bluuebunny/crossref_metadata_2025 huggingface dataset:
Diameter changes of the thoracic aorta caused by acute type B aortic dissection
Authors: Shimamoto Takeshi , Komiya Tatsuhiko , Matsuo Takeshiko
Published: December 2023

Background

The impact of type B acute aortic dissection (TBAAD) on historical pre-TBAAD diameters of the thoracic aorta is rarely reported. The aim of this study was to assess the extent of changes in aortic diameters induced by dissection, measured with a computed tomography (CT) scan obtained before and after TBAAD.

Methods

Between January 2004 and December 2014, CT angiography of 50 non-Marfan patients with nonbicuspid aortic valves diagnosed with TBAAD were compared to historical CTs on file.

Results

The ascending aorta and proximal arch showed negligible change. The proximal, mid, and distal aorta diameters changed compared with predissected values (107.7 ± 4.8%, 109.3 ± 4.9%, and 105.7 ± 5.8%, respectively). Neither sex, false lumen status, or mural calcification, nor prior thoracoabdominal aortic ectasia, correlated with the diameter change. Age ≥80 years in the proximal descending aorta did correlate with the diameter change (110.7 ± 4.0% vs 106.1 ± 4.6% p = 0.01).

Conclusions

Although identifying predicting factors for an aortic diameter increase all along with the thoracic aorta was still challenging, the degree of diameter change by aortic dissection was 105.7% to 109.3% in descending thoracic aorta, most prominent in middle descending aorta.
Comparing the diagnostic accuracy, reading time, and inter-rater agreement of breast MRI abbreviated and full protocols: a multi-reader study
Authors: Hellgren Roxanna , Tolocka Ernst , Saracco Ariel , Wilczek Brigitte , Sundbom Ann , Hall Per , Dickman Paul W
Published: December 2023

Background

Earlier studies have shown that abbreviated protocol magnetic resonance imaging (AB-MRI) has similar diagnostic accuracy as the full protocol (Full MRI).

Purpose

To compare the diagnostic accuracy, reading time, and inter-rater agreement of AB-MRI to Full MRI among women without known increased familial risk of breast cancer or prior biopsy.

Material and Methods

In total, 395 MRI examinations were included in this study. Three readers were blinded to all patient information. The AB-MRI and Full MRI were read separately and in a different random order for each of the readers. Scores 1–2 were considered test negative while scores 3–5 were test positive. A positive reference test was the diagnosis of malignancy; a negative reference test was the absence of a diagnosis of breast cancer within a two-year follow-up. We used a generalized estimating equations approach to compare sensitivity and specificity between the two protocols. We used t-tests to compare the average reading time and Krippendorff's alpha to compare inter-rater agreement.

Results

MRI examinations of 395 women (median age=56 years) were evaluated. For AB-MRI and Full MRI, respectively, the sensitivity was 93.0% (95% CI=90.6–95.0) vs. 92.0% (95% CI=89.4–94.1), the specificity was 91.7% (95% CI=90.3–92.9) vs. 94.3% (95% CI=93.2–95.3), average reading time was 67 vs. 126 s, and the inter-rater agreement 0.79 vs. 0.83. The difference in sensitivity was not statistically significant ( P=0.840), but the difference in specificity was significant ( P=0.003).

Conclusion

AB-MRI has similar sensitivity, but somewhat lower specificity. The average reading time for the abbreviated protocol is lower, as is inter-rater agreement.
Transfer learning for the generalization of artificial intelligence in breast cancer detection: a case-control study
Authors: Africano Gerson , Arponen Otso , Rinta-Kiikka Irina , Pertuz Said
Published: December 2023

Background

Some researchers have questioned whether artificial intelligence (AI) systems maintain their performance when used for women from populations not considered during the development of the system.

Purpose

To evaluate the impact of transfer learning as a way of improving the generalization of AI systems in the detection of breast cancer.

Material and Methods

This retrospective case-control Finnish study involved 191 women diagnosed with breast cancer and 191 matched healthy controls. We selected a state-of-the-art AI system for breast cancer detection trained using a large US dataset. The selected baseline system was evaluated in two experimental settings. First, we examined our private Finnish sample as an independent test set that had not been considered in the development of the system (unseen population). Second, the baseline system was retrained to attempt to improve its performance in the unseen population by means of transfer learning. To analyze performance, we used areas under the receiver operating characteristic curve (AUCs) with DeLong's test.

Results

Two versions of the baseline system were considered: ImageOnly and Heatmaps. The ImageOnly and Heatmaps versions yielded mean AUC values of 0.82±0.008 and 0.88±0.003 in the US dataset and 0.56 (95% CI=0.50–0.62) and 0.72 (95% CI=0.67–0.77) when evaluated in the unseen population, respectively. The retrained systems achieved AUC values of 0.61 (95% CI=0.55–0.66) and 0.69 (95% CI=0.64–0.75), respectively. There was no statistical difference between the baseline system and the retrained system.

