bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing systems for the care we need: A transformation journey in Southwestern Ontario
Authors: Sibbald Shannon L. , Elliott Jacobi , Smith Alexander , Chala Mulugeta B. , Dool Kontio Nancy , Alpaugh-Bishop Amber , Jarmain Sarah , Joshi Atharv , McMahon Mike , Meyer Matthew
Published: June 2023

Primary care is considered the foundation of any health system. In Ontario, Canada Bills 41 and 74 introduced in 2016 and 2019, respectively, aimed to move towards a primary care-focused and sustainable integrated care approach designed around the needs of local populations. These bills collectively set the stage for integrated care and population health management in Ontario, with Ontario Health Teams (OHTs) introduced as a model of integrated care delivery systems. OHTs aim to streamline patient connectivity through the healthcare system and improve outcomes aligned with the Quadruple Aim. When Ontario released a call for health system partners to apply to become an OHT, providers, administrators, and patient/caregiver partners from the Middlesex-London area were quick to respond. We highlight the critical elements and journey of the Middlesex-London Ontario Health Team since its start.
Dynamics simulation of folding wing UAVs launched from a high-altitude balloon platform
Authors: Zhang Hangyue , Yang Yanchu , Cai Rong
Published: June 2023

It is a new application of the high-altitude balloon system to launch multiple small folding wing unmanned aerial vehicles (UAVs). Based on the design of the launching system, we conduct numerical simulations of the ejection process from the balloon platform and the subsequent UAV wing deployment with trajectory leveling operation. We use the Kane method to establish the dynamic model of the balloon launching platform in the inertial coordinate system (ICS). By introducing the degree of freedom of UAV sliding along the sliding track, we realize the dynamic simulation of eight UAV launching processes and obtain the instantaneous separated states. The folding wing UAV first deploys its wings after ejection, which has the coupling characteristics between structural deformation and attitude adjustment. It is regarded as a multi-rigid body connecting structure composed of the fuselage and four wings. We establish the dynamic simulation model by the Kane method in the UAV body coordinate system (BCS). The Radau pseudo-spectral method is used to calculate the flight trajectory of each UAV. This paper is an engineering application research and can provide a simulation reference for the launching test of the balloon-borne folding wing UAV program.
Systematic Review of Time Delay Instruction for Teaching Young Children
Authors: Eyler Paige Bennett , Ledford Jennifer R.
Published: June 2023

Background: Previous reviews did not include sources that were published in the last 14 years, indicating a need for an updated synthesis on the time delay literature. Objectives: This review was designed to synthesize outcomes for studies assessing time delay prompting procedures for teaching young children. Data sources: PsycINFO and ProQuest Dissertations & Theses Global. Eligibility criteria: To meet inclusion criteria, studies had to be written in English, include a single case design with the primary intervention being time delay. Methods: We coded descriptive characteristics and evaluated rigor using the Single-Case Analysis and Review Framework. Results: A total of 33 published and unpublished sources were included. Results were mixed but suggest that time delay is effective for teaching young children with intellectual and developmental disabilities. Limitations: We did not calculate effect sizes or conduct a meta-analysis due to the inappropriateness of most effect size metrics for acquisition data. Conclusions: Additional research is needed to (a) determine in which contexts time delay can and will be used by endogenous implementers; (b) assess outcomes for children who are non-imitative; and (c) evaluate child preferences for learning variations.
REALizing and improving management of stable COPD in China: results of a multicentre, prospective, observational study (REAL)
Authors: Yang Ting , Cai Baiqiang , Cao Bin , Kang Jian , Wen Fuqiang , Chen Yahong , Jian Wenhua , Wang Chen
Published: June 2023

Background:

Chronic obstructive pulmonary disease (COPD) management in China is far from adequate; underdiagnosis and undertreatment are major barriers to optimal care and improved patient outcomes.

Objective:

To generate reliable information on COPD management, outcomes, treatment patterns and adherence, and disease knowledge in China in a real-world setting.

Design:

A 52-week multicentre, prospective, observational study.

Methods:

Outpatients (⩾40 years old) diagnosed with COPD were enrolled from 50 secondary and tertiary hospitals across six geographical regions. Data were collected in routine clinical practice.

Results:

Between June 2017 and January 2019, 5013 patients were enrolled and 4978 included in the analysis. Mean [standard deviation (SD)] age was 66.2 (8.9) years, 79.5% were male and 90% had moderate-to-very-severe airflow limitation. Annual rates of overall and severe exacerbation were 0.56 and 0.31, respectively. During 1 year, 1536 (30.8%) patients experienced ⩾1 exacerbation and 960 (19.3%) patients had ⩾1 exacerbation requiring hospitalization/emergency visit. Mean (SD) COPD assessment test score was 14.6 (7.6) at baseline and 10.6 (6.8) at follow-up; however, 42–55% of patients had persistent dyspnoea, chest tightness and wheezing at 1 year. The most prescribed treatments were inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) (36.0%), ICS/LABA + long-acting muscarinic antagonist (LAMA) (17.7%) and LAMA monotherapy (15.3%). Among patients with high exacerbation risk (GOLD Groups C and D), 10.1% and 13.1%, respectively, did not receive any long-acting inhalers; only 53.8% and 63.6% of Group C and D patients with ⩾1 exacerbation during follow-up were prescribed ICS-containing therapy, respectively. Mean (SD) adherence for long-acting inhalers was 59.0% (34.3%). Mean (SD) score for the COPD questionnaire was 6.7 (2.4).

