bluuebunny/crossref_metadata_2025 huggingface dataset:
Working conditions and mental health of migrants and refugees in Europe considering cultural origin– a systematic review
Authors: Herold Regina , Lieb Marietta , Borho Andrea , Voss Amanda , Unverzagt Susanne , Morawa Eva , Rothermund Eva , Erim Yesim
Published: March 2024

Background

Migrants and refugees/asylum seekers, as a large part of the European work force, are often confronted with unfavorable working conditions in the host country. Main aim of this systematic review was to compare the association of these working conditions with mental health between migrants and refugees/asylum seekers due to their diverse migration experiences and cultural origins, and between different European host countries.

Methods

Systematic search for eligible primary studies was conducted in three electronic databases (PubMed/MEDLINE, PsycINFO and CINAHL) using quantitative study designs written in English, German, French, Italian, Polish, Spanish or Turkish and published from January 1, 2016 to October 27, 2022. Primary health outcomes were diagnosed psychiatric and psychological disorders, suicide and suicide attempts, psychiatric and psychological symptoms, and perceived distress. Secondary health outcomes were more general concepts of mental health such as well-being, life satisfaction and quality of life. Two reviewers independently completed screening, data extraction and the methodological quality assessment of primary studies using the Newcastle-Ottawa-Scale. Descriptive summary of primary studies on working conditions and their relationship with mental health were conducted, comparing migrants and refugees/asylum seekers, migrants and refugees/asylum seekers of different cultural backgrounds (collectivistic and individualistic) and migrants and refugees/asylum seekers living in different host countries.

Results

Inclusion criteria were met by 19 primary studies. Voluntary migrants are more likely to experience overqualification in the host country than refugees. In all examined host countries, migrants and refugees suffer from unfavorable working conditions, with migrants from collectivistic countries being slightly at risk compared to migrants from individualistic countries. Most unfavorable working conditions are related to poor mental health, regardless of migrant status, cultural origin or host country.

Conclusions

Although the results should be interpreted with caution due to the small number of studies, it is evident that to maintain both the mental health and labor force of migrants and refugees/asylum seekers, their working conditions in host countries should be controlled and improved. Special attention should be paid to specific subgroups such as migrants from collectivistic societies.

Ethics and dissemination

This systematic review is excluded from ethical approval because it used previously approved published data from primary studies.

Trial registration number

CRD42021244840.
The effectiveness of a theory -based health education program on waterpipe smoking cessation in Iran: one year follow-up of a quasi-experimental research
Authors: Shahabi Nahid , Shahbazi Sighaldeh Shirin , Eshaghi Sani Kakhaki Hadi , Mohseni Shokrollah , Dadipoor Sara , El-Shahawy Omar
Published: March 2024

Background

The present research aimed to determine the effect of an educational intervention based on the extended theory of planned behavior (ETPB) on waterpipe (WT) smoking cessation in women.

Methods

The present quasi-experimental had a pre-test, post-test design with 3, 6 and 12 months follow-ups was conducted in Bandar Abbas city, south of Iran in December 2021-March 2023. A total of 448 women over the age of 15 (224 in the intervention group (IG), 224 in the control group (CG)), using a two-stage cluster sampling method participated. The educational intervention focused on WT smoking cessation implemented in 14 sessions. The educational methods in the training sessions were lectures, collaborative discussions, Q&As, brainstorming, role plays, and peer education. The main outcome was WT cessation behavior. Repeated measures ANOVA tests and post hoc were run to compare the IG and CG at baseline in terms of demographic variables, t-test and chi square test, and in the four points of time of data collection. The data were analyzed in Stata14. A p-value < 0.05 was considered as statistically significant.

Results

The mean and standard deviation of WT cessation behavior and all ETPB constructs in the IG was significantly higher than the CG. After the educational intervention, in the IG, the perceived behavioral control, attitude, subjective norm, intention and knowledge increased, and the weekly smoking and WT smoking habit decreased (P < 0.001). The CG did not have any significant change in other variables except for the increased knowledge score. During the 12-month follow-up, the cessation rate was 43.81% (P = 0.645) in the IG and 7.45% in the CG (P = 0.081).

Conclusions

The educational intervention positively affected WT smoking reduction and cessation in women through influencing the ETPB constructs. It is strongly recommended to design theory-based interventions beyond the individual level with an emphasis on interpersonal relationships to facilitate WT cessation as far as possible.
Frequency of cigarette smoking and its associated factors among men in East Africa: a pooled prevalence analysis of national survey using multinomial regression
Authors: Terefe Bewuketu , Jembere Mahlet Moges , Chekole Bogale , Assimamaw Nega Tezera , Gebeyehu Daniel Ayelegne
Published: March 2024

Background

Despite the harmful effects of smoking, there have been few studies to pinpoint the factors of this habit, and little is known about it in the East African region. For this reason, this study sought to determine the frequency and factors of cigarette smoking among men in the region.

