bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of anxiety and depression among university teachers during third wave of COVID-19
Authors: Saeed Hamid , Qureshi Amna Fakhar , Rasool Muhammad Fawad , Islam Muhammad , Hashmi Furqan Khurshid , Saeed Amna , Asad Rimsha , Arshad Arfa , Qureshi Azba Abid
Published: April 2023

Background

To estimate the determinants of anxiety and depression among university teachers in Lahore, Pakistan, during COVID-19.

Methods

A cross-sectional study was conducted by enrolling 668 teachers from the universities of Lahore, Pakistan. Data were collected using a questionnaire. Chi-square for significance and logistic regression for the association were used.

Results

Majorly, the university teachers, with an average age of 35.29 years, had regular jobs (72.8%), job experience of > 6 years (51.2%) and good self-reported health (55.4%). The majority of the teachers were working as lecturers (59.6%), lecturing in arts (33.5%) or general science (42.5%) departments, having MPhil (37.9%) or master (28.9%) degrees, and teaching via synchronous video (59.3%) mode. Anxiety and depression, severe and extremely severe, were higher among lecturers, MPhil or master degree holders, teachers lecturing arts and general science subjects, and in those on contract employment. Anxiety was significantly associated with academic departments; arts (OR;2.5, p = 0.001) and general science (OR;2.9, p = 0.001), poor health status (OR;4.4, p = 0.018), and contractual employment (OR;1.8, p = 0.003). Depression was associated with academic departments; arts (OR;2.7, p = 0.001) and general science (OR;2.5, p = 0.001), and health status (OR;2.3, p = 0.001).

Conclusion

Among university teachers, anxiety and depression, severe and extremely severe, were prevalent among lecturers having MPhil or master degrees, belonging to arts and general science departments, and among contract employees. Anxiety and depression were significantly associated with academic disciplines, lower cadre, and poor health status.
Mediating role of coping styles on the relationship between personality types and mental disorders in cardiovascular patients: a cross-sectional study in Iran
Authors: Yaghoubi Behzad , Nemati Reza , Agin Khosrow , Beigi Dehaghi Ali Mohammad , Gazmeh Meysam , Rezaei Farshad , Amirbandi Elham , Farhadi Akram
Published: April 2023

Background

Many mental problems lead to the occurrence of physical diseases, causing worse consequences of diseases. Despite many studies in the field of personality types and types of mental disorders, this relationship and the mediating role of coping styles in cardiovascular patients are still not well known. Therefore, the present study was conducted to investigate the mediating role of coping styles in the relationship between personality types and mental disorders in cardiovascular patients.

Method

The present study is a cross-sectional study that was conducted on 114 cardiovascular patients at the heart center in Bushehr, Iran. The sampling method is simple random sampling. Demographic information form, MCMI-III questionnaire, NEO-FFI questionnaire, and Lazarus and Folkman coping styles questionnaire were used to collect data. Data were analyzed using SPSS 22 and Amos 24 software. Descriptive statistics methods (mean, variance and percentage), Pearson correlation, and structural equation model (SEM) were applied to analyze the data.

Results

The findings showed that the two variables of personality types and problem-oriented explain 15.2% of the variable of mental disorders, of which 10.7% is related to the variable of personality types and 4.5% is related to the intermediate variable of problem-oriented. Among the personality types, the neurotic personality type has the biggest role (0.632) and has a direct and significant effect on mental disorders. Also, the personality types of extroversion (-0.460), agreeableness (-0.312), and responsibility (-0.986) exert inverse and significant effects on mental disorders.

Conclusion

The results of the present study showed the frequency of personality disorders and other mental disorders among heart patients. Problem-oriented coping style plays a mediating role between personality types and mental disorders.
An overview of cervical cancer epidemiology and prevention in the Baltic States
Authors: Kojalo Una , Tisler Anna , Parna Kersti , Kivite-Urtane Anda , Zodzika Jana , Stankunas Mindaugas , Baltzer Nicholas , Nygard Mari , Uuskula Anneli
Published: April 2023

Aims

To inform future Baltic States-specific policy analyses, we aimed to provide an overview of cervical cancer epidemiology and existing prevention efforts in Estonia, Latvia and Lithuania.

Methods

A structured desk review: we compiled and summarized data on current prevention strategies, population demography and epidemiology (high risk human papillomavirus (HPV) prevalence and cervical cancer incidence and mortality over time) for each Baltic State by reviewing published literature and official guidelines, performing registry-based analyses using secondary data and having discussions with experts in each country.

Results

We observed important similarities in the three Baltic States: high burden of the disease (high incidence and mortality of cervical cancer, changes in TNM (Classification of Malignant Tumors) stage distribution towards later stage at diagnosis), high burden of high-risk HPV in general population and suboptimal implementation of the preventive strategies as low screening and HPV vaccination coverage.

Conclusions

Cervical cancer remains a substantial health problem in the region and the efforts in addressing barriers by implementing a four-step plan for elimination cervical cancer in Europe should be made. This goal is achievable through evidence-based steps in four key areas: vaccination, screening, treatment, and public awareness.
HIV pre-exposure prophylaxis and diagnoses of sexually transmitted infections – observational data from German checkpoints, 01/2019–08/2021
Authors: Marcus Ulrich , Schink Susanne B. , Weber Christoph
Published: April 2023

Background

The impact of starting HIV pre-exposure prophylaxis (PrEP) on diagnoses of sexually transmitted infections (STI) remains unclear. We used data from German HIV/STI Checkpoints collected from 01/2019 to 08/2021 to determine the impact of PrEP use on syphilis, gonorrhoea and chlamydia diagnoses.

