bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Digital Finance on Provincial Carbon Productivity: Empirical Evidence from China
Authors: Liu Baijun , Chen Huaichao , Zhang Ying , Bai Shan
Published: December 2024

Based on the provincial panel data from China, this study explores the impact of digital finance on provincial carbon productivity. Further, the regional heterogeneity and spatial spillover effect, the moderating effects of financial supervision and environmental decentralization, and the mediating effect of green technology innovation are analyzed. The results show that digital finance can significantly improve provincial carbon productivity, and clearly promote carbon productivity in the underdeveloped provinces (i.e., central and western regions), but not in the economically developed provinces (i.e., eastern region). Digital finance has a positive spatial spillover effect on carbon productivity. In addition, financial supervision and environmental decentralization play moderating effects in the impact of digital finance on carbon productivity. Green technology innovation plays a partial mediating effect in the impact of digital finance on carbon productivity. This study provides a reference for improving carbon productivity and developing a low-carbon economy.
Do Quality Management Practices, Organizational Ambidexterity, and Green Innovation Influence Sustainable Performance? A Structural Equation Modeling approach
Authors: Sarmad Gibran Saleheen , Naseem Afshan , Shahzad Asjad , Ullah Mehran
Published: December 2024

This study examines the effects of embedding Quality Management practices (QMP), that is, quality training, employee relations, and management relations on Sustainable Performance (SP), and the mediating role of Organizational ambidexterity exploration (innovation exploration) and exploitation (innovation exploitation) between the relationship between QMP and SP in the manufacturing industry. Moreover, the role of Green Innovation is explored as a moderator in the ties of Organizational Ambidexterity Exploration (innovation exploration) and SP.  SmartPLS is used in this paper to analyze quantitative data collected from industry specialists and supply chain managers in the food, paint, and textile industries. The findings suggest that good management practices: management relations, employee training, and quality training, can help create a conducive environment for exploratory innovations, which can furthermore help improve the SP of the firm. In the case of exploration, incorporating green products and procedures can help the company achieve long-term success. QMP in ambidextrous manufacturing industries improves the firm’s social performance by meeting the needs of environmentally conscious stakeholders and ensuring healthy relationships, social welfare, customer satisfaction, and societal friendliness toward sustainable products through green product and process innovation.  Managers can take advantage of the inherent potential of quality management systems to integrate them into exploitative and exploratory activities and boost the company’s long-term profitability. This study explored a novel concept of green innovation as rare, valuable, inimitable, and organized, so it helps firms in the attainment of sustainable competitive advantage.
Research on Configurations for Marketing Performance of Science and Technology Enterprises in China Based on the TOE Framework
Authors: Zhang Jianing , Fan Jianhong , Yan Xianghong
Published: December 2024

Facing a complex and changeable business environment, enterprises are constantly looking for specific paths to improve their marketing performance, which may ultimately lead to a sustainable competitive advantage. Based on the Technology, Organization, and Environment (TOE) framework, this study uses a sample of 258 listed science and technology enterprises in China and applies the Fuzzy Set Qualitative Comparative Analysis (fsQCA) method to examine the relationship between six conditions, namely, R&D capability, information technology application capability, marketing level, enterprise scale, government support, market competition, and marketing performance of science and technology enterprises from a configurational perspective. The results show that no single condition qualifies as necessary for high marketing performance, but the role of high enterprise scale is prominent. Four paths generate high marketing performance of science and technology enterprises and four paths generate not-high marketing performance. These paths have an asymmetric causal relationship between high and not-high marketing performance. This study provides a new perspective for research on enterprise marketing performance and implications for enhancing the marketing performance of science and technology enterprises.
The Crosslinguistic Influence of L1 Morphological Awareness on L3 Lexical Inferencing: An Exploratory Study of L1 Japanese-L2 English-L3 Chinese Learners
Authors: Ke Sihui (Echo) , He Xuehong (Stella) , Zhao Guihua
Published: December 2024