Conclusion:

These results indicate a high burden of severe exacerbations and symptoms in Chinese outpatients with COPD, and low adherence with treatment guidelines, highlighting the need for more effective management nationwide.

Registration:

The trial was registered on 20 March 2017 (ClinicalTrials.gov identifier: NCT03131362).
Bispecific PSMA antibodies and CAR-T in metastatic castration-resistant prostate cancer
Authors: Zarrabi Kevin K. , Narayan Vivek , Mille Patrick J. , Zibelman Matthew R. , Miron Benjamin , Bashir Babar , Kelly William Kevin
Published: June 2023

Prostate cancer is the most common cancer among men and the second leading cause of cancer-related deaths in men in the United States. The treatment paradigm for prostate cancer has evolved with the emergence of a variety of novel therapies which have improved survival; however, treatment-related toxicities are abundant and durable responses remain rare. Immune checkpoint inhibitors have shown modest activity in a small subset of patients with prostate cancer and have not had an impact on most men with advanced disease. The discovery of prostate-specific membrane antigen (PSMA) and the understanding of its specificity to prostate cancer has identified it as an ideal tumor-associated antigen and has revived the enthusiasm for immunotherapeutics in prostate cancer. T-cell immunotherapy in the form of bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapy have shown exceptional success in treating various hematologic malignancies, and are now being tested in patients with prostate cancer with drug design centered on various target ligands including not just PSMA, but others as well including six-transmembrane epithelial antigen of the prostate 1 (STEAP1) and prostate stem cell antigen (PSCA). This summative review will focus on the data surrounding PSMA-targeting T-cell therapies. Early clinical studies with both classes of T-cell redirecting therapies have demonstrated antitumor activity; however, there are multiple challenges with this class of agents, including dose-limiting toxicity, ‘on-target, off-tumor’ immune-related toxicity, and difficulty in maintaining sustained immune responses within a complex and overtly immunosuppressive tumor microenvironment. Reflecting on experiences from recent trials has been key toward understanding mechanisms of immune escape and limitations in developing these drugs in prostate cancer. Newer generation BiTE and CAR T-cell constructs, either alone or as part of combination therapy, are currently under investigation with modifications in drug design to overcome these barriers. Ongoing innovation in drug development will likely foster successful implementation of T-cell immunotherapy bringing transformational change to the treatment of prostate cancer.
Therapeutic effects of thalidomide on patients with systemic sclerosis-associated interstitial lung disease
Authors: Pan Jie , Dong Fei , Ma Li , Zhao Cheng , Qin Fang , Wen Jing , Wei Wanling , Lei Ling
Published: June 2023

Objective:

To evaluate the clinical efficacy of thalidomide in patients with systemic sclerosis-associated interstitial lung disease.

Methods:

Ninety-six systemic sclerosis-associated interstitial lung disease patients who received basic glucocorticoid treatment and admitted between 2016 and 2020 were included in this study, including 48 cases in the thalidomide group (combination of thalidomide and cyclophosphamide) and 48 cases in control group (cyclophosphamide monotherapy). Evaluation items included clinical symptoms, modified Rodnan skin score, pulmonary function test, chest high-resolution computed tomography scores, and adverse effects between two groups after 24 weeks of treatment.

Results:

Remarkable improvements in several aspects were found in the thalidomide group, including modified Rodnan skin score, expiratory dyspnea score, cough visual analog scale score, total ground-glass opacity score, and total interstitial lung disease score. Compared to the control group, improvements in the thalidomide group were found, such as significantly decreased cough visual analog scale score and expectoration; increased number of platelets; improved pulmonary fibrosis ( p  = 0.056), and reduced carbon monoxide diffusing capacity ( p = 0.053). There were no statistically significant differences in the expiratory dyspnea score and predicted forced vital capacity between the two groups. Patients who experienced at least one adverse event in the control group and thalidomide group were 33.3% and 64.6% ( p = 0.002); while those with serious adverse events were 8.3% versus 12.5% ( p = 0.504). Venous thrombosis was found in one case in the thalidomide group.

Conclusion:

Thalidomide combined with cyclophosphamide can improve the symptoms of cough and expectoration in patients with systemic sclerosis-associated interstitial lung disease, and may slightly delay the progression of pulmonary fibrosis, but with the possibility of an increased risk of adverse events.
A Bibliometric Analysis on Business and Management Research During COVID-19 Pandemic: Trends and Prospects
Authors: Rani Anshu , Salanke Pavithra
Published: June 2023

