bluuebunny/crossref_metadata_2025 huggingface dataset:
CMS-NET: deep learning algorithm to segment and quantify the ciliary muscle in swept-source optical coherence tomography images
Authors: Chen Wen , Yu Xiangle , Ye Yiru , Gao Hebei , Cao Xinyuan , Lin Guangqing , Zhang Riyan , Li Zixuan , Wang Xinmin , Zhou Yuheng , Shen Meixiao , Shao Yilei
Published: March 2023

Background:

The ciliary muscle plays a role in changing the shape of the crystalline lens to maintain the clear retinal image during near work. Studying the dynamic changes of the ciliary muscle during accommodation is necessary for understanding the mechanism of presbyopia. Optical coherence tomography (OCT) has been frequently used to image the ciliary muscle and its changes during accommodation in vivo. However, the segmentation process is cumbersome and time-consuming due to the large image data sets and the impact of low imaging quality.

Objectives:

This study aimed to establish a fully automatic method for segmenting and quantifying the ciliary muscle on the basis of optical coherence tomography (OCT) images.

Design:

A perspective cross-sectional study.

Methods:

In this study, 3500 signed images were used to develop a deep learning system. A novel deep learning algorithm was created from the widely used U-net and a full-resolution residual network to realize automatic segmentation and quantification of the ciliary muscle. Finally, the algorithm-predicted results and manual annotation were compared.

Results:

For segmentation performed by the system, the total mean pixel value difference (PVD) was 1.12, and the Dice coefficient, intersection over union (IoU), and sensitivity values were 93.8%, 88.7%, and 93.9%, respectively. The performance of the system was comparable with that of experienced specialists. The system could also successfully segment ciliary muscle images and quantify ciliary muscle thickness changes during accommodation.

Conclusion:

We developed an automatic segmentation framework for the ciliary muscle that can be used to analyze the morphological parameters of the ciliary muscle and its dynamic changes during accommodation.
Preventing Wrong Tooth Extraction in Primary Care Oral Surgery: LocSSIPs – Key Aspects of Implementation for Achieving and Sustaining Compliance
Authors: Tagar Harjit Kaur
Published: March 2023

The success of Local Safety Standards for Invasive Procedures (LocSSIPs) in preventing wrong tooth extraction and other patient safety incidents is based on sustained staff compliance from the outset, ahead of implementation. This paper (the second of two on the topic of LocSSIPs) aims to equip primary care dental practitioners with key practical solutions to implement LocSSIPs successfully and sustainably, and the leadership knowledge to create a long-term, safe, patient-centred and just service.
Doctors’ Drugs and the Dangers of Dental Decay
Authors: Kelleher Martin G. , Ruparelia Roshni , Blum Igor R.
Published: March 2023

Many “anti-something” medications, which are prescribed by medical doctors for older patients, often for dubious reasons, result in a serious reduction in the quantity and quality of saliva. That drug-induced xerostomia can produce dangerous dental decay, particularly in already compromised dentitions.

This article suggests that doctors should undertake a personalised “benefits, risks, alternatives, nothing” (BRAN) analysis including an assessment of the possible dental decay risks, especially before prescribing combinations of “anti-” drugs for marginal conditions.

Doctors should consider carefully if alternative approaches are feasible which could produce acceptable outcomes without incurring those serious dental decay risks. Alternative approaches may include patients altering their diet and lifestyle to include more physical exercise for controlling conditions such as marginal hypertension, for example, or perhaps prescribing counselling/talking therapies for depression or anxiety.

If various “anti-” drugs really do have to be prescribed, this article describes cheap, pragmatic, and effective ways of mitigating the risks of already compromised dentitions developing new decay.
Management of difficult-to-treat asthma in adolescence and young adults
Authors: Mansur Adel H. , Prasad Nagakumar
Published: March 2023

The period of adolescence and young adulthood (AYA) has been proposed to extend from 11 to 25 years of age as patients in this age group face similar challenges. AYA is a time of fast and great physiological and psychological growth, in which an individual transitions from a young dependent child to a mature independent adult. Behaviour patterns during adolescence, such as risk taking and desire for privacy, can challenge parents or healthcare professionals' (HCPs') ability to help adolescents to manage their asthma.

Asthma itself tends to remit, become milder or worsen into a severe variant during adolescence. The pre-pubertal male predominance of asthma switches to a female predominance in late teen years. ∼10% of AYA with asthma have “difficult-to-treat asthma (DTA)”, characterised by poor asthma control despite treatment with inhaled corticosteroids (ICS) and other controller medications. DTA management in AYA requires a multidisciplinary team approach and systematic assessment that can address the key questions of objective confirmation of diagnosis, severity assessment, phenotyping, comorbidities, asthma mimickers or other drivers of poor control such as non-adherence to treatment.

A key task for HCPs is to establish the magnitude of the severe asthma componentversusother non-asthma drivers of symptoms (e.g.inducible laryngeal obstruction or breathing pattern disorder). Severe asthma is a subset of DTA and is determined once asthma diagnosis and its severity have been confirmed and adherence to controller (ICS) treatment has been assured. Severe asthma is a heterogeneous disease and appropriate phenotyping is necessary for the management of treatable traits and consideration for biologic therapies.