Methods

We used self-reported data on demographics, sexual behaviour, testing and PrEP use, as well as lab-confirmed diagnoses from visits to HIV/STI Checkpoints in Germany. PrEP use was categorized as (1) never used; (2) intention to use; (3) former use; (4) current on-demand use; (5) daily use. In multivariate regression analyses (MRA) with gonorrhoea, chlamydia, and syphilis diagnoses as outcomes, we controlled for age, number of sexual partners, number of condomless anal intercourse (CAI) partners in the last six months, and testing recency.

Results

For the analysis, we included 9,219 visits for gonorrhoea and chlamydia testing and 11,199 visits for syphilis testing conducted at checkpoints from 01/2019 to 08/2021. MRA identified age (aOR 0.98; 95%CI 0.97–0.99), number of sexual partners in the past six months (aOR 4.90; 95%CI 2.53–9.52 for 11 + partners), and use of chemsex substances (aOR 1.62; 95%CI 1.32-2.00) as risk factors for gonorrhoea, while age (aOR 0.99; 95%CI 0.98-1.00), number of CAI partners (aOR 3.19; 95%CI 2.32–4.41 for 5 + partners), partner sorting (aOR 1.30; 95%CI 1.09–1.54), and use of chemsex substances (aOR 1.29; 95%CI 1.05–1.59) were risk factors for chlamydia infections. For syphilis, the number of CAI partners (aOR 3.19; 95%CI 1.60–6.34 for 5 + partners) was found to be the only significant risk factor. There was a strong association between PrEP use and the number of sexual partners (≤ 5 vs.>5: aOR 3.58; 95%CI 2.15–5.97 for daily PrEP use), the number of CAI partners in the past six months (≤ 1 vs.>1: aOR 3.70; 95%CI 2.15–6.37 for daily PrEP use), and the number of STI tests performed (suggesting higher testing frequency). Both outcomes were also related to partner sorting, chemsex, and selling sex.

Conclusions

Checkpoint visits reporting current PrEP use or intention to start PrEP correlated with eligibility criteria for PrEP, i.e. high partner numbers, inconsistent condom use during anal intercourse, and use of chemsex drugs. Use of HIV-specific prevention methods such as HIV serosorting, PrEP sorting, and viral load sorting was reported more frequently. (Daily) PrEP use was an independent risk factor for a chlamydia diagnosis only.
Awareness and use of tobacco products among underage individuals: findings from the altria client services underage tobacco use survey 2020–2022
Authors: Cheng Hui G. , Vansickel Andrea R. , Largo Edward G.
Published: April 2023

Background

Tobacco use among underage individuals is a public health concern. Timely data about tobacco products, especially emerging products such as novel oral nicotine products (NPs), can provide critical information for the prevention of underage tobacco use. With a recent federal law raising the legal age of purchase of tobacco products from 18 to 21, it is of interest to benchmark awareness and use of tobacco products in the new underage population, young adults 18–20 years old. This study provides estimates on awareness and use of tobacco products among underage individuals 13–20 years old during May 2020 to August 2022 in the United States.

Methods

Altria Client Services Underage Tobacco Use Survey (UTUS) is a repeated cross-sectional survey conducted every quarter-year. A stratified random sampling approach was used to draw nationally representative samples of household dwelling individuals 13–20 years old. Information about the awareness and use of tobacco products was obtained via online self-administration or phone interviews after a consent/assent process.

Results

A sizable portion of underage individuals were aware of NPs (~ 40% among youth and ~ 50% among underage young adults), although past 30-day use was low (< 2%). The lowest levels of awareness and use were observed for heated tobacco products and snus. E-cigarettes were the most used tobacco products among underage individuals. Underage young adults (i.e., 18–20 year olds) were more likely to use tobacco products than youth (i.e., 13–17 year olds). There was no substantial change over time in the awareness and use of tobacco products during the study period despite a slight increase in past 30-day prevalence of e-cigarette use among youth between quarter 1 of 2021 and quarter 2 of 2022.

Conclusions

The awareness and use of tobacco products remained relatively stable between May 2020 and August 2022. There is a notable level of awareness of novel NPs among underage individuals.
Effect of educational intervention programme on the health-related quality of life (HRQOL) of individuals with type 2 diabetes mellitus in South-East, Nigeria
Authors: Okafor Christiana Nkiru , Akosile Christopher Olusanjo , Nkechi Chiejina Edith , Okonkwo Uchenna Prosper , Nwankwo Chinenye Mercy , Okoronkwo Ijeoma Lewechi , Okpala Pat Uzo , Afonne Anulika Johnson
Published: April 2023

Background

Diabetes is one of the most important chronic diseases that have a great impact on health as people with diabetes are constantly being reminded of their disease daily; they have to eat carefully, exercise, and test their blood glucose. They often feel challenged by their disease because of its day-to-day management demands and these affect their quality of life. The study aimed at determining the effect of an educational intervention program on the quality of life of Individuals with type 2 Diabetes Mellitus in South East, Nigeria.