Conclusion

Transfer learning with a small study sample did not yield a significant improvement in the generalization of the system.
AI-generated content tools and students’ critical thinking: Insights from a Chinese university
Authors: Zou Xiaozhu , Su Ping , Li Lexing , Fu Ping
Published: December 2023

This study examines the impact of artificial-intelligence-generated content tools on students’ critical thinking skills and their attitudes towards these tools. A survey of 851 students from a Chinese university was conducted to investigate their usage patterns, motivations, perceived benefits and risk awareness, and the importance of critical thinking skills. The study also explores how libraries and librarians can help students develop critical thinking skills. The findings reveal that male and non-binary students utilized artificial intelligence tools more frequently, highlighting a research gap. The study uncovers motivations such as saving time and effort. It also demonstrates students’ awareness of the risks and limitations, emphasizing the need for critical thinking skills in navigating artificial-intelligence-generated content tools. These findings have significant implications for academic libraries, as students expressed a desire for education and training in artificial intelligence literacy and critical thinking. Libraries can provide resources, workshops and guidance to empower students in informed and critical thinking practices.
B. G. Johns and his “famous blind men” the genesis of heroic blindness in Victorian England
Authors: Margo Curtis E , Harman Lynn E
Published: December 2023

In 1876, Bennett George Johns, a minister and chaplain at the school for the blind in St George's Field, published Blind People: Their Works and Ways; with Sketches of the Lives of Some Famous Blind Men. The book provided a window into the lives of the blind in Victorian England, with an emphasis on their education—or lack thereof. Johns was an observer of the blind and sympathetic to their plight. His depictions of schools were dispassionate, yet gently argued for improvement. Rather than rely on pity, he emphasized the benefits of institutionalized life and recounted the extraordinary achievements of four blind men. The creation of heroic historical figures had traditionally been employed to venerate political, military, or religious personages. Its use in shaping public perception of blindness was novel. This paper explores Johns's book as an early example of the innocent, myth-building of the blind and considers whether the process is always harmless.
The Chain of Cultural Disdain: Demystifying the Patterns of Intercultural Interactions on University Campuses in China
Authors: Cheng Ming , Yu Yun
Published: December 2023

Extant research has explored practices and challenges for developing intercultural interactions on campus, but there is limited work on how cultural disdain has affected the development of intercultural interaction between domestic and international students. Drawing on interviews with 25 international students and 14 Chinese students in two Chinese universities, this study reveals that China's social history of intercultural encounters and internationalisation, together with people's individual intercultural experiences have fuelled Chinese students’ perceptions of the superiority of English language and Anglo-Saxon culture. While Chinese students prioritise communication with peers who are English native speakers, they tend to develop deeper intercultural friendships with students from non-Anglo-Saxon countries. This study uses the theory of cultural disdain to interpret the complex dynamics of intercultural interaction on campuses. It argues that Chinese universities need to increase cultural diversity and foster equality between different cultural groups in order to promote fruitful intercultural interactions for all students.
Law beyond the glass skyscrapers: Encouraging law students to embrace regional life and practice
Authors: Hess Nadia , Giancaspro Mark , Plater David
Published: December 2023

The shortage of law graduates outside the city raises adverse implications for access to justice for Australian regional, rural and remote (RRR), and Aboriginal communities. This article discusses an extracurricular educational initiative implemented at the University of Adelaide Law School in 2021 and 2022 geared towards contributing to a solution for this problem. The initiative consisted of a series of immersion and exposure trips throughout regional South Australia for law students with interest in pursuing regional employment. This article discusses the initiative, the pedagogical rationale as well as the impact of the program, providing a blueprint for other universities considering similar initiatives.
Media Representations and Diversity in the 100 Years of Journalism & Mass Communication Quarterly
Authors: Moody-Ramirez Mia , Byerly Carolyn , Mishra Suman , Waisbord Silvio R.
Published: December 2023

The Journal and Mass Communication Quarterly (JMCQ) has documented the struggle members of marginalized groups face in their quest to be treated equally in media content and careers. In this analysis, we note that the journal’s century of articles documents the many historical shifts in the representation and treatment of women and minorities in media settings. Articles emphasize the lack of opportunities for advancement, management issues, and systemic inequities perpetuated by media content and practices. Less common were articles that examine the treatment of students and faculty in academia.
Media Effects Research in Journalism & Mass Communication Quarterly
Authors: Oliver Mary Beth , Raney Arthur A.
Published: December 2023

This article presents an analysis of media effects articles published in JMCQ from 1954 to 2020. Although the primary focus of our sample of articles focused on news, a wealth of additional topics were also examined, including attitude change, media selection, and sharing of media content. While some of this body of scholarship reflects more “traditional” conceptualizations of media effects research, others point to a broader conceptualization that reflects individuals as active in their selection, processing, evaluation, and even creation of media content.
Politics and Media in Journalism & Mass Communication Quarterly: A Centennial Research Retrospective
Authors: Valenzuela Sebastián , Bachmann Ingrid , Lawrence Regina G. , Gil de Zúñiga Homero
Published: December 2023