Finally, an important part of successful management of DTA in the AYA group is the provision of an effective transition of asthma care from paediatric to adult asthma services through setting up a well-designed asthma transition pathway tailored to the individual patient needs.
Progressive search in tandem mass spectrometry
Authors: Joh Yoonsung , Lee Kangbae , Kim Hyunwoo , Park Heejin
Published: March 2023

Background

High-throughput Proteomics has been accelerated by (tandem) mass spectrometry. However, the slow speed of mass spectra analysis prevents the analysis results from being up-to-date. Tandem mass spectrometry database search requires O(|S||D|) time where S is the set of spectra and D is the set of peptides in a database. With usual values of |S| and |D|, database search is quite time consuming. Meanwhile, the database for search is usually updated every month, with 0.5–2% changes. Although the change in the database is usually very small, it may cause extensive changes in the overall analysis results because individual PSM scores such as deltaCn and E-value depend on the entire search results. Therefore, to keep the search results up-to-date, one needs to perform database search from scratch every time the database is updated, which is very inefficient.

Results

Thus, we present a very efficient method to keep the search results up-to-date where the results are the same as those achieved by the normal search from scratch. This method, called progressive search, runs in O(|S||ΔD|) time on average where ΔD is the difference between the old and the new databases. The experimental results show that the progressive search is up to 53.9 times faster for PSM update only and up to 16.5 times faster for both PSM and E-value update.

Conclusions

Progressive search is a novel approach to efficiently obtain analysis results for updated database in tandem mass spectrometry. Compared to performing a normal search from scratch, progressive search achieves the same results much faster. Progressive search is freely available at: https://isa.hanyang.ac.kr/ProgSearch.html.
Implementation of evidence-based multiple focus integrated intensified TB screening to end TB (EXIT-TB) package in East Africa: a qualitative study
Authors: Isangula Kahabi , Philbert Doreen , Ngari Florence , Ajeme Tigest , Kimaro Godfather , Yimer Getnet , Mnyambwa Nicholaus P. , Muttamba Winters , Najjingo Irene , Wilfred Aman , Mshiu Johnson , Kirenga Bruce , Wandiga Steve , Mmbaga Blandina Theophil , Donard Francis , Okelloh Douglas , Mtesha Benson , Mohammed Hussen , Semvua Hadija , Ngocho James , Mfinanga Sayoki , Ngadaya Esther
Published: March 2023

Introduction

Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care.

Objective

We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up.

Methods

A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed.

Results

The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma.

Conclusion

The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.
Testing effects of partner support and use of oral contraception during relationship formation on severity of nausea and vomiting in pregnancy
Authors: Roberts Kateřina , Havlíček Jan , Kaňková Šárka , Klapilová Kateřina , Roberts S. Craig
Published: March 2023

Background

A recent study focusing on dietary predictors of nausea and vomiting in pregnancy (NVP) found that women with higher levels of partner support, and those who had used oral contraception (OC) when they met the father, both tended to report less severe NVP compared with previous non-users or those with less supportive partners. We provide a further test of these factors, using a large sample of women from four countries who retrospectively scored their NVP experience during their first pregnancy.

Methods

We recruited women who had at least one child to participate in a retrospective online survey. In total 2321 women completed our questionnaire including items on demographics, hormonal contraception, NVP, and partner support. We used general linear models and path analysis to analyse our data.

Results

Women who had used OC when they met the father of their first child tended to report lower levels of NVP, but the effect size was small and did not survive adding the participant’s country to the model. There was no relationship between NVP and partner support in couples who were still together, but there was a significant effect among those couples that had since separated: women whose ex-partner had been relatively supportive reported less severe NVP. Additional analyses showed that women who were older during their first pregnancy reported less severe NVP, and there were also robust differences between countries.

Conclusions

These results provide further evidence for multiple influences on women’s experience of NVP symptoms, including levels of perceived partner support.
Plasma exosome-derived connexin43 as a promising biomarker for melanoma patients
Authors: Shen Yue , Li Ming , Liao Li , Gao Suyue , Wang Yongzhen
Published: March 2023

Background

To examine the levels of exosome-derived connexin 43 (Cx43) in plasma and estimate its forecast value in patients with melanoma.

Methods

We measured the plasma exosome-derived Cx43 levels in the plasma of 112 melanoma patients and 50 healthy controls.

