bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival rate of ovarian cancer in Asian countries: a systematic review and meta-analysis
Authors: Maleki Zahra , Vali Mohebat , Nikbakht Hossein-Ali , Hassanipour Soheil , Kouhi Aida , Sedighi Saman , Farokhi Roya , Ghaem Haleh
Published: June 2023

Background

Ovarian cancer is amongst one of the most commonly occurring cancers affecting women, and the leading cause of gynecologic related cancer death. Its poor prognosis and high mortality rates can be attributed to the absence of specific signs and symptoms until advance stages, which frequently leads to late diagnosis. Survival rate of patients diagnosed with ovarian cancer can be used in order to better assess current standard of care; the aim of this study is to evaluate the survival rate of ovarian cancer patients in Asia.

Methods

Systematic review was performed on articles that were published by the end of August 2021 in five international databases, including Medline / PubMed, ProQuest, Scopus, Web of Knowledge, and Google Scholar. The Newcastle-Ottawa quality evaluation form was used for cohort studies to evaluate the quality of the articles. The Cochran-Q and I2 tests were used to calculate the heterogeneity of the studies. The Meta-regression analysis was also done according to when the study was published.

Results

A total of 667 articles were reviewed, from which 108 were included in this study because they passed the criteria. Based on a randomized model, the survival rates of ovarian cancer after 1, 3 and 5 years were respectively 73.65% (95% CI, 68.66–78.64), 61.31% (95% CI, 55.39–67.23) and 59.60% (95% CI, 56.06–63.13). Additionally, based on meta-regression analysis, there was no relationship between the year of study and survival rate.

Conclusions

The 1-year survival rate was higher than that of 3- and 5-year for ovarian cancer. This study provides invaluable information that can not only help establish better standard of care for treatment of ovarian cancer, but also assist in development of superior health interventions for prevention and treatment of the disease.
MicroRNA-5195-3p mediated malignant biological behaviour of insulin-resistant liver cancer cells via SOX9 and TPM4
Authors: Yan Jing , Xie Bei , Tian Ye , An Wenqin , Peng Zhiheng , Liu Zhuan , Li Jing , Li Linjing
Published: June 2023

Background

Primary liver cancer is a malignant tumour of the digestive system, ranking second in cancer mortality in China. In different types of cancer, such as liver cancer, microRNAs (miRNAs) have been shown to be dysregulated. However, little is known about the role of miR-5195-3p in insulin-resistant liver cancer.

Methods and results

In this study, in vitro and in vivo experiments were conducted to identify the altered biological behaviour of insulin-resistant hepatoma cells (HepG2/IR), and we proved that HepG2/IR cells had stronger malignant biological behaviour. Functional experiments showed that enhanced expression of miR-5195-3p could inhibit the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and chemoresistance of HepG2/IR cells, while impaired expression of miR-5195-3p in HepG2 cells resulted in the opposite effects. Bioinformatics prediction and dual luciferase reporter gene assays proved that SOX9 and TPM4 were the target genes of miR-5195-3p in hepatoma cells.

Conclusions

In conclusion, our study demonstrated that miR-5195-3p plays a critical role in insulin-resistant hepatoma cells and might be a potential therapeutic target for liver cancer.
Culturally adapted psychosocial interventions (CaPSI) for early psychosis in a low-resource setting: study protocol for a large multi-center RCT
Authors: Husain M. O. , Khoso A. B. , Kiran T. , Chaudhry N. , Husain M. I. , Asif M. , Ansari M. , Rajput A. H. , Dawood S. , Naqvi H. A. , Nizami A. T. , Tareen Z. , Rumi J. , Sherzad S. , Khan H. A. , Bhatia M. R. , Siddiqui K. M. S. , Zadeh Z. , Mehmood N. , Talib U. , de Oliveira C. , Naeem F. , Wang W. , Voineskos A. , Husain N. , Foussias G. , Chaudhry I. B.
Published: June 2023

Background

Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan.

Method

A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety).

Conclusions

A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP.

Trial registration

NCT05814913.
“I don’t know what I’m feeling for”: young women’s beliefs about breast cancer risk and experiences of breast awareness
Authors: Hindmarch Sarah , Gorman Louise , Hawkes Rhiannon E. , Howell Sacha J. , French David P.
Published: June 2023

Background

Younger women are often diagnosed with advanced breast cancer. Beliefs about risk are instrumental in motivating many health protective behaviours, but there may be confusion around which behaviour is appropriate to detect breast cancer earlier. Breast awareness, defined as an understanding of how the breasts look and feel so changes can be identified early, is widely recommended. In contrast, breast self-examination involves palpation using a specified method. We aimed to investigate young women’s beliefs about their risk and experiences of breast awareness.

Methods

Thirty-seven women aged 30–39 years residing in a North West region of England with no family or personal history of breast cancer participated in seven focus groups (n = 29) and eight individual interviews. Data were analysed using reflexive thematic analysis.

Results

Three themes were generated. “Future me’s problem” describes why women perceive breast cancer as an older woman’s disease. Uncertainty regarding checking behaviours highlights how confusion about self-checking behaviour advice has resulted in women infrequently performing breast checks. Campaigns as a missed opportunity highlights the potential negative effects of current breast cancer fundraising campaigns and the perceived absence of educational campaigning about breast cancer for this demographic.

