bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of high polycyclic aromatic hydrocarbon exposure on biological aging indicators
Authors: Campisi Manuela , Mastrangelo Giuseppe , Mielżyńska-Švach Danuta , Hoxha Mirjam , Bollati Valentina , Baccarelli Andrea A. , Carta Angela , Porru Stefano , Pavanello Sofia 
Published: March 2023

Abstract

Background
Aging represents a serious health and socioeconomic concern for our society. However, not all people age in the same way and air pollution has been shown to largely impact this process. We explored whether polycyclic aromatic hydrocarbons (PAHs), excellent fossil and wood burning tracers, accelerate biological aging detected by lymphocytes DNA methylation age (DNAmAge) and telomere length (TL), early nuclear DNA (nDNA) hallmarks of non-mitotic and mitotic cellular aging, and mitochondrial DNA copy number (mtDNAcn).

Methods
The study population consisted of 49 male noncurrent-smoking coke-oven workers and 44 matched controls. Occupational and environmental sources of PAH exposures were evaluated by structured questionnaire and internal dose (urinary 1-pyrenol). We estimated Occup_PAHs, the product of 1-pyrenol and years of employment as coke-oven workers, and Environ_PAHs, from multiple items (diet, indoor and outdoor). Biological aging was determined by DNAmAge, via pyrosequencing, and by TL and mtDNAcn, via quantitative polymerase chain reaction. Genomic instability markers in lymphocytes as target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)–DNA adduct], genetic instability (micronuclei), gene-specific (p53, IL6 and HIC1) and global (Alu and LINE-1 repeats) DNA methylation, and genetic polymorphisms (GSTM1) were also evaluated in the latent variable nDNA_changes. Structural equation modelling (SEM) analysis evaluated these multifaceted relationships.

Results
In univariate analysis, biological aging was higher in coke-oven workers than controls as detected by higher percentage of subjects with biological age older than chronological age (AgeAcc ≥ 0, p = 0.007) and TL (p = 0.038), mtDNAcn was instead similar. Genomic instability, i.e., genotoxic and epigenetic alterations (LINE-1, p53 and Alu) and latent variable nDNA_changes were higher in workers (p < 0.001). In SEM analysis, DNAmAge and TL were positively correlated with Occup_PAHs (p < 0.0001). Instead, mtDNAcn is positively correlated with the latent variable nDNA_changes (p < 0.0001) which is in turn triggered by Occup_PAHs and Environ_PAHs.

Conclusions
Occupational PAHs exposure influences DNAmAge and TL, suggesting that PAHs target both non-mitotic and mitotic mechanisms and made coke-oven workers biologically older. Also, differences in mtDNAcn, which is modified through nDNA alterations, triggered by environmental and occupational PAH exposure, suggested a nuclear-mitochondrial core-axis of aging. By decreasing this risky gerontogenic exposure, biological aging and the consequent age-related diseases could be prevented.
Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments
Authors: Yuan Zhennan , Li Yingpu , Zhang Sifan , Wang Xueying , Dou He , Yu Xi , Zhang Zhiren , Yang Shanshan , Xiao Min 
Published: March 2023

AbstractThe malignant tumor is a multi-etiological, systemic and complex disease characterized by uncontrolled cell proliferation and distant metastasis. Anticancer treatments including adjuvant therapies and targeted therapies are effective in eliminating cancer cells but in a limited number of patients. Increasing evidence suggests that the extracellular matrix (ECM) plays an important role in tumor development through changes in macromolecule components, degradation enzymes and stiffness. These variations are under the control of cellular components in tumor tissue via the aberrant activation of signaling pathways, the interaction of the ECM components to multiple surface receptors, and mechanical impact. Additionally, the ECM shaped by cancer regulates immune cells which results in an immune suppressive microenvironment and hinders the efficacy of immunotherapies. Thus, the ECM acts as a barrier to protect cancer from treatments and supports tumor progression. Nevertheless, the profound regulatory network of the ECM remodeling hampers the design of individualized antitumor treatment. Here, we elaborate on the composition of the malignant ECM, and discuss the specific mechanisms of the ECM remodeling. Precisely, we highlight the impact of the ECM remodeling on tumor development, including proliferation, anoikis, metastasis, angiogenesis, lymphangiogenesis, and immune escape. Finally, we emphasize ECM "normalization" as a potential strategy for anti-malignant treatment.
Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship
Authors: Ceranski A. Katharina , Carreño-Gonzalez Martha J. , Ehlers Anna C. , Colombo Maria Vittoria , Cidre-Aranaz Florencia , Grünewald Thomas G. P. 
Published: March 2023

