bluuebunny/crossref_metadata_2025 huggingface dataset:
Living arrangement of Indian elderly: a predominant predictor of their level of life satisfaction
Authors: Kandapan Binayak , Pradhan Jalandhar , Pradhan Itishree
Published: February 2023

Objective

This article aims to examine the level of life satisfaction (LS) among Indian older adults and to determine whether their living arrangement is one of the potential determinants of their level of LS.

Methods

Data was drawn from the first and most recent wave of Longitudinal Ageing Study in India conducted in 2017–18. Using the Satisfaction with Life Scale, the level of LS was assessed for 30,370 elderly aged 60 + . Bivariate analysis was carried out to see the variation in the level of LS across elderlies with different socio-demographic characteristics. To investigate the association between LS and living arrangements and the selected socio-demographic factors multinomial logistic regression model was fitted.

Result

The findings reveal that 25.4% and 45.5% of the elderlies have reported having a low and high level of LS, respectively. Living alone was associated with low level of LS. Co-residing with a spouse was associated with a higher likelihood of reporting high level of LS. The study also found that having both spouse and children as coresident increases the likelihood of reporting high level of LS (RRR = 3.15, 95%CI = 2.3–4.28). Elderly with self-reported poor health, limitation in more than two activities of daily living and presence of depressive symptoms were significantly associated with reporting low level of LS. However, being diagnosed with more than three chronic illnesses was associated with high level of LS (RRR = 1.41, 95%CI = 1.25–1.59). Older adults with the following characteristics were more likely to report a lower level of LS: male, 60–64 years old, no or few years of schooling, unmarried, working, rural resident, living in a poor household, Scheduled Caste and Tribe.

Conclusion

The level of life satisfaction in Indian older adults is significantly associated with their living arrangements, thus suggesting that the LS of older adults could be facilitated through interventions that consider their living arrangements. Older adults with various personal and household characteristics were identified as vulnerable groups, who should be the prime targets of the existing welfare policies.
GDNF-RET signaling and EGR1 form a positive feedback loop that promotes tamoxifen resistance via cyclin D1
Authors: Marks Brooke A. , Pipia Ilissa M. , Mukai Chinatsu , Horibata Sachi , Rice Edward J. , Danko Charles G. , Coonrod Scott A.
Published: February 2023

Background

Rearranged during transfection (RET) tyrosine kinase signaling has been previously implicated in endocrine resistant breast cancer, however the mechanism by which this signaling cascade promotes resistance is currently not well described. We recently reported that glial cell-derived neurotrophic factor (GDNF)-RET signaling appears to promote a positive feedback loop with the transcription factor early growth response 1 (EGR1). Here we investigate the mechanism behind this feedback loop and test the hypothesis that GDNF-RET signaling forms a regulatory loop with EGR1 to upregulate cyclin D1 (CCND1) transcription, leading to cell cycle progression and tamoxifen resistance.

Methods

To gain a better understanding of the GDNF-RET-EGR1 resistance mechanism, we studied the GDNF-EGR1 positive feedback loop and the role of GDNF and EGR1 in endocrine resistance by modulating their transcription levels using CRISPR-dCAS9 in tamoxifen sensitive (TamS) and tamoxifen resistant (TamR) MCF-7 cells. Additionally, we performed kinetic studies using recombinant GDNF (rGDNF) treatment of TamS cells. Finally, we performed cell proliferation assays using rGDNF, tamoxifen (TAM), and Palbociclib treatments in TamS cells. Statistical significance for qPCR and chromatin immunoprecipitation (ChIP)-qPCR experiments were determined using a student’s paired t-test and statistical significance for the cell viability assay was a one-way ANOVA.

Results

GDNF-RET signaling formed a positive feedback loop with EGR1 and also downregulated estrogen receptor 1 (ESR1) transcription. Upregulation of GDNF and EGR1 promoted tamoxifen resistance in TamS cells and downregulation of GDNF promoted tamoxifen sensitivity in TamR cells. Additionally, we show that rGDNF treatment activated GDNF-RET signaling in TamS cells, leading to recruitment of phospho-ELK-1 to the EGR1 promoter, upregulation of EGR1 mRNA and protein, binding of EGR1 to the GDNF and CCND1 promoters, increased GDNF protein expression, and subsequent upregulation of CCND1 mRNA levels. We also show that inhibition of cyclin D1 with Palbociclib, in the presence of rGDNF, decreases cell proliferation and resensitizes cells to TAM.

Conclusion

Outcomes from these studies support the hypotheses that GDNF-RET signaling forms a positive feedback loop with the transcription factor EGR1, and that GDNF-RET-EGR1 signaling promotes endocrine resistance via signaling to cyclin D1. Inhibition of components of this signaling pathway could lead to therapeutic insights into the treatment of endocrine resistant breast cancer.
Association between diverticular disease and colorectal cancer: a bidirectional mendelian randomization study
Authors: Zhang Yanxi , Zhang Han , Zhu Jinghan , He Yazhou , Wang Peng , Li Doudou , Liu Xiaozhuan , Jin Wen , Zhang Junxi , Xu Chuan , Yu Zengli , Zhao Xin , Cui Lingling
Published: February 2023

Background:

Diverticular disease has been inconsistently associated with colorectal cancer risk. We conducted a bidirectional Mendelian randomization study to assess this association.