Methods

A quasi-experimental controlled study involving three hundred and eighty-two (382) type 2 DM persons recruited from the tertiary health institutions in South East, Nigeria, and randomly assigned to intervention and control groups respectively. Data was collected from the diabetic clinics of the health institutions using the SF – 36 questionnaires. Pretest data collection was done, and thereafter, education on self-care was given to the intervention group. After a 6months follow-up, post-test data were collected from both groups. Analysis was done using an Independent t-test, Analysis of Covariance (ANCOVA), Paired Samples Test, and Spearman rank order correlation at 0.05 alpha level.

Results

The control group indicated significantly higher mean HRQOL scores in most domains of the HRQOL before intervention (t = -1.927 to -6.072, p < 0.05). However, 6 months after the intervention, the mean HRQOL scores of the intervention group increased significantly in all the domains of HRQOL (p < 0.05) with an effect size of 0.14 (Eta squared). A comparison of the two groups shows a statistically significant difference (64.72 ± 10.96 vs. 58.85 ± 15.23; t = 4.349. p = 0.001) after the intervention. Age was inversely correlated with some domains of HRQOL; as age increases, HRQOL decreases in those domains. Gender had no significant influence on HRQOL.

Conclusion

Educational intervention was effective in improving HRQOL in individuals with type 2 DM. Hence, it is recommended for inclusion in all diabetes care plans.
The new visceral adiposity index outperforms traditional obesity indices as a predictor of subclinical renal damage in Chinese individuals: a cross-sectional study
Authors: Sun Yue , Yan Yu , Liao Yueyuan , Chu Chao , Guo Tongshuai , Ma Qiong , Wang Yang , Wang Dan , Jia Hao , Mu Jianjun
Published: April 2023

Background

The new visceral adiposity index (NVAI) was superior to previous obesity indices in predicting cardiovascular diseases among Asians. Nevertheless, the utility of the NVAI for predicting chronic kidney disease is still unclear. The objective of this research was to explore the relationship between the NVAI and subclinical renal damage (SRD) and to investigate whether the NVAI outperforms other common obesity indices in predicting SRD in the Chinese population.

Methods

Participants in this cross-sectional study were from the Hanzhong Adolescent Hypertension Cohort. The NVAI and seven other common obesity indices were calculated, including body mass index, waist circumference, lipid accumulation product, visceral adiposity index, Chinese visceral adiposity index, a body shape index and metabolic score for visceral fat. Logistic regression models revealed the association between NVAI and SRD. The odds ratio (OR) and the 95% confidence interval (CI) were calculated to show the association between the two variables. The predictive power of eight obesity indices for SRD was evaluated through the receiver operating characteristic curve and area under the curve (AUC). In addition, the net reclassification index (NRI) and integrated discrimination improvement (IDI) were also applied to compare the incremental predictive value for SRD of different obesity indices.

Results

The median age of the 2358 subjects was 42.00 years. Across NVAI tertiles, the prevalence of SRD was 7.25%, 11.21%, and 21.60%, respectively. After adjusting for confounders, a high level of NVAI remained a risk factor for SRD. The ORs of the middle and top NVAI tertiles for SRD were 1.920 (95% CI: 1.322, 2.787) and 4.129 (95% CI: 2.750, 6.202), respectively. The AUC of the NVAI was 0.666 (95% CI: 0.647, 0.685), which was significantly larger than the AUC of any of the other obesity indicators. Moreover, the NRI and IDI were significantly improved when NVAI was added to the basic model for predicting SRD. Among eight obesity indices, NVAI had the highest NRI (0.392; 95% CI: 0.280, 0.503), and its IDI (0.021; 95% CI: 0.014, 0.027) was second only to that of the body mass index (0.023; 95% CI: 0.014, 0.032).

Conclusions

NVAI is independently and positively associated with SRD. Among the eight obesity indices, the NVAI shows the strongest predictive power for SRD in the Chinese population. The NVAI may be useful as an effective warning indicator of chronic kidney disease in Chinese adults.
Dental care and oral conditions are associated with the prevalence of sarcopenia in people with type 2 diabetes: a cross-sectional study
Authors: Takahashi Fuyuko , Hashimoto Yoshitaka , Okada Hiroshi , Kondo Yuriko , Kaji Ayumi , Sakai Ryosuke , Kawate Yuka , Okamura Takuro , Nakanishi Naoko , Majima Saori , Senmaru Takafumi , Ushigome Emi , Hamaguchi Masahide , Asano Mai , Yamazaki Masahiro , Fukui Michiaki
Published: April 2023

Background

Insulin resistance, which is closely associated with type 2 diabetes mellitus (T2DM), is a cause of sarcopenia and people with T2DM have a high risk of sarcopenia. Keeping good oral condition by dental care is important for people with T2DM. Keeping good oral condition by dental care is important for people with T2DM. This study has investigated the association between dental care or oral conditions and sarcopenia in people with T2DM.

Methods

Dental care and oral conditions were evaluated based on a self-reported questionnaire. Individuals with both low handgrip strength and low skeletal muscle mass index were diagnosed with sarcopenia.