As the global pandemic of COVID-19 has drawn significant attention with an increasing number of research studies appearing in the literature, it is imperative to analyse the recent trends of research and future thrust areas. In numerous fields of knowledge, including business and management, the COVID-19 problem has produced enormous research undertakings. A bibliometric study of the articles published during the COVID-19 period in the area of business and management is rare with the focus on the South-Asian context. The total number of articles identified for the purpose of research throughout the Scopus database was 3,648 using the COVID-19 keyword and limiting this search to published journal articles in the domain of business and management. Further, VOSviewer software was used to analyse data and finds were presented. VOSviewer software has given the results on the cluster of authors, country of publications, citation analysis, co-citation, keywords and significant journals of publication. Given that the COVID-19 epidemic is still far from being under control, more research is needed to determine the direction of future research and other current topics. This study will provide the prospects in COVID-19-related business research and will end by pointing out the implications of these results.
The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment
Authors: Fei Ming-Yue , Wang Yong , Chang Bin-He , Xue Kai , Dong Fangyi , Huang Dan , Li Xi-Ya , Li Zi-Juan , Hu Cheng-Long , Liu Ping , Wu Ji-Chuan , Yu Peng-Cheng , Hong Ming-Hua , Chen Shu-Bei , Xu Chun-Hui , Chen Bing-Yi , Jiang Yi-Lun , Liu Na , Zhao Chong , Jin Jia-Cheng , Hou Dan , Chen Xin-Chi , Ren Yi-Yi , Deng Chu-Han , Zhang Jia-Ying , Zong Li-juan , Wang Rou-Jia , Gao Fei-Fei , Liu Hui , Zhang Qun-Ling , Wu Ling-Yun , Yan Jinsong , Shen Shuhong , Chang Chun-Kang , Sun Xiao-Jian , Wang Lan
Published: June 2023

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.
Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization
Authors: Yang Ning , Zhang Ningzhi , Wang Zhiyi , Cao Wenye , He Xuejun , Zhang Wenxi , Xing Yiqiao
Published: June 2023

Background

Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein.

Results

A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells (HRMECs). We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. Additionally, the expression of six lncRNAs and eleven differentially expressed angiogenic genes were validated by qPCR in HRMECs with or without siLGALS1. Several hub genes, such as NRIR, ZFPM2-AS1, LINC0121, apelin, claudin-5, and C-X-C motif chemokine ligand 10, were found to potentially interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response.

Conclusions

The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.
Comparison between hydroxychloroquine and systemic corticosteroids in IgA nephropathy: a two-year follow-up study
Authors: Si Feng-Lei , Tang Chen , Lv Ji-Cheng , Shi Su-Fang , Zhou Xu-Jie , Liu Li-Jun , Zhang Hong
Published: June 2023

Background

Hydroxychloroquine (HCQ) is recommended as a treatment for IgA nephropathy (IgAN) to control proteinuria. The long-term effects of HCQ compared to systemic corticosteroid therapy remain unclear.

Methods

We conducted a retrospective case‒control study at Peking University First Hospital. Thirty-nine patients with IgAN who received HCQ for at least 24 months without corticosteroids (CSs) or other immunosuppressive agents were included. Thirty-nine matched patients who received systemic CS therapy were selected using propensity score matching. Clinical data over a 24-month period were compared.

Results

In the HCQ group, the level of proteinuria decreased from 1.72 [1.44, 2.35] to 0.97 [0.51, 1.37] g/d (-50.5 [-74.0, -3.4] %, P < 0.001) at 24 months. A significant decline in proteinuria was also found in the CS group, but no significant differences were found between the HCQ group and CS group in the levels of proteinuria (0.97 [0.51, 1.37] vs. 0.53 [0.25, 1.81] g/d, P = 0.707) and change rates (-50.5% [-74.0%, -3.4%] vs. -63.7% [-78.5%, -24.2%], P = 0.385) at 24 months. In addition, the decline rates of eGFR between the HCQ and CS groups were comparable (-7.9% [-16.1%, 5.8%] vs. -6.6% [-14.9%, 5.3%], P = 0.758). More adverse events were observed in the CS group.

Conclusions

Long-term use of HCQ can maintain stable renal function with minimal side effects. In patients who cannot tolerate corticosteroids, HCQ might be an effective and safe supportive therapy for IgAN.
Socio-demographic and environmental determinants of under-five child mortality in Ethiopia: using Ethiopian demographic and Health 2019 survey
Authors: Girma Meseret , Eshete Hiwot , Asrat Rahel , Gebremichael Mignote , Getahun Dereje , Awoke Tadesse
Published: June 2023

Background

The under-five mortality rate is a reliable indicator of a country’s general level of development and the wellbeing of its children. Life expectancy is a good indicator of a population’s standard of living.

Objectives

To identify Socio-demographic and Environmental determinants of under-five child mortality in Ethiopia.

Methods

A national representative cross sectional study and a quantitative study were conducted among 5753 households selected based on 2019 Mini-Ethiopian Demographic and Health Survey (EDHS-2019) data. The analysis was done using STATA version 14 statistical software. Bivariate and multivariate analyses were used. To assess the determinants of under-five child mortality in multivariate analysis, p values less than 0.05 were considered statistically significant, and odds ratios with 95% CI (confidence interval) were used.

Results

A total of 5,753 children were included in the study. Sex of the head of the household being female (AOR = 2:350, 95% CI: 1.310, 4.215), the U5CM for being their mother were currently married (AOR = 2:094, 95% CI: 1.076, 4.072), The odds of U5CM was less by 80% (AOR = 1.797, 95% CI: 1.159–2.782) with the number of under-five children at the household born 2-4th order as compared to those children born on the first order. For the mothers visit anti natal care four and above visit (AOR = 1:803, 95% CI: 1.032, 3.149), for the way of delivery (AOR = 0:478, 95% CI: 0.233, 0.982).