Results

The plasma exosome-derived Cx43 levels in patients with melanoma were substantially downregulated as opposed to the levels in healthy controls (P < 0.001). Kaplan–Meier analysis indicated that overall survival (OS) and disease-free survival (DFS) were poorer in patients with melanoma who exhibited lower levels of plasma exosome-derived Cx43 (both P < 0.001). The levels of plasma exosome-derived Cx43 were considerably elevated in patients with melanoma whose tumor was situated in the skin, tumor size < 10 cm, with Clark level I–III, TNM stages IIb–IV, and had no lymph node metastasis as opposed to patients whose tumor was situated in the viscera or mucosa, tumor size ≥ 10 cm, Clark level IV–V, TNM stages IIb–IV and had lymph node metastasis (all P < 0.05). The receiver operating characteristic (ROC) of plasma exosome-derived Cx43 for forecasting 5-year DFS in patients with melanoma was 0.78 (95% confidence interval (CI): 0.70–0.86), with a specificity of 77.78% and a sensitivity of 81.55%. The ROC of plasma exosome-derived Cx43 for forecasting 5-year OS of patients with melanoma was 0.77 (95% CI: 0.68–0.84), with a specificity of 80.0% and sensitivity of 65.98%.

Conclusion

The overall findings indicated that the levels of plasma exosome-derived Cx43 in patients with melanoma were considerably downregulated. It can therefore be inferred that the levels of plasma exosome-derived Cx43 might be a prospective prognostic indicator for 5 5-year OS and 5-year DFS of patients with melanoma.
Volume-accumulated reflectivity of the outer retina (integral) on spectral domain optical coherence tomography as a predictor of cone cell density: a pilot study
Authors: Li Wenting , Chen Wenwen , Zhou Xiyue , Jiang Tingting , Zhang Juan , Wang Min , Wu Jihong , Gu Junxiang , Chang Qing
Published: March 2023

Background

The study aims to investigate the relationship between the volume-accumulated reflectivity (termed “integral”) on spectral domain optical coherence tomography (SD-OCT) and cone density on adaptive optics (AO) imaging.

Methods

In this cross-sectional study, both eyes of 32 healthy subjects and 5 patients with inherited retinal diseases (IRD) were studied. The parameter, integral, was defined as the volume-accumulated reflectivity values in a selected region on OCT images; integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured at 2°, 3°, 4°, 5°and 6° eccentricity along the four meridians on fovea-centered OCT B-scans. Cone density in the same region was measured using a flood illumination adaptive optics camera RTX1.

Results

Integrals of EZ, IZ and cone density shared similar distribution patterns. Integral of the IZ was better correlated with cone density in both healthy people (r = 0.968, p < 0.001) and those with IRD (r = 0.823, p < 0.001) than direct measurements of reflectivity on OCT images. A strong correlation was found between best corrected visual acuity (BCVA) and cone density at 2° eccentricity (r = -0.857, p = 0.002). BCVA was also correlated with the integral of the IZ at the foveola (r = -0.746, p = 0.013) and fovea (r = -0.822, p = 0.004).

Conclusions

The new parameter “integral” of the photoreceptor outer segment measured from SD-OCT was noted to correlate with cone density and visual function in this pilot study.
Positioning of enhanced monofocal intraocular lenses between conventional monofocal and extended depth of focus lenses: a scoping review
Authors: Fernández Joaquín , Rocha-de-Lossada Carlos , Zamorano-Martín Francisco , Rodríguez-Calvo-de-Mora Marina , Rodríguez-Vallejo Manuel
Published: March 2023

Background

New intraocular lenses (IOLs) have emerged since the originally coined monofocal and multifocal IOLs. The extended depth of focus (EDoF) and enhanced monofocal IOLs (mono-EDoF) that have appeared in the last decade have caused some confusion in their classification. The aim of this review was to summarize the outcomes provided by mono-EDOF IOLs and to determine which of the endpoints, described by the American National Standard (ANSI) for EDoF IOLs, are fulfilled.

Methods

The MEDLINE, EMBASE, and WEB OF SCIENCE databases were searched. Two independent reviewers screened the studies for inclusion and data extraction. The search strategy was limited to studies published between 2020 and 2022, but not by language. The results are presented as a narrative summary accompanied by tables, in alignment with the objectives of this scoping review. Compliance with the endpoints for clinical outcomes described in the American National Standard Z80.35–2018 (ANSI) for EDoF lenses was checked and additional endpoints were defined.

Results

Two systematic reviews, 13 laboratory, 21 clinical, and two mixed studies were included. Tecnis Eyhance was the mono-EDOF with the highest volume of evidence to date. Although laboratory studies included other IOLs, clinical evidence for them is still scarce, with only one study of IsoPure compared to a standard monofocal IOL. Evidence in comparison to EDoF lenses is also scarce, even for Tecnis Eyhance, with only three studies including this lens in comparison to an EDoF lens. After evaluation of the ANSI criteria, agreement was found in the failure for the increase in depth of field equal to or greater than 0.5 D for a visual acuity (VA) level of 0.2 logMAR and none of the studies supported that the median monocular VA at intermediate distance was at least 0.2 logMAR.