Results

Among 266 people with T2DM, the proportions of sarcopenia, not having a family dentist, not having a toothbrushing behavior, poor chewing ability, and use of complete dentures were 18.0%, 30.5%, 33.1%, 25.2%, and 14.3%, respectively. The proportions of sarcopenia in people not having a family dentist (27.2% vs. 14.1%, p = 0.017), those with poor chewing ability (26.9% vs. 15.1%, p = 0.047), and use of complete dentures (36.8% vs. 14.9%, p = 0.002) were higher than those in people without. The proportion of sarcopenia in people without toothbrushing behavior tended to be higher than that in people with toothbrushing behavior (25.0% vs. 14.6%, p = 0.057). Not having a family dentist (adjusted odds ratio [OR] 2.48 [95% confidence interval (CI): 1.21–5.09], p = 0.013), poor chewing ability (adjusted OR 2.12 [95% CI: 1.01–4.46], p = 0.048), and use of complete dentures (adjusted OR 2.38 [95% CI: 1.01–5.99], p = 0.046) were related to the prevalence of sarcopenia.

Conclusions

This study revealed that dental care and oral conditions were associated with the prevalence of sarcopenia.
Scoping review of the association between bacterial vaginosis and emotional, sexual and social health
Authors: Brusselmans Judith , De Sutter An , Devleesschauwer Brecht , Verstraelen Hans , Cools Piet
Published: April 2023

Background

Bacterial vaginosis (BV) is a condition that, if symptomatic, is characterized by discharge and odor, with high recurrence rates even when treated. This study aims to review what literature exists on the association between BV and the emotional, sexual, and social health of women.

Methods

MEDLINE, Embase and Web of Science databases were searched from inception until November 2020. Studies reporting an association between women’s emotional, sexual and/or social health and symptomatic BV in a qualitative and/or quantitative manner were included. Selected studies were divided in three categories, i.e. reporting on the emotional, sexual and/or social association. All studies were critically evaluated and discussed.

Results

Sixteen studies were included. Concerning emotional health, we found eight studies that calculated the association between stress and BV, in four this was statistically significant. Four qualitative studies on emotional health showed that the severity of the symptoms influenced the impact on women’s lives. All studies on sexual health reported that many women experienced an impact on their relationship and sexual intimacy. Results for social life ranged from no association found to most of the study population showing avoidance behavior.

Conclusion

This review shows that symptomatic BV can be associated with diminished emotional, sexual, and social health, but there is too little evidence to state the extent of this association.
Perception of coronavirus disease (COVID-19) and its relationship with coping strategies and perceived social support in iranian people: a descriptive correlational study
Authors: Elahi Nasrin , Miladinia Mojtaba , Zarei Javad , Ghanbari Saeed
Published: April 2023

Background

Perception of the threatening disease leads to coping behaviors that can affect the treatment process. Social support can be one of the factors influencing the perception of the disease and coping strategies. Our study aimed to determine the perception of the disease, its relationship with coping strategies and social support in COVID-19 patients in Iran.

Methods

This cross-sectional study was conducted on 1014 patients who were hospitalized during October 2020 to May 2021 through multi-stage sampling method. The data-gathering instruments consisted a demographic information checklist, and standard questionnaires including disease perception, social support, and coping strategies. Correlation coefficient, multiple linear regression model, and simple linear regression model were used for data analysis.

Results

The mean age of the participants was 40.87 ± 12.42 and the majority of them were female (67.2%(, married (60.1%), and had relatives who had COVID-19 (82.6%). There was a significant inverse relationship between variables (identity, outcomes, emotional expressions etc.) and social support (> 0.01). Also there was a significant direct relationship between variables (self-control, therapeutic susceptibility etc.) and the coping behavior (p < 0.05). There was an inverse relationship between the variables (outcomes, self-blaming, sex, etc.) (P = 0.0001) and a direct one between the variables (education, disease phase, etc.) and perceived social support (P = 0.004).

Conclusions

These results show the importance of promoting positive coping strategies and social support in the face of large-scale health crises. The knowledge of nurses about the results of this study, who are responsible for the care and education of the patient, can be effective in the length of hospitalization and reducing costs.
Correlation between moral distress and clinical competence in COVID-19 ICU nurses
Authors: Kalani Zohreh , Barkhordari-Sharifabad Maasoumeh , Chehelmard Niloufar
Published: April 2023

Background

Nurses’ clinical competence is one of the fundamental necessities for providing safe and effective care. Moral distress, as one type of occupational stressors, can affect various aspects of clinical competence, especially under conditions of complicated medical settings such as the coronavirus disease 2019 (COVID-19) epidemic. This study was conducted with the aim of determining the relationship between moral distress and clinical competence in nurses working in COVID-19 intensive care units (ICUs).

Methods

The study was a cross-sectional study. A total of 194 nurses working in COVID-19 ICU affiliated to Shahid Sadoughi University of Medical Sciences, Yazd, central Iran, participated in the study. Data were collected using Demographic Information Questionnaire, Moral Distress Scale, and Clinical Competence Checklist. Data were analyzed with SPSS20 using descriptive and analytical statistics.

Results

The mean score of moral distress, clinical competence, and skills application were 1.79 ± 0/68, 65.16 ± 15.38, and 145.10 ± 38.20, respectively. Based on Pearson correlation coefficient, there was an inverse and significant relationship between the moral distress score and its dimensions with clinical competence and skills application (P < 0.001). Moral distress was a significant negative predictor that accounted for 17.9% of the variance in clinical competence (R2 = 0.179, P < 0.001) and 16% of the variance in utilization of clinical competence (R2 = 0.160, P < 0.001).