Methods:

Forty-three and seventy single-nucleotide polymorphisms associated with diverticular disease and colorectal cancer at the genome-wide significance level (p < 5 × 10− 8) were selected as instrumental variables from large-scale genome-wide association studies of European descent, respectively. Summary-level data for colon cancer, rectum cancer, and colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium and the UK Biobank study. Summary-level data for diverticular disease was derived from a genome-wide association study conducted in the UK Biobank population. The random effect inverse-variance weighted Mendelian randomization approach was used as the primary method and MR-Egger, weighted-median, and MR-PRESSO approaches were conducted as sensitivity analyses.

Results:

Genetically determined diverticular disease was associated with a higher risk of colorectal cancer (beta = 0.441, 95%CI: 0.081–0.801, P = 0.016) in the FinnGen population, but the association was not found in the UK Biobank (beta = 0.208, 95%CI: -0.291,0.532, P = 0.207). The positive association remained consistent direction in the three sensitivity analyses. In the stratified analysis in the FinnGen consortium, an association was found to exist between genetically predicted diverticular disease and colon cancer (beta = 0.489, 95%CI: 0.020–0.959, P = 0.041), rather than rectum cancer (beta = 0.328, 95%CI: -0.119-0.775, P = 0.151). Besides, we found a slight association between colorectal cancer and diverticular disease (beta = 0.007, 95%CI: 0.004–0.010, P < 0.001) when using colorectal cancer as exposome and diverticular disease as outcome. However, there is a large sample overlap in this step of analysis.

Conclusion:

This Mendelian randomization study suggests that diverticular disease may be a possible risk factor for colorectal cancer and colon cancer rather than rectum cancer in the FinnGen population.
Genetic studies in the Pakistani population reveal novel associations with ventricular septal defects (VSDs)
Authors: Sarwar Sumbal , Shabana  , Sajjad Khadija , Hasnain Shahida
Published: February 2023

Background

With prevalence up to 4%, Ventricular Septal Defect (VSD) is one of the leading causes of neonatal deaths. VSD is a common complex genetic disorder that has been associated with many genetic determinants. Variants from genes for the transcription factors including T-BoxTBX5andNFATc1(nuclear factor of activated T cells, cytoplasmic 1), Vascular endothelial growth factor (VEGF), ISLET1 (encoded by theISL1gene) and enzymeMTHFR, a methylene tetrahydrofolate reductase were selected. Genetic risk score (GRS) is a widely accepted approach used to convert the genetic data into prediction and assessment tool for disease susceptibility.

Methods

A total of 200 participants were recruited for the current study, 100 VSD patients and 100 controls. Genotyping of theISL1: rs1017,NFATc1: rs7240256,VEGF: rs36208048,TBX5: rs11067075, andMTHFR: rs1801133 variants was performed using tetra primer ARMS PCR and PCR-RFLP. For the statistical analysis, the software SPSS version 23 was used. Genotypic frequencies of cases and controls were calculated using chi-square (χ²) whereas allelic frequencies were calculated by using the SNPStats tool. The association of GRS quartiles with VSD was examined using binary logistic regression. Adjustedp-value 0.01 was used as significance threshold for all analyses.

Results

TheISL1(OD: 0.242, CI: 0.158–0.37,p-value: 2.15 × 10− 4:),NFATc1(OD: 2.53, CI: 1.64–3.89,p-value: 2.11 × 10− 5),TBX5(OD: 2.24, CI: 1.47–3.41,p-value:1.6 × 10− 4) andMTHFR(OD: 10.46, CI: 5.68–19.26,p-value: 2.09 × 10− 9:) variants were found to be in association with VSD. In contrast, theVEGF(OD: 0.952, CI: 0.56–1.62,p-value: 0.8921) variant did not show significance association with the VSD. For cases, the mean GRS score was 3.78 ± 1.285 while in controls it was 2.95 ± 1.290 (p-value: 0.479, CI: 0.474–1.190). Comparison of GRS between cases and control showed that mean GRS of cases was 1.90 ± 0.480 while in controls it was 1.68 ± 0.490 (p-value: 0.001, CI: 0.086–0.354). Higher quartiles were more prevalent in cases whereas lower quartiles were more prevalent in controls.

Conclusion

GRS of these five loci was strongly associated with VSD. Moreover, genetic risk score can provide better information for the association between variants and disease as compared to a single SNP. We also illustrated that the cumulative power of GRS is greater over the single SNP effect. This is a pilot scale study with a relatively small sample size whose findings should be replicated in a larger sample size for the unique local Pakistani population.
The effect of APN, hs-CRP and APN/hs-CRP in periodontitis with DAA
Authors: Cheng Rui , Xu Xiaojiang , Yang Shurong , mi Zhongqian , Zhao Yong , Wang Chong , Shi Xuexue , Gao Jinhua , Yu Feiyan , Ren Xiuyun
Published: February 2023

Background

Common chronic infections induced low-grade inflammation has been correlated with atherosclerosis as supported by strong evidence. The balance between pro-and anti-inflammatory factors was exploited to elucidate the effects of chronic periodontitis on diabetes-associated atherosclerosis.