Conclusions

Additional clinical evidence is required for other mono-EDOF IOLs beyond Tecnis Eyhance. Until the arrival of a standard classification, mono-EDOF should be better still classified as monofocal because the ANSI standards were not fully met.
Eye movement desensitization and reprocessing (EMDR) therapy or supportive counseling prior to exposure therapy in patients with panic disorder: study protocol for a multicenter randomized controlled trial (IMPROVE)
Authors: Endhoven Bart , De Cort Klara , Matthijssen Suzy J. M. A. , de Jongh Ad , van Minnen Agnes , Duits Puck , Schruers Koen R. J. , van Dis Eva A. M. , Krypotos Angelos M. , Gerritsen Lotte , Engelhard Iris M.
Published: March 2023

Background

Exposure-based therapy is the treatment of choice for anxiety disorders, but many patients do not benefit sufficiently from it. Distressing images of threat related to the future or past may maintain the anxiety symptomatology or impede exposure therapy. An intervention that targets threat-related imagery is eye movement desensitization and reprocessing (EMDR) therapy. The main goal of this multicenter randomized controlled trial is to investigate whether EMDR therapy plus exposure therapy, relative to supportive counseling plus exposure therapy, improves treatment efficacy, tolerability, and adherence in patients with panic disorder. In addition, we will examine potential predictors of optimal treatment allocation, mechanisms of change as well as the long term effects of treatment. Finally, we will assess cost-effectiveness.

Methods

A multicenter randomized controlled trial mixed design will be conducted. Participants will be 50 patients, aged ≥ 18, diagnosed with a panic disorder. They will be randomly assigned to one of two conditions: EMDR therapy (i.e., flashforward strategy) or supportive counseling (each consisting of four weekly sessions of 90 min each) prior to exposure therapy (consisting of eight weekly sessions of 90 min each). Assessments will be made pre-treatment (T1), between-treatments (T2), post-treatment (T3), one month post-treatment (FU1) and six months post-treatment (FU2) by an assessor blind to treatment condition. The primary outcome measure is severity of panic-related symptoms. Secondary outcome measures are: tolerability of exposure therapy (initial avoidance, willingness to start exposure therapy, considered drop-out; no-show and drop-out), related symptomatology (generalized anxiety, depression), and functional impairment.

Discussion

The primary goals of this research are to compare the efficacy, tolerability, and adherence of EMDR therapy plus exposure therapy and supportive counseling plus exposure therapy and to identify predictors, moderators, and mediators for treatment success. This multi-center research aims to make a significant contribution to our understanding as to how treatment for patients with anxiety disorders can be optimized, and elucidate who can benefit most from this novel approach.

Trial registration

ISRCTN—ISRCTN29668369: Improving anxiety treatment by modifying emotional memories before real-life exposure. Registered 27 June 2022—retrospectively registered. ISRCTN—ISRCTN29668369.
BPRS domains, items and subgroups analyses, and CGI-I ratings in pooled data from non-interventional studies of aripiprazole once-monthly in schizophrenia (REACT study)
Authors: Schöttle Daniel , Janetzky Wolfgang , Therrien Francois , Wiedemann Klaus
Published: March 2023

Background

Patients with schizophrenia may benefit from treatment with long-acting injectable (LAI) formulations of antipsychotics. Aripiprazole once-monthly (AOM) is an LAI that was tested in two non-interventional studies in Germany and Canada.

Methods

Here, we report on analyses of pooled data from the two non-interventional studies. Patients were treated with AOM under real-life conditions. Data were analyzed for a timeframe of 6 months. We analyzed data on Brief Psychiatric Rating Scale (BPRS) domains and items, BPRS total scores in various patient subgroups (male vs. female patients, patients with disease duration ≤ 5 years and > 5 years, patients with different levels of disease severity at baseline), Clinical Global Impression – Improvement (CGI-I) ratings for the total population and subgroups, and comorbidities for the total population.

Results

Data from 409 patients were included. 65.5% of the patients had comorbidities. Improvements were found in all BPRS domains and items. Furthermore, improvements were similar for male and female patients, patients with disease duration ≤ 5 years and > 5 years, and across different levels of disease severity at baseline. Numerically, more favorable results were found for younger patients, female patients, and those with shorter disease duration.

Conclusions

AOM can be an effective treatment in the broad range of patients, across sexes, regardless of patient age and duration of disease, independently of disease severity, and across symptoms.

Trial registration

NCT02131415 (May 6, 2014), vfa non-interventional studies registry 15960N.
Prevalence of comorbid depression and associated factors among hospitalized patients with type 2 diabetes mellitus in Hunan, China
Authors: Maimaitituerxun Rehanguli , Chen Wenhang , Xiang Jingsha , Kaminga Atipatsa C. , Wu Xin Yin , Chen Letao , Yang Jianzhou , Liu Aizhong , Dai Wenjie
Published: March 2023

Background

Depression and diabetes are major health challenges, with heavy economic social burden, and comorbid depression in diabetes could lead to a wide range of poor health outcomes. Although many descriptive studies have highlighted the prevalence of comorbid depression and its associated factors, the situation in Hunan, China, remains unclear. Therefore, this study aimed to identify the prevalence of comorbid depression and associated factors among hospitalized type 2 diabetes mellitus (T2DM) patients in Hunan, China.

