bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends of a decade in risk factors of patient delay among pulmonary tuberculosis patients during fast aging and urbanization - analysis of surveillance data from 2008 to 2017 in Wuhan, China
Authors: Wang Xiaojun , Li Yuehua , Fu Qian , Zhou Meilan 
Published: May 2023

Abstract
Background
Tuberculosis (TB) is a leading infectious cause of morbidity and mortality worldwide. However, delay in health care seeking has remained unacceptably high. The aim of this study was to clarify the trend of patient delay and its associated risk factors during rapid aging and urbanization in Wuhan, China from 2008 to 2017.

Methods
A total of 63,720 TB patients registered at Wuhan TB Information Management System from January 2008 to December 2017 were included. Long patient delay (LPD) was defined as patient delay longer than 14 days. Independent associations of area and household identity with LPD, as well their interaction effect, were tested by logistic regression models.

Results
Among 63,720 pulmonary TB patients, 71.3% were males, the mean age was 45.5 ± 18.8 years. The median patient delay was 10 days (IQR, 3–28). A total of 26,360 (41.3%) patients delayed for more than 14 days. The proportion of LPD decreased from 44.8% in 2008 to 38.3% in 2017. Similar trends were observed in all the subgroups by gender, age and household, except for living area. The proportion of LPD decreased from 46.3 to 32.8% in patients living near downtown and increased from 43.2 to 45.2% in patients living far from downtown. Further interaction effect analysis showed that among patients living far from downtown, the risk of LPD for local patients increased with age, while decreased with age for migrant patients.

Conclusion
Although the overall LPD among pulmonary TB patients declined in the past decade, the extent of reduction varied in different subgroups. The elderly local and young migrant patients living far from downtown are the most vulnerable groups to LPD in Wuhan, China.
Association between periodontitis and osteoporosis in United States adults from the National Health and Nutrition Examination Survey: a cross-sectional analysis
Authors: Peng Jing , Chen Jianming , Liu Yucheng , Lyu Jun , Zhang Bin 
Published: May 2023

Abstract
Objective
This cross-sectional study aimed to investigate the association between periodontitis and osteoporosis among US adults as well as the subgroup of menopausal women.

Background
Periodontitis and osteoporosis are both chronic inflammatory diseases characterized by local or systemic bone resorption. Since they share many risk factors, and the significant decrease in estrogen along with menopause is unfavorable for both diseases, it’s reasonable to assume that there exists some links between the two diseases, especially during the menopause.

Methods
We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2009–2010 and 2013–2014. Periodontitis (defined according to the CDC/AAP definition) and osteoporosis (assessed by the dual-energy radiation absorptiometry) data were available for 5736 participants, and 519 subjects were enrolled in the subgroup of menopausal women aged 45–60 years old. We used binary logistic regression analysis to examine the association between the two diseases both in crude and fully adjusted model.

Results
In the fully adjusted model, osteoporosis was significantly associated with an increased risk of periodontal disease (OR:1.66, 95% CI: 1.00–2.77) in the whole population. As to the subgroup of menopausal women, osteoporosis group had an adjusted OR of 9.66 (95% CI: 1.13–82.38) for developing severe periodontitis in the fully adjusted model.

Conclusions
Osteoporosis is significantly associated with periodontitis and the association is even more pronounced in menopausal women with severe periodontitis.
Cytotoxic activity of essential oil from Leaves of Myrcia splendens against A549 Lung Cancer cells
Authors: Montalvão Monalisa Martins , Felix Franciel Batista , Propheta dos Santos Edmilson William , Santos Jileno Ferreira , de Lucca Júnior Waldecy , Farias Atenilton Santos , de Souza Ribeiro Adauto , Cavaleiro Carlos , Machado Samísia Maria Fernandes , Scher Ricardo , Corrêa Cristiane Bani 
Published: May 2023

Abstract
Background
Plants of the Myrcia genus have been widely used in folk medicine to treat various diseases, including cancer. Myrcia splendens species has a diverse chemical constitution, but the biological activities of its essential oil have not been well investigated. In this study to out the chemistry characterization of essential oil (EO) from the leaves of the species M. splendens from Brazil and evaluate cytotoxic effect in A549 lung cancer cells.