Based on computerized and manual content analyses, we examined the theories, methods, topics, and authors’ backgrounds of the empirical articles revolving around politics and media published by Journalism & Mass Communication Quarterly (JMCQ) in its 100 years ( N = 424). The most common theories are agenda-setting, framing, and selective exposure, and quantitative methods prevail with single-country studies being more prevalent than comparative analyses. A considerable portion of research has focused on political news, particularly during campaigns. Male, U.S.-based authors dominate, but female-authored work has increased in the past decade. Challenges remain to make the research on politics and media in JMCQ more generalizable globally.
Retrospective and FMECA analysis of failures in closed-system devices
Authors: El Medkouri Safaa , Bhirich Nihal , Belahcen Mohammed Jaouad , Rahali Younes
Published: December 2023

Introduction

Cytotoxic drugs can be hazardous to healthcare workers involved in their preparation and/or administration. Exposure occurs during routine handling of drug vials and ampoules, preparation, administration and disposal of cytotoxic waste. The use of closed-system devices provides protection against exposure to cytotoxics, but these devices are the subject of numerous incidents. Given the nature of the drugs they contain, these incidents can be dangerous for the personnel handling them.

Objective

The aim of our study is to analyze material vigilance data relating to problems frequently encountered with the various consumables of the closed system and to assess the risk of exposure of personnel to cytotoxic drugs when using these using the Failure Mode and Criticality Analysis (FMECA) method.

Materials and methods

Our study was conducted at the pharmacy of the National Institute of Oncology, the closed system drug transfer device (CSDT) used is a ChemoClave-ICU®, This device is mechanical and needleless For the materiovigilance study we carried out a retrospective study over the period from 2019 to 2022, analyzing materiovigilance data collected by National Institute of Oncology's materiovigilance and pharmacovigilance cell. Our team, trained in the FMECA method, conducted the study over a three-month period, between September and November 2022. The method was used to assess the risks incurred by staff when using the CSDT device to prepare cytotoxic drugs.

Conclusion

Our study revealed that the most frequent incident was linked to a manufacturing defect in the device in question. According to the FMECA analysis, this incident represents a major risk, as its occurrence hampers the cytotoxic preparation process. CSDT have the advantage of being easy to use and acceptable to staff, but standards need to be developed and validated to assess the performance of these devices.
Safety and Pharmacokinetic Assessment of the FIC CLDN18.2/4-1BB Bispecific Antibody in Rhesus Monkeys
Authors: Wang Jing , Dong Tiantian , Gong Xinjiang , Li Deli , Sun Joanne , Luo Yi , Wu Huazhang
Published: December 2023

Gastric cancer is one of the most common cancers worldwide, particularly in China, with over half a million new cases and over 400 thousand deaths in 2022. Zolbetuximab, a first-in-class investigational monoclonal antibody (mAb) targeting tumor-associated antigen CLDN18.2 which is highly expressed on gastric cancer cells, was recently reported to meet the primary endpoint in Phase III trial as first-line treatment in CLDN18.2 positive and HER2-negative gastric cancers. In the present study, we developed a humanized bispecific antibody (bsAb) CLDN18.2/4-1BB named PM1032. PM1032 activates immune cells via CLDN18.2 mediated crosslinking of 4-1BB, a potent stimulator of T/NK cells. It induced strong immunological memory in multiple tumor-bearing animal models, indicating significant potential as an effective treatment for CLDN18.2 positive cancers such as gastric cancer. Since liver and gastrointestinal (GI) related toxicities were reported in 4-1BB and CLDN18.2 targeting programs during the clinical development, respectively, extensive pharmacokinetics (PK) and safety profile characterization of PM1032 was performed in rhesus monkeys. PM1032 had a half-life comparable to a conventional IgG1 mAb, and serum drug concentration increased in a dose-dependent pattern. Furthermore, PM1032 was generally well tolerated, with no significant abnormalities observed in toxicity studies, including the liver and stomach. In summary, PM1032 demonstrated good PK and an exceptional safety profile in rhesus monkeys supporting further investigation in clinical studies.
A new approach for single-haptic retropupillary iris-claw lens subluxation - The “fencing” technique
Authors: Almeida Júlio , Costa Tomás R. , Vivas Maria , Monteiro Catarina , Vaz Fernando T. , Silva Diana S. , Prieto Isabel
Published: December 2023

Introduction

Single-haptic iris-claw intraocular lens (IOL) dislocation is not an uncommon complication. A few different surgical techniques are available for its refixation but usually involve a more invasive approach. We aim to demonstrate an original and simple approach for refixation of single haptic retropupillary iris-claw IOL subluxations.

Methods

We present a case of an 80-year-old male with a single haptic retropupillary iris-claw IOL subluxation in a previously vitrectomized eye. We used a new surgical approach to refix this type of subluxation.

Results

This new technique uses only two 30-gauge needles (one of them connected to a viscosurgical device) to re-enclavate the subluxated haptic of the retropupillary iris-claw IOL. By minimising surgical manipulation, the patient's postoperative period was uneventful.