Conclusions

Young women expressed low perceived susceptibility to developing breast cancer in the near future. Women did not know what breast self-checking behaviours they should be performing and expressed a lack of confidence in how to perform a breast check appropriately due to limited knowledge about what to look and feel for. Consequently, women reported disengagement with breast awareness. Defining and clearly communicating the best strategy for breast awareness and establishing whether it is beneficial or not are essential next steps.
Persistent cornual pregnancy mimicking uterine arteriovenous malformation: a case report
Authors: Xie Zhuolin , Wang Yang , Chen Rong
Published: June 2023

Background

Uterine arteriovenous malformation(AVM) refers to the abnormal direct traffic between uterine arteries and veins, which can be characterized by the imaging examination, showing increased uterine vascularity and arteriovenous shunting. However, similar imaging manifestations can also be seen in a variety of conditions including retained production of conception, gestational trophoblastic disease, placental polyp, and vascular neoplasm.

Case presentation

Here we present a case of a 42-year-old woman who was suspected of suffering uterine AVM indicated by Doppler sonography and magnetic resonance imaging but was finally diagnosed with a persistent ectopic pregnancy located on the right uterine corner by pathology after laparoscopy. She recovered well after surgery.

Conclusion

Uterine AVM is a rare and serious condition. In general, it presents special radiological manifestations. However, when complicated with other diseases it can also be distorting. Standardized diagnosis and management are important.
Perceived health facility-related barriers and post-abortion care-seeking intention among women of reproductive age in Osun state, Nigeria
Authors: Oni Tosin Olajide , Adebowale Stephen Ayo , Afolabi Anuoluwapo Adeyimika , Akinyemi Akanni Ibukun , Banjo Olufunmilayo Olufunmilola
Published: June 2023

Background

Post-abortion care (PAC) prevents death and complications caused by unsafe abortion which is widespread in Nigeria. Yet, there is sparse community-based evidence on women’s intention to seek PAC should they have an abortion. This study examined the influence of perceived health facility-related barriers (HFRB) on post-abortion care-seeking intention (PACSI) among women of reproductive ages in Osun state, Nigeria.

Methods

The study focused on women in a sexual relationship and who were residents of Osun state. A community-based survey was implemented using a multi-stage sampling technique. The calculated sample size (with attrition) was 1200 and data were collected from women aged 15-49 years, using open data kit (ODK). However, 1,065 complete responses were received on the ODK server, indicating an 88.8% response rate. Models were estimated using ordered logistic regression (Ologit) (α0.05) and data analysis was performed using Stata 14.0.

Results

Mean age of the women was 29.3±7.6 years and 34.01% had the intention to seek PAC in health facilities. Lack of service confidentiality and unavailability of equipment specific to abortion were the two most reported barriers that would prevent women from seeking PAC. The adjusted Ologit model showed that respondents with perceived low HFRB had higher odds (aOR=1.60; CI=1.12-2.11) of seeking PAC in the health facility. Also, women who were employed and skilled were more likely (aOR=1.51; CI=1.13-2.01) while women who had PAC support from spouses/partners had higher odds of healthy PACSI (aOR=2.03; CI=1.48-2.78). Other identified predictors of PAC seeking intention included level of education, employment status, and spousal/partner support.

Conclusion

Perceived lack of trust in service provision and necessary equipment specific to abortion care had a negative influence on women’s PACSI in Osun state. Reassuring health interventions that focus on improving the public perception of healthcare services and confidence to use the facility will likely improve the patronage of health facility for post-abortion care in Osun sate.
Effects of corrective and breathing exercises on respiratory function of older adults with a history of COVID-19 infection: a randomized controlled trial
Authors: Sedaghati Parisa , Derakhshan Korosh Fakhimi , Ahmadabadi Somayeh , Moghaddam Seyed Reza Rahimi
Published: June 2023

Background

Patients with a history of COVID-19 infection may suffer from different physical problems. This study aimed to investigate the effect of corrective and breathing exercises on improving respiratory function among patients with a history of COVID-19 infection.

Methods

In this clinical trial study, thirty elderlies with a history of COVID-19 disease were divided into two groups (mean age 63.60 ± 3.56 experimental, 59.87 ± 2.99 control groups) based on the study inclusion criteria. Exercise interventions included two sections- breathing exercises and corrective exercises in the cervical and thoracic spine. The spirometry test, craniovertebral angle, and thoracic kyphosis test were used. To evaluate differences between variables, paired-samples t-test and ANCOVA were used (p-value < 0.01). Also, Eta-squared was measured to assess the effect size.

Results

Results showed a significant difference between the two groups in craniovertebral angle (P = 0.001), thoracic kyphosis (P = 0.007), and respiratory capacity including Forced expiratory volume in one second (FEV1) (P = 0.002), FEV1/FVC (P = 0.003), Peripheral oxygen saturation (SPO2) (P = 0.001), while no significant differences were observed between two groups in terms of chest anthropometric indices (P > 0.01). The Eta-squared value of 0.51 for the Craniovertebral angle and the SPO2 indicates a large effect size.