Methods
M. splendens EO was obtained by hydrodistillation and analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). EO was isolated and evaluated for cellular viability in tumor cell lines by MTT assay. The evaluation of the formation of clones and the migratory capacity of the A549 cells treated with EO was done by the clonogenic assay and the wound healing assay. Morphological changes were observed in A549 cells by fluorescence using Phalloidin/FITC and DAPI.

Results
22 compounds were identified in the chemical analysis of EO, corresponding to 88% of the sample. Major compounds were the sesquiterpenic hydrocarbons bicyclogermacrene (15.4%), germacrene D (8.9%) and E-caryophyllene (10.1%). The biological analysis of the EO showed high cytotoxic activity with an IC50 below 20 µg/ml in the THP-1, A549 and B16-F10 tumor cells. The treatment with EO reduced colony formation and inhibited the migratory capacity of A549 cells. Furthermore, apoptotic morphological changes in the nucleus and cytoplasm of A549 cells was observed after of treatment with EO.

Conclusion
The findings of this study suggest that the M. splendens EO has cytotoxic compounds for the A549 lung cancer cells. Treatment with the EO decreased the colony formation and reduced the ability of lung cancer cells to migrate. Future studies may be used to isolate compounds from the EO for the study of lung cancer.
From expert to novice and back: a qualitative study of interprofessional collaboration and the experiences of frontline healthcare professionals during the first wave of COVID-19
Authors: Heiden Malin , Bernild Camilla , Berg Selina Kikkenborg , Dagyaran Ilkay , Missel Malene , Christensen Signe Westh , Risom Signe Stelling , Højskov Ida Elisabeth 
Published: May 2023

Abstract
Background
The global coronavirus disease 2019 pandemic put extreme pressure on healthcare systems worldwide, forcing a heavy workload on healthcare professionals. Frontline treatment and care for patients with coronavirus disease 2019 compelled healthcare professionals to rapidly adapt to new working conditions. This study explores the experiences of frontline healthcare professionals to learn more about how frontline work affects their learning and skills development but also interprofessional collaboration during a pandemic.

Methods
In-depth, one-to-one semi-structured interviews were conducted with 22 healthcare professionals. A broad interdisciplinary group, the participants were employed in public hospitals in four of Denmark’s five regions. Using a reflexive methodology for the data analysis allowed reflexive interpretation when interpreting subjects and interpreting the interpretation.

Results
The study identified two empirical themes: into the unknown and in the same boat, which we critically interpreted using learning theory and theory on interprofessionalism. The study found that the healthcare professionals moved from being experts in their own fields to being novices in the frontline of the pandemic, and then back to being experts based on interprofessional collaboration that included shared reflection. Working in the frontline was imbued with a unique atmosphere in which workers were equals and functioned interdependently, the barriers normally obstructing interprofessional collaboration set aside to focus on combating the pandemic.

Conclusions
This study reveals new insights regarding knowledge on frontline healthcare professionals in terms of learning and developing new skills, as well as the importance of interprofessional collaboration. The insights contributed to the understanding of the importance of shared reflection and how the development of expertise was a socially embedded process where discussions were possible without fear of being ridiculed and healthcare professionals were willing to share their knowledge.
The degree of cortisol secretion is associated with diabetes mellitus and hypertension in patients with nonfunctioning adrenal tumors
Authors: Favero Vittoria , Aresta Carmen , Parazzoli Chiara , Cairoli Elisa , Eller-Vainicher Cristina , Palmieri Serena , Salcuni Antonio Stefano , Arosio Maura , Persani Luca , Scillitani Alfredo , Morelli Valentina , Chiodini Iacopo 
Published: May 2023

Abstract
Background
Similarly to cortisol-secreting adrenal tumors, also non-functioning adrenal tumors (NFAT) may be associated with an increased cardiovascular risk. We assessed in NFAT patients: (i) the association between hypertension (HT), diabetes mellitus (DM), obesity (OB), dyslipidemia (DL) and cardiovascular events (CVE) and cortisol secretion; (ii) the cut-off of the cortisol secretion parameters for identifying NFAT patients with a worse cardiometabolic profile.