Methods

This cross-sectional study involved 496 patients with T2DM who were referred to the endocrinology inpatient department of Xiangya Hospital affiliated to Central South University, Hunan. Participants’ data on socio-demographic status, lifestyle factors, T2DM-related characteristics, and social support were collected. Depression was evaluated using the Hospital Anxiety and Depression Scale-depression subscale. All statistical analyses were conducted using the R software version 4.2.1.

Results

The prevalence of comorbid depression among hospitalized T2DM patients in Hunan was 27.22% (95% Confidence Interval [CI]: 23.3–31.1%). Individuals with depression differed significantly from those without depression in age, educational level, per capita monthly household income, current work status, current smoking status, current drinking status, regular physical activity, duration of diabetes, hypertension, chronic kidney disease, stroke, fatty liver, diabetic nephropathy, diabetic retinopathy, insulin use, HbA1c, and social support. A multivariable logistic regression model showed that insulin users (adjusted OR = 1.86, 95% CI: 1.02–3.42) had a higher risk of depression, while those with regular physical activity (adjusted OR = 0.48, 95% CI: 0.30–0.77) or greater social support (adjusted OR = 0.20, 95% CI: 0.11–0.34) had a lower risk of depression. The area under the curve of the receiver operator characteristic based on this model was 0.741 with a sensitivity of 0.785 and specificity of 0.615.

Conclusions

Depression was moderately prevalent among hospitalized T2DM patients in Hunan, China. Insulin treatment strategies, regular physical activity, and social support were significantly independently associated with depression, and the multivariable model based on these three factors demonstrated good predictivity, which could be applied in clinical practice.
Mental health promotion in youth sporting clubs: predictors of stakeholder participation
Authors: Petersen Jasmine M , Drummond Murray , Crossman Sarah , Elliott Sam , Drummond Claire , Prichard Ivanka
Published: March 2023

Background

Young people are disproportionately affected by poor mental health. Youth sport settings hold immense potential to improve the mental health outcomes of this demographic. Efforts to leverage youth sport settings to promote mental health are limited by the lack of knowledge pertaining to engagement with mental health interventions in these settings. Therefore, this study aimed to examine the willingness of youth sporting club stakeholders (e.g., sportspersons, coaches, support staff, parents/guardians) to engage in mental health initiatives conducted by sporting clubs and ascertain possible determinants of engagement.

Methods

This study used an observational cross-sectional design. Participants completed an online survey assessing likelihood of supporting a mental health campaign, mental health literacy (help-seeking, inclusive attitudes), and perceived club support. Perceptions pertaining to the importance of youth mental health and sporting clubs supporting youth mental health were also assessed.

Results

The survey was completed by 275 stakeholders of youth sporting clubs in Australia (Mage = 40.2 ± 15.8 years, 60.3% female). The findings indicated that stakeholders were willing to participate in mental health initiatives in youth sport clubs. A linear regression analysis indicated that the significant predictors of stakeholders supporting such initiatives were older age (> 25–50 and > 50 years; β = 0.15, p = .033, β = 0.19, p = .005, respectively), along with perceived importance of youth mental health (β = 0.24, p = .003) and sporting clubs supporting youth mental health (β = 0.22, p = .004).

Conclusion

Youth sport settings have the capacity to improve the provision of mental health support among young people. There is a need for tailored approaches to enhance the engagement with, and effectiveness of, mental health resources in sport contexts.
Correlation between inflammatory cytokine expression in paraspinal tissues and severity of disc degeneration in individuals with lumbar disc herniation
Authors: Chen Xiaolong , Li Yongjin , Wang Wei , Cui Peng , Wang Yu , Lu Shibao
Published: March 2023

Purpose

Previous animal studies have discovered dysregulation of the local inflammatory state as a novel mechanism to explain structural changes in paraspinal muscles in association with disc degeneration. This study aimed to determine whether the expression of inflammatory genes in the multifidus muscle (MM) differs between individuals with disc degeneration and non-degeneration, which may cause changes in the cross-sectional area (CSA) of paraspinal muscles and clinical outcomes.

Methods

Muscles were procured from 60 individuals undergoing percutaneous endoscopic lumbar discectomy for lumbar disc herniation (LDH). Total and functional CSAs and fatty degeneration of paraspinal muscles on ipsilateral and unilateral sides were measured. Gene expression was quantified using qPCR assays. Paired t-test and Pearson’s correlation analysis were used to compare the mean difference and associations, respectively.

Results

There were significant differences in total CSAs of paraspinal muscles and functional CSA and fatty degeneration of MM between ipsilateral and unilateral sides. Participants in the disc degeneration group displayed higher fat infiltration in MM. The expression of TNF was moderately correlated with total CSAs of paraspinal muscles and functional CSA and fatty degeneration of MM. The expression of IL-1β was strongly correlated with the total and functional CSA of MM. The expression of TGF-β1 was moderately correlated with the functional CSA of MM. The expression of TNF, IL-1β, and TGF-β1 was moderate to strongly correlated with clinical outcomes.