Conclusions

The results showed the combination of corrective and breathing exercises could improve pulmonary function and correct cervical and thoracic posture in patients with a history of COVID-19 infection. Therefore, corrective and breathing exercises can be helpful as a complementary treatment along with pharmaceutical therapy to reduce chronic pulmonary complications in patients infected with COVID-19.

Trial registration

This research was registered in the Iranian Registry of Clinical Trials (IRCT registration number: IRCT20160815029373N7, First trial registration: 23/08/2021, Registration date: 01/09/2021).
Perception of neurology among undergraduate medical students – what can be done to counter neurophobia during clinical studies?
Authors: Jukna Šarūnas , Puteikis Kristijonas , Mameniškienė Rūta
Published: June 2023

Background and purpose

With a global increase in the burden of neurological diseases, the aversion towards neurology (neurophobia) may challenge the sufficient provision of new specialists in this field. We investigated the possible determinants of neurophobia among medical students and its influence on the intent to pursue neurology residency.

Methods

From September 2021 to March 2022, an online questionnaire was distributed to medical students in Lithuania. It included questions about knowledge, confidence, interest, and teaching quality of various medical specialties (including neurology), as well as the willingness to choose neurology for residency.

Results

Eight hundred fifty-two students responded to the survey (77.2% female) – they rated neurology as significantly more difficult than other medical areas and lacked confidence in assessing patients with neurological problems (p < 0.001). However, neurology was selected as one of the most interesting subjects and was reportedly well-taught. The prevalence of neurophobia among respondents was 58.9%. Most of them (207, 87.7%) indicated that neurology professors positively affected their outlook towards this medical specialty – such experience was associated with lower odds of neurophobia (odds ratio (OR) = 0.383, 95% confidence interval (CI) = 0.223 to 0.658). Being less neurophobic (OR = 1.785, 95% CI = 1.152 to 2.767) and having conducted neurology research (OR = 2.072, 95% CI = 1.145 to 3.747) increased the odds of a student being willing to pursue a career in neurology.

Conclusion

Neurophobia was frequent among students in Lithuania and was inversely related to the positive influence by neurology professors. Together with previous research experience in the field, low levels of neurophobia were associated with the inclination to enter neurology residency.
Impact of social media education on antimicrobial stewardship awareness among pharmacy, medical and nursing students and residents
Authors: Atallah Stephanie , Mansour Hanine , Dimassi Hani , Kabbara Wissam K
Published: June 2023

Background

Antimicrobial resistance has always been an important issue as antimicrobial therapies are becoming less effective due to incorrect use and overuse. Our objective was to evaluate the impact of social media education on spreading antimicrobial stewardship awareness among healthcare students and residents.

Methods

A prospective interventional study was conducted over 5 months, from November 2021 until March 2022. Weekly educational posts on infectious diseases were posted along with pre- and post- quizzes on a designated Facebook page. The primary endpoint of change in knowledge score was assessed using the independent t-test. Expected average pre-training is 2.5 over 5, and the expected average post-training is a minimum of 3.5 over 5 (common standard deviation of 1) for a minimum of 20% improvement that produces an effect size d = 1. Expecting a larger number of respondents on the pre-test than post-test, the ratio N1/N2 was set to 1.5. With the desired power set to 80% and alpha at 5%, sample size was determined as a minimum of 22 (N1) and 14 (N2). All analyses were carried at the 0.05 significance level.

Results

In the entry questionnaire, 85.6% (107/125) of participants believed that antibiotics are overused, 26.4% (33/125) confirmed that they overuse antibiotics, and 88.8% (111/125) confirmed the importance of having an antimicrobial stewardship program. 76.8% (96/125) of the participants regularly use social media for educational purposes and only 2.4% sometimes refer to social media as an educational tool. Improvement in knowledge was noted in all pre and post – quizzes except for two quizzes (prostatitis and acute cystitis – 18.4% and 13.2% improvement respectively). In total, there was a significant 36.2% improvement between all pre and post quizzes [min 13.2% and max 52.8% across all quizzes].

Conclusion

This intervention demonstrated the importance of social media as a valuable tool to enhance antimicrobial stewardship knowledge among pharmacy, medical and nursing students and residents. Future studies are needed to examine the impact of social media education on behaviors in practice.
Comparison of causal forest and regression-based approaches to evaluate treatment effect heterogeneity: an application for type 2 diabetes precision medicine
Authors: Venkatasubramaniam Ashwini , Mateen Bilal A. , Shields Beverley M. , Hattersley Andrew T. , Jones Angus G. , Vollmer Sebastian J. , Dennis John M.
Published: June 2023

Objective

Precision medicine requires reliable identification of variation in patient-level outcomes with different available treatments, often termed treatment effect heterogeneity. We aimed to evaluate the comparative utility of individualized treatment selection strategies based on predicted individual-level treatment effects from a causal forest machine learning algorithm and a penalized regression model.

Methods

Cohort study characterizing individual-level glucose-lowering response (6 month reduction in HbA1c) in people with type 2 diabetes initiating SGLT2-inhibitor or DPP4-inhibitor therapy. Model development set comprised 1,428 participants in the CANTATA-D and CANTATA-D2 randomised clinical trials of SGLT2-inhibitors versus DPP4-inhibitors. For external validation, calibration of observed versus predicted differences in HbA1c in patient strata defined by size of predicted HbA1c benefit was evaluated in 18,741 patients in UK primary care (Clinical Practice Research Datalink).