Methods

Data from recent demographic and health surveys carried out in ten East African countries between 2015 and 2022 were analyzed in this study. Data from 87,022 men was collected. The key factors affecting the smoking rates in the area were investigated using binary and multiple multinomial logistic regression. To ascertain if variables were statistically significant in the final model for binary regression and multiple regression, P values of ≤ 0.2 and < 0.05 were used respectively.

Results

Overall, about 14.69% of people currently smoke cigarettes. Of this about 11.03 (95% CI = 10.82, 11.24) was for daily active tobacco use. As compared to < 26-year-old men, men with an age range of 26–35 years (RRR = 2.17, 95% CI: 2.01,2.34), 36–45 years (RRR = 2.82, 95% CI: 2.60, 3.07), and > 45 years old (RRR = 3.68, 95% CI: 3.38, 4.02), were using cigarettes daily rather than no-smoking cigarettes. Men who had begun their first sexual intercourse at the age of 7–19 years (RRR = 6.27,95% CI, 5.35,7.35), 20–25 years (RRR = 4.01, 95% CI, 3.40,4.72), and greater than 25 years old (RRR = 3.08, 95% CI, 2.55,3.71) have shown a higher relative risk ratio to smoke cigarette daily rather than using not smoke cigarette respectively, married (RRR = 0.86, 95% CI, 0.79,0.93), divorced or widowed (RRR = 2.51, 95% CI, 2.27,2.77), middle wealth index (RRR = 2.11, 95% CI 1.98,2.24), and rich (RRR = 1.44, 95% CI, 1.34,1.54), secondary/higher education (RRR = 0.72, 05% CI, 0.66,0.77), rural men (RRR = 0.69, 95% CI, 0.65,0.73), employed men (RRR = 1.26,95% CI, 1.17,1.36), mass media exposure (RRR = 0.76, 95% CI, 0.73,0.81), men who have one sex partner (RRR = 1.23,95% CI,1.13,1.35), and more than one sex partner (RRR = 1.63, 95% CI, 1.47,1.79) more times as compared to those participants who had no sex partner respectively.

Conclusions

Men in East African nations were substantially more likely to smoke cigarettes if they were older, had less education, had a higher wealth index, were divorced or widowed, had many sexual relationships, had early sexual activity, resided in an urban area, were employed, or had no media exposure. The identified factors should be considered by policymakers and public health professionals to lower smoking initiation and increase smoking cessation among men.
Medical student perceptions of assessments of clinical reasoning in a general surgery clerkship
Authors: Tolsma Rachael , Shebrain Saad , Berry Shamsi Daneshvari , Miller Lisa
Published: March 2024

Background

Components factoring into general surgery clerkship grades vary by institution, and while evaluators attempt to remain unbiased when evaluating medical student performance, subjectivity and implicit bias remain an issue. Our institution recently implemented a case-based structured oral examination to provide the general surgery clerkship director objective insight into students’ clinical reasoning skills. We hypothesized that medical students believe this exam, along with graded clinical documentation and the Observed Standardized Clinical Encounter (OSCE), are fair assessments and increase students’ awareness of their clinical reasoning skills.

Methods

A survey was sent to third-year medical students in the classes of 2023 and 2024 at our institution who had completed their general surgery clerkship. Students rated five grading assessments (i.e., preceptor evaluations, the oral examination, clinical documentation, the OSCE, and the shelf exam) on fairness and the ability of the assessment to give them insight into their clinical reasoning on a five-point Likert scale 1–5 (with 1 = Strongly Agree, 5 = Strongly Disagree).

Results

One hundred and ten of 162 (67.9%) students responded to the survey. The shelf examination was the most highly regarded assessment tool followed by the oral examination. Seventy-three percent agreed or strongly agreed that the oral exam was a fair assessment, and 80% agreed or strongly agreed that it gave them insight into their clinical reasoning skills. Alternatively, only 41.8% of students agreed or strongly agreed that preceptor evaluations were fair assessments and 42.7% agreed or strongly agreed that it gave them insight into their clinical reasoning.

Conclusions

Third-year medical students on a general surgery clerkship favor the shelf examination and a case-based oral examination over other assessment tools regarding fairness and perception of their clinical reasoning. This type of examination can provide general surgery clerkship directors with additional objective data to assess medical students more fairly and improve students’ clinical reasoning.
The development of a novel sexual health promotion intervention for young people with mental ill-health: the PROSPEct project
Authors: Nolan Hayley , O’Donoghue Brian , Simmons Magenta , Zbukvic Isabel , Ratcliff Sophia , Milton Alyssa , Hughes Elizabeth , Thompson Andrew , Brown Ellie
Published: March 2024

Background

Young people with mental ill-health experience higher rates of high-risk sexual behaviour, have poorer sexual health outcomes, and lower satisfaction with their sexual wellbeing compared to their peers. Ensuring good sexual health in this cohort is a public health concern, but best practice intervention in the area remains under-researched. This study aimed to co-design a novel intervention to address the sexual health needs of young people with mental ill-health to test its effectiveness in a future trial undertaken in youth mental health services in Melbourne, Australia.

