bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-pandemic trends and Black:White inequities in life expectancy across the 30 most populous U.S. cities: a population-based study
Authors: Silva Abigail , Saiyed Nazia S. , Canty Emma , Benjamins Maureen R. 
Published: November 2023

Abstract
Background
Racial inequities in life expectancy, driven by structural racism, have been documented at the state and county levels; however, less information is available at the city level where local policy change generally happens. Furthermore, an assessment of life expectancy during the decade preceding COVID-19 provides a point of comparison for life expectancy estimates and trends post COVID-19 as cities recover.

Methods
Using National Vital Statistics System mortality data and American Community Survey population estimates, we calculated the average annual city-level life expectancies for the non-Hispanic Black (Black), non-Hispanic White (White), and total populations. We then calculated the absolute difference between the Black and White life expectancies for each of the 30 cities and the U.S. We analyzed trends over four time periods (2008-2010, 2011-2013, 2014-2016, and 2017-2019).

Results
In 2017-2019, life expectancies ranged from 72.75 years in Detroit to 83.15 years in San Francisco (compared to 78.29 years for the U.S.). Black life expectancy ranged from 69.94 years in Houston to 79.04 years in New York, while White life expectancy ranged from 75.18 years in Jacksonville to 86.42 years in Washington, DC. Between 2008-2010 and 2017-2019, 17 of the biggest cities experienced a statistically significant improvement in life expectancy, while 9 cities experienced a significant decrease. Black life expectancy increased significantly in 14 cities and the U.S. but decreased significantly in 4 cities. White life expectancy increased significantly in 17 cities and the U.S. but decreased in 8 cities. In 2017-2019, the U.S. and all but one of the big cities had a significantly longer life expectancy for the White population compared to the Black population. There was more than a 13-year difference between Black and White life expectancies in Washington, DC (compared to 4.18 years at the national level). From 2008-2010 to 2017-2019, the racial gap decreased significantly for the U.S. and eight cities, while it increased in seven cities.

Conclusion
Urban stakeholders and equity advocates need data on mortality inequities that are aligned with city jurisdictions to help guide the allocation of resources and implementation of interventions.
Interleukin-6 upregulates extracellular matrix gene expression and transforming growth factor β1 activity of tendon progenitor cells
Authors: Altmann Nadine , Bowlby Charles , Coughlin Haley , Belacic Zarah , Sullivan Stasia , Durgam Sushmitha 
Published: November 2023

Abstract
Background
Prolonged inflammation during tendon healing and poor intrinsic healing capacity of tendon are causal factors associated with tendon structural and functional degeneration. Tendon cells, consisting of mature tenocytes and tendon progenitor cells (TPC) function to maintain tendon structure via extracellular matrix (ECM) synthesis. Tendon cells can succumb to tissue cytokine/chemokine alterations during healing and consequently contribute to tendon degeneration. Interleukin-(IL-)1β, IL-6 and TNFα are key cytokines upregulated in injured tendons; the specific effects of IL-6 on flexor tendon-derived TPC have not been discerned.

Methods
Passage 3 equine superficial digital flexor tendon (SDFT)-derived TPC were isolated from 6 horses. IL-6 impact on the viability (MMT assay with 0, 1, 5 and 10 ng/mL concentrations), migration (scratch motility assay at 0, 10ng/mL concentration) of TPC in monolayer culture were assessed. IL-6 effect on tendon ECM and chondrogenic gene expression (qRT-PCR), TGFβ1 gene expression and activity (ELISA), and MMP-1, -3 and − 13 gene expression of TPC was evaluated.

Results
IL-6 decreased TPC viability and migration. IL-6 treatment at 10 ng/mL significantly up-regulated TGFβ1 gene expression (6.3-fold; p = 0.01) in TPC, and significantly increased the TGFβ1 concentration in cell culture supernates. IL-6 (at 10 ng/mL) significantly up-regulated both tendon ECM (COL1A1:5.3-fold, COL3A1:5.4-fold, COMP 5.5-fold) and chondrogenic (COL2A1:3.9-fold, ACAN:6.2-fold, SOX9:4.8-fold) mRNA expression in TPC. Addition of SB431542, a TGFβ1 receptor inhibitor, to TPC in the presence of IL-6, attenuated the up-regulated tendon ECM and chondrogenic genes.