Patients and methods
In 615 NFAT patients (with cortisol levels after 1 mg overnight dexamethasone suppression test, F-1mgDST < 1.8 µg/dL [50 nmol/L]) F-1mgDST and adrenocorticotroph hormone (ACTH) levels and data on HT, DM, OB, DL and CVEs prevalence were retrospectively collected.

Results
HT, DM and HT plus DM were associated with F-1mgDST levels (area under the ROC curve: 0.588 ± 0.023, 0.610 ± 0.028, 0.611 ± 0.033, respectively, p < 0.001 for all comparisons) but not with ACTH. The cut-off for identifying patients with either HT or DM or HT plus DM was set at ≥ 1.2 µg/dL (33 nmol/L). As compared with patients with F-1mgDST < 1.2 µg/dL (n = 289), patients with F-1mgDST 1.2–1.79 µg/dL (33–49.4 nmol/L) (n = 326) had lower ACTH levels (17.7 ± 11.9 vs 15.3 ± 10.1 pg/mL, respectively, p = 0.008), older age (57.5 ± 12.3 vs 62.5 ± 10.9 years, respectively, p < 0.001), and higher prevalence of HT (38.1% vs 52.5% respectively p < 0.001), DM (13.1% vs 23.3%, respectively, p = 0.001), HT plus DM (8.3% vs 16.9%, respectively, p < 0.002) and CVE (3.2% vs 7.3%, respectively, p = 0.028). F-1mgDST 1.2–1.79 µg/dL was associated with either HT (odd ratio, OR, 1.55, 95% confidence interval, 95% CI 1.08–2.23, p = 0.018) or DM (OR 1.60, 95% CI 1.01–2.57, p = 0.045) after adjusting for age, gender, OB, DL, and DM (for HT) or HT (for DM), and with the presence of HT plus DM (OR 1.96, 95% CI 1.12–3.41, p = 0.018) after adjusting for age, gender, OB and DL.

Conclusions
In NFAT patients, F-1mgDST 1.2–1.79 µg/dL seems to be associated with a higher prevalence of HT and DM and a worse cardiometabolic profile, even if the poor accuracy of these associations suggests caution in interpreting these results.
The synergistic effect of the triglyceride-glucose index and serum uric acid on the prediction of major adverse cardiovascular events after coronary artery bypass grafting: a multicenter retrospective cohort study
Authors: Wu Zhenguo , Cheng Cheng , Sun Xiangfei , Wang Juan , Guo Dachuan , Chen Sha , Zhang Yerui , Liu Xiaoyu , Liu Li , Zhang Cheng , Yang Jianmin 
Published: May 2023