AbstractHypoxia develops during the growth of solid tumors and influences tumoral activity in multiple ways. Low oxygen tension is also present in the bone microenvironment where Ewing sarcoma (EwS) – a highly aggressive pediatric cancer – mainly arises. Hypoxia inducible factor 1 subunit alpha (HIF-1-a) is the principal molecular mediator of the hypoxic response in cancer whereas EWSR1::FLI1 constitutes the oncogenic driver of EwS. Interaction of the two proteins has been shown in EwS. Although a growing body of studies investigated hypoxia and HIFs in EwS, their precise role for EwS pathophysiology is not clarified to date. This review summarizes and structures recent findings demonstrating that hypoxia and HIFs play a role in EwS at multiple levels. We propose to view hypoxia and HIFs as independent protagonists in the story of EwS and give a perspective on their potential clinical relevance as prognostic markers and therapeutic targets in EwS treatment.
Association between triglyceride glucose index and subclinical left ventricular systolic dysfunction in patients with type 2 diabetes
Authors: Chen Yanyan , Fu Jianfang , Wang Yi , Zhang Ying , Shi Min , Wang Cheng , Li Mengying , Wang Li , Liu Xiangyang , Ta Shengjun , Liu Liwen , Li Zeping , Li Xiaomiao , Zhou Jie 
Published: March 2023

Abstract
Background
The triglyceride glucose (TyG) index has been considered a new biomarker for the diagnosis of angiocardiopathy and insulin resistance. However, the association of the TyG index with subclinical left ventricular (LV) systolic dysfunction still lacks comprehensive exploration. This study was carried out to examine this relationship in patients with type 2 diabetes mellitus (T2DM).

Methods
A total of 150 T2DM patients with preserved LV ejection fraction (LVEF ≥ 50%) from June 2021 to December 2021 were included in this study. The subclinical LV function was evaluated through global longitudinal strain (GLS), with the predefined GLS < 18% as the cutoff for subclinical LV systolic dysfunction. The TyG index calculation was obtained according to ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2), which was then stratified into quartiles (TyG index—Q).

Results
Analyses of clinical characteristics in the four TyG indexes-Q (Q1 (TyG index ≤ 8.89) n = 38, Q2 (8.89 < TyG index ≤ 9.44) n = 37, Q3 (9.44 < TyG index ≤ 9.83) n = 38, and Q4 (TyG index > 9.83) n = 37) were conducted. A negative correlation of the TyG index with GLS (r = -0.307, P < 0.001) was revealed according to correlation analysis. After gender and age were adjusted in multimodel logistic regression analysis, the higher TyG index (OR 6.86; 95% CI 2.44 to 19.30; P < 0.001, Q4 vs Q1) showed a significant association with GLS < 18%, which was still maintained after further adjustment for related clinical confounding factors (OR 5.23, 95% CI 1.12 to 24.51, p = 0.036, Q4 vs Q1). Receiver operator characteristic analysis indicated a diagnostic capacity of the TyG index for GLS < 18% (area under curve: 0.678; P < 0.001).

Conclusions
A higher TyG index had a significant association with subclinical LV systolic dysfunction in T2DM patients with preserved ejection fraction, and the TyG index may have the potential to exert predictive value for myocardial damage.
Lipid metabolism-related miRNAs with potential diagnostic roles in prostate cancer
Authors: Zhai Tianyuan , Dou Meng , Ma Yubo , Wang Hong , Liu Fang , Zhang Liandong , Chong Tie , Wang Ziming , Xue Li 
Published: March 2023

Abstract
Background
Prostate cancer (PCa), the second most prevalent solid tumor among men worldwide, has caused greatly increasing mortality in PCa patients. The effects of lipid metabolism on tumor growth have been explored, but the mechanistic details of the association of lipid metabolism disorders with PCa remain largely elusive.