Conclusion

Considering the relationship between moral distress, clinical competence and skills application, to maintain the quality of nursing services, nursing managers can strengthen clinical competence and skills application by using strategies to deal with and reduce moral distress in nurses, especially in critical situations.
Nursing faculty perceptions of simulation culture readiness in Saudi universities: a cross-sectional study
Authors: Almotairy Monir M. , Algabbashi Maram , Alshutwi Sitah , Shibily Faygah , Alsharif Fatmah , Almutairi Wedad , Nahari Ahmed
Published: April 2023

Background

Academic programs are increasing simulation-based learning in Saudi Arabia during COVID-19 pandemic; however, there is limited knowledge about these universities’ simulation culture readiness. Thus, the purpose of this study was to explore faculty perceptions of the readiness to integrate simulation into nursing programs.

Methods

This cross-sectional correlational study recruited faculty members in four nursing colleges at Saudi universities using the simulation culture organizational readiness survey 36-item questionnaire. A total of 88 faculty members from four Saudi universities were included. Descriptive, Pearson’s correlation, independent sample t-test, and analysis of covariance analysis were utilized in this study.

Results

Nearly 39.8% and 38.6% of the participants had Moderately and Very Much overall readiness for the simulation-based education (SBE), respectively. There were significant correlations between the summary impression on simulation culture readiness measures and simulation culture organizational readiness survey subscales (p < 0.001). Three simulation culture organizational readiness survey subscales (defined need and support for change, readiness for culture change, and time, personnel, and resource readiness) and the overall readiness for SBE were correlated with age, years since highest degree, years of experience in academia, and years using simulation in teaching (p < 0.05). The sustainability practices to embed culture subscale and summary impression were only correlated significantly with the number of years using simulation in teaching (p = 0.016 and 0.022, respectively). Females had a significantly higher mean in the sustainability practices to embed culture subscale (p = 0.006) and the overall readiness for simulation-based education (p = 0.05). Furthermore, there were significant differences among the highest degree in the overall readiness for SBE (p = 0.026), summary impression (p = 0.001), the defined need and support subscale (p = 0.05), the sustainability practices to embed culture subscale (p = 0.029), and the time, personnel, and resource readiness subscale (p = 0.015).

Conclusions

Favorable simulation culture readiness results suggest great opportunities to advance clinical competencies in academic curricula and optimize educational outcomes. Nurse academic leaders should identify needs and resources to enhance simulation readiness and encourage the integration of simulation in nursing education.
RNAlysis: analyze your RNA sequencing data without writing a single line of code
Authors: Teichman Guy , Cohen Dror , Ganon Or , Dunsky Netta , Shani Shachar , Gingold Hila , Rechavi Oded
Published: April 2023

Background

Among the major challenges in next-generation sequencing experiments are exploratory data analysis, interpreting trends, identifying potential targets/candidates, and visualizing the results clearly and intuitively. These hurdles are further heightened for researchers who are not experienced in writing computer code since most available analysis tools require programming skills. Even for proficient computational biologists, an efficient and replicable system is warranted to generate standardized results.

Results

We have developed RNAlysis, a modular Python-based analysis software for RNA sequencing data. RNAlysis allows users to build customized analysis pipelines suiting their specific research questions, going all the way from raw FASTQ files (adapter trimming, alignment, and feature counting), through exploratory data analysis and data visualization, clustering analysis, and gene set enrichment analysis. RNAlysis provides a friendly graphical user interface, allowing researchers to analyze data without writing code. We demonstrate the use of RNAlysis by analyzing RNA sequencing data from different studies using C.elegans nematodes. We note that the software applies equally to data obtained from any organism with an existing reference genome.

Conclusions

RNAlysis is suitable for investigating various biological questions, allowing researchers to more accurately and reproducibly run comprehensive bioinformatic analyses. It functions as a gateway into RNA sequencing analysis for less computer-savvy researchers, but can also help experienced bioinformaticians make their analyses more robust and efficient, as it offers diverse tools, scalability, automation, and standardization between analyses.
The UAS thioredoxin-like domain of UBXN7 regulates E3 ubiquitin ligase activity of RNF111/Arkadia
Authors: Amhaz Sadek , Boëda Batiste , Chouchène Mouna , Colasse Sabrina , Dingli Florent , Loew Damarys , Henri Julien , Prunier Céline , Levy Laurence
Published: April 2023

Background

E3 ubiquitin ligases play critical roles in regulating cellular signaling pathways by inducing ubiquitylation of key components. RNF111/Arkadia is a RING E3 ubiquitin ligase that activates TGF-β signaling by inducing ubiquitylation and proteasomal degradation of the transcriptional repressor SKIL/SnoN. In this study, we have sought to identify novel regulators of the E3 ubiquitin ligase activity of RNF111 by searching for proteins that specifically interacts with its RING domain.

Results

We found that UBXN7, a member of the UBA-UBX family, directly interacts with the RING domain of RNF111 or its related E3 RNF165/ARK2C that shares high sequence homology with RNF111. We showed that UBXN7 docks on RNF111 or RNF165 RING domain through its UAS thioredoxin-like domain. Overexpression of UBXN7 or its UAS domain increases endogenous RNF111, while an UBXN7 mutant devoid of UAS domain has no effect. Conversely, depletion of UBXN7 decreases RNF111 protein level. As a consequence, we found that UBXN7 can modulate degradation of the RNF111 substrate SKIL in response to TGF-β signaling. We further unveiled this mechanism of regulation by showing that docking of the UAS domain of UBXN7 inhibits RNF111 ubiquitylation by preventing interaction of the RING domain with the E2 conjugating enzymes. By analyzing the interactome of the UAS domain of UBXN7, we identified that it also interacts with the RING domain of the E3 TOPORS and similarly regulates its E3 ubiquitin ligase activity by impairing E2 binding.