AbstractBackgroundElevated serum uric acid (SUA) is regarded as a risk factor for the development of cardiovascular diseases. Triglyceride-glucose (TyG) index, a novel surrogate for insulin resistance (IR), has been proven to be an independent predictor for adverse cardiac events. However, no study has specifically focused on the interaction between the two metabolic risk factors. Whether combining the TyG index and SUA could achieve more accurate prognostic prediction in patients undergoing coronary artery bypass grafting (CABG) remains unknown.MethodsThis was a multicenter, retrospective cohort study. A total of 1225 patients who underwent CABG were included in the final analysis. The patients were grouped based on the cut-off value of the TyG index and the sex-specific criteria of hyperuricemia (HUA). Cox regression analysis was conducted. The interaction between the TyG index and SUA was estimated using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). The improvement of model performance yielded by the inclusion of the TyG index and SUA was examined by C-statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The goodness-of-fit of models was evaluated using the Akaike information criterion (AIC), Bayesian information criterion (BIC) and χ2likelihood ratio test.ResultsDuring follow-up, 263 patients developed major adverse cardiovascular events (MACE). The independent and joint associations of the TyG index and SUA with adverse events were significant. Patients with higher TyG index and HUA were at higher risk of MACE (Kaplan–Meier analysis: log-rankP < 0.001; Cox regression: HR = 4.10; 95% CI 2.80–6.00,P < 0.001). A significant synergistic interaction was found between the TyG index and SUA [RERI (95% CI): 1.83 (0.32–3.34),P = 0.017; AP (95% CI): 0.41 (0.17–0.66),P = 0.001; SI (95% CI): 2.13 (1.13–4.00),P = 0.019]. The addition of the TyG index and SUA yielded a significant improvement in prognostic prediction and model fit [change in C-statistic: 0.038,P < 0.001; continuous NRI (95% CI): 0.336 (0.201–0.471),P < 0.001; IDI (95% CI): 0.031 (0.019–0.044),P < 0.001; AIC: 3534.29; BIC: 3616.45; likelihood ratio test:P < 0.001).ConclusionsThe TyG index interacts synergistically with SUA to increase the risk of MACE in patients undergoing CABG, which emphasizes the need to use both measures concurrently when assessing cardiovascular risk.
PKM2/STAT1-mediated PD-L1 upregulation on neutrophils during sepsis promotes neutrophil organ accumulation by serving an anti-apoptotic role
Authors: Li Yinjiaozhi , Tan Ruoming , Li Ranran , Tian Rui , Liu Zhaojun , Wang Xiaoli , Chen Erzhen , Pan Tingting , Qu Hongping 
Published: May 2023

Abstract
Background
Delayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored.

Methods
Peripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry.

Results
PD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1−/− mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis.

Conclusion
In this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets.
Preloading with drugs before entry to the nighttime entertainment district: presentation, intoxication rates, and effects of police presence during assessment
Authors: Hughes Lee R. J. , Allen Corey , Devilly Grant J. 
Published: May 2023

Abstract
Background
Past research has either focused on alcohol or drug preloading before a night out, but not on the interaction between them. With increased risks of harm through interaction effects, we wished to build upon previous research in this area. We sought to determine who drug preloads, why do people engage in this practice, what drug/s are people using, and how inebriated they are as they enter the NED. Additionally, we examined what impact varying levels of police presence has on the collections of sensitive data in this context.

Methods
We captured estimates of drug and alcohol preloading from 4723 people entering nighttime entertainment districts (NEDs) in Queensland, Australia. Data collection occurred under three varying conditions of police presence (i.e., no police present, police present but not engaging with participants, and police engaging with participants).

Results
People who admitted to preloading drugs were found to be younger in age than non-drug admitters, more likely to be male than female, use one type of drug (mostly stimulants) rather than multiple (if we exclude alcohol), significantly more intoxicated upon arrival, and more subjectively affected from their use of alcohol and drugs as Breath Approximated Alcohol Concertation levels increased. People were more likely to admit having used drugs in the absence of police, but this had only a small effect.

Conclusions
People who drug preload are a vulnerable subset of the youth population that is susceptible to experiencing harms in this context. As they drink more alcohol, they experience higher affects than those who do not report to also take drugs. Police engagement through service rather than force may mitigate some risks. Further enquiry is needed to better understand those who engage in this practice and to have quick, cheap, objective tests of what drugs these people are using.
Preventative effect of TSPO ligands on mixed antibody-mediated rejection through a Mitochondria-mediated metabolic disorder
Authors: Zhang Yannan , He Jiannan , Yang Zhe , Zheng Haofeng , Deng Haoxiang , Luo Zihuan , Sun Qipeng , Sun Qiquan 
Published: May 2023