Results

Heterogeneity in treatment effects was detected in clinical trial participants with both approaches (proportion predicted to have a benefit on SGLT2-inhibitor therapy over DPP4-inhibitor therapy: causal forest: 98.6%; penalized regression: 81.7%). In validation, calibration was good with penalized regression but sub-optimal with causal forest. A strata with an HbA1c benefit > 10 mmol/mol with SGLT2-inhibitors (3.7% of patients, observed benefit 11.0 mmol/mol [95%CI 8.0–14.0]) was identified using penalized regression but not causal forest, and a much larger strata with an HbA1c benefit 5–10 mmol with SGLT2-inhibitors was identified with penalized regression (regression: 20.9% of patients, observed benefit 7.8 mmol/mol (95%CI 6.7–8.9); causal forest 11.6%, observed benefit 8.7 mmol/mol (95%CI 7.4–10.1).

Conclusions

Consistent with recent results for outcome prediction with clinical data, when evaluating treatment effect heterogeneity researchers should not rely on causal forest or other similar machine learning algorithms alone, and must compare outputs with standard regression, which in this evaluation was superior.
Effectiveness of oncology nurse navigator on the incidence of postoperative pulmonary complications in gastric cancer patients undergoing radical gastrectomy
Authors: Yan Yamin , Jin Peili , Yu Zhenghong , Tang Zhaoqing , Lu Jingjing , Hu Yan , Zhang Yuxia
Published: June 2023

Background

Management of postoperative pulmonary complications (PPCs) can be challenging in gastric cancer patients undergoing radical gastrectomy and is always associated with poor prognosis. Even though oncology nurse navigator (ONN) provide effective and critical individualized care to patients, little is known about their impact on the occurrence of PPCs in gastric cancer patients. This study aimed to determine whether ONN decreases the incidence of PPCs in gastric cancer patients.

Methods

This was a retrospective review in which data for gastric cancer patients at one centre was evaluated before and after an ONN hired. An ONN was introduced to patients at their initial visit to manage pulmonary complications throughout treatment. The research was conducted from 1 August 2020 to 31 January 2022. The study participants were divided into the non-ONN group (from 1 August 2020 to 31 January 2021) and the ONN group (from 1 August 2021 to 31 January 2022). The incidence and severity of PPCs between the groups were then compared.

Results

ONN significantly decreased the incidence of PPCs (15.0% vs. 9.8%) (OR = 2.532(95% CI: 1.087–3.378, P = 0.045)), but there was no significant difference in the components of PPCs including pleural effusion, atelectasis, respiratory infection, and pneumothorax. The severity of PPCs was also significantly higher in the non-ONN group (p = 0.020). No significant statistical difference was observed for the major pulmonary complications (grade ≥ 3) between the two groups (p = 0.286).

Conclusions

Role of ONN significantly decrease the incidence of PPCs in gastric cancer patients undergoing radical gastrectomy.
A survey exploring the practices of smoking cessation support among hospital-based healthcare providers
Authors: Farver-Vestergaard Ingeborg , Hjorth Peter , Pisinger Charlotta , Larsen Pia Veldt , Løkke Anders
Published: June 2023

Background

Hospital visits constitute a ‘window of opportunity’ for initiating smoking cessation attempts, and healthcare providers (HCPs) play an important role in supporting patients to stop smoking. Yet, the current practices of supporting smoking cessation in the hospital setting are largely unexplored. The aim of this study was to explore practices of smoking cessation support among hospital-based HCPs.

Methods

HCPs working in a large hospital in the secondary care sector completed an online, cross-sectional survey, including sociodemographic and work-related factors as well as 21 questions assessing practices of smoking cessation support based on the “five As” framework. Descriptive statistics were computed, and predictors of HCPs giving patients advice to stop smoking were explored using logistic regression analysis.

Results

All employees (N = 3998) in the hospital received a survey link; 1645 (41.1%) HCPs with daily patient contact completed the survey. Smoking cessation support in the hospital setting was limited with regard to assessment of smoking; providing information and advice; planning and referral for further support; and follow-up on smoking cessation attempts. Almost half (44.8%) of participating HCPs with daily patient contact never or rarely advise their patients to stop smoking. Physicians were more likely than nurses to advice patients to stop smoking, and HCPs in outpatient clinics were more likely to give advice than inpatient clinic HCPs.

Conclusion

Smoking cessation support is very limited in the hospital-based healthcare setting. This is problematic, as hospital visits can be windows of opportunity to help patients change their health behaviour. An intensified focus on the implementation of hospital-based smoking cessation support is needed.
Utilization of insecticide-treated nets and associated factors among childbearing women in Northern Nigeria
Authors: Solanke Bola Lukman , Soladoye Daniel Alabi , Birsirka Ibrahim Adamu , Abdurraheem Anifat , Salau Omowumi Romoke
Published: June 2023

Background

Studies have explored the correlates of insecticide-treated nets in Nigeria. The few studies that focused on Northern Nigeria mostly examined individual correlates, but largely ignored the community correlates. Also, the persistence of armed insurgencies in the region calls for more research attention. This study examines the utilization and the associated individual and community factors of insecticide-treated nets in Northern Nigeria.