It is generally agreed that first language (L1) morphological awareness, the ability to reflect upon, analyze and manipulate morphemes and morphological structure of words, can transfer and facilitate second language (L2) reading subskill acquisition. However, the facilitative role of L1 morphological awareness is unclear in the literature investigating third language (L3) reading. This study explored if and how L1 morphological awareness and L2 reading subcomponent skills contribute jointly to L3 lexical inferencing in syllabic L1 Japanese-alphabetic L2 English-morphosyllabic L3 Chinese university learners. Sixty-seven students were recruited from novice-level, first-year Chinese classes from a Japanese university. Only 56 students completed 7 computerized or paper-and-pencil tasks, including L1 Japanese morphological awareness, L2 English morphological awareness, L2 English vocabulary knowledge, L2 English lexical inferencing, L3 Chinese morphological awareness, L3 Chinese vocabulary knowledge, and L3 Chinese lexical inferencing. They also completed a self-reported proficiency questionnaire survey. Correlational and regression analyses were conducted. The results suggested that there was only a significant association between L1 Japanese morphological awareness and L3 Chinese lexical inferencing, and there were no significant correlations between L2 English reading subcomponent skills and L3 Chinese lexical inferencing. Discussion is provided regarding the crosslinguistic influence of L1 morphological awareness in L3 reading development and the implications for L3 reading instruction.
Strategies for Positive Outcomes of Negative Mentoring Experiences at Workplace: Protege Perspectives
Authors: Gupta Amit
Published: December 2024

Mentoring literature is skewed towards positive experiences, and we have limited knowledge about negative mentoring experiences (NMEs) and the value such experiences bring to protégés. Hence, scholars have sought more research on the case of NMEs including their outcomes for protégés.

This qualitative study, conducted with 12 protégés in India, bridges the above gaps and makes significant contributions. First, it pioneers in informing us about the strategies adopted by protégés in handling NMEs and extends the literature by discovering relational outcomes from NMEs for protégés. Second, it suggests a new expanded model of mentoring, with dimensions beyond the classical phases of mentorship postulated by Kram (1985 , Mentoring at Work: Developmental Relationships in Organisational Life). Third, it extends the NME literature beyond the Western models and introduces Indian values in handling NMEs. This article suggests avenues for further research on the new models of mentoring and the applicability of Indian management principles in mentorship practice.
Findings From the Todurujo na Kadurok (Empowering Youth) HIV Self-Testing and Edutainment Comic Randomized Controlled Trial With Refugee Youth in a Humanitarian Setting in Uganda
Authors: Logie Carmen H. , Loutet Miranda G. , Okumu Moses , MacKenzie Frannie , Coelho Madelaine , Lukone Simon Odong , Kisubi Nelson , Malhi Aiman , Kyambadde Peter , Mbuagbaw Lawrence
Published: December 2024

Introduction

Humanitarian settings are underserved by HIV self-testing (HIV-ST).

Methods

We conducted a randomized controlled trial to evaluate the effectiveness of HIV-ST (Arm 1), HIV-ST alongside edutainment comics (Arm 2), and edutainment comics (Arm 3), compared with the standard of care (SOC), in increasing HIV testing with refugee youth aged 16–24 in the Bidi Bidi Refugee Settlement, Uganda. Intervention effects on HIV testing at 3-month follow-up (T2) were assessed using generalized estimating equation models alongside open-ended questions.

Results

Retention was 98% ( n = 117/120) at T2. In adjusted analyses compared with the SOC, HIV testing changes from baseline to T2 were highest in Arm 2 (adjusted odds ratio [aOR]: 8.46; 95% confidence interval [CI]: 2.87–24.97), followed by Arm 3 (aOR: 4.14; 95% CI: 1.58–10.87), with no significant differences in Arm 1.