Conclusions

Taken together, our results demonstrate that UBXN7 acts as a direct regulator for the E3 ubiquitin ligases RNF111, RNF165, and TOPORS and reveal that a thioredoxin-like domain can dock on specific RING domains to regulate their E3 ubiquitin ligase activity.
1,6-Hexanediol regulates angiogenesis via suppression of cyclin A1-mediated endothelial function
Authors: Jiang Yongying , Lei Gongyun , Lin Ting , Zhou Nan , Wu Jintao , Wang Zhou , Fan Yihui , Sheng Hongzhuan , Mao Renfang
Published: April 2023

Background

Angiogenesis plays important roles in physiological and pathologic conditions, but the mechanisms underlying this complex process often remain to be elucidated. In recent years, liquid–liquid phase separation (LLPS) has emerged as a new concept to explain many cellular functions and diseases. However, whether LLPS is involved in angiogenesis has not been studied until now. Here, we investigated the potential role of LLPS in angiogenesis and endothelial function.

Results

We found 1,6-hexanediol (1,6-HD), an inhibitor of LLPS, but not 2,5-hexanediol (2,5-HD) dramatically decreases neovascularization of Matrigel plug and angiogenesis response of murine corneal in vivo. Moreover, 1,6-HD but not 2,5-HD inhibits microvessel outgrowth of aortic ring and endothelial network formation. The endothelial function of migration, proliferation, and cell growth is suppressed by 1,6-HD. Global transcriptional analysis by RNA-sequencing reveals that 1,6-HD specifically blocks cell cycle and downregulates cell cycle-related genes including cyclin A1. Further experimental data show that 1,6-HD treatment greatly reduces the expression of cyclin A1 but with minimal effect on cyclin D1, cyclin E1, CDK2, and CDK4. The inhibitory effect of 1,6-HD on cyclin A1 is mainly through transcriptional regulation because proteasome inhibitors fail to rescue its expression. Furthermore, overexpression of cyclin A1 in HUVECs largely rescues the dysregulated tube formation upon 1,6-HD treatment.

Conclusions

Our data reveal a critical role of LLPS inhibitor 1,6-HD in angiogenesis and endothelial function, which specifically affects endothelial G1/S transition through transcriptional suppression of CCNA1, implying LLPS as a possible novel player to modulate angiogenesis, and thus, it might represent an interesting therapeutic target to be investigated in clinic angiogenesis-related diseases in future.
Sleep traits and risk of end-stage renal disease: a mendelian randomization study
Authors: Li Kaixin , Zhao Jiaxi , Yang Wenjing , Ye Zhibin
Published: April 2023

Background

Epidemiological evidence relating sleep disorders to end-stage renal disease (ESRD) has been obscure. The present study is sought to examine the association between sleep traits and ESRD.

Methods

For this analysis, we selected genetic instruments for sleep traits from published genome-wide association studies (GWAS). As instrumental variables, independent genetic variations linked with seven sleep-related features (sleep duration, getting up in the morning, daytime napping, chronotype of morning/evening person, sleeplessness/insomnia, non-snoring, and daytime dozing) were chosen. A two-sample Mendelian randomization (TSMR) study was conducted to assess the causal relationship between sleep traits and ESRD (N = 33,061). The reverse MR analysis subsequently determined the causal relationship between ESRD and sleep traits. The causal effects were estimated using inverse variance weighted, MR-Egger, weighted median. To conduct sensitivity studies, Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plot were used. To study the potential mediators, multivariable mendelian randomization analyses were undertaken further.

Results

Genetically predicted sleeplessness/ insomnia (OR = 6.11, 95%CI 1.00-37.3, P = 0.049, FDR = 0.105), getting up in the morning easily(OR = 0.23, 95%CI 0.063–0.85; P = 0.0278, FDR = 0.105), non-snoring (OR = 4.76E-02, 95%CI 2.29E-03-0.985, P = 0.0488, FDR = 0.105) was suggestively associated with the risk of ESRD. However, we found no evidence favoring a causal association between other sleep traits and ESRD through the IVW method.

Conclusion

The present TSMR found no strong evidence of a bidirectional causal association between genetically predicted sleep traits and ESRD.
Pulmonary rehabilitation after severe exacerbation of COPD: a nationwide population study
Authors: Guecamburu Marina , Coquelin Anaëlle , Rapin Amandine , Le Guen Nelly , Solomiac Agnès , Henrot Pauline , Erbault Marie , Morin Sandrine , Zysman Maéva
Published: April 2023

Background

Acute exacerbations of chronic obstructive pulmonary disease (COPD) lead to a significant reduction in quality of life and an increased mortality risk. Current guidelines strongly recommend pulmonary rehabilitation (PR) after a severe exacerbation. Studies reporting referral for PR are scarce, with no report to date in Europe. Therefore, we assessed the proportion of French patients receiving PR after hospitalization for COPD exacerbation and factors associated with referral.