Methods

Study subjects encompassed 30 SPF male rats randomly divided into four groups: A group (NC), B group (T2DM), C group (CP), D group (DM + CP). After developing the model, blood samples were collected from the angular vein analyze serum APN, hs-CRP, and blood lipid. the carotid artery was isolated for HE staining.

Result

Compared with group A, the serum APN in group B, C and D decreased gradually with the progression of the disease. Serum hs-CRP in group B, C and D was significantly increased. At T3, T4 and T5 in group B, C and D, APN/hs-CRP significantly decreased. TC, LDL and TG significantly increased in group B, D; HDL significantly decreased in group C. Carotid artery HE staining showed: compared with group A, different degrees of endothelial defect, destruction of elastic fibers in the middle membrane, disorder of smooth muscle arrangement, and partial dissolution 、 fragmentation and Calcium salt deposition necrosis occurred in group B, C and D.

Conclusion

Enhanced systemic inflammation, decreased adiponectin level, and disorganized lipid metabolism with or without type 2 diabetes attributed to local inflammation of periodontitis can result in an imbalance of pro-inflammatory and anti-inflammatory effects. Therefore, it’s more meaningful to predict the progression of DAA with anti-inflammatory/pro-inflammatory variation.
Using a simulation-based approach to promote structured and interactive nursing clinical handover: a pre- and post-evaluation pilot study in bilingual Hong Kong
Authors: Pun Jack
Published: February 2023

Effective clinical nursing handover involves the transfer of responsibility and accountability for patient care between nurses, leading to better patient safety and continuity of care. Nurses in bilingual contexts, such as Hong Kong – where nurses are trained in English but communicate in Cantonese – may find it challenging to deliver a safe clinical handover. This article reports a pilot study in which a simulation-based approach is being developed to enhance nursing handover with structured and interactive interactions, using handover protocols such as ISBAR (introduction, situation, background, assessment, recommendation and readback) and CARE-team (connect, ask, respond, empathise) protocols in a bilingual context. The study has a pre‐ and post-evaluation design involving a questionnaire survey before and after a 4‐hour workshop. Fourteen selected bilingual nurses in Hong Kong were trained according to the ISBAR and CARE-team protocols, and their perceptions of complete and structured handovers were evaluated before and after training using the questionnaire. The nurses reported that they were more self-confident in their handover experiences, with a deeper understanding of ISBAR and CARE-team protocols after the simulation-based training intervention, leading to better (i.e., more structured and interactive) clinical handover between nurses. Overall, the staff perceived their handover communication to have improved using simulation-based training.
Transformational leadership and predictors of resilience among registered nurses: a cross-sectional survey in an underserved area
Authors: Abdul Salam Hana’a , Dumit Nuhad Yazbik , Clinton Michael , Mahfoud Ziyad
Published: February 2023

Background

High resilience increases nurses' ability to cope with job-related stressors and enhances job satisfaction and, consequently, their retention. The study aims to identify resilience predictors and perceptions of transformational leadership in a convenience sample of registered nurses in Lebanon.

Methods

An anonymous cross-sectional survey of a convenience sample of 240 registered nurses working for more than a year at three private hospitals in an underserved area in South Lebanon was used. The survey instrument included demographic questions, the True Resilience Scale ©, and the Global Transformational Leadership Scale. Multiple linear regression was used to assess the predictors of resilience after a descriptive analysis of the study variables.

Results

The survey response rate was 85%. The nurses' mean resilience score was 119.4 (SD 15.3), and their perception of transformational leadership score was M = 25.0, SD = 6.8. Compared to bedside nurses, nurse managers, nurses with more than five years of experience, and nurses in critical nursing units had statistically significant higher resilience scores (p < 0.05). Resilience scores and perception of global transformational leadership were moderately correlated (r = 0.53, p < 0.05). In the final multiple linear regression model, 30% of the variation in resilience scores was explained by designation (p < 0.05) and perception of Global Transformational Leadership (p < 0.01). Perception of global transformational leadership scores explained 29% of the variance in resilience scores. Designation and perception of global transformational leadership predicted resilience in this sample.

Conclusions

A national survey of the Lebanese nursing workforce is needed to achieve an improved predictive model and support policy developments to increase resilience among bedside nurses and retain them in the nursing workforce. Nurse administrators can help by strengthening their transformational leadership behaviors. Consistent use of transformational leadership styles will strengthen bedside nurses' resilience, increase nurse retention, and help sustain the Lebanese nursing workforce.
Interpreter use in sustained nurse home visiting: interpreter experience and support
Authors: Bonakdar Tehrani Mehrnoush , Baird Kelly , Trajkovski Suza , Kaplun Catherine , Bruce Tracey , Kemp Lynn
Published: February 2023

Background

The aim of this study was to explore the experiences of healthcare interpreters working with child and family health nurses (CFHNs) in providing child and family health nursing (CFHN) services and sustained nurse home visiting (SNHV) programs to culturally and linguistically diverse (CALD) families with limited English proficiency.