Conclusion
IL-6 alters TPC phenotype during in vitro monolayer culture. Pro- and anti-inflammatory roles of IL-6 have been implicated on tendon healing. Our findings demonstrate that IL-6 induces TGFβ1 activity in TPC and affects the basal TPC phenotype (as evidenced via increased tendon ECM and chondrogenic gene expressions). Further investigation of this biological link may serve as a foundation for therapeutic strategies that modulate IL-6 to enhance tendon healing.
Reduced burnout in medical and health science students during the pandemic COVID-19 - a follow-up study of a single institution in Hungary
Authors: Sipos David , Biro Anett Anna , Busa Flora , Freihat Omar , Tollár József , Pandur Attila András , Kovács Árpád , Deutsch Krisztina , Csima Melinda Petőné 
Published: November 2023

Abstract
Background
The coronavirus pandemic has significantly impacted lives worldwide, especially of medical and health science students. In Hungary, education has been relegated to the online space, with a substantial proportion of students having to attend medical secondments. Increased stress, uncertainty, and the presence of medical secondments can have an impact on students’ premature burnout.

Methods
In 2021, we conducted a follow-up survey among students of the University of Pécs studying medicine and health sciences in two data collection periods (from March to May and September to November). Our online questionnaire consisted of the Maslach Burnout Inventory General Survey for Students and our self-designed questionnaire. We used descriptive and paired two-sample t-tests for data analysis at a 95% confidence interval (p ≤ 0.05).

Results
We excluded from our survey respondents whose data we could not follow-up; finally, 183 students’ responses were analyzed. The majority of students were female (n = 148; 80.9%). Overall, there was a significant decrease in both exhaustion (EX) and cynicism (CY) scores (p = 0.001; p = 0.004). Female respondents had higher EX scores, but a significant decrease was observed for both genders (p ≤ 0.05). Excluding paramedic students, a significant decrease in EX scores was observed for the specialties we studied (p ≤ 0.05). General medicine students’ CY scores decreased; physiotherapy students’ profesisonal efficacy (PE) scores increased significantly (p ≤ 0.05). Students who were on medical secondments (n = 127; 69. 4%) were found to be more affected by burnout, but in all cases, these scores significantly improved (p ≤ 0.05). Students serving in the National Ambulance Service (n = 76; 41.5%), Hospitals (n = 44; 24.0%), or both (n = 7; 3.8%) had a significant decrease in their burnout score (p ≤ 0.05). Students who served in either a hospital or a hospital and National Ambulance Service had significantly improved CY and PE scores (p ≤ 0.05). Students concerned about their health had elevated EX and CY scores, which also improved (p ≤ 0.05).

Conclusions
In conclusion, medical secondments positively affected student burnout scores for medicine and health sciences students at our institution. This fact implies that it is necessary to have more internships in real-life settings during the training.

Trial registration
Our survey has been approved by the Medical Research Council (Case No IV/4573-1/2021/ECU).
Epididymal RNase T2 contributes to astheno-teratozoospermia and intergenerational metabolic disorder through epididymosome-sperm interaction
Authors: Ma Zhuoyao , Li Jinyu , Fu Li , Fu Rong , Tang Ningyuan , Quan Yanmei , Xin Zhixiang , Ding Zhide , Liu Yue 
Published: November 2023

Abstract
Background
The epididymis is crucial for post-testicular sperm development which is termed sperm maturation. During this process, fertilizing ability is acquired through the epididymis-sperm communication via exchange of protein and small non-coding RNAs (sncRNAs). More importantly, epididymal-derived exosomes secreted by the epididymal epithelial cells transfer sncRNAs into maturing sperm. These sncRNAs could mediate intergenerational inheritance which further influences the health of their offspring. Recently, the linkage and mechanism involved in regulating sperm function and sncRNAs during epididymal sperm maturation are increasingly gaining more and more attention.

Methods
An epididymal-specific ribonuclease T2 (RNase T2) knock-in (KI) mouse model was constructed to investigate its role in developing sperm fertilizing capability. The sperm parameters of RNase T2 KI males were evaluated and the metabolic phenotypes of their offspring were characterized. Pandora sequencing technology profiled and sequenced the sperm sncRNA expression pattern to determine the effect of epididymal RNase T2 on the expression levels of sperm sncRNAs. Furthermore, the expression levels of RNase T2 in the epididymal epithelial cells in response to environmental stress were confirmed both in vitro and in vivo.