Conclusion

HIV self-testing is feasible for refugee youth in Uganda and can be supplemented with edutainment comics to advance HIV prevention efforts.
Addressing Threats to Validity in Supervised Machine Learning: A Framework and Best Practices for Education Researchers
Authors: Anglin Kylie
Published: December 2024

Given the rapid adoption of machine learning methods by education researchers, and the growing acknowledgment of their inherent risks, there is an urgent need for tailored methodological guidance on how to improve and evaluate the validity of inferences drawn from these methods. Drawing on an integrative literature review and extending a well-known framework for theorizing validity in the social sciences, this article provides both an overview of threats to validity in supervised machine learning and plausible approaches for addressing such threats. It collates a list of current best practices, brings supervised learning challenges into a unified conceptual framework, and offers a straightforward reference guide on crucial validity considerations. Finally, it proposes a novel research protocol for researchers to use during project planning and for reviewers and scholars to use when evaluating the validity of supervised machine learning applications.
Civic Performance Outcomes and Market Morality: Using NAEP to Address the Civic Efficacy of Charter Schools
Authors: Johnson Chrystal S. , Gyimah Godwin , Lu Chenchen , Maeda Yukiko , Sdunzik Jennifer
Published: December 2024

Advancing civic learning and competence remains a fundamental objective in social studies education. Persistent civic performance outcome gaps, similar to other educational achievement disparities, are influenced by race, class, and other social constraints. Charter schools, known for their innovative structures and curricula, are often proposed as a solution for enhancing civic outcomes, particularly for Black and Hispanic youth. This study analyzes the National Assessment of Educational Progress (NAEP) 2014 and 2018 Civics Grade 8 results using a multilevel regression model to assess whether charter schools improve civic outcomes compared to traditional public and private schools. Key variables examined include race/ethnicity, school type, and teacher credentials. The findings reveal that charter schools perform comparably to traditional public schools in fostering civic knowledge and skills. Teacher time spent on civics instruction nor teacher credentials relate to student civic performance outcomes.
Medical Humanities in Resident Training: A Pilot Study of Specific Courses in a Large Comprehensive Hospital in China
Authors: Yang Xiaoyun , Guo Lifang , Chen Xiaoxiong , Zhang Ju , Xiang Qiang
Published: December 2024

Background

The importance of integrating humanities into medical education has been recognized. However, the medical humanities curriculum is usually lacking during standardized training for residents in China. This study aims to determine the feasibility and effectiveness of pilot-specific courses in medical humanities in standardized residency training.

Methods

We designed specific courses in medical humanities, composed of 3 courses: Identifying and Managing Common Psychological Disorders of Patients, Patient-Clinician Communication, and Medical Dispute Cases Analysis and Resolution. The courses were scheduled monthly throughout the one semester, and a total of 118 residents participated in the curriculum. Participants completed the evaluation containing ethic-legal knowledge and humanistic competencies related to course content before and after the curriculum.

Results

Most participant residents had a bachelor's degree (85.6%) and were in the first year of standardized residency training (61.0%). Their disciplinary backgrounds are diverse, encompassing 18 different clinical medical specialties. The residents’ average scores of postcourse self-assessments keep a steady increase in humanistic competencies compared with precourse average scores. All postcourse self-assessments showed significant improvement compared to precourse ( P < .05), particularly in influential communication skills and diagnostic associations of processing ability.

Conclusion

The specific courses in medical humanities are feasible and effective in teaching residents in China. The pre-post course evaluation indicates that this humanities-based curriculum significantly improved residents’ ethic-legal knowledge and humanistic competencies during standardized residency training.
Transforming the Medical School Admissions Process: Prioritizing Team-Based Skills and Patient-Centered Values
Authors: Hung Isaac Y. , Kain Alexandra , Vetter Thomas R.
Published: December 2024

This article examines the need for reform in medical school admissions to better align with the collaborative and patient-centered nature of contemporary healthcare. Traditional admissions processes prioritize academic excellence, often neglecting essential interpersonal and team-based skills. We advocate for several strategies to address this gap. Firstly, diversifying admissions committees to include healthcare professionals such as nurses and pharmacists, as well as patients can provide insights into candidates’ teamwork abilities. Secondly, incorporating group interviews and exercises can better assess applicants’ interpersonal skills and collaboration potential. We also propose leveraging the “Voice of the Consumer” (VOC) concept, using patient and family feedback to guide the selection of future physicians. This aligns with the shift toward shared decision-making in patient care. The paper underscores the importance of interprofessional education in addressing communication challenges within healthcare. By integrating these reforms early in medical education, we can cultivate physicians who excel in both evidence-based and patient-centered care. This perspective calls for a holistic evaluation process in medical school admissions, prioritizing patient-centered values and effective teamwork to develop healthcare professionals capable of navigating modern healthcare complexities.
Historical changes in words meaning “characters” in Chinese civilization
Authors: Takahito Yamada
Published: December 2024