Conclusion

Multivariate logistic analysis reflected that way of delivery, mothers had being currently marred, sex of the head of the household and number of antenatal care visit were found to be significant predictors of under-five child mortality. So, government policy, nongovernmental organizations, and all concerned bodies should be focused on the major determinants of under-five child mortality and put in a lot more effort to reduce under-five child mortality.
The translation and psychometrics Persian version of irrational food belief scale
Authors: Afsahi Fatemeh , Alimehdi Mansoor , Sharif-Nia Hamid
Published: June 2023

Background

This study aimed to translate into the Irrational Food Belief Scale proposed by Osberg into the Persian language and determine the psychometric properties of in Iranian culture.

Methods

Osberg’s 57-item scale was translated into Persian by using the forward-backward method. The scale’s validity was examined using face validity, content validity, and construct validity (exploratory and confirmatory factor analysis). Its reliability was assessed with Cronbach’s alpha and McDonald’s Omega coefficient. Exploratory factor analysis and confirmatory factor analysis was performed by SPSS 28 (500 subjects) and also by AMOS 26 (500 subjects). The participants completed the demographic questionnaire and the Irrational Food Belief Scale (IFBS) over the Internet.

Results

After translation into Persian, the validity of the scale was determined by impact score, quantitative and qualitative face validity (modification of 10 items) and qualitative content validity (modification of 8 items), and quantitative content validity (CVR, CVI and Kappa coefficient), which were greater than 0.46, 0.86, and 0.85, respectively. In exploratory factor analysis, 30 items were removed and the remaining 27 items were loaded on five factors, including behavioral and psychological aspects, nutritional attitudes, healthy eating, controlled eating, and diet, which described 30.95% of the total variance. Confirmatory factor analysis showed that the 5-factor model was the best fitting model to explain the data.

Conclusion

Considering the need for a tool about in irrational food beliefs, this tool was unable to explain all these dimensions well. It is recommended to create a new questionnaire for the Iranian culture.
Efficacy and safety of Kumpe access catheter for pre-percutaneous nephrolithotomy renal access in modified supine percutaneous nephrolithotomy
Authors: Kang Jun-Koo , Lee Sang Hee , Kim Seok-Gi , Kim Ju-Bin , Lee Jeong-Yeon , Ha Seon-Yeon , Ha Chan-Geun , Hong Soon-Ho , Chung Jae-Wook , Ha Yun-Sok , Lee Jun Nyung , Chun So Young , Kim Bum Soo
Published: June 2023

Introduction

Traditionally, a pigtail catheter (PCN) is placed for preoperative renal access before performing percutaneous nephrolithotomy (PCNL). However, PCN can hamper the passage of the guidewire to the ureter, due to which, access tract can be lost. Therefore, Kumpe Access Catheter (KMP) has been proposed for preoperative renal access before PCNL. In this study, we analyzed the efficacy and safety of KMP for surgical outcomes in modified supine PCNL compared to those in PCN.

Materials and methods

From July 2017 to December 2020, 232 patients underwent modified supine PCNL at a single tertiary center, of which 151 patients were enrolled in this study after excluding patients who underwent bilateral surgery, multiple punctures, or combined operations. Enrolled patients were divided into two groups according to the type of pre-PCNL nephrostomy catheter used: PCN versus KMP. A pre-PCNL nephrostomy catheter was selected based on the radiologist’s preference. A single surgeon performed all PCNL procedures. Patient characteristics and surgical outcomes, including stone-free rate, operation time, radiation exposure time (RET), and complications, were compared between the two groups.

Results

Of the 151 patients, 53 underwent PCN placement, and 98 underwent KMP placement for pre-PCNL nephrostomy. Patient baseline characteristics were comparable between the two groups, except for the renal stone type and multiplicity. The operation time, stone-free rate, and complication rate were not significantly different between the two groups; however, RET was significantly shorter in the KMP group.

Conclusion

The surgical outcomes of KMP placement were comparable to those of PCN and showed shorter RET during modified supine PCNL. Based on our results, we recommend KMP placement for pre-PCNL nephrostomy, particularly for reducing RET during supine PCNL.
Evaluation of apical extrusion of debris and centering ability in different nickel-titanium files during curved root canal preparation
Authors: Yu Dongsheng , Guo Li , Gao Jing , Liu Jie , Yang Deqin
Published: June 2023

Background

Curved root canals lead to difficulties in cleaning, shaping and filling the root canal system. Apical extrusion of debris and root canal transportation are important factors causing postoperative complications. In clinical practice, commonly selected instruments include multifile NiTi systems, such as M3-Pro PLUS (M3-PRO), Orodeka Plex 2.0 (ODP), Rotate (ROT), and Protaper Gold (PTG), as well as single-file NiTi systems, such as M3-L Platinum 2019 (M3L), Waveone Gold (WOG), and Reciproc Blue (RCB). This study aimed to comprehensively evaluate the differences in the apical extrusion of debris and centering ability of the above NiTi files.