Conclusion

The results show that there were differences in the characteristics of paraspinal muscles between the ipsilateral and unilateral sides, which were affected by disc degeneration and the degree of fat infiltration. High-fat filtration and reduction of CSA of MM are associated with inflammatory dysfunction. There was evidence of a dysregulated inflammatory profile in MM in individuals with poor clinical outcomes.
Adherence to Mediterranean dietary quality index and risk of breast cancer in adult women: a case-control study
Authors: Djafari Farhang , Ghorbaninejad Parivash , Firouzabadi Fatemeh Dehghani , Sheikhhossein Fatemeh , Shahinfar Hossein , Safabakhsh Maryam , Imani Hossein , Shab-Bidar Sakineh
Published: March 2023

Background

Breast cancer (BC) is the fifth most prevalent cause of cancer-related deaths in Iran. Given that the role of whole-diet on cancer risk is important, this study aimed to assess the association of MedDQI and breast cancer risk.

Methods

This hospital-based case-control study was performed on 150 women with pathologically confirmed breast cancer within the period of less than 3 months. Controls were 150 apparently healthy that were matched by age. Dietary data was collected using a validated questionnaire. To examine participants’ adherence to MedDQI, the MedDQI was created according to foods and nutrients highlighted or minimized in the MedDQI construction.

Results

After adjusting for possible confounders, participants in the highest quartile of the MedDQI score had 55% lower odds of breast cancer than women in the bottom quartile (OR: 0.45, 95% CI: 0.21, 0.94, P trend: 0.02). Stratified analysis by menopausal status showed such association in postmenopausal women (OR: 0.24, 95% CI: 0.07, 0.8, P trend: 0.055) after controlling for age and energy intake.

Conclusion

The results showed an inverse association between adherence to the MedDQI and risk of breast cancer among Iranian women. More prospective studies are needed to confirm our results.
Identification of potential biomarkers and therapeutic targets for posttraumatic acute respiratory distress syndrome
Authors: Qi Peng , Huang Mengjie , Li Tanshi
Published: March 2023

Background

Despite improved supportive care, posttraumatic acute respiratory distress syndrome (ARDS) mortality has improved very little in recent years. Additionally, ARDS diagnosis is delayed or missed in many patients. We analyzed co-differentially expressed genes (co-DEGs) to explore the relationships between severe trauma and ARDS to reveal potential biomarkers and therapeutic targets for posttraumatic ARDS.

Methods

Two gene expression datasets (GSE64711 and GSE76293) were downloaded from the Gene Expression Omnibus. The GSE64711 dataset included a subset of 244 severely injured trauma patients and 21 healthy controls. GSE76293 specimens were collected from 12 patients with ARDS who were recruited from trauma intensive care units and 11 age- and sex-matched healthy volunteers. Trauma DEGs and ARDS DEGs were identified using the two datasets. Subsequently, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein–protein interaction network analyses were performed to elucidate the molecular functions of the DEGs. Then, hub genes of the co-DEGs were identified. Finally, to explore whether posttraumatic ARDS and septic ARDS are common targets, we included a third dataset (GSE100159) for corresponding verification.

Results

90 genes were upregulated and 48 genes were downregulated in the two datasets and were therefore named co-DEGs. These co-DEGs were significantly involved in multiple inflammation-, immunity- and neutrophil activation-related biological processes. Ten co-upregulated hub genes (GAPDH, MMP8, HGF, MAPK14, LCN2, CD163, ENO1, CD44, ARG1 and GADD45A) and five co-downregulated hub genes (HERC5, IFIT2, IFIT3, RSAD2 and IFIT1) may be considered potential biomarkers and therapeutic targets for posttraumatic ARDS. Through the verification of the third dataset, posttraumatic ARDS may have its own unique targets worthy of further exploration.

Conclusion

This exploratory analysis supports a relationship between trauma and ARDS pathophysiology, specifically in relationship to the identified hub genes. These data may serve as potential biomarkers and therapeutic targets for posttraumatic ARDS.
Attenuation of IFN signaling due to m6A modification of the host epitranscriptome promotes EBV lytic reactivation
Authors: Bose Dipayan , Lin Xiang , Gao Le , Wei Zhi , Pei Yonggang , Robertson Erle S.
Published: March 2023

Background

Reactivation of Epstein Barr virus (EBV) leads to modulation of the viral and cellular epitranscriptome. N6-methyladenosine (m6A) modification is a type of RNA modification that regulates metabolism of mRNAs. Previous reports demonstrated that m6A modification affects the stability and metabolism of EBV encoded mRNAs. However, the effect of reactivation on reprograming of the cellular mRNAs, and how this contributes to successful induction of lytic reactivation is not known.

Methods

Methylated RNA immunoprecipitation sequencing (MeRIP-seq), transcriptomic RNA sequencing (RNA-seq) and RNA pull-down PCR were used to screen and validate differentially methylated targets. Western blotting, quantitative real-time PCR (RT-qPCR) and immunocytochemistry were used to investigate the expression and localization of different proteins. RNA stability and polysome analysis assays were used to detect the half-lives and translation efficiencies of downstream genes. Insertion of point mutation to disrupt the m6A methylation sites was used to verify the effect of m6A methylation on its stability and expression levels.