Conclusions

We highlight a new, quick, safe, and unusual surgical approach to single-haptic retropupillary iris-claw IOL dislocation in vitrectomized eyes. Because of its characteristics, we named it the “fencing” IOL repositioning technique.
Hybrid lubrication model study of slip ring combination seal under the influence of frictional heat
Authors: Zhang Yi , Lou Zichen , Wei Fu , Lin Shuai , Hu Ling , He Wei
Published: December 2023

This paper presents an experimental and theoretical investigation into the factors influencing the sealing performance of combined slip rings. Factoring in the frictional heat from micro convex bodies and convective heat exchange between the slip ring, oil film, and air, we formulate a thermoelastic flow hybrid lubrication model for the combined slip ring seal. This model calculates the distribution of oil film thickness, pressure, temperature, velocity, and viscosity in the sealing zone, drawing on the generalized average Reynolds equation and the transmembrane average energy equation, in conjunction with the heat conduction equation of the slip ring. Utilizing the Archard wear model, we also examine the wear characteristics of the combined slip ring seal, providing insights into seal wear under these conditions. The model enables an analysis of the interplay between parameters and their impact on seal performance. The method proposed accurately predicts friction and leakage in line with experimental data, thereby providing a theoretical foundation for further numerical investigation of seal characteristics.
Methotrexate and cardiovascular prevention: an appraisal of the current evidence
Authors: Mangoni Arduino A. , Sotgia Salvatore , Zinellu Angelo , Carru Ciriaco , Pintus Gianfranco , Damiani Giovanni , Erre Gian Luca , Tommasi Sara
Published: December 2023

New evidence continues to accumulate regarding a significant association between excessive inflammation and dysregulated immunity (local and systemic) and the risk of cardiovascular events in different patient cohorts. Whilst research has sought to identify novel atheroprotective therapies targeting inflammation and immunity, several marketed drugs for rheumatological conditions may serve a similar purpose. One such drug, methotrexate, has been used since 1948 for treating cancer and, more recently, for a wide range of dysimmune conditions. Over the last 30 years, epidemiological and experimental studies have shown that methotrexate is independently associated with a reduced risk of cardiovascular disease, particularly in rheumatological patients, and exerts several beneficial effects on vascular homeostasis and blood pressure control. This review article discusses the current challenges with managing cardiovascular risk and the new frontiers offered by drug discovery and drug repurposing targeting inflammation and immunity with a focus on methotrexate. Specifically, the article critically appraises the results of observational, cross-sectional and intervention studies investigating the effects of methotrexate on overall cardiovascular risk and individual risk factors. It also discusses the putative molecular mechanisms underpinning the atheroprotective effects of methotrexate and the practical advantages of using methotrexate in cardiovascular prevention, and highlights future research directions in this area.
Acacetin Combined with Wortmannin Activated Insulin Signaling Pathway by Inhibiting the Induction Effect of PI3Kp110 on IRS-1 Serine Phosphorylation to Improve Myocardial Fibrosis in Fructose-Induced SHR Rats
Authors: Zhao Lirui , Yuan Peipei , Zhang Qi , Zhang Yan , Zheng Yajuan , Li Saifei , Chen Yi , Li Panying , Ruan Yuan , Feng Weisheng , Zheng Xiaoke
Published: December 2023

Objective

To explore the intervention mechanism of acacetin combined with wortmannin on myocardial fibrosis in fructose-induced SHR rats.

Methods

Using fructose-induced SHR rats combined with HUVEC cell induced by high-sugar DMEM, the intervention mechanism of acacetin combined with wortmannin on myocardial fibrosis in rats was explored.

Results

In fructose-induced SHR rats, the intervention results of acacetin on myocardial fibrosis showed that acacetin significantly downregulated serum REN, Ang II, ET-1 levels, and upregulated serum PGE2 and NO levels ( P < 0.05 or P < 0.01). The combination of wortmannin showed further enhanced effect on the level of ET-1 and PGE2 ( P < 0.05). Acacetin and wortmannin significantly increased the expression of CD31 protein and CD31, VE-cadherin mRNA levels in the heart, decreased the expression of CVF, α-SMA protein and CVF, α-SMA, Vimentin and Fibronectin mRNA levels, and enhanced the improvement effect after the combination of acacetin and wortmannin ( P < 0.05 or P < 0.01). Both acacetin and wortmannin significantly activated the level of PI3Kp85 in myocardium ( P < 0.05 or P < 0.01), and wortmannin significantly inhibited PI3Kp110 ( P < 0.01). While, acacetin combined with wortmannin, the activation effect on PI3Kp85 was enhanced, and the inhibitory effect on PI3Kp110 was weakened ( P < 0.01). In HUVEC endothelial mesenchymal transformation model, wortmannin significantly inhibited the phosphorylation of IRS-1 serine ( P < 0.01); After PI3Kp85 silencing, both acacetin and wortmannin inhibited the activation of PI3 K downstream protein AKT phosphorylation ( P < 0.01).

Conclusion

Acacetin synergistic with PI3 K inhibitor wortmannin inhibits the induction effect of PI3Kp110 on IRS-1 serine phosphorylation, indirectly activates insulin signaling pathway, modulates vasoactive factors, alleviates cardiac endothelial mesenchymal transformation in fructose-induced SHR rats, and improves myocardial fibrosis.
The impact of studies with no events in both arms on meta-analysis of rare events: A simulation study using generalized linear mixed model
Authors: Xu Chang , Lin Lifeng
Published: December 2023

Objective

The common approach to meta-analysis with double-zero studies is to remove such studies. Our previous work has confirmed that exclusion of these studies may impact the results. In this study, we undertook extensive simulations to investigate how the results of meta-analyses would be impacted in relation to the proportion of such studies.