Methods

We followed the 2022 Medical Research Council (MRC) guidelines for developing and evaluating complex interventions. This involved synthesising evidence from the ‘top down’ (published evidence) and ‘bottom up’ (stakeholder views). We combined systematic review findings with data elicited from qualitative interviews and focus groups with young people, carers, and clinicians and identified critical cultural issues to inform the development of our intervention.

Results

Existing evidence in the field of sexual health in youth mental health was limited but suggested the need to address sexual wellbeing as a concept broader than an absence of negative health outcomes. The Information-Motivation-Belief (IMB) model was chosen as the theoretical Framework on which to base the intervention. Interviews/focus groups were conducted with 29 stakeholders (18 clinicians, three carers, and eight young people). Synthesis of the evidence gathered resulted in the co-design of a novel intervention consisting of an initial consultation and four 60-90-minute sessions delivered individually by a young ‘sex-positive’ clinician with additional training in sexual health. Barriers and supports to intervention success were also identified.

Conclusions

Using the MRC Framework has guided the co-design of a potentially promising intervention that addresses the sexual health needs of young people with mental ill-health. The next step is to test the intervention in a one-arm feasibility trial.
Individual and social determinants of COVID-19 vaccine hesitancy and uptake in Northwest Syria
Authors: Al-Abdulla Orwa , Alaref Maher , Kallström Agneta , Kauhanen Jussi
Published: March 2024

Introduction

The COVID-19 outbreak devastated the fragmented health system in Syria, a war-torn country, and exaggerated the demands for humanitarian assistance. COVID-19 vaccination was rolled out in Northwest Syria, an area out of government control, in May 2021. However, vaccine acceptance rates are still minimal, which is reflected in the meager percentage of vaccinated people. The study aims to investigate the effectiveness of the humanitarian actors’ plans to address the COVID-19 vaccine hesitancy and conclude practical strategies for boosting vaccine uptake in Northwest Syria.

Methods and materials

Two questionnaires were developed to collect data from humanitarian organizations involved in the COVID-19 vaccination campaign and people from northwest Syria. Data analysis was performed using SPSS 22 data analysis program.

Results

According to the findings, 55.5% of people refused the COVID-19 vaccine. The results showed a knowledge gap and lack of evidence regarding humanitarian actors’ strategies to address the vaccine’s low uptake. Besides, it was found that doctors and medical workers were reliable sources of information about the vaccine. However, they were not systematically engaged in community mobilization and risk communication to promote people’s perspectives on the vaccine.

Conclusion

Risk communication and community engagement programs were not significantly associated with increasing the COVID-19 acceptance rate. Humanitarian actors must reconsider their strategies to address vaccine hesitancy in Northwest Syria. These strategies should engage medical professionals through dialogue sessions on the realities of the pandemic and vaccine development mechanism based on a compelling and evidence-based approach.
Association between patient ethnicity and prostate cancer diagnosis following a prostate-specific antigen test: a cohort study of 730,000 men in primary care in the UK
Authors: Down Liz , Barlow Melissa , Bailey Sarah E. R. , Mounce Luke T. A. , Merriel Samuel W. D. , Watson Jessica , Martins Tanimola
Published: March 2024

Background

Black men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited.

Methods

This retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis.

The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors.

Results

730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70–79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men.

Conclusions

More prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.
Prognosis of mechanically ventilated patients with COVID-19 after failure of high-flow nasal cannula: a retrospective cohort study
Authors: Hyun Dong-gon , Lee Su Yeon , Ahn Jee Hwan , Hong Sang-Bum , Lim Chae-Man , Koh Younsuck , Huh Jin Won
Published: March 2024

Background

There is an argument whether the delayed intubation aggravate the respiratory failure in Acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). We aimed to investigate the effect of high-flow nasal cannula (HFNC) failure before mechanical ventilation on clinical outcomes in mechanically ventilated patients with COVID-19.

Methods

This retrospective cohort study included mechanically ventilated patients who were diagnosed with COVID-19 and admitted to the intensive care unit (ICU) between February 2020 and December 2021 at Asan Medical Center. The patients were divided into HFNC failure (HFNC-F) and mechanical ventilation (MV) groups according to the use of HFNC before MV. The primary outcome of this study was to compare the worst values of ventilator parameters from day 1 to day 3 after mechanical ventilation between the two groups.

Results

Overall, 158 mechanically ventilated patients with COVID-19 were included in this study: 107 patients (67.7%) in the HFNC-F group and 51 (32.3%) in the MV group. The two groups had similar profiles of ventilator parameter from day 1 to day 3 after mechanical ventilation, except of dynamic compliance on day 3 (28.38 mL/cmH2O in MV vs. 30.67 mL/H2O in HFNC-F, p = 0.032). In addition, the HFNC-F group (5.6%) had a lower rate of ECMO at 28 days than the MV group (17.6%), even after adjustment (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11–0.83; p = 0.045).