Methods

Seventy 3D-printed resin teeth were used (n = 10). The apically extruded debris was collected in a preweighed centrifuge tube. The resin teeth with or without root canal preparation were cut into separate cross sections at 1 mm, 3 mm, 5 mm, and 7 mm away from the root apex, and then the root canal transportation and centering ratio of each cross section were calculated.

Results

Apical extrusion of debris was highest in RCB but lowest in OD-P (P < 0.05). Root call deviation was lowest in ROT at the 3 mm level, in PTG at the 5 mm level, and in PTG and ROT at the 7 mm level (P < 0.05). The centering ratio of NiTi files was highest in the RCB group at the 3 mm level, in the PTG group at the 5 mm level, in the ROT group at the 7 mm level (P < 0.05).

Conclusions

For NiTi files with the same system, the cross-sectional design is the greatest factor affecting the extrusion of debris, and motion mode is the second. In addition, the multifile system could reduce the degree of root canal transportation.
Cervical cancer screening among English- and Spanish-speaking Hispanic women in an urban safety net health system, 2015–2020
Authors: Amboree Trisha L. , Parker Susan Lackey , Bulsara Shaun , Anderson Matthew L. , Schmeler Kathleen M. , Chiao Elizabeth Y. , Montealegre Jane R.
Published: June 2023

Background

The Hispanic population is heterogeneous with differences in health behaviors across subgroups by nativity and preferred language. We evaluated cervical cancer screening adherence among English- and Spanish-speaking Hispanic patients receiving care at a safety net health system.

Methods

Electronic health records were used to identify 46,094 women aged 30–65. Up to date (UTD) screening was defined based on date of last Pap test, human papillomavirus (HPV) test, or Pap/HPV co-test.

Results

Overall, 81.5% of 31,297 Hispanic women were UTD. English-speaking Hispanic women had a lower prevalence of being UTD when compared to Spanish-speaking Hispanic women (aPR: 0.94, 95% CI: 0.93 – 0.96). Further, those with indigent healthcare plans had a higher prevalence of being UTD when compared to those with private insurance (aPR: 1.10, 95% CI: 1.09 – 1.12), while all other health insurance plans were associated with lower UTD screening when compared to private insurance.

Conclusions

These findings suggest screening differences within the Hispanic population, highlighting the need for disaggregated research assessing heterogeneity within racial/ethnic groups, specifically among Hispanic populations.
Academic resilience in UK pharmacy education – a pilot study applying love and break up letters methodology
Authors: Mawdsley Andrew , Willis Sarah C.
Published: June 2023

Introduction

Academic resilience is seen as a positive attribute that supports academic attainment and protects against attrition and burnout. Studies have reported that UK pharmacy students have lower academic resilience and wellbeing than the general UK student population but the reasons for this have not been established. This study pilots the use of a novel methodology, love and break-up letter methodology (LBM), to explore these issues focusing on the lived experience of pharmacy students.

Method

Final year undergraduate pharmacy study were purposely recruited to the study. Employing LBM, each participant was invited to write reflective love and break-up letters to their academic resilience in higher education during a focus group. Letters and transcripts of subsequent focus group discussion on the feelings and ideas expressed in the letters were thematically analysed.

Results

Three meta-themes were identified within the data; the curriculum as gas lighting; the curriculum as abusive; and the curriculum as controlling. Students described how the curriculum diminishes academic resilience by working against their sense of agency and self-esteem. A constant threat of failure emerged as defining the student lived experience; students felt controlled by a curriculum with negative impacts on wellbeing and perseverance.

Discussion

This is the first study to use LBM to explore academic resilience in UK pharmacy students. The results provide evidence that some students view the pharmacy curriculum as a source of relentless adversity that is responsible for promoting a hidden negative connection between students and their education. Further study is required to determine if the results can be generalised across the UK pharmacy student body to explain why UK pharmacy students have lower academic resilience than other UK university students and the steps needed to improve academic resilience in UK pharmacy students.
The relationships among overcommitment, effort-reward imbalance, safety climate, emotional labour and quality of working life for hospital nurses: a structural equation modeling
Authors: Liang Hui Yu , Tseng Tzu Yi , Dai Hung Da , Chuang Jin Yun , Yu Shu
Published: June 2023

Background

Quality of working life (QWL) is a highly important issue for nurses. Nurses with lower QWL tend to have lower job performance and intention to stay. The aim of this study was to apply a theoretical model to examine the structural relationships among overcommitment, effort-reward imbalance (ERI), safety climate, emotional labour and QWL for hospital nurses.

Methods

A cross-sectional study design and a simple random sampling method were used to recruit 295 nurses in a teaching hospital and used a structured questionnaire was used to collect data.

Results

Overall, the nurses’ QWL was moderate. Our theoretical model showed a good model fit. Overcommintment had a significant direct positive effect on ERI (β = 0.35,p < 0.001) and indirect effects on safety climate (β= -0.149,p = 0.001), emotional labour (β = 0.105,p = 0.001) and QWL (β= -0.061,p = 0.004). Additionally, ERI not only had significant direct effects on safety climate (β= -0.42,p < 0.001), emotional labour (β = 0.30,p < 0.001) and QWL (β= -0.17,p < 0.001) but also indirectly affected QWL through safety climate (β= -0.304,p = 0.001) and emotional labour (β= -0.042,p = 0.005). Both safety climate (β = 0.72,p < 0.001) and emotional labour (β= -0.14,p = 0.003) showed significant direct effects on QWL. Our final model accounted for 72% of the variance in QWL.

