma Xiao-Ying , Shao Long , Di Zheng-Lin , Huang Zhe-Yu 
Published: June 2023

Abstract
Background
This study aimed to accurately evaluate the matching of proximal and distal femoral segments and fitting of the femur–femoral stem in patients with Crowe type IV developmental dysplasia of the hip (DDH) who have undergone subtrochanteric osteotomy at different locations with an implanted Wagner cone stem to improve the rate of the bone union at the osteotomy site.

Methods
Three-dimensional femur morphology of 40 patients with Crowe type IV DDH was evaluated at each cross-section to determine the femoral cortical bone area. This study focused on five osteotomy lengths (2.5, 3, 3.5, 4, and 4.5 cm). The overlapped area between the proximal and distal cortical bone segments was defined as the contact area (S, mm2), and the contact area to distal cortical bone area ratio was defined as the coincidence rate (R). Three indicators were used to evaluate the matching and fitting of the osteotomy sites with the implanted Wagner cone stems: (1) higher S and R between the proximal and distal segments; (2) the effective fixation length of the femoral stem at the distal segments being at least 1.5 cm; and (3) osteotomy did not involve the isthmus.

Results
In all groups, S significantly decreased in the two proximal levels above the 0.5 cm level below the lesser trochanter (LT) compared with those below this level. In comparison, at osteotomy lengths from 2.5 to 4 cm, R significantly decreased in the three proximal levels. The optimal osteotomy levels ranged from 1.5 and 2.5 cm below the LT for an appropriately sized stem.

Conclusions
Subtrochanteric osteotomy at the optimal level not only ensures fitting of the femur–femoral stem but also meets the requirements of a higher S and R to ensure adequate reduction and stabilization at the osteotomy site, which may contribute to the bone union. Although the optimal osteotomy level varies with the size of the femoral stem and the length of the subtrochanteric osteotomy, the optimal osteotomy levels for an appropriately sized Wagner cone femoral stem implantation range from 1.5 to 2.5 cm below the LT.
The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap
Authors: Walker Keenan A. , Le Page Lydia M. , Terrando Niccolò , Duggan Michael R. , Heneka Michael T. , Bettcher Brianne M. 
Published: June 2023

AbstractPeripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon that has been identified as a risk factor for Alzheimer’s disease. While the role of chronic peripheral inflammation has been well characterized in the context of dementia and other age-related conditions, less is known about the neurologic contribution of acute inflammatory insults that take place outside the central nervous system. Herein, we define acute inflammatory insults as an immune challenge in the form of pathogen exposure (e.g., viral infection) or tissue damage (e.g., surgery) that causes a large, yet time-limited, inflammatory response. We provide an overview of the clinical and translational research that has examined the connection between acute inflammatory insults and Alzheimer’s disease, focusing on three categories of peripheral inflammatory insults that have received considerable attention in recent years: acute infection, critical illness, and surgery. Additionally, we review immune and neurobiological mechanisms which facilitate the neural response to acute inflammation and discuss the potential role of the blood–brain barrier and other components of the neuro-immune axis in Alzheimer’s disease. After highlighting the knowledge gaps in this area of research, we propose a roadmap to address methodological challenges, suboptimal study design, and paucity of transdisciplinary research efforts that have thus far limited our understanding of how pathogen- and damage-mediated inflammatory insults may contribute to Alzheimer’s disease. Finally, we discuss how therapeutic approaches designed to promote the resolution of inflammation may be used following acute inflammatory insults to preserve brain health and limit progression of neurodegenerative pathology.
Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy
Authors: Yang Luming , Chu Zhaole , Liu Meng , Zou Qiang , Li Jinyang , Liu Qin , Wang Yazhou , Wang Tao , Xiang Junyu , Wang Bin 
Published: June 2023

AbstractAmino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound transporters, key metabolic enzymes, and sensors such as mTOR and GCN2 play critical roles in controlling immune cell differentiation and function. As such, anti-cancer immune responses could be enhanced by supplement of specific essential amino acids, or targeting the metabolic enzymes or their sensors, thereby developing novel adjuvant immune therapeutic modalities. To further dissect metabolic regulation of anti-tumor immunity, this review summarizes the regulatory mechanisms governing reprogramming of amino acid metabolism and their effects on the phenotypes and functions of tumor-infiltrating immune cells to propose novel approaches that could be exploited to rewire amino acid metabolism and enhance cancer immunotherapy.
Immunotherapies targeting GPRC5D in relapsed or refractory multiple myeloma: latest updates from 2022 ASH Annual Meeting
Authors: Xia Jieyun , Li Zhenyu , Xu Kailin 
Published: June 2023

AbstractB cell maturation antigen (BCMA)-targeted immunotherapy has shown unprecedented results in the treatment of relapsed or refractory (R/R) multiple myeloma (MM). However, disease progression remains an issue attributed to variable BCMA expression, BCMA downregulation, and heterogeneity of tumor antigens in MM. Therefore, additional treatment options with novel therapeutic targets are warranted. G protein-coupled receptor, class C group 5 member D (GPRC5D), an orphan receptor expressed on malignant plasma cells with limited expression in normal tissue, has emerged as a promising therapeutic target for R/R MM. GPRC5D-targeted chimeric antigen receptor (CAR)-T and CAR-NK cell therapy, as well as bispecific T cell engagers, offer remarkable anti-tumor activities. We summarized some latest reports on GPRC5D-targeted treatments for R/R MM from the 2022 ASH Annual Meeting (ASH 2022).
m6A-mediated upregulation of LINC01003 regulates cell migration by targeting the CAV1/FAK signaling pathway in glioma
Authors: Zhu Xiaolong , Wu Xingwei , Yang Hui , Xu Qiancheng , Zhang Mengying , Liu Xiaocen , Lv Kun 
Published: June 2023

Abstract
Background
Long non-coding RNAs (lncRNAs) play important roles in the progression of glioma. Here, we examined the potential functions of a lncRNA, LINC01003, in glioma and characterized the underlying molecular mechanisms.