Because each character roughly corresponds to one word, the written language of China is characterized as being composed of what are known as “logograms.” However, in Japanese, the symbols used to write written language daily are referred to by a two-character word, “文字 WenZi .” Sometimes they are also referred to by a one-character word, “字 Zi ,” or another two-character word, “漢字 HanZi.” The following questions remain: Why is this idea represented in a manner so removed from its core concept? And why do multiple representations of this same idea exist? To answer these questions, this article analyzes history to explore how words referring to “character symbol” changed over the course of Chinese civilization.
Wildlife as an affective multiplicity: Approaching Deleuzo–Guattarian pack-animals
Authors: Zariņa Anita , Vinogradovs Ivo , Svece Artis
Published: December 2024

Our study explores the ways, in which humans living and working in national parks, encounter, conceive and think about wild animals. The study is framed through the lens of Deleuzo–Guattarian concepts, notably wildlife as ‘affective multiplicities’ and ‘pack-animals’. Through ethnographic exploration in Latvian national parks, we uncover a spectrum of human responses to wildlife, from affectionate engagements to conflicts arising from conservation and livelihood practices. Our findings highlight the critical role of affective relationality and multiplicity in understanding human–wildlife coexistence. It suggests that Deleuzo–Guattarian pack-animal category offer a valuable framework for discussing coexistence, urging more research to deepen understanding of affective human–wildlife relations. This research underscores the importance of considering affective encounters and the multiplicity of wildlife in conservation and management practices, proposing a nuanced approach to human–wildlife coexistence that embraces ecological complexity and the myriad forms of life within nature.
Comparative Evaluation of L Plate Versus Z Plate for One Point Fixation in Zygomatic Fractures
Authors: Shah Nishita , Mahajan Amit D. , Rathi Parth , Shah Aditya , Daithankar Sharvari , Patil Gouri
Published: December 2024

The zygomatic bone’s lateral prominence and convexity make it the most important bone to provide aesthetic facial appearance and set the face width, but at the same time, this prominence and convexity make this bone more susceptible to injury. Among facial injuries, zygomatic-complex fractures or tripod fractures are the second most common fractures after nasal fractures. This study has performed a comparative assessment of fixation of zygomatic buttress by L and Z shaped plate. Fourteen zygomatic-complex fracture patients were selected and split into two groups, further divided into two subgroups (A, B). Group A patients were treated with a titanium Z shaped plate and Group B with L shape plate. One point fixation was performed and was observed in terms of stability, aesthetics and prevention of vertical or horizontal axis of rotation of the fracture segment. Z-shaped plates showed some advantage over L-shaped plates so there use can be preferred in complex fractures where comminuted bone pieces are scattered.
Tele-Mindfulness Program for Mental Health in Previously Hospitalized COVID-19 Patients: A quasi-experimental study
Authors: Milani Giada , Zerbinati Luigi , Grassi Luigi , Fregna Giulia , Schincaglia Nicola , Baroni Andrea , Lamberti Nicola , Manfredini Fabio , Straudi Sofia
Published: December 2024

Background:

Nearly half of subjects after COVID-19 still experience symptoms after 12 weeks, as described in the Post-Covid Syndrome (PCS). Other than the physical alterations perceived, mental health disorders have been frequently reported. Mindfulness-Based Interventions (MBIs) showed beneficial effects on psychological well-being in patients with respiratory dysfunctions, but they have been rarely tested in severe COVID-19 survivors.

Objective:

In a quasi-experimental study, test the clinical and psychological effects of a 12-week Tele–MBI in previously hospitalized COVID-19 patients and analyze the feasibility of the intervention.

Methods:

Subjects earlier hospitalized due to COVID-19 were enrolled 12 weeks after the infection onset, they were assigned to the intervention group (TG) or to the control one (n-TG). Subjects enrolled in the TG attended a 12-week home-based T-MBI and patients of both groups received multimodal rehabilitation interventions according to their own therapeutic needs. Mental health (anxiety, depression, post-traumatic stress disorder (PTSD) symptoms, sleep quality, self-efficacy, and resilience) and quality of life were detected before and after treatment. The feasibility of the T-MBI applied was also investigated.