Methods

The study adopted a cross-sectional design. Data were extracted from the 2021 Nigeria Malaria Indicator Survey (NMIS). A weighted sample size of 6873 women was analysed. The outcome variable was the utilization of insecticide-treated nets. The explanatory variables selected at the individual/household level were maternal age, maternal education, parity, religion, sex of head of household, household wealth, and household size. The variables selected at the community level were the type of place of residence, geo-political zone of residence, the proportion of children under five who slept under a bed net, the proportion of women aged 15–49 who heard malaria media messages, and the community literacy level. Two variables, namely, the number of mosquito bed nets in the household, and the number of rooms used for sleeping were included for statistical control. Three multilevel mixed-effect regression models were fitted.

Results

The majority of childbearing women (71.8%) utilized insecticide-treated nets. Parity and household size were the significant individual/household characteristics associated with the utilization of insecticide-treated nets. The proportion of under-five children in the community who slept under mosquito bed nets, and the geopolitical zone of residence were significant community correlates of the use of insecticide-treated nets. In addition, the number of rooms for sleeping, and the number of mosquito bed nets in the households were significantly associated with the utilization of insecticide-treated nets.

Conclusion

Parity, household size, number of sleeping rooms, number of treated bed nets, geo-political zone of residence, and proportion of under-five children sleeping under bed nets are important associated factors of the utilization of insecticide-treated nets in Northern Nigeria. Existing malaria preventive initiatives should be strengthened to target these characteristics.
Positive correlation between snoring and dyslipidemia in adults: results from NHANES
Authors: Tian Ying , Li Dongna , Mu Huijuan , Wei Sining , Guo Dong
Published: June 2023

Background

A few studies have shown that snoring, in certain populations, is associated with dyslipidemia. However, there are currently no large-scale national studies available that explore this association. Thus, for further clarification, studies using a large sample of the general population need to be conducted. This study aimed to explore this association using the National Health and Nutrition Examination Survey (NHANES) database.

Methods

A cross-sectional survey was conducted using data from the NHANES database; 2005 to 2008 and 2015 to 2018 datasets were used (weighted to be representative of United States adults aged ≥ 20 years). Information on snoring status, lipid levels, and confounding factors were included. Logistic regression of the generalized linear model was used to analyze the relationship between snoring and dyslipidemia, and hierarchical analysis, interaction analysis, and sensitivity analysis were used to explore the stability of the results.

Results

Data from 28,687 participants were analyzed, and 67% of the participants had some degree of snoring. The fully adjusted multivariate logistic regression results demonstrated that snoring frequency was significantly positively associated with dyslipidemia (P < 0.001 for linear trend). Adjusted odds ratios (aORs) of dyslipidemia among those who snored rarely, occasionally, and frequently were 1.1 (95% confidence interval [CI], 1.02–1.18), 1.23 (95% CI, 1.10–1.38), and 1.43 (95% CI, 1.29–1.58), respectively, compared with that among those who never snored. In addition, age and snoring frequency showed a correlation (P = 0.02). Sensitivity analysis demonstrated that frequent snoring was significantly associated with lipid levels (all P ≤ 0.01 for linear trend), including increased low-density lipoprotein cholesterol (LDL-C) (β = 0.09 mmol/L; 95% CI, 0.02–0.16), triglyceride (TG) (β = 0.18 mmol/L; 95% CI, 0.10–0.26), total cholesterol (TC) (β = 0.11 mmol/L; 95% CI, 0.05–0.16), and decreased high-density lipoprotein cholesterol (HDL-C) (β=-0.04 mmol/L; 95% CI, -0.06–-0.03).

Conclusions

A statistically significant positive association was identified between sleep snoring and dyslipidemia. It was suggested that sleep snoring interventions may reduce the risk of dyslipidemia.
Prevalence, risk factors, treatment uptake and treatment outcome of hepatitis C virus in people who inject drugs at the needle and syringe program in Uppsala, Sweden
Authors: Kågström E. , Lannergård A. , El Khosht J. , Lörelius P. , Månflod J. , Strömdahl S.
Published: June 2023

Background

The World Health Organization has set a goal to reach world elimination of hepatitis C virus (HCV) by 2030. Needle and syringe programs (NSP) for people who inject drugs (PWID) are crucial to achieve this goal. The NSP in Uppsala, Sweden, was opened in 2016 and has since 2018 provided HCV treatment for PWID. The aim of this study was to investigate HCV prevalence, risk factors and treatment uptake and outcome in NSP participants.

Methods

Data from 450 PWID registered at the Uppsala NSP between 2016-11-01 and 2021-12-31 were collected from the national quality registry InfCare NSP. Data from the 101 PWID treated for HCV at the Uppsala NSP were collected through patient journal review. Descriptive and inferential analysis was performed. Ethical approval was obtained from the Ethical Review Board in Uppsala (dnr 2019/00215).