Conclusions

Among mechanically ventilated COVID-19 patients, HFNC failure before mechanical ventilation was not associated with deterioration of respiratory failure.
PPP2R1B abolishes colorectal cancer liver metastasis and sensitizes Oxaliplatin by inhibiting MAPK/ERK signaling pathway
Authors: Liu Wei , Tang Jingtong , Gao Wei , Sun Jian , Liu Gang , Zhou Jianping
Published: March 2024

Background

Patients with colorectal cancer (CRC) with liver metastasis or drug resistance have a poor prognosis. Previous research has demonstrated that PPP2R1B inactivation results in the development of CRC. However, the role of PPP2R1B in CRC metastasis and drug resistance is unclear.

Methods

Venny 2.1 was used to determine the intersection between survival-related differentially expressed genes (DEGs) and liver metastasis-related DEGs according to RNA-seq data from The Cancer Genome Atlas (TCGA) and the GEO database (GSE179979). LC‒MS/MS and coimmunoprecipitation were performed to predict and verify the substrate protein of PPP2R1B. Gene Set Variation Analysis (GSVA) was subsequently utilized to assess pathway enrichment levels. The predictive performance of PPP2R1B was assessed by regression analysis, Kaplan–Meier (KM) survival analysis and drug sensitivity analysis. Immunohistochemistry (IHC), qRT-PCR and western blotting were performed to measure the expression levels of related mRNAs or proteins. Biological features were evaluated by wound healing, cell migration and invasion assays and CCK-8 assays. A mouse spleen infection liver metastasis model was generated to confirm the role of PPP2R1B in the progression of liver metastasis in vivo.

Results

According to bioinformatics analysis, PPP2R1B is significantly associated with liver metastasis and survival in CRC patients, and these findings were further verified via immunohistochemistry (IHC), qPCR and Western blotting. Pathway enrichment and LC‒MS/MS analysis revealed that PPP2R1B is negatively associated with the MAPK/ERK signalling pathway. Additionally, PD98059, a MAPK/ERK pathway inhibitor, inhibited EMT in vitro by reversing the changes in key proteins involved in EMT signalling (ZEB1, E-cadherin and Snail) and ERK/MAPK signalling (p-ERK) mediated by PPP2R1B. Oxaliplatin sensitivity prediction and validation revealed that PPP2R1B silencing decreased Oxaliplatin chemosensitivity, and these effects were reversed by PD98059 treatment. Moreover, PPP2R1B was coimmunoprecipitated with p-ERK in vitro. A negative correlation between PPP2R1B and p-ERK expression was also observed in clinical CRC samples, and the low PPP2R1B/high p-ERK coexpression pattern indicated a poor prognosis in CRC patients. In vivo, PPP2R1B silencing significantly promoted liver metastasis.

Conclusions

This study revealed that PPP2R1B induces dephosphorylation of the p-ERK protein, inhibits liver metastasis and increases Oxaliplatin sensitivity in CRC patients and could be a potential candidate for therapeutic application in CRC.
Macrophage membrane (MMs) camouflaged near-infrared (NIR) responsive bone defect area targeting nanocarrier delivery system (BTNDS) for rapid repair: promoting osteogenesis via phototherapy and modulating immunity
Authors: Xue Peng , Chang Zhiyong , Chen Hao , Xi Hongzhong , Tan Xiaoxue , He Shuai , Qiao Haishi , Jiang Xiaohong , Liu Xin , Du Bin
Published: March 2024

Bone defects remain a significant challenge in clinical orthopedics, but no targeted medication can solve these problems. Inspired by inflammatory targeting properties of macrophages, inflammatory microenvironment of bone defects was exploited to develop a multifunctional nanocarrier capable of targeting bone defects and promoting bone regeneration. The avidin-modified black phosphorus nanosheets (BP-Avidin, BPAvi) were combined with biotin-modified Icaritin (ICT-Biotin, ICTBio) to synthesize Icaritin (ICT)-loaded black phosphorus nanosheets (BPICT). BPICT was then coated with macrophage membranes (MMs) to obtain MMs-camouflaged BPICT (M@BPICT). Herein, MMs allowed BPICT to target bone defects area, and BPICT accelerated the release of phosphate ions (PO43−) and ICT when exposed to NIR irradiation. PO43− recruited calcium ions (Ca2+) from the microenvironment to produce Ca3(PO4)2, and ICT increased the expression of osteogenesis-related proteins. Additionally, M@BPICT can decrease M1 polarization of macrophage and expression of pro-inflammatory factors to promote osteogenesis. According to the results, M@BPICT provided bone growth factor and bone repair material, modulated inflammatory microenvironment, and activated osteogenesis-related signaling pathways to promote bone regeneration. PTT could significantly enhance these effects. This strategy not only offers a solution to the challenging problem of drug-targeted delivery in bone defects but also expands the biomedical applications of MMs-camouflaged nanocarriers.