Methods

A mixed methods longitudinal research design was conducted to develop, implement and evaluate a training and practice support model for healthcare interpreters working with nurses and CALD families in providing CFHN services and SNHV programs in three major local health services in Sydney, Australia. One pre-training survey with 24 healthcare interpreters was conducted; field notes were recorded during training and implementation; and a post-implementation focus group with six healthcare interpreters was conducted. Quantitative survey data were analysed descriptively using Alchemer. The focus group was audio-recorded for transcription purposes, and this and the field notes were thematically analysed applying a socioecological framework.

Results

Three themes were identified from the initial, pre-training survey: facilitate communication and delivery accurately; a bridge linking the clients and the healthcare practitioners; and make everybody feel comfortable. Practice support implementation was negatively impact by system and COVID-19 related barriers. Four themes were developed from evaluative phase of the study including: system-related issues; interpreters’ challenges; working with nurses; and client session related issues.

Conclusion

Quality interpreting was favourably influenced by adequate time for interpreting the session including a pre- and post-briefing session with CFHNs, an appropriate mode of interpretation, allocation of female interpreters and the same interpreters with CALD mothers and clarity about interpreter role and cultural comfort. These strategies support the quality of communication and relationships in delivery of CFHN services and SNHV programs to CALD mothers with limited English proficiency.
Dual-specificity phosphatases 22-deficient T cells contribute to the pathogenesis of ankylosing spondylitis
Authors: Chen Ming-Han , Chuang Huai-Chia , Yeh Yi-Chen , Chou Chung-Tei , Tan Tse-Hua
Published: February 2023

Background

Dual-specificity phosphatases (DUSPs) can dephosphorylate both tyrosine and serine/threonine residues of their substrates and regulate T cell-mediated immunity and autoimmunity. The aim of this study was to investigate the potential roles of DUSPs in ankylosing spondylitis (AS).

Methods

Sixty AS patients and 45 healthy controls were enrolled in this study. Associations of gene expression of 23 DUSPs in peripheral T cells with inflammatory cytokine gene expression and disease activity of AS were analyzed. Finally, we investigated whether the characteristics of AS are developed in DUSP-knockout mice.

Results

The mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in peripheral T cells were significantly higher in AS group than those of healthy controls (all p < 0.05), while DUSP22 (also named JKAP) mRNA levels were significantly lower in AS group than healthy controls (p < 0.001). The mRNA levels of DUSP4, DUSP5, DUSP6, DUSP7, and DUSP14 in T cells were positively correlated with mRNA levels of tumor necrosis factor-α (TNF-α), whereas DUSP22 was inversely correlated (all p < 0.05). In addition, inverse correlations of DUSP22 gene expression in peripheral T cells with C-reactive protein, erythrocyte sedimentation rate, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were observed (all p < 0.05). More importantly, aged DUSP22 knockout mice spontaneously developed syndesmophyte formation, which was accompanied by an increase of TNF-α+, interleukin-17A+, and interferon-γ+ CD3+ T cells.

Conclusions

DUSP22 may play a crucial role in the pathogenesis and regulation of disease activity of AS.
Serological testing of an equal-volume milk sample – a new method to estimate the seroprevalence of small ruminant lentivirus infection?
Authors: Potârniche Adrian-Valentin , Czopowicz Michał , Szaluś-Jordanow Olga , Moroz-Fik Agata , Mickiewicz Marcin , Biernacka Kinga , Witkowski Lucjan , Markowska-Daniel Iwona , Bagnicka Emilia , Cerbu Constantin , Olah Diana , Trif Emilia , Spinu Marina , Kaba Jarosław
Published: February 2023

Background

In cattle attempts to evaluate within-herd prevalence of various infectious and parasitic diseases by bulk-tank milk (BTM) testing with ELISA have been made with moderate success. The fact that BTM is composed of variable and unknown volumes of milk from individual lactating animals weakens the relationship between numerical result of the ELISA and the within-herd prevalence. We carried out a laboratory experimental study to evaluate if a pooled milk sample created by mixing an equal volume of individual milk samples from seropositive and seronegative goats, henceforth referred to as an equal-volume milk sample (EVMS), would allow for accurate estimation of within-herd seroprevalence of caprine arthritis-encephalitis (CAE) using 3 different commercial ELISAs. By mixing randomly selected milk samples from seronegative and seropositive goats, 193 EVMS were created – 93 made of seronegative samples and 100 with the proportion of seropositive individual milk samples (EVMS%POS) ranging from 1 to 100%. EVMS%POScould be considered as a proxy for the within-herd seroprevalence. Then, OD of EVMS (ODEVMS) of the 193 EVMS was measured using 3 commercial ELISAs for CAE – 2 indirect and 1 competitive.

Results

The cut-off values of ODEVMSindicating SRLV infection were determined. The regression functions were developed to link ODEVMSwith EVMS%POS. A significant monotonic relationship between ODEVMSmeasured with 2 commercial indirect ELISAs and EVMS%POSwas identified. Two regression models developed on this basis described approximately 90% of variability and allowed to estimate EVMS%POS, when it was below 50%. High ODEVMSindicated EVMS%POSof > 50%.