Conclusion

Our results highlight the necessity of improving the QWL of nurses. Policymakers and hospital administrators should develop policies and strategies that encourage nurses to exhibit an appropriate level of commitment, balance effort and reward, establish a climate of safety, and reduce emotional labour to improve the QWL of hospital nurses.
Mendelian randomization indicates that atopic dermatitis contributes to the occurrence of diabetes
Authors: Lu Feiwei , Wu Boting , Wang Yongshi
Published: June 2023

Background

An association has been indicated between atopic dermatitis (AD), a prevalent chronic inflammatory skin disease, and diabetes mellitus. However, the exact causal relationship between AD and both type 1 diabetes (T1D) and type 2 diabetes (T2D) remains controversial. This study aimed to explore the causal association between AD and diabetes by Mendelian Randomization (MR) approaches.

Methods

Public genetic summary data for AD was obtained from EAGLE study. Single nucleotide polymorphisms of diabetes were retrieved from four genome-wide association studies that had been performed in European populations. Inverse variance weighted (IVW) in MR analysis was used as the primary means of causality estimation. Several complementary analyses and sensitivity analyses were performed to calculate MR estimates and to enhance the causal inference, respectively. The R package ‘TwoSampleMR’ was used for analysis.

Results

Genetically predicted AD led to a higher risk of T1D (OR, 1.19; 95% CI, 1.05, 1.34;P = 0.006) and T2D (OR, 1.07; 95% CI, 1.02, 1.11;P = 0.003) based on random-effect IVW method. The complementary analyses provided similar positive results. Cochran’s Q test and I2statistics indicated moderate heterogeneity between AD and both T1D and T2D. No significant horizontal pleiotropy was detected by MR-Egger Intercept p except summary data from FinnGen consortium.

Conclusion

Genetically predicted AD is a risk factor for both T1D and T2D. These findings imply potential shared pathological mechanisms between AD and diabetes, thus suggesting the significance of early clinical diagnosis and prevention of AD in reducing the incidence of diabetes.
Mitochondrial DNA induces nucleus pulposus cell pyroptosis via the TLR9-NF-κB-NLRP3 axis
Authors: Lu Peng , Zheng Huayong , Meng Hao , Liu Chuan , Duan Lianhong , Zhang Jianzheng , Zhang Zhicheng , Gao Jie , Zhang Yang , Sun Tiansheng
Published: June 2023

Background

Nucleus pulposus cell (NPC) death and progressive reduction play important roles in intervertebral disc degeneration (IVDD). As part of a damage-associated molecular pattern, mitochondrial DNA (mtDNA) can be recognized by TLR9 and triggers the expression of NF-κB and NLRP3 inflammasomes, inducing pyroptosis and inflammatory response. However, whether mtDNA induces NPC pyroptosis via the TLR9-NF-κB-NLRP3 axis and promotes IVDD remains uncertain.

Methods

We constructed an in vitro NPC oxidative stress injury model to clarify the mechanism of mtDNA release, TLR9-NF-κB signaling pathway activation, and NPC injury. We further verified the mechanism of action underlying the inhibition of mtDNA release or TLR9 activation in NPC injury in vitro. We then constructed a rat punctured IVDD model to understand the mechanism inhibiting mtDNA release and TLR9 activation in IVDD.

Results

We used human NP specimen assays to show that the expression levels of TLR9, NF-κB, and NLRP3 inflammasomes correlated with the degree of IVDD. We demonstrated that mtDNA mediated TLR9-NF-κB-NLRP3 axis activation in oxidative stress-induced human NPC pyroptosis in vitro. Oxidative stress can damage the mitochondria of NPCs, causing the opening of the mitochondrial permeability transition pores (mPTP) and leading to the release of mtDNA into the cytosol. Furthermore, inhibition of mPTP opening or TLR9 activation blocked TLR9-NF-κB-NLRP3 axis activation and thereby mediated NPC pyroptosis and IVDD.

Conclusion

mtDNA plays a key role in mediating NPC pyroptosis and IVDD via the TLR9-NF-κB-NLRP3 axis. Our findings provide new potential targets for IVDD.
Encouraging visual outcomes in children with idiopathic and JIA associated uveitis: a population-based study
Authors: Siiskonen Mira , Hirn Iida , Pesälä Roosa , Ohtonen Pasi , Hautala Nina
Published: June 2023

Background

Pediatric uveitis is typically asymptomatic and may become chronic affecting ocular structures and vision. We evaluated visual outcomes, clinical features, medication, and uveitis activity in children with either idiopathic uveitis (idio-U) or juvenile idiopathic arthritis associated uveitis (JIA-U).

Methods

A longitudinal, population-based cohort study of children with uveitis in 2008–2017. The data included parameters for age, gender, age at diagnosis, laterality, chronicity, anatomical distribution, etiology, systemic association, uveitis activity, medication, and visual outcomes.