Methods
The GEIPA2 and Chinese Glioma Genome Atlas (CCGA) databases were employed to analyze gene expression and the overall survival curve in patients with glioma. The functions of LINC01003 in glioma growth and migration were assessed by loss-of-function experiments in vitro and in vivo. RNA sequencing was used to determine the signaling pathways effected by LINC01003. Bioinformatics analysis and RNA immunoprecipitation (RIP) assays were used to explore the mechanism underlying the N6-methyladenine (m6A) modification-dependent upregulation of LINC01003 in glioma.

Results
LINC01003 expression was upregulated in glioma cell lines and tissues. Higher LINC01003 expression predicted shorter overall survival time in glioma patients. Functionally, LINC01003 knockdown inhibited the cell cycle and cell proliferation and migration in glioma cells. Mechanistically, RNA sequencing revealed that LINC01003 mediated the focal adhesion signaling pathway. Furthermore, LINC01003 upregulation is induced by m6A modification regulated by METTL3.

Conclusion
This study characterized LINC01003 as a lncRNA that contributes to tumorigenesis in glioma and demonstrated that the LINC01003-CAV1-FAK axis serves as a potential therapeutic target for glioma.
Effect of pelvic floor muscle training on reports of urinary incontinence in obese women undergoing a low-calorie diet before bariatric surgery — protocol of a randomized controlled trial
Authors: Mendes Pauliana C. S. , Fretta Tatiana B. , Camargo Milena F. C. , Driusso Patricia , Homsi Jorge Cristine 
Published: June 2023

Abstract

Background

Obesity represents a growing threat to health with multiple negative impacts including urinary incontinence. Pelvic floor muscle training (PFMT) is the first line of treatment for urinary incontinence. Both surgical and conservative weight loss results in improvement of urinary incontinence reports in obese women and we hypothesize that a low-calorie diet in combination with PFMT would result in additional beneficial effects to urinary symptoms in women with UI compared would with weight loss alone.

Objective
To assess the effect of a low-calorie diet plus PFMT protocol in obese women’s urinary incontinence reports.

Methods
This is a protocol for a randomized controlled trial that will include obese women reporting UI and being able to contract their pelvic floor muscles. The participants will be randomly allocated in two groups: group 1 will participate in a 12-week protocol of low-calorie diet delivered by a multi-professional team at a tertiary hospital; group II will receive the same low-calorie diet protocol during 12 weeks and will additionally participate in 6 group sessions of supervised PFMT delivered by a physiotherapist. The primary outcome of the study is self-reported UI, and severity and impact of UI on women’s quality of life will be assessed by the ICIQ-SF score. The secondary outcomes will be adherence to the protocols assessed using a home diary, pelvic floor muscle function assessed by bidigital vaginal palpation and the modified Oxford grading scale, and women’s self-perception of their PFM contraction using a questionnaire. Satisfaction with treatments will be assessed using a visual analog scale. The statistical analysis will be performed by intention to treat and multivariate analysis of mixed effects will be used to compare outcomes. The complier average causal effects (CACE) method will be used to assess adherence. There is an urgent need for a high-quality RCT to investigate if the association of a low-calorie diet and PFMT can provide a larger effect in the improvement of urinary incontinence reports in women with obesity.

Trial registration
Clinical Trials NCT04159467. Registered on 08/28/2021.
Synthesis and drag reduction properties of a hydrophobically associative polymer containing ultra-long side chains
Authors: Jing Xianwu , Liu Youquan , Zhao Wanwei , Pu Junhong 
Published: June 2023

AbstractDifferent from common hydrophobic associative polymers, a new hydrophobic associative polyacrylamide (HAPAM) with ultra-long side chains was synthesized and aimed to be used as drag reducer in this work. Firstly, a water-soluble hydrophobic monomer (named AT114) was obtained by alcoholysis reaction with acryloyl chloride and triton 114, then the drag reducer was obtained by radical copolymerization of AM, AMPS and AT114. The structures of AT114 and drag reducer were characterized by IR and NMR. Slick water was obtained by dissolving a small amount drag reducer in water. Although the viscosity of slick water varied greatly in fresh water and brine, the drag reduction rate always remained at a high level when flowing in pipelines. When the concentration of the drag reducer was 0.03% in fresh water, drag reduction rate can be up to 76.7%, while in high concentration brine, still as high as 76.2%. It shows that salt has no obvious negative impact on the drag reduction rate. That is also to say, in the case of low viscosity, the viscosity change has no obvious impact on drag reduction rate. From the Cryo-TEM observation, it can be concluded that the drag reducer forms sparse network structures in water, which is the direct reason for drag reducing effect. This finding provides knowledge regarding the development of new drag reducers.