Results

The mean age was 35 years. 75% were males (336/450), and 25% were females (114/450). The overall HCV prevalence was 48% (215/450) with a declining trend over time. Factors associated with a higher risk of HCV were older age at registration (OR 1.025, 95% CI 1.004–1.046), lower age at injection drug debut (OR 0.963, 95% CI 0.932–0.996), lower education level (OR 1.829, 95% CI 1.185–2.821) and higher number of total visits at the NSP (OR 1.005, 95% CI 1.001–1.009). The overall HCV treatment uptake was 47% (101/215), of which 77% (78/101) completed HCV treatment. The HCV treatment compliance was 88% (78/89). 99% (77/78) were cured with a sustained virologic response 12 weeks after completed treatment. The reinfection rate over the study period was 9/77 (11.7%); all were male with mean age of 36.

Conclusions

HCV prevalence, treatment uptake and treatment outcome have improved since the opening of the Uppsala NSP. However, further measures are needed to reach the HCV elimination goal. Outreach HCV treatment programs for PWID should be explored and evaluated in combination with further implementation of low-threshold programs.
The effect of neutrophil extracellular traps in venous thrombosis
Authors: Li Weiwei , Wang Zixiang , Su Chen’guang , Liao Zheng , Pei Yinxuan , Wang Jianli , Li Zixin , Fu Shijie , Liu Jinlong
Published: June 2023

Neutrophil extracellular traps (NETs) as special release products of neutrophils have received extensive attention. They are composed of decondensed chromatin and coated with nucleoproteins, including histones and some granulosa proteins. NETs can form a network structure to effectively capture and eliminate pathogens and prevent their spread. Not only that, recent studies have shown that NETs also play an important role in venous thrombosis. This review provides the most important updated evidence regarding the mechanism of NETs formation and the role of NETs in the process of venous thrombosis. The potential prophylactic and therapeutic value of NETs in venous thrombotic disease will also be discussed.
LRRC6 regulates biogenesis of motile cilia by aiding FOXJ1 translocation into the nucleus
Authors: Kim Dong Yun , Sub Yu Jin , Kim Hye-Youn , Cho Kyeong Jee , Choi Won Il , Choi Yo Jun , Lee Min Goo , Hildebrandt Friedhelm , Gee Heon Yung
Published: June 2023

Background

LRRC6 is an assembly factor for dynein arms in the cytoplasm of motile ciliated cells, and when mutated, dynein arm components remained in the cytoplasm. Here, we demonstrate the role of LRRC6 in the active nuclear translocation of FOXJ1, a master regulator for cilia-associated gene transcription.

Methods

We generated Lrrc6 knockout (KO) mice, and we investigated the role of LRRC6 on ciliopathy development by using proteomic, transcriptomic, and immunofluorescence analysis. Experiments on mouse basal cell organoids confirmed the biological relevance of our findings.

Results

The absence of LRRC6 in multi-ciliated cells hinders the assembly of ODA and IDA components of cilia; in this study, we showed that the overall expression of proteins related to cilia decreased as well. Expression of cilia-related transcripts, specifically ODA and IDA components, dynein axonemal assembly factors, radial spokes, and central apparatus was lower in Lrrc6 KO mice than in wild-type mice. We demonstrated that FOXJ1 was present in the cytoplasm and translocated into the nucleus when LRRC6 was expressed and that this process was blocked by INI-43, an importin α inhibitor.

Conclusions

Taken together, these results hinted at the LRRC6 transcriptional regulation of cilia-related genes via the nuclear translocation of FOXJ1.
HMGB3 promotes the malignant phenotypes and stemness of epithelial ovarian cancer through the MAPK/ERK signaling pathway
Authors: Ma Hanlin , Qi Gonghua , Han Fang , Gai Panpan , Peng Jiali , Kong Beihua
Published: June 2023

Background

Ovarian cancer, particularly epithelial ovarian cancer (EOC), is the leading cause of cancer-related mortality among women. Our previous study revealed that high HMGB3 levels are associated with poor prognosis and lymph node metastasis in patients with high-grade serous ovarian carcinoma; however, the role of HMGB3 in EOC proliferation and metastasis remains unknown.

Methods

MTT, clonogenic, and EdU assays were used to assess cell proliferation. Transwell assays were performed to detect cell migration and invasion. Signaling pathways involved in HMGB3 function were identified by RNA sequencing (RNA-seq). MAPK/ERK signaling pathway protein levels were evaluated by western blot.

Results

HMGB3 knockdown inhibited ovarian cancer cell proliferation and metastasis, whereas HMGB3 overexpression facilitated these processes. RNA-seq showed that HMGB3 participates in regulating stem cell pluripotency and the MAPK signaling pathway. We further proved that HMGB3 promotes ovarian cancer stemness, proliferation, and metastasis through activating the MAPK/ERK signaling pathway. In addition, we demonstrated that HMGB3 promotes tumor growth in a xenograft model via MAPK/ERK signaling.

Conclusions

HMGB3 promotes ovarian cancer malignant phenotypes and stemness through the MAPK/ERK signaling pathway. Targeting HMGB3 is a promising strategy for ovarian cancer treatment that may improve the prognosis of women with this disease.
Predicting tumor repopulation through the gene panel derived from radiation resistant colorectal cancer cells
Authors: Song Yanwei , Deng Zheng , Sun Haoran , Zhao Yucui , Zhao Ruyi , Cheng Jin , Huang Qian
Published: June 2023

Background

Tumor cells with the capability of radiation resistance can escape the fate of cell death after radiotherapy, serving as the main cause of treatment failure. Repopulation of tumors after radiotherapy is dominated by this group of residual cells, which greatly reduce the sensitivity of recurrent tumors to the therapy, resulting in poor clinical outcomes. Therefore, revealing the mechanism of radiation resistant cells participating in tumor repopulation is of vital importance for cancer patients to obtain a better prognosis.