Results

A total of 119 patients aged < 16 years with uveitis were included. Uveitis was idio-U in 23% and associated with JIA in 77% of cases. 37% of the patients in the idio-U group and 65% in the JIA-U were girls (p = 0.014). The mean age at first uveitis was 10.0 (SD 3.4) years in idio-U and 5.5 (SD 3.3) years in JIA-U (p < 0.001). Anterior location of uveitis was noted in 74% in idio-U and 99% in JIA-U (p < 0.001). Mostly, uveitis was chronic (59% in idio-U and 75% in JIA-U) and bilateral (56% in idio-U and 64% in JIA-U). Topical corticosteroids were initially used by 89% and 100%, systemic corticosteroids by 30% and 27% in some extent during the follow-up, disease-modifying antirheumatic drugs (DMARDs) by 33% and 85% (p < 0.001) of the patients in idio-U and JIA-U, respectively. Biologic disease-modifying antirheumatic drugs (bDMARDs) were more common in JIA-U (55% vs. 15% in idio-U, respectively, p < 0.001). Most patients had normal visual acuity (Snellen > 0.8, [6/7.5]) in the affected eye and bilaterally in 85% idio-U and 70% JIA-U. Only 5 patients (4%) had visual impairment in one, but none in both eyes. Uveitis activity by SUN classification was 0 + in 81% and 72%, 0.5 + in 19% and 25%, and 1 + in 0% and 3% in the idio-U and JIA-U, respectively.

Conclusions

Children with uveitis have good visual acuity and a low rate for visual impairment. In addition, modern treatment with DMARDs and bDMARDs seems to save vision.
Immune profile of primary and recurrent epithelial ovarian cancer cases indicates immune suppression, a major cause of progression and relapse of ovarian cancer
Authors: Kumar Pavan , Ranmale Samruddhi , Mehta Sanket , Tongaonkar Hemant , Patel Vainav , Singh Amit Kumar , Mania-Pramanik Jayanti
Published: June 2023

Background

Ovarian cancer is the third most prevalent cancer in Indian women. Relative frequency of High grade serous epithelial ovarian cancer (HGSOC) and its associated deaths are highest in India which suggests the importance of understanding their immune profiles for better treatment modality. Hence, the present study investigated the NK cell receptor expression, their cognate ligands, serum cytokines, and soluble ligands in primary and recurrent HGSOC patients. We have used multicolor flow cytometry for immunophenotyping of tumor infiltrated and circulatory lymphocytes. Procartaplex, and ELISA were used to measure soluble ligands and cytokines of HGSOC patients.

Results

Among the enrolled 51 EOC patients, 33 were primary high grade serous epithelial ovarian cancer (pEOC) and 18 were recurrent epithelial ovarian cancer (rEOC) patients. Blood samples from 46 age matched healthy controls (HC) were used for comparative analysis. Results revealed, frequency of circulatory CD56Bright NK, CD56Dim NK, NKT-like, and T cells was reduced with activating receptors while alterations in immune subsets with inhibitory receptors were observed in both groups. Study also highlights differential immune profile of primary and recurrent ovarian cancer patients. We have found increased soluble MICA which might have acted as “decoy” molecule and could be a reason of decrease in NKG2D positive subsets in both groups of patients. Furthermore, elevated level of serum cytokines IL-2, IL-5, IL-6, IL-10, and TNF-α in ovarian cancer patients, might be associated with ovarian cancer progression. Profiling of tumor infiltrated immune cells revealed the reduced level of DNAM-1 positive NK and T cells in both groups than their circulatory counterpart, which might have led to decrease in NK cell’s ability of synapse formation.

Conclusions

The study brings out differential receptor expression profile on CD56BrightNK, CD56DimNK, NKT-like, and T cells, cytokines levels and soluble ligands which may be exploited to develop alternate therapeutic approaches for HGSOC patients. Further, few differences in the circulatory immune profiles between pEOC and rEOC cases, indicates the immune signature of pEOC undergoes some changes in circulation that might facilitated the disease relapse. They also maintains some common immune signatures such as reduced expression of NKG2D, high level of MICA as well as IL-6, IL10 and TNF-α, which indicates irreversible immune suppression of ovarian cancer patients. It is also emphasized that a restoration of cytokines level, NKG2D and DNAM-1on tumor infiltrated immune cells may be targeted to develop specific therapeutic approaches for high-grade serous epithelial ovarian cancer.
Assignment of the somatic A/B compartments to chromatin domains in giant transcriptionally active lampbrush chromosomes
Authors: Krasikova Alla , Kulikova Tatiana , Rodriguez Ramos Juan Sebastian , Maslova Antonina
Published: June 2023

Background

The three-dimensional configuration of the eukaryotic genome is an emerging area of research. Chromosome conformation capture outlined genome segregation into large scale A and B compartments corresponding mainly to transcriptionally active and repressive chromatin. It remains unknown how the compartmentalization of the genome changes in growing oocytes of animals with hypertranscriptional type of oogenesis. Such oocytes are characterized by highly elongated chromosomes, called lampbrush chromosomes, which acquire a typical chromomere-loop appearance, representing one of the classical model systems for exploring the structural and functional organization of chromatin domains.