Abstract
Background
Immune-mediated rejection was the major cause of graft dysfunction. Although the advances in immunosuppressive agents have markedly reduced the incidence of T-cell-mediated rejection after transplantation. However, the incidence of antibody-mediated rejection (AMR) remains high. Donor-specific antibodies (DSAs) were considered the major mediators of allograft loss. Previously, we showed that treatment with 18-kDa translocator protein (TSPO) ligands inhibited the differentiation and effector functions of T cells and reduced the rejection observed after allogeneic skin transplantation in mice. This study we further investigate the effect of TSPO ligands on B cells and DSAs production in the recipients of mixed-AMR model.

Methods
In vitro, we explored the effect of treatment with TSPO ligands on the activation, proliferation, and antibody production of B cells. Further, we established a heart-transplantation mixed-AMR model in rats. This model was treated with the TSPO ligands, FGIN1-27 or Ro5-4864, to investigate the role of ligands in preventing transplant rejection and DSAs production in vivo. As TSPO was the mitochondrial membrane transporters, we then investigated the TSPO ligands effect on mitochondrial-related metabolic ability of B cells as well as expression of downstream proteins.

Results
In vitro studies, treatment with TSPO ligands inhibited the differentiation of B cells into CD138+CD27+ plasma cells; reduced antibodies, IgG and IgM, secretion of B cells; and suppressed the B cell activation and proliferation. In the mixed-AMR rat model, treatment with FGIN1-27 or Ro5-4864 attenuated DSA-mediated cardiac-allograft injury, prolonged graft survival, and reduced the numbers of B cells, including IgG+ secreting B cells, T cells and macrophages infiltrating in grafts. For the further mechanism exploration, treatment with TSPO ligands inhibited the metabolic ability of B cells by downregulating expression of pyruvate dehydrogenase kinase 1 and proteins in complexes I, II, and IV of the electron transport chain.

Conclusions
We clarified the mechanism of action of TSPO ligands on B-cell functions and provided new ideas and drug targets for the clinical treatment of postoperative AMR.
The effect of metformin on influenza vaccine responses in nondiabetic older adults: a pilot trial
Authors: Martin Dominique E. , Cadar Andreia N. , Panier Hunter , Torrance Blake L. , Kuchel George A. , Bartley Jenna M. 
Published: May 2023

Abstract
Background
Aging is associated with progressive declines in immune responses leading to increased risk of severe infection and diminished vaccination responses. Influenza (flu) is a leading killer of older adults despite availability of seasonal vaccines. Geroscience-guided interventions targeting biological aging could offer transformational approaches to reverse broad declines in immune responses with aging. Here, we evaluated effects of metformin, an FDA approved diabetes drug and candidate anti-aging drug, on flu vaccination responses and markers of immunological resilience in a pilot and feasibility double-blinded placebo-controlled study.

Results
Healthy older adults (non-diabetic/non-prediabetic, age: 74.4 ± 1.7 years) were randomized to metformin (n = 8, 1500 mg extended release/daily) or placebo (n = 7) treatment for 20 weeks and were vaccinated with high-dose flu vaccine after 10 weeks of treatment. Peripheral blood mononuclear cells (PBMCs), serum, and plasma were collected prior to treatment, immediately prior to vaccination, and 1, 5, and 10 weeks post vaccination. Increased serum antibody titers were observed post vaccination with no significant differences between groups. Metformin treatment led to trending increases in circulating T follicular helper cells post-vaccination. Furthermore, 20 weeks of metformin treatment reduced expression of exhaustion marker CD57 in circulating CD4 T cells.

Conclusions
Pre-vaccination metformin treatment improved some components of flu vaccine responses and reduced some markers of T cell exhaustion without serious adverse events in nondiabetic older adults. Thus, our findings highlight the potential utility of metformin to improve flu vaccine responses and reduce age-related immune exhaustion in older adults, providing improved immunological resilience in nondiabetic older adults.