Methods
The RNA sequencing data of the GSE45604 and The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) datasets were extracted from the Gene Expression Omnibus (GEO) and UCSC Xena databases, respectively. The Molecular Signatures Database (MSigDB) was utilized to identify lipid metabolism-related genes. The limma R package was used to identify differentially expressed lipid metabolism-related genes (DE-LMRGs) and differentially expressed microRNAs (DEMs). Moreover, least absolute shrinkage and selection operator (LASSO), extreme gradient boosting (XGBoost), and support vector machine-recursive feature elimination (SVM-RFE) were applied to select signature miRNAs and construct a lipid metabolism-related diagnostic model. The expression levels of selected differentially expressed lipid metabolism-related miRNAs (DE-LMRMs) in PCa and benign prostate hyperplasia (BPH) specimens were verified using quantitative real-time polymerase chain reaction (qRT‒PCR). Furthermore, a transcription factor (TF)-miRNA‒mRNA network was constructed. Eventually, Kaplan‒Meier (KM) curves were plotted to illustrate the associations between signature miRNA-related mRNAs and TFs and overall survival (OS) along with biochemical recurrence-free survival (BCR).

Results
Forty-seven LMRMs were screened based on the correlation analysis of 29 DE-LMRGs and 56 DEMs, in which 27 LMRMs were stably expressed in the GSE45604 dataset. Subsequently, receiver operating characteristic (ROC) curves and machine learning methods were employed to develop a lipid metabolism-related diagnostic signature, which may be of diagnostic value for PCa patients. qRT‒PCR results showed that all seven key DE-LMRMs were differentially expressed between PCa and BPH tissues. Eventually, a TF-miRNA‒mRNA network was constructed.

Conclusions
These results suggested that 7 key diagnostic miRNAs were closely related to PCa pathological processes and provided new targets for the diagnosis and treatment of PCa. Moreover, CLIC6 and SCNN1A linked to miR-200c-3p had good prognostic potential and provided valuable insights into the pathogenesis of PCa.
Components of the sympathetic nervous system as targets to modulate inflammation – rheumatoid arthritis synovial fibroblasts as neuron-like cells?
Authors: Cheng Xinkun , Lowin Torsten , Honke Nadine , Pongratz Georg 
Published: March 2023

Abstract
Background
Catecholamines are major neurotransmitters of the sympathetic nervous system (SNS) and they are of pivotal importance in regulating numerous physiological and pathological processes. Rheumatoid arthritis (RA) is influenced by the activity of the SNS and its neurotransmitters norepinephrine (NE) and dopamine (DA) and early sympathectomy alleviates experimental arthritis in mice. In contrast, late sympathectomy aggravates RA, since this procedure eliminates anti-inflammatory, tyrosine hydroxylase (TH) positive cells that appear in the course of RA. While it has been shown that B cells can take up, degrade and synthesize catecholamines it is still unclear whether this also applies to synovial fibroblasts, a mesenchymal cell that is actively engaged in propagating inflammation and cartilage destruction in RA. Therefore, this study aims to present a detailed description of the catecholamine pathway and its influence on human RA synovial fibroblasts (RASFs).

Results
RASFs express all catecholamine-related targets including the synthesizing enzymes TH, DOPA decarboxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase. Furthermore, vesicular monoamine transporters 1/2 (VMAT1/2), dopamine transporter (DAT) and norepinephrine transporter (NET) were detected. RASFs are also able to degrade catecholamines as they express monoaminoxidase A and B (MAO-A/MAO-B) and catechol-O-methyltransferase (COMT). TNF upregulated VMAT2, MAO-B and NET levels in RASFs. DA, NE and epinephrine (EPI) were produced by RASFs and extracellular levels were augmented by either MAO, COMT, VMAT or DAT/NET inhibition but also by tumor necrosis factor (TNF) stimulation. While exogenous DA decreased interleukin-6 (IL-6) production and cell viability at the highest concentration (100 μM), NE above 1 μM increased IL-6 levels with a concomitant decrease in cell viability. MAO-A and MAO-B inhibition had differential effects on unstimulated and TNF treated RASFs. The MAO-A inhibitor clorgyline fostered IL-6 production in unstimulated but not TNF stimulated RASFs (10 nM-1 μM) while reducing IL-6 at 100 μM with a dose-dependent decrease in cell viability in both groups. The MAO-B inhibitor lazabemide hydrochloride did only modestly decrease cell viability at 100 μM while enhancing IL-6 production in unstimulated RASFs and decreasing IL-6 in TNF stimulated cells.