Methods

Two standard generalized linear mixed models (GLMMs) were employed for the meta-analysis. The statistical properties of the two GLMMs were first examined in terms of percentage bias, mean squared error, and coverage. We then repeated all the meta-analyses after excluding double-zero studies. Direction of estimated effects and p-values for including against excluding double-zero studies were compared in nine ascending groups classified by the proportion of double-zero studies within a meta-analysis.

Results

Based on 50,000 simulated meta-analyses, the two GLMMs almost achieved unbiased estimation and reasonable coverage in most of the situations. When excluding double-zero studies, 0.00%–4.47% of the meta-analyses changed the direction of effect size, and 0.61%–8.78% changed direction of the significance of p-value. When the proportion of double-zero studies increased in a meta-analysis, the probability of the effect size changed the direction increased; when the proportion was about 40%–60%, it has the largest impact on the change of p-values.

Conclusion

Double-zero studies can impact the results of meta-analysis and excluding them may be problematic. The impact of such studies on meta-analysis varies by the proportion of such studies within a meta-analysis.
Surgical and bronchoscopic pulmonary function-improving procedures in lung emphysema
Authors: Everaerts Stephanie , Vandervelde Christelle M. , Shah Pallav , Slebos Dirk-Jan , Ceulemans Laurens J.
Published: December 2023

COPD is a highly prevalent, chronic and irreversible obstructive airway disease without curative treatment. Standard therapeutic strategies, both non-pharmacological and pharmacological, have only limited effects on lung function parameters of patients with severe disease. Despite optimal pharmacological treatment, many patients with severe COPD still have a high burden of dyspnoea and a poor quality of life. If these patients have severe lung emphysema, with hyperinflation as the driver of symptoms and exercise intolerance, lung volume reduction may be an effective treatment with a significant impact on lung function, exercise capacity and quality of life. Currently, different lung volume reduction approaches, both surgical and bronchoscopic, have shown encouraging results and have been implemented in COPD treatment recommendations. Nevertheless, choosing the optimal lung volume reduction strategy for an individual patient remains challenging. Moreover, there is still room for improving durability of effect and safety in all available procedures. Ongoing and innovative research is essential to push this field forwards. This review provides an overview of results and limitations of the current lung volume reduction options for patients with severe lung emphysema and hyperinflation.
Treatable traits in asthma during pregnancy: a call for a shift towards a precision-based management approach
Authors: Joshi Esha , Gibson Peter G. , McDonald Vanessa M. , Murphy Vanessa E.
Published: December 2023

Asthma is the most common chronic medical condition in pregnancy. Asthma exacerbations in pregnancy are unpredictable, and are associated with adverse maternal and fetal perinatal outcomes such as preterm birth and low birthweight. Goals of asthma management in pregnancy are to establish effective asthma control and prevent exacerbations. Optimising the management of asthma in pregnancy is an important goal of practice and future research.

Treatable traits is a precision medicine paradigm proposed for the management of airways diseases, which holistically addresses the complexity and heterogeneity of airways disease. It is an individualised treatment approach that aims to improve outcomes. This makes treatable traits well suited for pregnant women with asthma, who have a high prevalence of obesity, mental health conditions, poor symptom perception and suboptimal asthma management skills including low treatment adherence. These traits are measurable and treatable. In this review, we explore current knowledge on the burden of asthma, maternal and perinatal consequences of asthma during pregnancy, the treatable traits paradigm, the prevalence of treatable traits in pregnant women with asthma, and consider how the treatable traits paradigm can be integrated into the management of asthma in pregnancy.
Clinical–radiological–pathological correlation in pulmonary hypertension with unclear and/or multifactorial mechanisms
Authors: Lichtblau Mona , Mayer Laura , Gopalan Deepa , Dorfmüller Peter , Ulrich Silvia
Published: December 2023

Ever since the second world symposium on pulmonary hypertension (PH) held in Evian, France, in 1998, PH has been classified into five major clinical groups. Group 5 PH includes a variety of distinct conditions with unclear and/or multifactorial underlying pathologies. Management of these patients is challenging as the number of patients within these groups is often small, not all individuals with certain underlying conditions are affected by PH and patients exhibit distinct symptoms due to different underlying diseases. Studies and clinical trials in these groups are largely lacking and mostly restricted to case series and registry reports. Nonetheless, the worldwide burden of group 5 PH is estimated to be significant in terms of the prevalence of some associated diseases. Group 5 PH encompasses six subgroups, including haematological disorders (inherited and acquired chronic haemolytic anaemia and chronic myeloproliferative disorders), systemic disorders (sarcoidosis, pulmonary Langerhans's cell histiocytosis and neurofibromatosis type 1), metabolic disorders (glycogen storage diseases and Gaucher disease), chronic renal failure with or without haemodialysis, pulmonary tumour thrombotic microangiopathy and fibrosing mediastinitis.
A comprehensive analysis of immune features and construction of an immune gene diagnostic model for sepsis
Authors: Xue Haiyan , Xiao Ziyan , Zhao Xiujuan , Li Shu , Wang Zhenzhou , Zhao Jie , Zhu Fengxue
Published: December 2023