Conclusion

Our study introduces the concept of serological testing of EVMS as a method of detecting SRLV-infected herds and estimating the proportion of strongly seropositive goats. Further field studies are warranted to assess practical benefits of EVMS serological testing.
Roles of cancer-associated fibroblasts (CAFs) in anti- PD-1/PD-L1 immunotherapy for solid cancers
Authors: Pei Liping , Liu Yang , Liu Lin , Gao Shuochen , Gao Xueyan , Feng Yudi , Sun Zhenqiang , Zhang Yan , Wang Chengzeng
Published: February 2023

In recent years, breakthroughs have been made in tumor immunotherapy. However, tumor immunotherapy, particularly anti-PD-1/PD-L1 immune checkpoint inhibitors, is effective in only a small percentage of patients in solid cancer. How to improve the efficiency of cancer immunotherapy is an urgent problem to be solved. As we all know, the state of the tumor microenvironment (TME) is an essential factor affecting the effectiveness of tumor immunotherapy, and the cancer-associated fibroblasts (CAFs) in TME have attracted much attention in recent years. As one of the main components of TME, CAFs interact with cancer cells and immune cells by secreting cytokines and vesicles, participating in ECM remodeling, and finally affecting the immune response process. With the in-depth study of CAFs heterogeneity, new strategies are provided for finding targets of combination immunotherapy and predicting immune efficacy. In this review, we focus on the role of CAFs in the solid cancer immune microenvironment, and then further elaborate on the potential mechanisms and pathways of CAFs influencing anti-PD-1/PD-L1 immunotherapy. In addition, we summarize the potential clinical application value of CAFs-related targets and markers in solid cancers.
Ginsenoside Rg1 attenuates the NASH phenotype by regulating the miR-375-3p/ATG2B/PTEN-AKT axis to mediate autophagy and pyroptosis
Authors: Chen Xuanxin , Xue Wei , Zhang Jia , Peng Jiayi , Huang Wenxiang
Published: February 2023

Background

Nonalcoholic steatohepatitis (NASH) is one of the most frequent liver diseases at present, and there is no radical treatment. The consequences of a variety of ginsenoside compounds on this situation have before been reported, however, the specific effect on the monomeric ginsenoside Rg1 (Rg1) and its associated underlying molecular mechanism stay unknown.

Material and methods

In vitro, the cell models were constructed by exposing free fatty acids (FFAs) to HepG2 cells. A methionine and choline deficiency (MCD)-induced NASH mouse model was also established over 5–6 weeks of treatment. Rg1 is a traditional Chinese medicine monomer. These NASH models were treated with Rg1 and analyzed by qRT-PCR, Western Blot, sequencing, Oil red O staining, immunofluorescence, enzyme activity, HE staining, ELISA, double luciferase reporter assay, and immunohistochemistry.

Results

Overexpression of ATG2B, an autophagy-related protein, attenuated lipid droplet accumulation and reduces ALT, AST, inflammatory cytokines, hydrogen peroxide, and pyroptosis in established mouse and cellular models of NASH and increased levels of ATP and autophagy. The binding sites of miR-375-3p and ATG2B were verified by bioinformatic prediction and a dual-luciferase reporter gene. Knockdown of miR-375-3p promoted autophagy and inhibited pyroptosis. ATG2B knockdown substantially attenuated the impact of miR-375-3p on NASH. Rg1 appears to regulate the occurrence and development of NASH inflammation through miR-375-3p and ATG2B in vitro and in vivo, and is regulated by PTEN-AKT pathway.

Conclusions

This study showed that Rg1 participates in autophagy and pyroptosis through the miR-375-3p/ATG2B/PTEN-AKT pathway, thereby alleviating the occurrence and development of NASH, for that reason revealing Rg1 as a candidate drug for NASH.
Incidence and risk factors of venous thrombotic events in patients with interstitial lung disease during hospitalization
Authors: Sun Haishuang , Liu Min , Yang Xiaoyan , Xi Linfeng , Xu Wenqing , Deng Mei , Ren Yanhong , Xie Wanmu , Dai Huaping , Wang Chen
Published: February 2023

Background

Studies on the incidence of venous thromboembolism (VTE) events in patients with interstitial lung disease (ILD) are limited and the results are inconsistent. The aim of this research was to investigate the incidence and risk factors of VTE in ILD during hospitalization.

Materials and methods

In this retrospective, cross-sectional, observational study, a total of 5009 patients diagnosed with ILD from January 2016 to March 2022 in our hospital were retrospectively included. In ILD patients, VTE including pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT) were screened from the electronic medical record system. Diagnosis of PTE and DVT were performed by CT pulmonary angiography (CTPA), CTV or ultrasound. And then the incidence and risk factors of VTE in different types of ILD were assessed.