Results

Here, we compared the distribution of A/B compartments in chicken somatic cells with chromatin domains in lampbrush chromosomes. We found that in lampbrush chromosomes, the extended chromatin domains, restricted by compartment boundaries in somatic cells, disintegrate into individual chromomeres. Next, we performed FISH-mapping of the genomic loci, which belong to A or B chromatin compartments as well as to A/B compartment transition regions in embryonic fibroblasts on isolated lampbrush chromosomes. We found, that in chicken lampbrush chromosomes, clusters of dense compact chromomeres bearing short lateral loops and enriched with repressive epigenetic modifications generally correspond to constitutive B compartments in somatic cells. A compartments align with lampbrush chromosome segments with smaller, less compact chromomeres, longer lateral loops, and a higher transcriptional status. Clusters of small loose chromomeres with relatively long lateral loops show no obvious correspondence with either A or B compartment identity. Some genes belonging to facultative B (sub-) compartments can be tissue-specifically transcribed during oogenesis, forming distinct lateral loops.

Conclusions

Here, we established a correspondence between the A/B compartments in somatic interphase nucleus and chromatin segments in giant lampbrush chromosomes from diplotene stage oocytes. The chromomere-loop structure of the genomic regions corresponding to interphase A and B compartments reveals the difference in how they are organized at the level of chromatin domains. The results obtained also suggest that gene-poor regions tend to be packed into chromomeres.
B cell subsets in adult-onset Still’s disease: potential candidates for disease pathogenesis and immunophenotyping
Authors: Fang Xiangyu , Ye Hua , Xie Yang , Wei Chaonan , Liu Shuyan , Yao Haihong , Li Zhanguo , Jia Yuan , Hu Fanlei
Published: June 2023

Background

Adult-onset Still’s disease (AOSD) is a systemic autoinflammatory disorder of unknown etiology. B cells are critical participants in different rheumatic diseases, and their roles in AOSD are rarely investigated. This study aimed to unveil the B cell subset features in AOSD and provide evidence for B cell-based diagnosis and targeted therapies of AOSD.

Methods

B cell subsets in the peripheral blood of AOSD patients and healthy controls (HCs) were detected by flow cytometry. Firstly, the frequencies of B cell subsets were compared. Then, the correlation analysis was performed to explore the correlation between B cell subsets and clinical manifestations in AOSD. Finally, unbiased hierarchical clustering was performed to divide AOSD patients into three groups with different B cell subset features, and the clinical characteristics of the three groups were compared.

Results

The frequencies of B cell subsets were altered in AOSD patients. Disease-promoting subsets (such as naïve B cells, double negative B cells (DN B cells), and plasmablasts) increased, and potential regulatory subsets (such as unswitched memory B cells (UM B cells) and CD24hiCD27+ B cells (B10 cells)) decreased in the peripheral blood of AOSD patients. In addition, the altered B cell subsets in AOSD correlated with the clinical and immunological features, such as immune cells, coagulation features, and liver enzymes. Intriguingly, AOSD patients could be divided into three groups with distinct B cell immunophenotyping: group 1 (naïve B cells-dominant), group 2 (CD27+ memory B cells-dominant), and group 3 (precursors of autoantibody-producing plasma cells-dominant). Moreover, these three group patients demonstrated differential manifestations, including immune cells, liver or myocardial enzymes, coagulation features, and systemic score.

Conclusions

B cell subsets are significantly altered in AOSD patients, potentially contributing to the disease pathogenesis. These findings would inspire B cell-based diagnosis and targeted therapies for this refractory disease.
CITED1 as a marker of favourable outcome in anti-endocrine treated, estrogen-receptor positive, lymph-node negative breast cancer
Authors: Dahlgren Malin , Lettiero Barbara , Dalal Hina , Mårtensson Kira , Gaber Alexander , Nodin Björn , Gruvberger-Saal Sofia K. , Saal Lao H. , Howlin Jillian
Published: June 2023

Objective

To investigate CITED1 as a potential biomarker of anti-endocrine response and breast cancer recurrence, given its previously determined role in mediating estrogen-dependant transcription. The study is a continuation of earlier work establishing the role of CITED1 in mammary gland development.

Results

CITED1 mRNA is associated with estrogen-receptor positivity and selectively expressed in the GOBO dataset of cell lines and tumours representing the luminal-molecular subtype. In patients treated with tamoxifen, higher CITED1 correlated with better outcome, suggesting a role in anti-estrogen response. The effect was particularly evident in the subset of estrogen-receptor positive, lymph-node negative (ER+/LN−) patients although noticeable divergence of the groups was apparent only after five years. Tissue microarray (TMA) analysis further validated the association of CITED1 protein, by immunohistochemistry, with favourable outcome in ER+, tamoxifen-treated patients. Although we also found a favourable response to anti-endocrine treatment in a larger TCGA dataset, the tamoxifen-specific effect was not replicated. Finally, MCF7 cells overexpressing CITED1 showed selective amplification of AREG but not TGFα suggesting that maintenance of specific ERα-CITED1 mediated transcription is important for the long-term response to anti-endocrine therapy. These findings together confirm the proposed mechanism of action of CITED1 and support its potential use as a prognostic biomarker.