Sepsis is a life-threatening syndrome resulting from immune system dysfunction that is caused by infection. It is of great importance to analyze the immune characteristics of sepsis, identify the key immune system related genes, and construct diagnostic models for sepsis. In this study, the sepsis transcriptome and expression profiling data were merged into an integrated dataset containing 277 sepsis samples and 117 non-sepsis control samples. Single-sample gene set enrichment analysis (ssGSEA) was used to assess the immune cell infiltration. Two sepsis immune subtypes were identified based on the 22 differential immune cells between the sepsis and the healthy control groups. Weighted gene co-expression network analysis (WCGNA) was used to identify the key module genes. Then, 36 differentially expressed immune-related genes were identified, based on which a robust diagnostic model was constructed with 11 diagnostic genes. The expression of 11 diagnostic genes was finally assessed in the training and validation datasets respectively. In this study, we provide comprehensive insight into the immune features of sepsis and establish a robust diagnostic model for sepsis. These findings may provide new strategies for the early diagnosis of sepsis in the future.
Machine learning and phylogenetic analysis allow for predicting antibiotic resistance in M. tuberculosis
Authors: Yurtseven Alper , Buyanova Sofia , Agrawal Amay Ajaykumar , Bochkareva Olga O. , Kalinina Olga V.
Published: December 2023

Background

Antimicrobial resistance (AMR) poses a significant global health threat, and an accurate prediction of bacterial resistance patterns is critical for effective treatment and control strategies. In recent years, machine learning (ML) approaches have emerged as powerful tools for analyzing large-scale bacterial AMR data. However, ML methods often ignore evolutionary relationships among bacterial strains, which can greatly impact performance of the ML methods, especially if resistance-associated features are attempted to be detected. Genome-wide association studies (GWAS) methods like linear mixed models accounts for the evolutionary relationships in bacteria, but they uncover only highly significant variants which have already been reported in literature.

Results

In this work, we introduce a novel phylogeny-related parallelism score (PRPS), which measures whether a certain feature is correlated with the population structure of a set of samples. We demonstrate that PRPS can be used, in combination with SVM- and random forest-based models, to reduce the number of features in the analysis, while simultaneously increasing models’ performance. We applied our pipeline to publicly available AMR data from PATRIC database for Mycobacterium tuberculosis against six common antibiotics.

Conclusions

Using our pipeline, we re-discovered known resistance-associated mutations as well as new candidate mutations which can be related to resistance and not previously reported in the literature. We demonstrated that taking into account phylogenetic relationships not only improves the model performance, but also yields more biologically relevant predicted most contributing resistance markers.
Empowering community health professionals for effective air pollution information communication
Authors: Tan Tricia , Junghans Cornelia , Varaden Diana
Published: December 2023

Background

Air pollution remains a significant public health risk, particularly in urban areas. Effective communication strategies remain integral to overall protection by encouraging the adoption of personal air pollution exposure reduction behaviours. This study aims to explore how community health professionals can be empowered to communicate air pollution information and advice to the wider community, to encourage the uptake of desired behaviours in the population.

Methods

The study adopted a qualitative methodology, where four homogenous Focus Group Discussions (FGDs) were held with a range of community health professionals, including Health Care Professionals, Community Health and Wellbeing Workers (CHWWs) and Social Prescribing Link Workers (SPLW). A classical content analysis was conducted with the Structural Empowerment Theory (SET) and Psychological Empowerment Theory (PET) as guiding concepts.

Results

Five key themes were identified: from a structural empowerment perspective: [1] resources and support, [2] knowledge. From a psychological empowerment perspective: [3] confidence as advisor, [4] responsibility as advisor, and [5] residents’ receptiveness to advice. It was concluded that advice should be risk stratified, clear, easy to follow and provide alternatives.

Conclusion

This study identified ways for community health professionals to be empowered by local councils or other organisations in providing advice on air pollution, through the provision of essential structural support and opportunities to enhance their knowledge and confidence in the subject. Implementing recommendations from this study would not only empower community health professionals to advise on air pollution to the wider community but also increase adherence to health advice.
Comparison of LASSO and random forest models for predicting the risk of premature coronary artery disease
Authors: Wang Jiayu , Xu Yikang , Liu Lei , Wu Wei , Shen Chunjian , Huang Henan , Zhen Ziyi , Meng Jixian , Li Chunjing , Qu Zhixin , he Qinglei , Tian Yu
Published: December 2023

Purpose

With the change of lifestyle, the occurrence of coronary artery disease presents a younger trend, increasing the medical and economic burden on the family and society. To reduce the burden caused by this disease, this study applied LASSO Logistic Regression and Random Forest to establish a risk prediction model for premature coronary artery disease(PCAD) separately and compared the predictive performance of the two models.