Graphical Abstract
Gentulizumab, a novel anti-CD47 antibody with potent antitumor activity and demonstrates a favorable safety profile
Authors: Wang Tao , Wang Si-Qin , Du Yin-Xiao , Sun Dan-Dan , Liu Chang , Liu Shuang , Sun Ying-Ying , Wang Hai-Long , Zhang Chun-Sheng , Liu Hai-Long , Jin Lei , Chen Xiao-Ping
Published: March 2024

Background

Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells.

Methods

In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059.

Results

GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile.

Conclusion

GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer.
Thyroid hormone protects human lung epithelial cells from cold preservation and warm reperfusion-induced injury
Authors: Bojic Dejan , Aujla Tanroop , Sugihara Junichi , Wong Aaron , Keshavjee Shaf , Liu Mingyao
Published: March 2024

Background

Cellular stress associated with static-cold storage (SCS) and warm reperfusion of donor lungs can contribute to ischemia–reperfusion (IR) injury during transplantation. Adding cytoprotective agents to the preservation solution may be conducive to reducing graft deterioration and improving post-transplant outcomes.

Methods

SCS and warm reperfusion were simulated in human lung epithelial cells (BEAS-2B) by exposing cells to low potassium dextran glucose solution at 4 °C for different periods and then switching back to serum-containing culture medium at 37 °C. Transcriptomic analysis was used to explore potential cytoprotective agents. Based on its results, cell viability, caspase activity, cell morphology, mitochondrial function, and inflammatory gene expression were examined under simulated IR conditions with or without thyroid hormones (THs).

Results

After 18 h SCS followed by 2 h warm reperfusion, genes related to inflammation and cell death were upregulated, and genes related to protein synthesis and metabolism were downregulated in BEAS-2B cells, which closely mirrored gene profiles found in thyroid glands of mice with congenital hypothyroidism. The addition of THs (T3 or T4) to the preservation solution increases cell viability, inhibits activation of caspase 3, 8 and 9, preserves cell morphology, enhances mitochondrial membrane potential, reduces mitochondrial superoxide production, and suppresses inflammatory gene expression.

Conclusion

Adding THs to lung preservation solutions may protect lung cells during SCS by promoting mitochondrial function, reducing apoptosis, and inhibiting pro-inflammatory pathways. Further in vivo testing is warranted to determine the potential clinical application of adding THs as therapeutics in lung preservation solutions.
Results from omic approaches in rat or mouse models exposed to inhaled crystalline silica: a systematic review
Authors: Morin Laura , Lecureur Valérie , Lescoat Alain
Published: March 2024

Background

Crystalline silica (cSiO2) is a mineral found in rocks; workers from the construction or denim industries are particularly exposed to cSiO2 through inhalation. cSiO2 inhalation increases the risk of silicosis and systemic autoimmune diseases. Inhaled cSiO2 microparticles can reach the alveoli where they induce inflammation, cell death, auto-immunity and fibrosis but the specific molecular pathways involved in these cSiO2 effects remain unclear. This systematic review aims to provide a comprehensive state of the art on omic approaches and exposure models used to study the effects of inhaled cSiO2 in mice and rats and to highlight key results from omic data in rodents also validated in human.

Methods

The protocol of systematic review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible articles were identified in PubMed, Embase and Web of Science. The search strategy included original articles published after 1990 and written in English which included mouse or rat models exposed to cSiO2 and utilized omic approaches to identify pathways modulated by cSiO2. Data were extracted and quality assessment was based on the SYRCLE’s Risk of Bias tool for animal studies.

Results

Rats and male rodents were the more used models while female rodents and autoimmune prone models were less studied. Exposure of animals were both acute and chronic and the timing of outcome measurement through omics approaches were homogeneously distributed. Transcriptomic techniques were more commonly performed while proteomic, metabolomic and single-cell omic methods were less utilized. Immunity and inflammation were the main domains modified by cSiO2 exposure in lungs of mice and rats. Less than 20% of the results obtained in rodents were finally verified in humans.

Conclusion

Omic technics offer new insights on the effects of cSiO2 exposure in mice and rats although the majority of data still need to be validated in humans. Autoimmune prone model should be better characterised and systemic effects of cSiO2 need to be further studied to better understand cSiO2-induced autoimmunity. Single-cell omics should be performed to inform on pathological processes induced by cSiO2 exposure.
Globalization, platform work, and wellbeing—a comparative study of Uber drivers in three cities: London, Helsinki, and St Petersburg
Authors: Koivusalo Meri , Svynarenko Arseniy , Mbare Benta , Perkiö Mikko
Published: March 2024

Background

Globalization of platform work has become a challenge for wider social and employment relations and wellbeing of workers, yet on-location work remains governed also by local regulatory context. Understanding common challenges across countries and potential for regulatory measures is essential to enhance health and wellbeing of those who work in platform economy. Our comparative study on platform work analyzed concerns of Uber drivers in three cities with a different regulatory and policy context.