Results

We report that during EBV reactivation the m6A eraser ALKBH5 is significantly downregulated leading to enhanced methylation of the cellular transcripts DTX4 and TYK2, that results in degradation of TYK2 mRNAs and higher efficiency of translation of DTX4 mRNAs. This resulted in attenuation of IFN signaling that promoted progression of viral lytic replication. Furthermore, inhibition of m6A methylation of these transcripts led to increased production of IFN, and a substantial reduction in viral copy number, which suggests abrogation of lytic viral replication.

Conclusion

Our findings illuminate the significance of m6A modification in overcoming the innate immune response during EBV reactivation. We now report that during lytic reactivation EBV targets the RNA methylation system of the host to attenuate the innate immune response by suppressing the interferon signaling which facilitates successful lytic replication of the virus.
Engineering Streptomyces albulus to enhance ε-poly-L-lysine production by introducing a polyphosphate kinase-mediated ATP regeneration system
Authors: Yang Hao , Zhu Daojun , Kai Lang , Wang Liang , Zhang Hongjian , Zhang Jianhua , Chen Xusheng
Published: March 2023

Background

ε-Poly-L-lysine (ε-PL) is a natural and safe food preservative that is mainly produced by filamentous and aerobic bacteria Streptomyces albulus. During ε-PL biosynthesis, a large amount of ATP is used for the polymerization of L-lysine. A shortage of intracellular ATP is one of the major factors limiting the increase in ε-PL production. In previous studies, researchers have mainly tried to increase the oxygen supply to enhance intracellular ATP levels to improve ε-PL production, which can be achieved through the use of two-stage dissolved oxygen control, oxygen carriers, heterologous expression of hemoglobin, and supplementation with auxiliary energy substrates. However, the enhancement of the intracellular ATP supply by constructing an ATP regeneration system has not yet been considered.

Results

In this study, a polyphosphate kinase (PPK)-mediated ATP regeneration system was developed and introduced into S. albulus to successfully improve ε-PL production. First, polyP:AMP phosphotransferase (PAP) from Acinetobacter johnsonii was selected for catalyzing the conversion of AMP into ADP through an in vivo test. Moreover, three PPKs from different microbes were compared by in vitro and in vivo studies with respect to catalytic activity and polyphosphate (polyP) preference, and PPK2Bcg from Corynebacterium glutamicum was used for catalyzing the conversion of ADP into ATP. As a result, a recombinant strain PL05 carrying coexpressed pap and ppk2Bcg for catalyzing the conversion of AMP into ATP was constructed. ε-PL production of 2.34 g/L was achieved in shake-flask fermentation, which was an increase of 21.24% compared with S. albulus WG608; intracellular ATP was also increased by 71.56%. In addition, we attempted to develop a dynamic ATP regulation route, but the result was not as expected. Finally, the conditions of polyP6 addition were optimized in batch and fed-batch fermentations, and the maximum ε-PL production of strain PL05 in a 5-L fermenter was 59.25 g/L by fed-batch fermentation, which is the highest ε-PL production reported in genetically engineered strains.

Conclusions

In this study, we proposed and developed a PPK-mediated ATP regeneration system in S. albulus for the first time and significantly enhanced ε-PL production. The study provides an efficient approach to improve the production of not only ε-PL but also other ATP-driven metabolites.
Fine-scale spatial distribution of deltamethrin resistance and population structure of Anopheles funestus and Anopheles arabiensis populations in Southern Mozambique
Authors: Das Smita , Máquina Mara , Phillips Keeley , Cuamba Nelson , Marrenjo Dulcisaria , Saúte Francisco , Paaijmans Krijn P. , Huijben Silvie
Published: March 2023

Background

Insecticide resistance in malaria vectors can be spatially highly heterogeneous, yet population structure analyses frequently find relatively high levels of gene flow among mosquito populations. Few studies have contemporaneously assessed phenotypic, genotypic and population structure analysis on mosquito populations and none at fine geographical scales. In this study, genetic diversity, population structure, and insecticide resistance profiles of Anopheles funestus and Anopheles arabiensis were examined across mosquito populations from and within neighbouring villages.

Methods

Mosquitoes were collected from 11 towns in southern Mozambique, as well as from different neighbourhoods within the town of Palmeira, during the peak malaria transmission season in 2016. CDC bottle bioassay and PCR assays were performed with Anopheles mosquitoes at each site to determine phenotypic and molecular insecticide resistance profiles, respectively. Microsatellite analysis was conducted on a subsample of mosquitoes to estimate genetic diversity and population structure.

Results

Phenotypic insecticide resistance to deltamethrin was observed in An. funestus sensu stricto (s.s.) throughout the area, though a high level of mortality variation was seen. However, 98% of An. funestus s.s. were CYP6P9a homozygous resistant. An. arabiensis was phenotypically susceptible to deltamethrin and 99% were kdr homozygous susceptible. Both Anopheles species exhibited high allelic richness and heterozygosity. Significant deviations from Hardy–Weinberg equilibrium were observed, and high linkage disequilibrium was seen for An. funestus s.s., supporting population subdivision. However, the FST values were low for both anophelines (− 0.00457 to 0.04213), Nm values were high (9.4–71.8 migrants per generation), AMOVA results showed almost 100% genetic variation among and within individuals, and Structure analysis showed no clustering of An. funestus s.s. and An. arabiensis populations. These results suggest high gene flow among mosquito populations.