Methods

The data are obtained from 1004 patients with coronary artery disease admitted to a third-class hospital in Liaoning Province from September 2019 to December 2021. The data from 797 patients were ultimately evaluated. The dataset of 797 patients was randomly divided into the training set (569 persons) and the validation set (228 persons) scale by 7:3. The risk prediction model was established and compared by LASSO Logistic and Random Forest.

Result

The two models in this study showed that hyperuricemia, chronic renal disease, carotid artery atherosclerosis were important predictors of premature coronary artery disease. A result of the AUC between the two models showed statistical difference (Z = 3.47, P < 0.05).

Conclusions

Random Forest has better prediction performance for PCAD and is suitable for clinical practice. It can provide an objective reference for the early screening and diagnosis of premature coronary artery disease, guide clinical decision-making and promote disease prevention.
This needs to be a journey that we’re actually on together’—the introduction of integrated care systems for children and young people in England: a qualitative study of the views of local system stakeholders during winter 2021/22
Authors: Hope Steven , Stepanova Evgenia , Lloyd-Houldey Oliver , Hillier-Brown Frances , Hargreaves Dougal , Nicholls Dasha , Summerbell Carolyn , Viner Russell M. , Dedat Zainab , Owen Emily C. , Scott Stephanie
Published: December 2023

Background

Integrated care has become a central feature of health system reform worldwide. In England, Integrated Care Systems (ICS) are intended to improve integration across public health, the National Health Service (NHS), education and social care. By April 2021, England had been divided into 42 geographical areas, each tasked with developing local ICS provision. However, it was not clear how ICSs would address the specific needs of children and young people (CYP). This study elicited the views of senior professional stakeholders in the first year of the ICS national roll out, to learn how integrated care for CYP was being implemented within the ICSs and future plans for service provision.

Methods

A qualitative analysis of in-depth interviews with stakeholders, including healthcare professionals, NHS managers and local authority leaders (n = 25) selected from a diverse sample of ICSs (n = 7) across England, conducted during winter 2021/22. Reflexive thematic analysis involving a collaborative coding approach was used to analyse interview transcripts.

Results

Four themes were identified, indicating challenges and opportunities for ICSs in relation to the health of CYP: 1) Best start in life (a more holistic approach to health afforded by integrated care); 2) Local and national contexts (tensions between local and national settings and priorities); 3) Funding and planning (instituting innovative, long-term plans using limited existing CYP funding streams); 4) Organisational complexities (integrating the work of diverse organisations).

Conclusions

The views of stakeholders, provided at the beginning of the journey towards developing local ICS CYP provision, revealed a common aspiration to change focus from provision of acute, largely adult-orientated services towards one with a broader, population health remit, including prevention and early intervention. This would be delivered by integration of a range of local services, including health, education, housing and social care, to set CYP on a life-long path towards improved health and wellbeing. Yet there was an awareness that change would take place over time within existing national policy and funding frameworks, and would require overcoming organisational barriers through further developing local collaborations and partnerships. As ICSs mature, the experiences of stakeholders should continue to be canvassed to identify practical lessons for successful CYP integrated care.
ALOX5 acts as a key role in regulating the immune microenvironment in intrahepatic cholangiocarcinoma, recruiting tumor-associated macrophages through PI3K pathway
Authors: Chen Jialu , Tang Yue , Qin Delong , Yu Xiaopeng , Tong Huanjun , Tang Chengwei , Tang Zhaohui
Published: December 2023

Background

Intrahepatic cholangiocarcinoma (ICC) is poorly treated due to the presence of an inhibitory immune microenvironment. Tumor-associated macrophages (TAM) are an important component of TME. ALOX5 is an important lipid metabolism enzyme in cancer progression, but the mechanism by which it regulates TAM to promote ICC progression is unknown. The aim of this study was to investigate the potential mechanism of TAM regulation by ALOX5 and the translational effect of targeting ALOX5.

Methods

In this study, we investigated the association between the spatial localization of epithelial cells and TAMs by combining scRNA-seq analysis with multiplex immunofluorescence analysis. Through bulk sequencing analysis and spatial analysis, lipid metabolism genes closely related to TAM infiltration were screened. In vitro co-culture model was constructed to verify that ALOX5 and its downstream metabolite LTB4 promote M2 macrophage migration. Bulk sequencing after co-culture combined with single-cell analysis was performed to identify key pathways for up-regulation of M2 macrophage migration. Finally, the effect of CSF1R inhibitor (PLX3397) combined with ALOX5 inhibitor (Zileuton) in vivo was investigated by by xenograft tumor formation experiment in nude mice.

Results

ALOX5 in ICC cells was a key lipid metabolism gene affecting the infiltration of M2 macrophages in TME. Mechanically, LTB4, a metabolite downstream of ALOX5, recruited M2 macrophages to migrate around tumor cells by binding to BLT1/BLT2 and activating the PI3K pathway, which ultimately lead to the promotion of ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor effectively reduced tumor volume and M2 macrophage infiltration abundance.