Methods

Drawing from current understanding on employment and precarity as social determinants of health we gathered comparative documentary and contextual data on regulatory environment complemented with key informant views of regulators, trade unions, and platform corporations (N = 26) to provide insight on the wider regulatory and policy environment. We used thematic semi-structured interviews to examine concerns of Uber drivers in Helsinki, St Petersburg, and London (N = 60). We then analysed the driver interviews to identify common and divergent concerns across countries.

Results

Our results indicate that worsening of working conditions is not inevitable and for drivers the terms of employment is a social determinant of health. Drivers compensated declining pay with longer working hours. Algorithmic surveillance as such was of less concern to drivers than power differences in relation to terms of work.

Conclusions

Our results show scope for regulation of platform work especially for on-location work concerning pay, working hours, social security obligations, and practices of dismissal.
Re-evaluating a historic cohort of sinonasal and skull base mucoepidermoid carcinoma: an institutional experience
Authors: Hu Chunyan , Lin Lan , Ye Ming , Liu Yifeng , Huang Qiang , Yuan Cuncun , Sun Ji , Sun Hui
Published: March 2024

Aims

Primary mucoepidermoid carcinomas (MECs) of the sinonasal tract and nasopharynx are rare entities that represent a diagnostic challenge, especially in biopsy samples. Herein, we present a case series of MECs of the sinonasal and skull base and its mimics to evaluate the clinicopathological and molecular characteristics in order to avoid misdiagnosis.

Methods

We reviewed the pathology records of patients diagnosed from 2014 to 2022. Thirty MECs were consecutively diagnosed during that period.

Results

Based on morphological and fluorescence in situ hybridization (FISH) analyses, 30 tumors originally diagnosed as MECs were separated into MAML2 fusion-positive (7 cases) and MAML2 fusion-negative groups (23 cases), in which 14 tumors were positive for the EWSR1::ATF1 fusion; these tumors were reclassified to have hyalinizing clear cell carcinoma (HCCC). The remaining nine MAML2 FISH negative cases were reconfirmed as squamous cell carcinoma (SCC, 3 cases) which showed keratinization and high Ki-67 expression; DEK::AFF2 carcinomas (2 cases), in which DEK gene rearrangement was detected by FISH; and MECs as previously described (4 cases) with typical morphological features. Including 7 MAML2 rearrangements tumors, 11 MEC cases had a male-to-female ratio of 4.5:1, and 6 tumors arose from the nasopharyngeal region, while 5 tumors arose from the sinonasal region. The prognosis of this series of salivary gland-type MECs was favorable.

Conclusions

Our study confirmed that HCCC runs the risk of being misdiagnosed as MEC in the sinonasal tract and nasopharynx, particularly with biopsy specimens. Careful histological evaluation with supporting molecular testing can facilitate pathological diagnoses.
Cerebrospinal fluid and blood exosomes as biomarkers for amyotrophic lateral sclerosis; a systematic review
Authors: Darabi Shahram , Ariaei Armin , Rustamzadeh Auob , Afshari Dariush , Charkhat Gorgich Enam Alhagh , Darabi Leila
Published: March 2024

Background

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today’s diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.

Methods

PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.

Results

A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.

Conclusion

Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.
Zinc finger protein 468 up-regulation of TFAM contributes to the malignant growth and cisplatin resistance of breast cancer cells
Authors: Jia Zhaoyang , Wang Feng , Li Gongzhuo , Jiang Ping , Leng Yuanxiu , Ke Longzhu , Luo Li , Gao Wei
Published: March 2024

Background

Because of the progress on the diagnosis and treatment for patients with breast cancer (BC), the overall survival of the patients has been improved. However, a number of BC patients cannot benefit from the existing therapeutic strategies as the essential molecular events triggering the development of BC are not well understood. Previous studies have shown that abnormal expression of zinc finger proteins is involved in the development of various malignancies, whereas it remains largely unclear on their significance during the progression of BC. In this study, we aimed to explore the clinical relevance, cellular function and underlying mechanisms of zinc finger protein 468 (ZNF468) in BC.

Methods

The clinical relevance of ZNF468 and TFAM was analyzed based on TCGA database. Overexpression or knockdown of ZNF468 and TFAM were performed by transfecting the cells with overexpression plasmids and siRNAs, respectively. Overexpression and knockdown efficacy was checked by immunoblotting. CCK-8, colony formation, transwell and apoptosis experiments were conducted to check the cellular function of ZNF468 and TFAM. The content of mtDNA was measured by the indicated assay kit. The effects of cisplatin on BC cells were detected by CCK-8 and colony formation assays. The regulation of ZNF468 on TFAM was analyzed by RT-qPCR, immunoblotting, dual luciferase activity and ChIP-qPCR assays.