Results:

A total of 88 subjects were included (44 in the TG and 44 in the n-TG; 63.6% males, mean age 64.4 ± 10.6). Most characteristics were similar between groups at the baseline; TG patients showed greater improvements in different psychological metrics (anxiety, depression, PTSD, resilience, and self-efficacy) compared to n-TG while no differences were found for perceived quality of life. T-MBI was well-accepted by patients.

Conclusion:

Tele-Mindfulness program seems effective in reducing anxiety, depression, and post-traumatic stress disorder symptoms and increasing resilience and self-efficacy in subjects who required hospitalization due to COVID-19.
The Impact of the Berlin Airport Project on the Business Performance of Its Owner Company
Authors: Gemünden Hans Georg , Mertens Susanne , Krehl Harald , Wolf Karl-Heinz , Kock Alexander
Published: December 2024

We assess the impact of the Airport Project Berlin Brandenburg (BER) on the business performance of its owner company, using financial accounting data from Flughafengesellschaft Berlin Brandenburg m.b.H. (FBB) and eight control cases for 2005 through 2023. We analyze how the BER project influenced FBB’s revenues, cost, profitability, equity, and liabilities. The total value consumed by the BER project amounts to €11.915 billion. A forecast of business prospects until 2030 indicates enduring problems. We contribute to the literature by empirically quantifying the impact of poor governance and decision-making failures on project stakeholders. Further, our study shows the usefulness of publicly available financial data for analyzing megaprojects.
Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease
Authors: Kambara Yui , Fujiwara Hideaki , Yamamoto Akira , Gotoh Kazuyoshi , Tsuji Shuma , Kunihiro Mari , Oyama Tadashi , Terao Toshiki , Sato Ayame , Tanaka Takehiro , Peltier Daniel , Seike Keisuke , Nishimori Hisakazu , Asada Noboru , Ennishi Daisuke , Fujii Keiko , Fujii Nobuharu , Matsuoka Ken-ichi , Soga Yoshihiko , Reddy Pavan , Maeda Yoshinobu
Published: December 2024

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in graft-versus-host disease (GVHD) pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients after hematopoietic cell transplantation (HCT) associated with increased chronic GVHD (cGVHD), even in patients receiving posttransplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut, with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes both before and after transplantation activated antigen-presenting cells, thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increase in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.
Nbeal2 Knockout Mice Are Not Protected Against Hypoxia-Induced Pulmonary Vascular Remodeling and Pulmonary Hypertension
Authors: Posey Janelle , Jordan Mariah , Lewis Caitlin V , Sul Christina , Dobrinskikh Evgenia , Swindle Delaney , Denorme Frederik , Irwin David , Di Paola Jorge , Stenmark Kurt , Nozik Eva , Delaney Cassidy
Published: December 2024

Inflammation drives the initiation and progression of pulmonary hypertension (PH). Platelets, increasingly recognized as immune cells, are activated and increased in the lungs of patients with PH. Platelet activation leads to the release of α-granule chemokines, many of which are implicated in PH. We hypothesized that hypoxia-induced secretion of platelet α-granule stored proteins and PH would be prevented in Nbeal2 -/-, α-granule deficient mice. WT and Nbeal2 -/- mice were maintained in normoxia or exposed to 10% hypobaric hypoxia for 3, 14, 21, or 35 days. We observed macrothrombocytopenia, increased circulating neutrophils and monocytes, and increased lung interstitial macrophages in Nbeal2 -/- mice at baseline. Hypoxia-induced platelet activation was attenuated, and hypoxia-induced increase in lung PF4 and platelets was delayed in Nbeal2 -/- mice compared to WT mice. Finally, although pulmonary vascular remodeling (PVR) and PH were attenuated at day 21, Nbeal2 -/- mice were not protected against hypoxia-induced PVR and PH at day 35. While this mutation also impacted circulating monocytes, neutrophils, and lung IMs, all of which are critical in the development of experimental PH, we gained further support for the role of platelets and α-granule proteins, such as PF4, in PH progression and pathogenesis and made several observations that expand our understanding of α-granule deficient mice in chronic hypoxia.
Cost-Effectiveness of Voncento Prophylaxis Versus On-Demand Treatment in von Willebrand Disease in the United Kingdom
Authors: Wilson Michele R , Castaman Giancarlo , Thomas William , Millar Carolyn M , Escolar Gines , Miesbach Wolfgang A. , McDade Cheryl L , Tomic Radovan , Yan Songkai
Published: December 2024