Methods

This was a national retrospective study based on the French health insurance database. Patients hospitalized in 2017 with COPD exacerbation were identified from the exhaustive French medico-administrative database of hospitalizations. In France, referral to PR has required as a stay in a specialized PR center or unit accredited to provide multidisciplinary care (exercise training, education, etc.) and admission within 90 days after discharge was assessed. Multivariate logistic regression was used to assess the association between patients’ characteristics, comorbidities according to the Charlson index, treatment, and PR uptake.

Results

Among 48,638 patients aged ≥ 40 years admitted for a COPD exacerbation, 4,182 (8.6%) received PR within 90 days after discharge. General practitioner’s (GP) density (number of GPs for the population at regional level) and PR center facilities (number of beds for the population at regional level) were significantly correlated with PR uptake (respectively r = 0.64 and r = 0.71). In multivariate analysis, variables independently associated with PR uptake were female gender (aOR 1.36 [1.28–1.45], p < 0.0001), age (p < 0.0001), comorbidities (p = 0.0013), use of non-invasive ventilation and/or oxygen therapy (aOR 1.52 [1.41–1.64], p < 0.0001) and administration of long-acting bronchodilators (p = 0.0038).

Conclusion

This study using the French nationally exhaustive health insurance database shows that PR uptake after a severe COPD exacerbation is dramatically low and must become a high-priority management strategy.
Biomarkers of cellular senescence in idiopathic pulmonary fibrosis
Authors: Aversa Zaira , Atkinson Elizabeth J. , Carmona Eva M. , White Thomas A. , Heeren Amanda A. , Jachim Sarah K. , Zhang Xu , Cummings Steven R. , Chiarella Sergio E. , Limper Andrew H. , LeBrasseur Nathan K.
Published: April 2023

Background

Cellular senescence is a cell fate in response to diverse forms of age-related damage and stress that has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The associations between circulating levels of candidate senescence biomarkers and disease outcomes have not been specifically studied in IPF. In this study we assessed the circulating levels of candidate senescence biomarkers in individuals affected by IPF and controls and evaluated their ability to predict disease outcomes.

Methods

We measured the plasma concentrations of 32 proteins associated with senescence in Lung Tissue Research Consortium participants and studied their relationship with the diagnosis of IPF, parameters of pulmonary and physical function, health-related quality of life, mortality, and lung tissue expression of P16, a prototypical marker of cellular senescence. A machine learning approach was used to evaluate the ability of combinatorial biomarker signatures to predict disease outcomes.

Results

The circulating levels of several senescence biomarkers were significantly elevated in persons affected by IPF compared to controls. A subset of biomarkers accurately classified participants as having or not having the disease and was significantly correlated with measures of pulmonary function, health-related quality of life and, to an extent, physical function. An exploratory analysis revealed senescence biomarkers were also associated with mortality in IPF participants. Finally, the plasma concentrations of several biomarkers were associated with their expression levels in lung tissue as well as the expression of P16.

Conclusions

Our results suggest that circulating levels of candidate senescence biomarkers are informative of disease status, pulmonary and physical function, and health-related quality of life. Additional studies are needed to validate the combinatorial biomarkers signatures that emerged using a machine learning approach.
IRAK-M has effects in regulation of lung epithelial inflammation
Authors: Li Jia , Zheng Zhoude , Liu Yi , Zhang Hongbing , Zhang Youming , Gao Jinming
Published: April 2023

Background

Epithelial barrier is important for asthma development by shaping immune responses. Airway expressing-IL-1 receptor-associated kinase (IRAK)-M of Toll-like receptor pathway was involved in immunoregulation of airway inflammation through influencing activities of macrophages and dendritic cells or T cell differentiation. Whether IRAK-M has effect on cellular immunity in airway epithelial cells upon stimulation remains unclear.

Methods

We modeled cellular inflammation induced by IL-1β, TNF-α, IL-33, and house dust mite (HDM) in BEAS-2B and A549 cells. Cytokine production and pathway activation were used to reflect the effects of IRAK-M siRNA knockdown on epithelial immunity. Genotyping an asthma-susceptible IRAK-M SNP rs1624395 and measurement of serum CXCL10 levels were performed in asthma patients.

Results

IRAK-M expression was significantly induced in BEAS-2B and A549 cells after inflammatory stimulation. IRAK-M knockdown increased the lung epithelial production of cytokines and chemokines, including IL-6, IL-8, CXCL10, and CXCL11, at both mRNA and protein levels. Upon stimulation, IRAK-M silencing led to overactivation of JNK and p38 MAPK in lung epithelial cells. While antagonizing JNK or p38 MAPK inhibited increased secretion of CXCL10 in IRAK-M silenced-lung epithelium. Asthma patients carrying G/G genotypes had significantly higher levels of serum CXCL10 than those carrying homozygote A/A.

Conclusion

Our findings suggested that IRAK-M has effect on lung epithelial inflammation with an influence on epithelial secretion of CXCL10 partly mediated through JNK and p38 MAPK pathways. IRAK-M modulation might indicate a new insight into asthma pathogenesis from disease origin.
Modeling of clinical phenotypes in systemic lupus erythematosus based on the platelet transcriptome and FCGR2a genotype
Authors: Cornwell MacIntosh G. , Bannoudi Hanane El , Luttrell-Williams Elliot , Engel Alexis , Barrett Tessa J. , Myndzar Khrystyna , Izmirly Peter , Belmont H. Michael , Clancy Robert , Ruggles Kelly V. , Buyon Jill P. , Berger Jeffrey S.
Published: April 2023

Background

The clinical heterogeneity of SLE with its complex pathogenesis remains challenging as we strive to provide optimal management. The contribution of platelets to endovascular homeostasis, inflammation and immune regulation highlights their potential importance in SLE. Prior work from our group showed that the Fcγ receptor type IIa (FcγRIIa)–R/H131 biallelic polymorphism is associated with increased platelet activity and cardiovascular risk in SLE. The study was initiated to investigate the platelet transcriptome in patients with SLE and evaluate its association across FcγRIIa genotypes and distinct clinical features.