Results
Overexpression of RNase T2 caused severe subfertility associated with astheno-teratozoospermia in mice caput epididymis, and furthermore contributed to the acquired metabolic disorders in the offspring, including hyperglycemia, hyperlipidemia, and hyperinsulinemia. Pandora sequencing showed altered profiles of sncRNAs especially rRNA-derived small RNAs (rsRNAs) and tRNA-derived small RNAs (tsRNAs) in RNase T2 KI sperm compared to control sperm. Moreover, environmental stress upregulated RNase T2 in the caput epididymis.

Conclusions
The importance was demonstrated of epididymal RNase T2 in inducing sperm maturation and intergenerational inheritance. Overexpressed RNase T2 in the caput epididymis leads to astheno-teratozoospermia and metabolic disorder in the offspring.
Association between the triglyceride–glucose index and left ventricular global longitudinal strain in patients with coronary heart disease in Jilin Province, China: a cross-sectional study
Authors: Na Lin , Cui Wenjing , Li Xinqi , Chang Jing , Xue Xin 
Published: November 2023

Abstract
Background
This study aimed to investigate the association between the triglyceride–glucose (TyG) index and left ventricular global longitudinal strain (GLS) in patients with coronary heart disease and to examine the role of left ventricular GLS in detecting early changes in cardiac function in patients with coronary heart disease in the subclinical stage.

Methods
A cross-sectional study involving 178 participants with symptomatic coronary artery disease excluding myocardial infarction or left ventricular dysfunction was conducted in Jilin Province, China. Basic clinical, biochemical, and echocardiographic data were obtained from all participants. Myocardial strain parameters were compared between patients with higher TyG index and those with lower TyG index, and the association between the gradually elevated TyG index and on subclinical cardiac function in patients with coronary heart disease was evaluated.

Results
The GLS of left ventricle was lower in the higher TyG index group than in the lower TyG index group. As the TyG index increases, the GLS progressively decreases. The results remained stable after adjusting for confounding factors.

Conclusions
A higher TyG index maybe independently associated with subclinical left ventricular dysfunction in patients with coronary heart disease.
Potentiating humoral and cellular immunity using a novel hybrid polymer-lipid nanoparticle adjuvant for HBsAg-VLP vaccine
Authors: Liu Xuhan , Min Qiuxia , Song Huiping , Yue Aochun , Li Qin , Zhou Qing , Han Wei 
Published: November 2023

AbstractAluminium adjuvants are commonly used in vaccines to stimulate the immune system, but they have limited ability to promote cellular immunity which is necessary for clearing viral infections like hepatitis B. Current adjuvants that do promote cellular immunity often have undesired side effects due to the immunostimulants they contain. In this study, a hybrid polymer lipid nanoparticle (HPLNP) was developed as an efficient adjuvant for the hepatitis B surface antigen (HBsAg) virus-like particle (VLP) vaccine to potentiate both humoral and cellular immunity. The HPLNP is composed of FDA approved polyethylene glycol-b-poly (l-lactic acid) (PEG-PLLA) polymer and cationic lipid 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP), and can be easily prepared by a one-step method. The cationic optimised vaccine formulation HBsAg/HPLNP (w/w = 1/600) can maximise the cell uptake of the antigen due to the electrostatic adsorption between the vaccine nanoparticle and the cell membrane of antigen-presenting cells. The HPLNP prolonged the retention of the antigen at the injection site and enhanced the lymph node drainage of antigen, resulting in a higher concentration of serum anti-HBsAg IgG compared to the HBsAg group or the HBsAg/Al group after the boost immunisation in mice. The HPLNP also promoted a strong Th1-driven immune response, as demonstrated by the significantly improved IgG2a/IgG1 ratio, increased production of IFN-γ, and activation of CD4 + and CD8 + T cells in the spleen and lymph nodes. Importantly, the HPLNP demonstrated no systemic toxicity during immunisation. The advantages of the HPLNP, including good biocompatibility, easy preparation, low cost, and its ability to enhance both humoral and cellular immune responses, suggest its suitability as an efficient adjuvant for protein-based vaccines such as HBsAg-VLP. These findings highlight the promising potential of the HPLNP as an HBV vaccine adjuvant, offering an alternative to aluminium adjuvants currently used in vaccines.
TMT quantitative proteomics reveals key proteins relevant to microRNA-1-mediated regulation in osteoarthritis
Authors: Jiang Pinpin , Liang Dan , Wang Hang , Zhou Raorao , Che Xianda , Cong Linlin , Li Penghua , Wang Chunfang , Li Wenjin , Wei Xiaochun , Li Pengcui 
Published: November 2023