Methods

Co-expressed genes were searched by using genetic data of radiation resistant cells (from GEO database) and TCGA colorectal cancer. Univariate and multivariate Cox regression analysis were performed to define the most significant co-expressed genes for establishing prognostic indicator. Logistic analysis, WGCNA analysis, and other types of tumors were included to verify the predictive ability of the indicator. RT-qPCR was carried out to test expression level of key genes in colorectal cancer cell lines. Colongenic assay was utilized to test the radio-sensitivity and repopulation ability of key gene knockdown cells.

Results

Prognostic indicator based on TCGA colorectal cancer patients containing four key radiation resistance genes (LGR5, KCNN4, TNS4, CENPH) was established. The indicator was shown to be significantly correlated with the prognosis of colorectal cancer patients undergoing radiotherapy, and also had an acceptable predictive effect in the other five types of cancer. RT-qPCR showed that expression level of key genes was basically consistent with the radiation resistance level of colorectal cancer cells. The clonogenic ability of all key gene knockdown cells decreased after radiation treatment compared with the control groups.

Conclusions

Our data suggest that LGR5, KCNN4, TNS4 and CENPH are correlated with radiation sensitivity of colorectal cancer cells, and the indicator composed by them can reflect the prognosis of colorectal cancer patients undergoing radiation therapy. Our data provide an evidence of radiation resistant tumor cells involved in tumor repopulation, and give patients undergoing radiotherapy an approving prognostic indicator with regard to tumor progression.
Proteins from toad’s parotoid macroglands: do they play a role in gland functioning and chemical defence?
Authors: Kowalski Krzysztof , Marciniak Paweł , Rychlik Leszek
Published: June 2023

Background

Parotoid gland secretion of bufonid toads is a rich source of toxic molecules that are used against predators, parasites and pathogens. Bufadienolides and biogenic amines are the principal compounds responsible for toxicity of parotoid secretion. Many toxicological and pharmacological analyses of parotoid secretions have been performed, but little is known about the processes related to poison production and secretion. Therefore, our aim was to investigate protein content in parotoids of the common toad, Bufo bufo, to understand the processes that regulate synthesis and excretion of toxins as well as functioning of parotoid macroglands.

Results

Applying a proteomic approach we identified 162 proteins in the extract from toad’s parotoids that were classified into 11 categories of biological functions. One-third (34.6%) of the identified molecules, including acyl-CoA-binding protein, actin, catalase, calmodulin, and enolases, were involved in cell metabolism. We found many proteins related to cell division and cell cycle regulation (12.0%; e.g. histone and tubulin), cell structure maintenance (8.4%; e.g. thymosin beta-4, tubulin), intra- and extracellular transport (8.4%), cell aging and apoptosis (7.3%; e.g. catalase and pyruvate kinase) as well as immune (7.0%; e.g. interleukin-24 and UV excision repair protein) and stress (6.3%; including heat shock proteins, peroxiredoxin-6 and superoxide dismutase) response. We also identified two proteins, phosphomevalonate kinase and isopentenyl-diphosphate delta-isomerase 1, that are involved in synthesis of cholesterol which is a precursor for bufadienolides biosynthesis. STRING protein-protein interaction network predicted for identified proteins showed that most proteins are related to metabolic processes, particularly glycolysis, stress response and DNA repair and replication. The results of GO enrichment and KEGG analyses are also consistent with these findings.

Conclusion

This finding indicates that cholesterol may be synthesized in parotoids, and not only in the liver from which is then transferred through the bloodstream to the parotoid macroglands. Presence of proteins that regulate cell cycle, cell division, aging and apoptosis may indicate a high epithelial cell turnover in parotoids. Proteins protecting skin cells from DNA damage may help to minimize the harmful effects of UV radiation. Thus, our work extends our knowledge with new and important functions of parotoids, major glands involved in the bufonid chemical defence.
Acute and post-acute sequelae of SARS-CoV-2 infection: a review of risk factors and social determinants
Authors: Wang Chumeng , Ramasamy Akshara , Verduzco-Gutierrez Monica , Brode W. Michael , Melamed Esther
Published: June 2023

SARS-CoV-2 infection leading to Coronavirus Disease 2019 (COVID-19) has caused more than 762 million infections worldwide, with 10–30% of patients suffering from post-acute sequelae of SARS-CoV-2 infections (PASC). Initially thought to primarily affect the respiratory system, it is now known that SARS-CoV-2 infection and PASC can cause dysfunction in multiple organs, both during the acute and chronic stages of infection. There are also multiple risk factors that may predispose patients to worse outcomes from acute SARS-CoV-2 infection and contribute to PASC, including genetics, sex differences, age, reactivation of chronic viruses such as Epstein Barr Virus (EBV), gut microbiome dysbiosis, and behavioral and lifestyle factors, including patients’ diet, alcohol use, smoking, exercise, and sleep patterns. In addition, there are important social determinants of health, such as race and ethnicity, barriers to health equity, differential cultural perspectives and biases that influence patients’ access to health services and disease outcomes from acute COVID-19 and PASC. Here, we review risk factors in acute SARS-CoV-2 infection and PASC and highlight social determinants of health and their impact on patients affected with acute and chronic sequelae of COVID-19.
Role and clinical implication of autophagy in COVID-19
Authors: Shan Tianjiao , Li Lan-ya , Yang Jin-Ming , Cheng Yan
Published: June 2023