Conclusion

In ICC, LTB4, a metabolite secreted by ALOX5 of epithelial cells, binded to BLT1/BLT2 on TAM surface to activate PI3K pathway and promote TAM migration, thus promoting ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor for ICC is a promising combination therapy modality.
NOD2 attenuates osteoarthritis via reprogramming the activation of synovial macrophages
Authors: Li Changchuan , Ouyang Zhuji , Huang Yuhsi , Lin Sipeng , Li Shixun , Xu Jing , Liu Taihe , Wu Jionglin , Guo Peidong , Chen Zhong , Wu Haoyu , Ding Yue
Published: December 2023

Objective

Synovial inflammation, which precedes other pathological changes in osteoarthritis (OA), is primarily initiated by activation and M1 polarization of macrophages. While macrophages play a pivotal role in the inflammatory process of OA, the mechanisms underlying their activation and polarization remain incompletely elucidated. This study aims to investigate the role of NOD2 as a reciprocal modulator of HMGB1/TLR4 signaling in macrophage activation and polarization during OA pathogenesis.

Design

We examined NOD2 expression in the synovium and determined the impact of NOD2 on macrophage activation and polarization by knockdown and overexpression models in vitro. Paracrine effect of macrophages on fibroblast-like synoviocytes (FLS) and chondrocytes was evaluated under conditions of NOD2 overexpression. Additionally, the in vivo effect of NOD2 was assessed using collagenase VII induced OA model in mice.

Results

Expression of NOD2 was elevated in osteoarthritic synovium. In vitro experiments demonstrated that NOD2 serves as a negative regulator of HMGB1/TLR4 signaling pathway. Furthermore, NOD2 overexpression hampered the inflammatory paracrine effect of macrophages on FLS and chondrocytes. In vivo experiments revealed that NOD2 overexpression mitigated OA in mice.

Conclusions

Supported by convincing evidence on the inhibitory role of NOD2 in modulating the activation and M1 polarization of synovial macrophages, this study provided novel insights into the involvement of innate immunity in OA pathogenesis and highlighted NOD2 as a potential target for the prevention and treatment of OA.
Genome-wide identification and spatiotemporal expression analysis of cadherin superfamily members in echinoderms
Authors: Chess Macie M. , Douglas William , Saunders Josiah , Ettensohn Charles A.
Published: December 2023

Background

Cadherins are calcium-dependent transmembrane cell–cell adhesion proteins that are essential for metazoan development. They consist of three subfamilies: classical cadherins, which bind catenin, protocadherins, which contain 6–7 calcium-binding repeat domains, and atypical cadherins. Their functions include forming adherens junctions, establishing planar cell polarity (PCP), and regulating cell shape, proliferation, and migration. Because they are basal deuterostomes, echinoderms provide important insights into bilaterian evolution, but their only well-characterized cadherin is G-cadherin, a classical cadherin that is expressed by many embryonic epithelia. We aimed to better characterize echinoderm cadherins by conducting phylogenetic analyses and examining the spatiotemporal expression patterns of cadherin-encoding genes during Strongylocentrotus purpuratus development.

Results

Our phylogenetic analyses conducted on two echinoid, three asteroid, and one crinoid species identified ten echinoderm cadherins, including one deuterostome-specific ortholog, cadherin-23, and an echinoderm-specific atypical cadherin that possibly arose in an echinoid-asteroid ancestor. Catenin-binding domains in dachsous-2 orthologs were found to be a deuterostome-specific innovation that was selectively lost in mouse, while those in Fat4 orthologs appeared to be Ambulacraria-specific and were selectively lost in non-crinoid echinoderms. The identified suite of echinoderm cadherins lacks vertebrate-specific innovations but contains two proteins that are present in protostomes and absent from mouse. The spatiotemporal expression patterns of four embryonically expressed cadherins (fat atypical cadherins 1 and 4, dachsous-2, and protocadherin-9) were dynamic and mirrored the expression pattern of Frizzled 5/8, a non-canonical Wnt PCP pathway receptor protein essential for archenteron morphogenesis.

Conclusions

The echinoderm cadherin toolkit is more similar to that of an ancient bilaterian predating protostomes and deuterostomes than it is to the suite of cadherins found in extant vertebrates. However, it also appears that deuterostomes underwent several cadherin-related innovations. Based on their similar spatiotemporal expression patterns and orthologous relationships to PCP-related and tumor-suppressing proteins, we hypothesize that sea urchin cadherins may play a role in regulating the shape and growth of embryonic epithelia and organs. Future experiments will examine cadherin expression in non-echinoid echinoderms and explore the functions of cadherins during echinoderm development.
Comments on: “Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials”
Authors: Cheng Fang
Published: December 2023

The meta-analysis by Wang et al. (Stem Cell Res Ther 14(1):103, 2023) aims to explore whether mesenchymal stem cells are effective for perianal fistulas. The authors indicated that the difference in cell types, cell sources and cell dosages did not influence mesenchymal stem cells’ efficacy, which may not be accurate. I think that local treatment with higher dosages of mesenchymal stem cells seems to not result in a higher healing rate. And, future trials should focus on donor characteristics considering past medical history of further autoimmunity, timely and cost-effective treatment to lighten the optimized therapeutic goals. In the future, it will be interesting to assess the safety and feasibility of injection of fibrin glue combined with mesenchymal stem cells in perianal fistulas.