Methods

Fifty-one patients fulfilling established criteria for SLE (mean age = 41.1 ± 12.3, 100% female, 45% Hispanic, 24% black, 22% Asian, 51% white, mean SLEDAI = 4.4 ± 4.2 at baseline) were enrolled and compared with 18 demographically matched control samples. The FCGR2a receptor was genotyped for each sample, and RNA-seq was performed on isolated, leukocyte-depleted platelets. Transcriptomic data were used to create a modular landscape to explore the differences between SLE patients and controls and various clinical parameters in the context of FCGR2a genotypes.

Results

There were 2290 differentially expressed genes enriched for pathways involved in interferon signaling, immune activation, and coagulation when comparing SLE samples vs controls. When analyzing patients with proteinuria, modules associated with oxidative phosphorylation and platelet activity were unexpectedly decreased. Furthermore, genes that were increased in SLE and in patients with proteinuria were enriched for immune effector processes, while genes increased in SLE butdecreasedin proteinuria were enriched for coagulation and cell adhesion. A low-binding FCG2Ra allele (R131) was associated with decreases in FCR activation, which further correlated with increases in platelet and immune activation pathways. Finally, we were able to create a transcriptomic signature of clinically active disease that performed significantly well in discerning SLE patients with active clinical disease form those with inactive clinical disease.

Conclusions

In aggregate, these data demonstrate the platelet transcriptome provides insight into lupus pathogenesis and disease activity, and shows potential use as means of assessing this complex disease using a liquid biopsy.
Altered cerebellar lobular volumes correlate with clinical deficits in siblings and children with ASD: evidence from toddlers
Authors: Kumar Manoj , Hiremath Chandrakanta , Khokhar Sunil Kumar , Bansal Eshita , Sagar Kommu John Vijay , Padmanabha Hansashree , Girimaji Akhila S. , Narayan Shweta , Kishore M. Thomas , Yamini B. K. , Jac Fredo A. R. , Saini Jitender , Bharath Rose Dawn
Published: April 2023

Background

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social and communication skills, narrow interests, and repetitive behavior. It is known that the cerebellum plays a vital role in controlling movement and gait posture. However, recently, researchers have reported that the cerebellum may also be responsible for other functions, such as social cognition, reward, anxiety, language, and executive functions.

Methods

In this study, we ascertained volumetric differences from cerebellar lobular analysis from children with ASD, ASD siblings, and typically developing healthy controls. In this cross-sectional study, a total of 30 children were recruited, including children with ASD (N = 15; mean age = 27.67 ± 5.1 months), ASD siblings (N = 6; mean age = 17.5 ± 3.79 months), and typically developing children (N = 9; mean age = 17.67 ± 3.21 months). All the MRI data was acquired under natural sleep without using any sedative medication. We performed a correlation analysis with volumetric data and developmental and behavioral measures obtained from these children. Two-way ANOVA and Pearson correlation was performed for statistical data analysis.

Results

We observed intriguing findings from this study, including significantly increased gray matter lobular volumes in multiple cerebellar regions including; vermis, left and right lobule I–V, right CrusII, and right VIIb and VIIIb, respectively, in children with ASD, compared to typically developing healthy controls and ASD siblings. Multiple cerebellar lobular volumes were also significantly correlated with social quotient, cognition, language, and motor scores with children with ASD, ASD siblings, and healthy controls, respectively.

Conclusions

This research finding helps us understand the neurobiology of ASD and ASD-siblings, and critically advances current knowledge about the cerebellar role in ASD. However, results need to be replicated for a larger cohort from longitudinal research study in future.
Biomolecular condensates: insights into early and late steps of the HIV-1 replication cycle
Authors: Di Nunzio Francesca , Uversky Vladimir N. , Mouland Andrew J.
Published: April 2023

A rapidly evolving understanding of phase separation in the biological and physical sciences has led to the redefining of virus-engineered replication compartments in many viruses with RNA genomes. Condensation of viral, host and genomic and subgenomic RNAs can take place to evade the innate immunity response and to help viral replication. Divergent viruses prompt liquid–liquid phase separation (LLPS) to invade the host cell. During HIV replication there are several steps involving LLPS. In this review, we characterize the ability of individual viral and host partners that assemble into biomolecular condensates (BMCs). Of note, bioinformatic analyses predict models of phase separation in line with several published observations. Importantly, viral BMCs contribute to function in key steps retroviral replication. For example, reverse transcription takes place within nuclear BMCs, called HIV-MLOs while during late replication steps, retroviral nucleocapsid acts as a driver or scaffold to recruit client viral components to aid the assembly of progeny virions. Overall, LLPS during viral infections represents a newly described biological event now appreciated in the virology field, that can also be considered as an alternative pharmacological target to current drug therapies especially when viruses become resistant to antiviral treatment.