The ongoing coronavirus disease 2019 (COVID-19) pandemic constitutes a serious public health concern worldwide. Currently, more than 6 million deaths have occurred despite drastic containment measures, and this number is still increasing. Currently, no standard therapies for COVID-19 are available, which necessitates identifying effective preventive and therapeutic agents against COVID-19. However, developing new drugs and vaccines is a time-consuming process, and therefore, repurposing the existing drugs or redeveloping related targets seems to be the best strategy to develop effective therapeutics against COVID-19. Autophagy, a multistep lysosomal degradation pathway contributing to nutrient recycling and metabolic adaptation, is involved in the initiation and progression of numerous diseases as a part of an immune response. The key role of autophagy in antiviral immunity has been extensively studied. Moreover, autophagy can directly eliminate intracellular microorganisms by selective autophagy, that is, “xenophagy.” However, viruses have acquired diverse strategies to exploit autophagy for their infection and replication. This review aims to trigger the interest in the field of autophagy as an antiviral target for viral pathogens (with an emphasis on COVID-19). We base this hypothesis on summarizing the classification and structure of coronaviruses as well as the process of SARS-CoV-2 infection and replication; providing the common understanding of autophagy; reviewing interactions between the mechanisms of viral entry/replication and the autophagy pathways; and discussing the current state of clinical trials of autophagy-modifying drugs in the treatment of SARS-CoV-2 infection. We anticipate that this review will contribute to the rapid development of therapeutics and vaccines against COVID-19.
Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1
Authors: Fame Ryann M. , Xu Huixin , Pragana Aja , Lehtinen Maria
Published: June 2023

Regulation of the volume and electrolyte composition of the cerebrospinal fluid (CSF) is vital for brain development and function. The Na-K-Cl co-transporter NKCC1 in the choroid plexus (ChP) plays key roles in regulating CSF volume by co-transporting ions and mediating same-direction water movements. Our previous study showed ChP NKCC1 is highly phosphorylated in neonatal mice as the CSF K+ level drastically decreases and that overexpression of NKCC1 in the ChP accelerates CSF K+ clearance and reduces ventricle size [1]. These data suggest that NKCC1 mediates CSF K+ clearance following birth in mice. In this current study, we used CRISPR technology to create a conditional NKCC1 knockout mouse line and evaluated CSF K+ by Inductively Coupled Plasma Optical Emission spectroscopy (ICP-OES). We demonstrated ChP-specific reduction of total and phosphorylated NKCC1 in neonatal mice following embryonic intraventricular delivery of Cre recombinase using AAV2/5. ChP-NKCC1 knockdown was accompanied by a delayed perinatal clearance of CSF K+. No gross morphological disruptions were observed in the cerebral cortex. We extended our previous results by showing embryonic and perinatal rats shared key characteristics with mice, including decreased ChP NKCC1 expression level, increased ChP NKCC1 phosphorylation state, and increased CSF K+ levels compared to adult. Collectively, these follow up data support ChP NKCC1’s role in age-appropriate CSF K+ clearance during neonatal development.
A cluster-randomized trial of a brief multi-component intervention to improve tobacco outcomes in substance use treatment
Authors: Guydish Joseph , McCuistian Caravella , Hosakote Sindhushree , Le Thao , Masson Carmen L. , Campbell Barbara K. , Delucchi Kevin
Published: June 2023

Background

Smoking prevalence is high among people in substance use disorder (SUD) treatment, and program interventions to address smoking are often complex and lengthy. This cluster-randomized trial tested whether a brief multi-component intervention impacted tobacco outcomes among staff and clients.

Methods

Seven SUD treatment programs were randomly assigned to the multi-component intervention or to waitlist control. The 6-month intervention included a leadership motivation assessment, program incentives, 4 staff training sessions and a leadership learning community session. Survey data were collected from staff and clients at pre- and post-intervention. Outcomes were first compared across condition (intervention vs waitlist control), and then examined pre- to post-intervention with condition collapsed.

Results

Staff in the intervention (n = 48) and control conditions (n = 26) did not differ at post-intervention on smoking prevalence, self-efficacy to help clients quit, or practices used to help clients quit smoking. Intervention clients (n = 113) did not differ from controls (n = 61) in smoking prevalence or receipt of tobacco services. Pre-post comparisons collapsed across condition showed a decrease in client and staff smoking prevalence, which could not be attributed to the intervention, and a decrease in client receipt of cessation medication.

Conclusion

The brief multi-component intervention did not support changes in smoking prevalence or in tobacco-related services received by clients. Other intervention features are needed to reduce smoking among SUD clients.

Trial registration

Randomization occurred at the program level and outcomes measured are program-level measures. Accordingly, the trial is not registered.