Results

Among 5009 patients with ILD, VTE was detected in 129 (2.6%) patients, including 15(0.3%) patients with both PTE and DVT, 34 (0.7%) patients with PTE and 80 (1.6%) patients with DVT. 85.1% of patients with APE were in the intermediate-low risk group. The incidence of VTE in Anti-Neutrophil Cytoplasmic Antibodies -associated vasculitis related ILD (ANCA-AV-ILD), hypersensitivity pneumonitis and idiopathic pulmonary fibrosis (IPF) respectively was 7.9% and 3.6% and 3.5%. In patients with connective tissue disease-associated ILD (CTD-ILD), the incidence of VTE, DVT, PTE, combined PTE and DVT respectively was 3.0%, 2.3%, 0.4% and 0.3%. Among the various risk factors, different ILD categories, age ≥ 80 years (OR 4.178, 95% CI 2.097–8.321, P < 0.001), respiratory failure (OR 2.382, 95% CI 1.533–3.702, P < 0.001) and varicose veins (OR 3.718, 95% CI 1.066–12.964, P = 0.039) were independent risk factors of VTE. The incidence of VTE in patients with ILD increased with the length of time in hospital from 2.2% (< 7 days) to 6.4% (> 21 days).

Conclusion

The incidence of VTE during hospitalization in ILD patients was 2.6%, with a 1.6% incidence of DVT, higher than the 0.7% incidence of PTE. Advanced age, ILD categories, respiratory failure and varicose veins as independent risk factors for the development of VTE should be closely monitored.
Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease
Authors: Sui Yuan , Li Shuping , Fu Xue-Qi , Zhao Zhizhuang Joe , Xing Shu
Published: February 2023

Background

Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up.

Methods

Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses.

Results

The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway.

Conclusion

The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.
BCG-induced trained immunity: history, mechanisms and potential applications
Authors: Chen Jingjing , Gao Li , Wu Xinya , Fan Yuxin , Liu Meixiao , Peng Li , Song Jieqin , Li Bingxue , Liu Aihua , Bao Fukai
Published: February 2023

The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases.
BAX as the mediator of C-MYC sensitizes acute lymphoblastic leukemia to TLR9 agonists
Authors: Bai Ling , Zhou Lei , Han Wei , Chen Jingtao , Gu Xiaoyi , Hu Zheng , Yang Yongguang , Li Wei , Zhang Xiaoying , Niu Chao , Chen Yongchong , Li Hui , Cui Jiuwei
Published: February 2023

Background

The prognosis of B-cell acute lymphoblastic leukemia (B-ALL) has improved significantly with current first-line therapy, although the recurrence of B-ALL is still a problem. Toll-like receptor 9 (TLR9) agonists have shown good safety and efficiency as immune adjuvants. Apart from their immune regulatory effect, the direct effect of TLR9 agonists on cancer cells with TLR9 expression cannot be ignored. However, the direct effect of TLR9 agonists on B-ALL remains unknown.

Methods

We discussed the relationship between TLR9 expression and the clinical characteristics of B-ALL and explored whether CpG 685 exerts direct apoptotic effect on B-ALL without inhibiting normal B-cell function. By using western blot, co-immunoprecipitation, immunofluorescence co-localization, and chromatin immunoprecipitation, we explored the mechanism of the apoptosis-inducing effect of CpG 685 in treating B-ALL cells. By exploring the mechanism of CpG 685 on B-ALL, the predictive biomarkers of the efficacy of CpG 685 in treating B-ALL were explored. These efficiencies were also confirmed in mouse model as well as clinical samples.

Results

High expression of TLR9 in B-ALL patients showed good prognosis. C-MYC-induced BAX activation was the key to the effect of CpG oligodeoxynucleotides against B-ALL. C-MYC overexpression promoted P53 stabilization, enhanced Bcl-2 associated X-protein (BAX) activation, and mediated transcription of the BAX gene. Moreover, combination therapy using CpG 685 and imatinib, a BCR-ABL kinase inhibitor, could reverse resistance to CpG 685 or imatinib alone by promoting BAX activation and overcoming BCR-ABL1-independent PI3K/AKT activation.

Conclusion

TLR9 is not only a prognostic biomarker but also a potential target for B-ALL therapy. CpG 685 monotherapy might be applicable to Ph− B-ALL patients with C-MYC overexpression and without BAX deletion. CpG 685 may also serve as an effective combinational therapy against Ph+ B-ALL.
Pristane induced lupus mice as a model for neuropsychiatric lupus (NPSLE)
Authors: Yun Yang , Wang Xuejiao , Xu Jingyi , Jin Chenye , Chen Jingyu , Wang Xueru , Wang Jianing , Qin Ling , Yang Pingting
Published: February 2023

Background

The pristane-induced lupus (PIL) model is a useful tool for studying environmental-related systemic lupus erythematosus (SLE). However, neuropsychiatric manifestations in this model have not been investigated in detail. Because neuropsychiatric lupus (NPSLE) is an important complication of SLE, we investigated the neuropsychiatric symptoms in the PIL mouse model to evaluate its suitability for NPSLE studies.