AbstractOsteoarthritis (OA) is the second-commonest arthritis, but pathogenic and regulatory mechanisms underlying OA remain incompletely understood. Here, we aimed to identify the mechanisms associated with microRNA-1 (miR-1) treatment of OA in rodent OA models using a proteomic approach. First, N = 18 Sprague Dawley (SD) rats underwent sham surgery (n = 6) or ACL transection (n = 12), followed at an interval of one week by randomization of the ACL transection group to intra-articular administration of either 50 µL placebo (control group) or miR-1 agomir, a mimic of endogenous miR-1 (experimental group). After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and immunohistochemically stained for the presence of MMP-13. Second, N = 30 Col2a1-cre-ERT2 /GFPf1/fl -RFP-miR-1 transgenic mice were randomized to intra-articular administration of either placebo (control group, N = 15) or tamoxifen, an inducer of miR-1 expression (experimental group, N = 15), before undergoing surgical disruption of the medial meniscus (DMM) after an interval of five days. After allowing for eight weeks of remodeling, articular cartilage tissue was harvested and underwent differential proteomic analysis. Specifically, tandem mass tagging (TMT) quantitative proteomic analysis was employed to identify inter-group differentially-expressed proteins (DEP), and selected DEPs were validated using real-time quantitative polymerase chain reaction (RT-qPCR) technology. Immunohistochemically-detected MMP-13 expression was significantly lower in the experimental rat group, and proteomic analyses of mouse tissue homogenate demonstrated that of 3526 identified proteins, 345 were differentially expressed (relative up- and down-regulation) in the experimental group. Proteins Fn1, P4ha1, P4ha2, Acan, F2, Col3a1, Fga, Rps29, Rpl34, and Fgg were the *top ten most-connected proteins, implying that miR-1 may regulate an expression network involving these proteins. Of these ten proteins, three were selected for further validation by RT-qPCR: the transcript of Fn1, known to be associated with OA, exhibited relative upregulation in the experimental group, whereas the transcripts of P4ha1 and Acan exhibited relative downregulation. These proteins may thus represent key miR-1 targets during OA-regulatory mechanisms, and may provide additional insights regarding therapeutic mechanisms of miR-1 in context of OA.
A comprehensive model for assessing and classifying patients with thrombotic microangiopathy: the TMA-INSIGHT score
Authors: Addad Vanessa Vilani , Palma Lilian Monteiro Pereira , Vaisbich Maria Helena , Pacheco Barbosa Abner Mácola , da Rocha Naila Camila , de Almeida Cardoso Marilia Mastrocolla , de Almeida Juliana Tereza Coneglian , de Paula de Sordi Monica AP , Machado-Rugolo Juliana , Arantes Lucas Frederico , de Andrade Luis Gustavo Modelli 
Published: November 2023

Abstract
Background
Thrombotic Microangiopathy (TMA) is a syndrome characterized by the presence of anemia, thrombocytopenia and organ damage and has multiple etiologies. The primary aim is to develop an algorithm to classify TMA (TMA-INSIGHT score).

Methods
This was a single-center retrospective cohort study including hospitalized patients with TMA at a single center. We included all consecutive patients diagnosed with TMA between 2012 and 2021. TMA was defined based on the presence of anemia (hemoglobin level < 10 g/dL) and thrombocytopenia (platelet count < 150,000/µL), signs of hemolysis, and organ damage. We classified patients in eight categories: infections; Malignant Hypertension; Transplant; Malignancy; Pregnancy; Thrombotic Thrombocytopenic Purpura (TTP); Shiga toxin-mediated hemolytic uremic syndrome (STEC-SHU) and Complement Mediated TMA (aHUS). We fitted a model to classify patients using clinical characteristics, biochemical exams, and mean arterial pressure at presentation.

Results
We retrospectively retrieved TMA phenotypes using automatic strategies in electronic health records in almost 10 years (n = 2407). Secondary TMA was found in 97.5% of the patients. Primary TMA was found in 2.47% of the patients (TTP and aHUS). The best model was LightGBM with accuracy of 0.979, and multiclass ROC-AUC of 0.966. The predictions had higher accuracy in most TMA classes, although the confidence was lower in aHUS and STEC-HUS cases.