Conclusions
RASFs possess a complete and functional catecholamine machinery whose function is altered under inflammatory conditions. Results from this study shed further light on the involvement of sympathetic neurotransmitters in RA pathology and might open therapeutic avenues to counteract inflammation with the MAO enzymes being key candidates.
Analytical methods for assessing antimicrobial activity of nanomaterials in complex media: advances, challenges, and perspectives
Authors: Zhang Xuzhi , Hou Xiangyi , Ma Liangyu , Shi Yaqi , Zhang Dahai , Qu Keming 
Published: March 2023

AbstractAssessing the antimicrobial activity of engineered nanomaterials (ENMs), especially in realistic scenarios, is of great significance for both basic research and applications. Multiple analytical methods are available for analysis via off-line or on-line measurements. Real-world samples are often complex with inorganic and organic components, which complicates the measurements of microbial viability and/or metabolic activity. This article highlights the recent advances achieved in analytical methods including typical applications and specifics regarding their accuracy, cost, efficiency, and user-friendliness. Methodological drawbacks, technique gaps, and future perspectives are also discussed. This review aims to help researchers select suitable methods for gaining insight into antimicrobial activities of targeted ENMs in artificial and natural complex matrices.
A realist review of best practices and contextual factors enhancing treatment of opioid dependence in Indigenous contexts
Authors: Henderson Rita , McInnes Ashley , Danyluk Ava , Wadsworth Iskotoah’ka , Healy Bonnie , Crowshoe Lindsay 
Published: March 2023

Abstract
Objectives
The objective of this study was to examine international literature to identify best practices for treatment of opioid dependence in Indigenous contexts.

Methods
We utilized a systematic search to identify relevant literature. The literature was analysed using a realist review methodology supported by a two-step knowledge contextualization process, including a Knowledge Holders Gathering to initiate the literature search and analysis, and five consensus-building meetings to focus and synthesize relevant findings. A realist review methodology incorporates an analysis of the complex contextual factors in treatment by identifying program mechanisms, namely how and why different programs are effective in different contexts.

Results
A total of 27 sources were identified that met inclusion criteria. Contextual factors contributing to opioid dependence described in the literature often included discussions of a complex interaction of social determinants of health in the sampled community. Twenty-four articles provided evidence of the importance of compassion in treatment. Compassion was evidenced primarily at the individual level, in interpersonal relationships based on nonjudgmental care and respect for the client, as well as in more holistic treatment programs beyond biophysical supports such as medically assisted treatment. Compassion was also shown to be important at the structural level in harm reduction policies. Twenty-five articles provided evidence of the importance of client self-determination in treatment programs. Client self-determination was evidenced primarily at the structural level, in community-based programs and collaborative partnerships based in trust and meaningful engagement but was also shown to be important at the individual level in client-directed care. Identified outcomes moved beyond a reduction in opioid use to include holistic health and wellness goals, such as improved life skills, self-esteem, feelings of safety, and healing at the individual level. Community-level outcomes were also identified, including more families kept intact, reduction in drug-related medical evacuations, criminal charges and child protection cases, and an increase in school attendance, cleanliness, and community spirit.

Conclusions
The findings from this realist review indicate compassion and self-determination as key program mechanisms that can support outcomes beyond reduced incidence of substance use to include mitigating systemic health inequities and addressing social determinants of health in Indigenous communities, ultimately healing the whole human being.
“The new normal has become a nonstop crisis”: a qualitative study of burnout among Philadelphia’s harm reduction and substance use disorder treatment workers during the COVID-19 pandemic
Authors: Unachukwu Ijeoma C. , Abrams Matthew P. , Dolan Abby , Oyekemi Kehinde , Meisel Zachary F. , South Eugenia C. , Aronowitz Shoshana V. 
Published: March 2023

Abstract
Background
The COVID-19 pandemic worsened the ongoing overdose crisis in the United States (US) and caused significant mental health strain and burnout among health care workers (HCW). Harm reduction, overdose prevention, and substance use disorder (SUD) workers may be especially impacted due to underfunding, resources shortages, and chaotic working environments. Existing research on HCW burnout primarily focuses on licensed HCWs in traditional environments and fails to account for the unique experiences of harm reduction workers, community organizers, and SUD treatment clinicians.