von Willebrand factor (VWF) concentrates may be required for on-demand treatment (ODT) or long-term prophylaxis (LTP) in von Willebrand disease (VWD). This study assesses the cost-effectiveness of LTP compared with ODT in VWD patients treated with Voncento in the United Kingdom (UK). A Markov structure was developed to estimate quality-adjusted life years (QALYs) and costs of VWD treatment over a lifetime horizon. Treatment options included ODT or LTP. For both options, we assumed plasma-derived VWF/factor VIII (pdVWF/FVIII) 2.4:1 (Voncento) as the VWF product used. Clinical parameters were obtained from published literature and Voncento's summary characteristics. Utility weights were obtained from published literature. Costs (in 2021 GBP) and outcomes were discounted annually by 3.5%. Sensitivity analyses were conducted. Three baseline annual bleed rate (ABR) scenarios (11, 26.5 and 39.6) were considered. In the base-case analyses, Voncento LTP resulted in lower costs (-£831,206) and greater QALY (6.14) versus ODT. Savings were primarily due to reductions in product use required (-£529,571) and bleed-related other medical costs (-£301,352). Compared with ODT, LTP also resulted in 322.52 fewer major bleeds and 515.68 fewer minor bleeds over a lifetime horizon. Probabilistic sensitivity analyses showed dominance in 96.12% of simulations and cost-effectiveness in 97.68% of simulations. For the 39.6 ABR scenario, LTP was also dominant compared with ODT. Results suggest that Voncento LTP is more effective and cost-saving compared with ODT in the UK for VWD patients with higher ABR. Prophylaxis for patients with frequent bleeds is likely to be a cost-saving and effective strategy.
Digital twins for chronic lung diseases
Authors: Gonsard Apolline , Genet Martin , Drummond David
Published: December 2024

Digital twins have recently emerged in healthcare. They combine advances in cyber–physical systems, modelling and computation techniques, and enable a bidirectional flow of information between the physical and virtual entities. In respiratory medicine, progress in connected devices and artificial intelligence make it technically possible to obtain digital twins that allow real-time visualisation of a patient's respiratory health. Advances in respiratory system modelling also enable the development of digital twins that could be used to predict the effectiveness of different therapeutic approaches for a patient. For researchers, digital twins could lead to a better understanding of the gene–environment–time interactions involved in the development of chronic respiratory diseases. For clinicians and patients, they could facilitate personalised and timely medicine, by enabling therapeutic adaptations specific to each patient and early detection of disease progression. The objective of this review is to allow the reader to explore the concept of digital twins, their feasibility in respiratory medicine, their potential benefits and the challenges to their implementation.
The epithelial era of asthma research: knowledge gaps and future direction for patient care
Authors: Brightling Christopher E. , Marone Gianni , Aegerter Helena , Chanez Pascal , Heffler Enrico , Pavord Ian D. , Rabe Klaus F. , Uller Lena , Dorscheid Del ,   the Epithelial Science Expert Group
Published: December 2024

The Epithelial Science Expert Group convened on 18–19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated. The role of the bronchial epithelial cells in lower airway diseases beyond severe asthma was considered, as well as the role of the epithelium in upper airway diseases such as chronic rhinosinusitis. The biology and application of biomarkers in patient care was also discussed. The Epithelial Science Expert Group also explored future research needs by identifying the current knowledge and research gaps in asthma management and ranking them by priority. It was identified that there is a need to define and support early assessment of asthma to characterise patients at high risk of severe asthma. Furthermore, a better understanding of asthma progression is required. The development of new treatments and diagnostic tests as well as the identification of new biomarkers will also be required to address the current unmet needs. Finally, an increased understanding of epithelial dysfunction will determine if we can alter disease progression and achieve clinical remission.
Maternal high-fat diet orchestrates offspring hepatic cholesterol metabolism via MEF2A hypermethylation-mediated CYP7A1 suppression
Authors: Zhang Ling , Zou Wenyu , Zhang Shixuan , Wu Honghua , Gao Ying , Zhang Junqing , Zheng Jia
Published: December 2024