Results

ZNF468 was overexpressed in BC patients and inversely correlated with their prognosis. Based on overexpression and knockdown assays, we found that ectopic expression of ZNF468 was essential for the proliferation, growth and migration of BC cells. The expression of ZNF468 also negatively regulated the sensitivity of BC cells to the treatment of cisplatin. Mechanistically, ZNF468 potentiated the transcription activity of TFAM gene via direct binding on its promoter. Lastly, we demonstrated that ZNF468 up-regulation of TFAM was important for the growth, migration and cisplatin resistance in BC cells.

Conclusion

Our study indicates that ZNF468 promotes BC cell growth and migration via transcriptional activation of TFAM. ZNF468/TFAM axis can serve as the diagnostic and therapeutic target, as well as the predictor of cisplatin effectiveness in BC patients.
HSPB1 as an RNA-binding protein mediates the pathological process of osteoarthritis
Authors: Fu Qiang , Li Yi , Shi Chunhua
Published: March 2024

Heat-shock protein beta1 (HSPB1) is a member of the small HSP family, downregulated in osteoarthritis (OA) chondrocytes and demonstrated the capacity to serve as an RNA-binding protein (RBP). This work aimed to explore the profile of HSPB1 bound RNA and reveal the potential regulation mechanism of HSPB1 in OA. In this work, we captured an unbiased HSPB1-RNA interaction map in Hela cells using the iRIP-seq. The results demonstrated that HSPB1 interacted with plentiful of mRNAs and genomic location toward the CDS region. Functional enrichment of HSPB1-related peaks showed the involvement in gene expression, translation initiation, cellular protein metabolic process, and nonsense-mediated decay. HOMER software analysis showed that HSPB1 bound peaks were over-represented in GAGGAG sequences. In addition, ABLIRC and CIMS algorithm indicated that HSPB1 bound to AU-rich motifs and the proportion of AU-rich peaks in 3′ UTR were slightly higher than that in other regions. Moreover, HSPB1-binding targets analysis revealed several gens were associated with OA including EGFR, PLEC, COL5A1, and ROR2. The association of OA-related mRNAs to HSPB1 was additionally confirmed in OA tissues by the quantitative RIP-PCR experiments. Further experiment demonstrated the downregulation of HSPB1 in OA tissues. In conclusion, our current study confirmed HSPB1 as an RNA-binding protein and revealed its potential function in the pathological process of OA, providing a reliable insight to further investigate the molecular regulation mechanism of HSPB1 in OA.
Levels of 91 circulating inflammatory proteins and risk of lumbar spine and pelvic fractures and peripheral ligament injuries: a two-sample mendelian randomization study
Authors: Huang Huiyu , Fu Zhaojun , Yang Min , Hu Haigang , Wu Chao , Tan Lun
Published: March 2024

Objective

Lumbar spine and pelvic fractures(LPF) are combined with peripheral ligament injuries(PLI), frequently. It has been reported that the site of fracture injury is usually paralleled by the secretion of inflammatory proteins. This study aimed to investigate the causal relationship between 91 circulating inflammatory proteins and LPF and PLI by using a Two-sample Mendelian randomization (MR) analysis.

Methods

Single nucleotide polymorphisms (SNPs) associated with 91 circulating inflammatory proteins, as exposures were selected from a large genome-wide association study (GWAS). The genetic variant data for LPF and PLI as outcomes from the FinnGen consortium. The inverse-variance-weighted (IVW) method was utilized as the main analysis for exposures and outcomes. In addition, the final results were reinforced by the methods of MR Egger, weighted median, simple mode, and weighted mode. The sensitivity analyses were used to validate the robustness of results and ensure the absence of heterogeneity and horizontal pleiotropy. MR-Steiger was used to assess whether the causal direction was correct to avoid reverse causality.

Results

This study has shown that Beta-nerve growth factor(Beta-NGF) and Interferon gamma(IFN-gamma) are both involved in the occurrence of LPF and PLI, and they are reducing the risk of occurrence(OR:0.800, 95%CI: 0.650–0.983; OR:0.723, 95%CI:0.568–0.920 and OR:0.812, 95%CI:0.703–0.937; OR:0.828, 95%CI:0.700–0.980). Similarly, Axin-1 and Sulfotransferase 1A1 (SULT-1A1) were causally associated with LPF(OR:0.687, 95%CI:0.501–0.942 and OR:1.178,95%CI:1.010–1.373). Furthermore, Interleukin-4(IL-4), Macrophage inflammatory protein 1a(MIP-1a), and STAM binding protein(STAM-BP) were causally associated with PLI(OR:1.236, 95% CI: 1.058–1.443; OR:1.107, 95% CI: 1.008–1.214 and OR:0.759, 95% CI: 0.617–0.933). The influence of heterogeneity and horizontal pleiotropy were further excluded by sensitivity analysis.