Conclusion
Secondary conditions were the most common etiologies of TMA. We retrieved comorbidities, associated conditions, and mean arterial pressure to fit a model to predict TMA and define TMA phenotypic characteristics. This is the first multiclass model to predict TMA including primary and secondary conditions.
The role of Nurr1-miR-30e-5p-NLRP3 axis in inflammation-mediated neurodegeneration: insights from mouse models and patients’ studies in Parkinson’s disease
Authors: Li Tianbai , Tan Xiang , Tian Lulu , Jia Congcong , Cheng Cheng , Chen Xi , Wei Min , Wang Yuanyuan , Hu Yiying , Jia Qiqi , Ni Yang , Al-Nusaif Murad , Li Song , Le Weidong 
Published: November 2023

AbstractNuclear receptor related-1 (Nurr1), a ligand-activated transcription factor, is considered a potential susceptibility gene for Parkinson’s disease (PD), and has been demonstrated to possess protective effects against inflammation-induced neuronal damage. Despite the evidence showing decreased NURR1 level and increased pro-inflammatory cytokines in cell and animal models as well as in PD patients’ peripheral blood mononuclear cells (PBMCs), the underlying mechanism remains elusive. In this study, we investigated the molecular mechanism of Nurr1 in PD-related inflammation. Through the miRNA-sequencing and verification in PBMCs from a cohort of 450 individuals, we identified a significant change of a Nurr1-dependent miRNA miR-30e-5p in PD patients compared to healthy controls (HC). Additionally, PD patients exhibited an elevated plasma interleukin-1β (IL-1β) level and increased nucleotide-binding domain-like receptor protein 3 (NLRP3) expression in PBMCs compared to HC. Statistical analyses revealed significant correlations among NURR1, miR-30e-5p, and NLRP3 levels in the PBMCs of PD patients. To further explore the involvement of Nurr1-miR-30e-5p-NLRP3 axis in the inflammation-mediated PD pathology, we developed a mouse model (Nurr1flox+/Cd11b−cre+, Nurr1cKO) conditionally knocking out Nurr1 in Cd11b-expressing cells. Our investigations in Nurr1cKO mice unveiled significant dopaminergic neurodegeneration following lipopolysaccharide-induced inflammation. Remarkably, Nurr1 deficiency triggered microglial activation and activated NLRP3 inflammasome, resulting in increased IL-1β secretion. Coincidently, we found that miR-30e-5p level was significantly decreased in the PBMCs and primary microglia of Nurr1cKO mice compared to the controls. Furthermore, our in vitro experiments demonstrated that miR-30e-5p specifically targeted NLRP3. In Nurr1-knockdown microglia, NLRP3 expression was upregulated via miR-30e-5p. In summary, our findings highlight the involvement of Nurr1-miR-30e-5p-NLRP3 axis in the inflammation-mediated neurodegeneration in PD, the results of which may offer promising prospects for developing PD biomarkers and targeted therapeutic interventions.
Impact of the COVID-19 pandemic on the sexual and reproductive health of adolescents in Alberta, Canada
Authors: Meherali Salima , Rehmani Amyna Ismail , Ahmad Mariam , Adewale Bisi , Kauser Samar , Lebeuf Simone , Benoit James , Scott Shannon D. 
Published: November 2023

Abstract
Purpose
The COVID-19 pandemic led to major service disruptions in the healthcare sector, especially regarding sexual and reproductive health services. However, the impact of the pandemic on Canadian adolescents is relatively unknown. This study aimed to investigate the impacts of the COVID-19 pandemic and associated public health measures on the sexual and reproductive health (SRH) of adolescents in Alberta, Canada.

Methods
A qualitative study using an interpretive description (ID) approach and community-based participatory research principles was conducted to capture the subjective experience and perceptions of adolescents and service providers. With the collaboration of the Adolescent Advisory Group and community partners, 18 adolescents and 15 service providers were recruited for the study through purposive sampling. Findings from the qualitative interviews were analyzed using thematic analysis.

Results
Three major themes emerged from the analysis: (1) COVID-19 SRH experience, (2) barriers to SRH, and (3) adolescent SRH strategies. Our findings highlight numerous barriers and challenges that prevented adolescents from accessing SRH education, products, and services.

Conclusion
The COVID-19 pandemic had a profound impact on the SRH and the well-being of adolescents. Our study reflects the need for diverse SRH strategies to maintain continued access to SRH resources during disruptive events, such as the pandemic.