Results

PIL mice showed olfactory dysfunction accompanied by an anxiety- and depression-like phenotype at month 2 or 4 after pristane injection. The levels of cytokines (IL-1β, IFN-α, IFN-β, IL-10, IFN-γ, IL-6, TNF-α and IL-17A) and chemokines (CCL2 and CXCL10) in the brain and blood–brain barrier (BBB) permeability increased significantly from week 2 or month 1, and persisted throughout the observed course of the disease. Notably, IgG deposition in the choroid plexus and lateral ventricle wall were observed at month 1 and both astrocytes and microglia were activated. Persistent activation of astrocytes was detected throughout the observed course of the disease, while microglial activation diminished dramatically at month 4. Lipofuscin deposition, a sign of neuronal damage, was detected in cortical and hippocampal neurons from month 4 to 8.

Conclusion

PIL mice exhibit a series of characteristic behavioral deficits and pathological changes in the brain, and therefore might be suitable for investigating disease pathogenesis and for evaluating potential therapeutic targets for environmental-related NPSLE.
The effect of dextrose prolotherapy versus placebo/other non‐surgical treatments on pain in chronic plantar fasciitis: a systematic review and meta‐analysis of clinical trials
Authors: Ahadi Tannaz , Cham Masumeh Bagherzadeh , Mirmoghtadaei Mahtab , Raissi Gholam Reza , Janbazi Lobaneh , Zoghi Ghazal
Published: February 2023

Background

Prolotherapy is the injection of a small volume of sclerosing or irritant solutions into an injured tissue. We aimed to investigate the effect of dextrose prolotherapy (DPT) versus placebo/other non‐surgical treatments on pain in chronic plantar fasciitis.

Methods

We searched seven electronic databases (PubMed/MEDLINE, Web of Science, EMBASE, Scopus, ProQuest, CENTRAL, PEDro) from inception to December 31, 2021 with no language restriction for publications comparing the effect of DPT with placebo/other non‐surgical treatments in patients with chronic plantar fasciitis. Our primary outcome was pain and the secondary outcomes were foot function and plantar fascia thickness. The risk of bias was assessed using the Cochrane Collaboration's tool.

Results

Overall, eight studies with a total of 449 patients were included in the meta‐analysis. All the included studies reported short‐term pain. A large effect size (dppc2 = ‐0.97, 95% confidence interval [CI] ‐1.84 to ‐0.10) was observed favoring the use of DPT to reduce pain in patients with chronic plantar fasciitis in the short‐term. The results for foot function improvement (dppc2 = ‐1.28, 95% CI ‐2.49 to ‐0.07) and plantar fascia thickness reduction (dppc2 = ‐1.02, 95% CI ‐1.99 to ‐0.05) in the short‐term were also in favor of DPT.

Conclusions

Since almost all the included studies had high risk of bias and multiple trials lacked long‐term follow‐ups, further high‐quality research is required to determine the long‐term effects of DPT vs placebo/other non‐surgical interventions.
UPDATE - 2022 Italian guidelines on the management of bronchiolitis in infants
Authors: Manti Sara , Staiano Annamaria , Orfeo Luigi , Midulla Fabio , Marseglia Gian Luigi , Ghizzi Chiara , Zampogna Stefania , Carnielli Virgilio Paolo , Favilli Silvia , Ruggieri Martino , Perri Domenico , Di Mauro Giuseppe , Gattinara Guido Castelli , D’Avino Antonio , Becherucci Paolo , Prete Arcangelo , Zampino Giuseppe , Lanari Marcello , Biban Paolo , Manzoni Paolo , Esposito Susanna , Corsello Giovanni , Baraldi Eugenio
Published: February 2023

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.
SampleQC: robust multivariate, multi-cell type, multi-sample quality control for single-cell data
Authors: Macnair Will , Robinson Mark
Published: February 2023

Quality control (QC) is a critical component of single-cell RNA-seq (scRNA-seq) processing pipelines. Current approaches to QC implicitly assume that datasets are comprised of one cell type, potentially resulting in biased exclusion of rare cell types. We introduce , which robustly fits a Gaussian mixture model across multiple samples, improves sensitivity, and reduces bias compared to current approaches. We show via simulations that is less susceptible to exclusion of rarer cell types. We also demonstrate on a complex real dataset (867k cells over 172 samples). is general, is implemented in R, and could be applied to other data types.
Proteomic analysis of exosome-like vesicles from Fasciola gigantica adult worm provides support for new vaccine targets against fascioliasis
Authors: Sheng Zhao-An , Wu Cui-Lan , Wang Dong-Ying , Zhong Shu-Hong , Yang Xi , Rao Guo-Shun , Peng Hao , Feng Shi-Wen , Li Jun , Huang Wei-Yi , Luo Hong-Lin
Published: February 2023

Background

Extracellular vesicles (EVs) released by helminths play an important role in parasite-host communication. However, little is known about the characteristics and contents of the EVs of Fasciola gigantica, a parasitic flatworm that causes tropical fascioliasis. A better understanding of EVs released by F. gigantica will help elucidate the mechanism of F. gigantica-host interaction and facilitate the search for new vaccine candidates for the control and treatment of fascioliasis.