Conclusion

Despite a relatively high level of phenotypic variation in the An. funestus population, molecular analysis shows the population is admixed. These data indicate that CYP6P9a resistance markers do not capture all phenotypic variation in the area, but also that resistance genes of high impact are likely to easily spread in the area. Conversely, other strategies, such as transgenic mosquito release programmes will likely not face challenges in this locality.
Combination therapy based on dual-target biomimetic nano-delivery system for overcoming cisplatin resistance in hepatocellular carcinoma
Authors: Huang Yufen , Kou Qinjie , Su Yanrong , Lu Lu , Li Xisheng , Jiang Haiye , Gui Rong , Huang Rong , Nie Xinmin , Li Jian
Published: March 2023

Strategies to overcome toxicity and drug resistance caused by chemotherapeutic drugs for targeted therapy against hepatocellular carcinoma (HCC) are urgently needed. Previous studies revealed that high oxidored-nitro domain-containing protein 1(NOR1) expression in HCC was associated with cisplatin (DDP) resistance. Herein, a novel dual-targeting nanocarrier system AR-NADR was generated for the treatment of DDP resistance in HCC. The core of the nanocarrier system is the metal–organic frameworks (MOF) modified with nuclear location sequence (NLS), which loading with DDP and NOR1 shRNA (R). The shell is an A54 peptide inserted into the erythrocyte membrane (AR). Our results show that AR-NADR efficiently internalized by tumor cells due to its specific binding to the A54 receptors that are abundantly expressed on the surface of HCC cells and NLS peptide-mediated nuclear entry. Additionally, DDP is more likely to be released due to the degradation of Ag-MOF in the acidic tumor microenvironment. Moreover, by acting as a vector for gene delivery, AR-NADR effectively inhibits tumor drug resistance by suppressing the expression of NOR1, which induces intracellular DDP accumulation and makes cells sensitive to DDP. Finally, the anti-HCC efficacy and mechanisms of AR-NADR were systematically elucidated by a HepG2/DDP cell model as well as a tumor model. Therefore, AR-NADR constitutes a key strategy to achieve excellent gene silencing and antitumor efficacy, which provides effective gene therapy and precise treatment strategies for cisplatin resistance in HCC.

Graphical Abstract
Risk factors for thrombolysis-related intracranial hemorrhage: a systematic review and meta-analysis
Authors: Chen Jiana , Zeng Zhiwei , Fang Zongwei , Ma Fuxin , Lv Meina , Zhang Jinhua
Published: March 2023

Background

Thrombolysis-related intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been updated.

Aim

We conducted a systematic review to identify risk factors for thrombolysis-related intracranial hemorrhage.

Method

The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316160). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods.

Results

Of 6083 citations, we included 105 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with age, National Institutes of Health stroke scale, leukoaraiosis, hypertension, atrial fibrillation, diabetes, total cholesterol, proteinuria, fibrinogen levels, creatinine, homocysteine, early infarct signs, antiplatelet therapy and anticoagulant therapy; In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and weight, sex, platelet count, uric acid, albumin and white matter hyperintensity. Leukoaraiosis, cardiovascular disease, total cholesterol, white blood cell count, proteinuria, fibrinogen levels, creatinine, homocysteine and early CT hypodensities are not included in most intracranial hemorrhage risk assessment models.

Conclusion

This study informs risk prediction for thrombolysis-related intracranial hemorrhage, it also informs guidelines for intracranial hemorrhage prevention and future research.
Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy
Authors: Shi Saixian , Chen Ye , Luo Zhijian , Nie Guojun , Dai Yan
Published: March 2023

Doxorubicin (DOX) is a powerful and commonly used chemotherapeutic drug, used alone or in combination in a variety of cancers, while it has been found to cause serious cardiac side effects in clinical application. More and more researchers are trying to explore the molecular mechanisms of DOX-induced cardiomyopathy (DIC), in which oxidative stress and inflammation are considered to play a significant role. This review summarizes signaling pathways related to oxidative stress and inflammation in DIC and compounds that exert cardioprotective effects by acting on relevant signaling pathways, including the role of Nrf2/Keap1/ARE, Sirt1/p66Shc, Sirt1/PPAR/PGC-1α signaling pathways and NOS, NOX, Fe2+signaling in oxidative stress, as well as the role of NLRP3/caspase-1/GSDMD, HMGB1/TLR4/MAPKs/NF-κB, mTOR/TFEB/NF-κB pathways in DOX-induced inflammation. Hence, we attempt to explain the mechanisms of DIC in terms of oxidative stress and inflammation, and to provide a theoretical basis or new idea for further drug research on reducing DIC.