Background

Maternal overnutrition, prevalent among women of childbearing age, significantly impacts offspring health throughout their lifetime. While DNA methylation of metabolic-related genes mediates the transmission of detrimental effects from maternal high-fat diet (HFD), its role in programming hepatic cholesterol metabolism in offspring, particularly during weaning, remains elusive.

Methods

Female C57BL/6 J mice were administered a HFD or control diet, before and during, gestation and lactation. Hepatic cholesterol metabolism genes in the liver of offspring were evaluated in terms of their expression. The potential regulator of cholesterol metabolism in the offspring’s liver was identified, and the function of the targeted transcription factor was evaluated through in vitro experiments. The methylation level of the target transcription factor was assessed using the MassARRAY EpiTYPER platform. To determine whether transcription factor expression is influenced by DNA methylation, in vitro experiments were performed using 5-azacitidine and Lucia luciferase activity assays.

Results

Here, we demonstrate that maternal HFD results in higher body weight and hypercholesterolemia in the offspring as early as weaning age. Maternal HFD feeding exacerbates hepatic cholesterol accumulation in offspring primarily by inhibiting cholesterol elimination to bile acids, with a significant decrease of hepatic cholesterol 7α-hydroxylase (CYP7A1). RNA-seq analysis identified myocyte enhancer factor 2A (MEF2A) as a key transcription factor in the offspring liver, which was significantly downregulated in offspring of HFD-fed dams. MEF2A knockdown led to CYP7A1 downregulation and lipid accumulation in HepG2 cells, while MEF2A overexpression reversed this effect. Dual luciferase reporter assays confirmed direct modulation of CYP7A1 transcription by MEF2A. Furthermore, the reduced MEF2A expression was attributed to DNA hypermethylation in the Mef2a promoter region. This epigenetic modification manifested as early as the fetal stage.

Conclusions

This study provides novel insights into how maternal HFD orchestrates hepatic cholesterol metabolism via MEF2A hypermethylation-mediated CYP7A1 suppression in offspring at weaning.
Opportunities for nanomaterials in more sustainable aviation
Authors: Pendashteh Afshin , Mikhalchan Anastasiia , Blanco Varela Tamara , Vilatela Juan J.
Published: December 2024

New materials for electrical conductors, energy storage, thermal management, and structural elements are required for increased electrification and non-fossil fuel use in transport. Appropriately assembled as macrostructures, nanomaterials can fill these gaps. Here, we critically review the materials science challenges to bridge the scale between the nanomaterials and the large-area components required for applications. We introduce a helpful classification based on three main macroscopic formats (fillers in a matrix, random sheets or aligned fibres) of high-aspect ratio nanoparticles, and the corresponding range of bulk properties from the commodity polymer to the high-performance fibre range. We review progress over two decades on macroscopic solids of nanomaterials (CNTs, graphene, nanowires, etc.), providing a framework to rationalise the transfer of their molecular-scale properties to the scale of engineering components and discussing strategies that overcome the envelope of current aerospace materials. Macroscopic materials in the form of organised networks of high aspect ratio nanomaterials have higher energy density than regular electrodes, superior mechanical properties to the best carbon fibres, and electrical and thermal conductivity above metals. Discussion on extended electrical properties focuses on nanocarbon-based materials (e.g., doped or metal-hybridised) as power or protective conductors and on conductive nanoinks for integrated conductors. Nanocomposite electrodes are enablers of hybrid/electric propulsion by eliminating electrical transport limitations, stabilising emerging high energy density battery electrodes, through high-power pseudocapacitive nanostructured networks, or downsizing Pt-free catalysts in flying fuel cells. Thermal management required in electrified aircraft calls for nanofluids and loop heat pipes of nanoporous conductors. Semi-industrial interlaminar reinforcement using nanomaterials addresses present structural components. Estimated improvements for mid-range aircraft include > 1 tonne weight reduction, eliminating hundreds of CO2 tonnes released per year and supporting hybrid/electric propulsion by 2035.
Non-extractable residues (NER) in persistence assessment: effect on the degradation half-life of chemicals
Authors: Jespersen Cindy , Trapp Stefan , Kästner Matthias
Published: December 2024