Conclusion

This study provides new insights into the relationship between circulating inflammatory proteins and LPF and PLI, and may provide new clues for predicting this risk.
Short-term effects of Mediterranean diet on nutritional status in adults affected by Osteogenesis Imperfecta: a pilot study
Authors: De Amicis Ramona , Bertoli Simona , Bruno Amalia , De Carlo Giulia , Battezzati Alberto , Foppiani Andrea , Leone Alessandro , Lo Mauro Antonella
Published: March 2024

Background

Osteogenesis Imperfecta (OI) is a heterogeneous group of connective tissue disorders, characterized by varying degrees of skeletal fragility. Patients experience a range of comorbidities, such as obesity, cardiovascular, and gastrointestinal complications, especially in adulthood. All aspects that could benefit from dietary intervention. The aim of this study was to evaluate the effects of a 6-months restricted Mediterranean Diet (rMD) on nutritional status in adult patients affected by OI.

We carried out a 6-months longitudinal pilot study. 14 adults (median age: 35 years; 7 women; 7 OI type III) where recruited in 2019 among the members of As.It.O.I., the Italian Association of Osteogenesis Imperfecta. As.It.O.I. All the evaluations were performed at the University of Milan, Italy. The rMD provided a reduction of 30% from daily total energy expenditure. 45% of calories derived from carbohydrates, 35% from fat and 0.7–1.0 g/kg of body weight from proteins. Comparisons of continuous variables after 6 months of intervention were performed by the paired t-test. All P-values were two-tailed, and p < 0.05 was considered significant.

Results

Patients showed significant improvement in anthropometric measurements (BMI = 30.5 vs 28.1 kg/cm2, p < 0.001; Body Fat % = 32.9 vs 29.9, p = 0.006; Waist circumferences = 83.6 vs 79.6 cm; p < 0.001; Arm Fat Area = 29.8 vs 23.07 cm2; p < 0.011) and energy expenditure (REE/kg = 27.2 vs 29.2 kcal/kg, p < 0.001). Glucose and lipid profiles improved (Δglycemia = − 8.6 ± 7.3 mg/dL, p = 0.003; ΔTC = − 14.6 ± 20.1 mg/dL, p = 0.036; ΔLDL = − 12.0 ± 12.1 mg/dL, p = 0.009). Adherence to the MD significantly increased, moving from a moderate to a strong adherence and reporting an increased consumption of white meat, legumes, fish, nuts, fruits and vegetables.

Conclusion

A rMD was effective in improving nutritional status and dietary quality in adults with OI. These results underscores the need to raise awareness of nutrition as part of the multidisciplinary treatment of this disease.
Overcoming doxorubicin resistance in triple-negative breast cancer using the class I-targeting HDAC inhibitor bocodepsin/OKI-179 to promote apoptosis
Authors: Smoots Stephen G. , Schreiber Anna R. , Jackson Marilyn M. , Bagby Stacey M. , Dominguez Adrian T A. , Dus Evan D. , Binns Cameron A. , MacBeth Morgan , Whitty Phaedra A. , Diamond Jennifer R. , Pitts Todd M.
Published: March 2024

Background

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a poor prognosis. Doxorubicin is part of standard curative therapy for TNBC, but chemotherapy resistance remains an important clinical challenge. Bocodepsin (OKI-179) is a small molecule class I histone deacetylase (HDAC) inhibitor that promotes apoptosis in TNBC preclinical models. The purpose of this study was to investigate the combination of bocodepsin and doxorubicin in preclinical TNBC models and evaluate the impact on terminal cell fate, including apoptosis and senescence.

Methods

TNBC cell lines were treated with doxorubicin and CellTiter-Glo was used to assess proliferation and determine doxorubicin sensitivity. Select cell lines were treated with OKI-005 (in vitro version of bocodepsin) and doxorubicin and assessed for proliferation, apoptosis as measured by Annexin V/PI, and cell cycle by flow cytometry. Immunoblotting was used to assess changes in mediators of apoptosis, cell cycle arrest, and senescence. Senescence was measured by the senescence-associated β-galactosidase assay. An MDA-MB-231 xenograft in vivo model was treated with bocodepsin, doxorubicin, or the combination and assessed for inhibition of tumor growth. shRNA knockdown of p53 was performed in the CAL-51 cell line and proliferation, apoptosis and senescence were assessed in response to combination treatment.

Results

OKI-005 and doxorubicin resulted in synergistic antiproliferative activity in TNBC cells lines regardless of p53 mutation status. The combination led to increased apoptosis and decreased senescence. In vivo, the combination resulted in increased tumor growth inhibition compared to either single agent. shRNA knock-down of p53 led to increased doxorubicin-induced senescence that was decreased with the addition of OKI-005 in vitro.

Conclusion

The addition of bocodepsin to doxorubicin resulted in synergistic antiproliferative activity in vitro, improved tumor growth inhibition in vivo, and promotion of apoptosis which makes this a promising combination to overcome doxorubicin resistance in TNBC. Bocodepsin is currently in clinical development and has a favorable toxicity profile compared to other HDAC inhibitors supporting the feasibility of evaluating this combination in patients with TNBC.