Methods
We conducted a qualitative secondary analysis descriptive study of 30 Philadelphia-based harm reduction workers, community organizers, and SUD treatment clinicians about their experiences working in their roles during the COVID-19 pandemic in July–August 2020. Our analysis was guided by Shanafelt and Noseworthy’s model of key drivers of burnout and engagement. We aimed to assess the applicability of this model to the experiences of SUD and harm reduction workers in non-traditional settings.

Results
We deductively coded our data in alignment with Shanafelt and Noseworthy’s key drivers of burnout and engagement: (1) workload and job demands, (2) meaning in work, (3) control and flexibility, (4) work-life integration, (5) organizational culture and values, (6) efficiency and resources and (7) social support and community at work. While Shanafelt and Noseworthy’s model broadly encompassed the experiences of our participants, it did not fully account for their concerns about safety at work, lack of control over the work environment, and experiences of task-shifting.

Conclusions
Burnout among healthcare providers is receiving increasing attention nationally. Much of this coverage and the existing research have focused on workers in traditional healthcare spaces and often do not consider the experiences of community-based SUD treatment, overdose prevention, and harm reduction providers. Our findings indicate a gap in existing frameworks for burnout and a need for models that encompass the full range of the harm reduction, overdose prevention, and SUD treatment workforce. As the US overdose crisis continues, it is vital that we address and mitigate experiences of burnout among harm reduction workers, community organizers, and SUD treatment clinicians to protect their wellbeing and to ensure the sustainability of their invaluable work.
A scoping review of implementation considerations for harm reduction vending machines
Authors: Russell Erin , Johnson Jessica , Kosinski Zach , Kaplan Callie , Barnes Nicole , Allen Sean , Haroz Emily 
Published: March 2023

Abstract
Background
Community-based harm reduction vending machines (HRVM) are not new to the field of public health; numerous countries have implemented them in response to the needs of people who use drugs over the last three decades. However, until recently, few existed in the United States. Given the rapidity with which communities are standing up harm reduction vending machines, there is a pressing need for a consolidated examination of implementation evidence. This scoping review summarizes existing literature using multiple implementation science frameworks.

Methods
The scoping review was conducted in five stages including (1) Identify the research question; (2) Identify relevant studies; (3) Select the publications based on inclusion/exclusion criteria; (4) Review and extract data; and, (5) Summarize results. PubMed, Embase, and Web of Science were searched and authors screened publications in English from any year. Data were extracted by applying implementation constructs from RE-AIM and the Consolidated Framework for Implementation Research (CFIR). Both frameworks provided a useful lens through which to develop knowledge about the facilitators and barriers to HRVM implementation. The review is reported according to PRISMA guidelines.

Results
After applying the full inclusion and exclusion criteria, including the intervention of interest (“vending machines”) and population of interest (“people who use drugs”), a total of 22 studies were included in the scoping review. None of the studies reported on race, making it difficult to retroactively apply a racial equity lens. Among those articles that examined effectiveness, the outcomes were mixed between clear effectiveness and inconclusive results. Evidence emerged, however, to address all CFIR constructs, and positive outcomes were observed from HRVM’s after-hour availability and increased program reach.

Recommendations
HRVM implementation best practices include maximizing accessibility up to 24 h, 7 days a week, offering syringe disposal options, ensuring capability of data collection, and allowing for anonymity of use. Organizations that implement HRVM should establish strong feedback loops between them, their program participants, and the broader community upfront. Considerations for future research include rigorous study designs to evaluate effectiveness outcomes (e.g. reduced drug overdose deaths) and examination of HRVM reach among ethnic and racial communities.