Methods

Two different populations of EVs (15k EVs and 100k EVs) were purified from adult F. gigantica culture media by ultracentrifugation. The morphology and size of the purified EVs were determined by transmission electron microscopy (TEM) and by the Zetasizer Nano ZSP high performance particle characterization system. With the aim of identifying diagnostic markers or potential vaccine candidates, proteins within the isolated 100k EVs were analyzed using mass spectrometry-based proteomics (LC–MS/MS). Mice were then vaccinated with excretory/secretory products (ESPs; depleted of EVs), 15k EVs, 100k EVs and recombinant F. gigantica heat shock protein 70 (rFg-HSP70) combined with alum adjuvant followed by challenge infection with F. gigantica metacercariae. Fluke recovery and antibody levels were used as measures of vaccine protection.

Results

TEM analysis and nanoparticle tracking analysis indicated the successful isolation of two subpopulations of EVs (15k EVs and 100k EVs) from adult F. gigantica culture supernatants using differential centrifugation. A total of 755 proteins were identified in the 100k EVs. Exosome biogenesis or vesicle trafficking proteins, ESCRT (endosomal sorting complex required for transport) pathway proteins and exosome markers, heat shock proteins and 14-3-3 proteins were identified in the 100k EVs. These results indicate that the isolated 100k EVs were exosome-like vesicles. The functions of the identified proteins may be associated with immune regulation, immune evasion and virulence. Mice immunized with F. gigantica ESPs, 15k EVs, 100k EVs and rFg-HSP70 exhibited a reduction in fluke burden of 67.90%, 60.38%, 37.73% and 56.6%, respectively, compared with the adjuvant control group. The vaccination of mice with F. gigantica 100k EVs, 15k EVs, ESP and rFg-HSP70 induced significant production of specific immunoglobulins in sera, namely IgG, IgG1 and IgG2a.

Conclusion

The results of this study suggest that proteins within the exosome-like vesicles of F. gigantica have immunomodulatory, immune evasion and virulence functions. This knowledge may lead to new strategies for immunotherapy, vaccination and the diagnosis of fascioliasis.

Graphical Abstract
Extramedullary relapse of Immunoglobulin A-kappa myeloma manifesting as plasmacytoma of the pleura without bone marrow involvement and following autologous bone marrow transplant: a case report
Authors: Rezvani Alireza , Shahriarirad Reza , Fallahi Mohammad Javad , Zeighami Ali
Published: February 2023

Background

Recurrence of multiple myeloma is among the most challenging issues for patients and treating physicians reported after autologous stem cell transplantation. However, extramedullary involvement after chemotherapy and transplantation has been rarely reported, especially as pleural manifestations. Protein electrophoresis indicated immunoglobulin A monoclonal kappa plasma cell neoplasm in our case.

Case presentation

A 48-year-old middle-eastern man was referred to our clinic with cough, dyspnea, fever, and left side pleural effusion. A year after chemotherapy and autologous bone marrow transplantation, the patient presented with features in favor of pleural relapse, without bone marrow involvement. Protein electrophoresis demonstrated immunoglobulin A monoclonal kappa plasma cell neoplasm in our case. The patient was effectively treated with dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide with no notable adverse effects.

Conclusion

Physicians should be aware of various presentations of multiple myeloma relapse, especially in autologous stem cell transplantation patients. Atypical and unique presentations such as the pleural involvement warrant further reporting of evidence to provide early management and treatment options.
ICU patients with infectious complications after abdominopelvic surgery: Is thoracic CT in addition to abdominal CT helpful?
Authors: Nebelung Heiner , Wotschel Natalie , Held Hanns-Christoph , Kirchberg Johanna , Weitz Jürgen , Radosa Christoph Georg , Laniado Michael , Hoffmann Ralf-Thorsten , Plodeck Verena
Published: February 2023

Background

The aim of this study was to assess the usefulness of adding thoracic CT to abdominal CT in intensive care unit (ICU) patients with signs of infection after abdominopelvic surgery.

Methods

143 thoracoabdominal CTs of ICU patients with signs of infection after abdominopelvic surgery were retrospectively reviewed for thoracic pathologies. It was determined if pathologic findings were visible only on thoracic CT above the diaphragmatic dome or also on abdominal CT up to the diaphragmatic dome. All thoracic pathologies visible only above the diaphragmatic dome were retrospectively analyzed by an ICU physician in terms of clinical relevance. Diagnostic and therapeutic efficacy of thoracic CT were assessed with regard to an infectious focus and to other pathologic findings.

Results

297 pathologic thoracic findings were recorded. 26 of the 297 findings could only be detected on images obtained above the diaphragmatic dome (in 23 of 143 CTs). A change in patient management was initiated due to only one of the 26 supradiaphragmatic findings. Diagnostic efficacy of thoracic CT in addition to abdominal CT to identify an infectious focus was 3.5% (95%-CI: 0.5–6.5%) and therapeutic efficacy was 0.7% (95%-CI: 0–2.1%). With regard to all pathologic thoracic findings, diagnostic efficacy was 16.1% (95%-CI: 10.1–22.1%) and therapeutic efficacy remained at 0.7%.

Conclusions

Additional thoracic CT to detect an infectious focus in ICU patients after abdominopelvic surgery leads to identification of the focus in only 3.5% and to changes in patient management in only 0.7%. Other relevant findings are more common (16.1%), but very rarely affect patient management.