The ECHA guidance on persistence (P) assessment has been updated with respect to non-extractable residues (NER). Unless further characterized, total NER shall be considered as non-degraded parent compound. We investigated how different NER fractions affect degradation half-lives (DegT50) of chemicals and the P assessment. Total NER consist of the fractions sorbed/sequestered (NER I), covalently bound (NER II), and bioNER (incorporated into the biomass, NER III). NER I pose a risk due to potential release, NER II have much lower release potential, and bioNER do not have any. NER I and NER II are considered as xenoNER. Data from 46 degradation tests with 24 substances were analyzed to find DegT50 for four scenarios: (i) extractable parent compound, (ii) parent plus total NER, (iii) parent plus xenoNER, and (iv) parent plus NER I. The microbial turnover to biomass (MTB) model was applied to calculate bioNER, and then xenoNER were calculated as total NER minus bioNER. The half-lives were determined by the fit program CAKE, using single first-order kinetics (SFO) for all fits. We found increasing degradation half-lives for the scenarios: extractable parent only < parent + NER I < parent + xenoNER < parent + total NER. A third of all chemicals show half-lives above the persistence criterion (120 days in OECD 307 and 308, and 40 days in OECD 309) for scenario i, and two thirds with scenario ii and, therefore, would be classified as ‘persistent’. For two compounds, the subtraction of bioNER led to a change to ‘not persistent’. The inclusion of NER in the P assessment (ECHA 2017, 2023) will thus have significant effects on the DegT50 of compounds and the persistence assessment. Experimental quantification of NER I (scenario iv) significantly reduces half-lives, in comparison to total NER (scenario ii). The results are closer to half-lives for parent only (scenario i) and give the lowest acceptable DegT50 below the vP criteria under the latest guidance. In addition, refining the DegT50 based on modelled bioNER can provide a more realistic option for persistence assessment, without laborious and costly analyses for NER I determination, when considered in the regulatory assessment of persistence. Moreover, bioNER can also be calculated for existing test data.
Wide-field fluorescein angiography findings in active anterior scleritis
Authors: Romo-Aguas Juan C. , Zavaleta-Mercado Miguel , Cheja-Kalb Rashel , Hubbe-Tena Claudia , Concha-del-Río Luz Elena
Published: December 2024

Objective

Describe the proportion of patients with wide-field fluorescein angiographic (WFFA) findings in patients with active anterior scleritis.

Methods

An observational, descriptive, cross-sectional study of the WFFA findings of patients with active anterior scleritis including nodular, diffuse, or necrotizing involvement was performed. Studies were performed with the Heidelberg Spectralis module (102º). Images were saved and assessed by two masked co-authors.

Results

Seventy-nine eyes from 39 patients, 31 (79%) females with a mean age of 50.5 years ± 13.98. Mean best-corrected visual acuity (BCVA) of 0.1343 ± 0.2475 logMar or 20/27. WFFA findings were observed in 39.58% of eyes with active scleritis and in 16.66% of eyes without scleritis. Systemic association was present at 50%, with ANCA-associated vasculitis being the most prevalent. WFFA findings were more frequent in cases of anterior diffuse scleritis and correlated with scleritis severity when central and peripheral leakage (p < 0.022) and cystoid macular edema (p < 0.013) were present.

Conclusions

Almost 40% of eyes with anterior scleritis have WFFA findings of vascular leakage and 16% of eyes without scleritis. Retinal vascular leakage needs to be explored as a sign of local and/or systemic activity in patients with anterior scleritis and may have implications for disease severity and management.
Primary ciliary dyskinesia as a rare cause of male infertility: case report and literature overview
Authors: Novák Jan , Horáková Lenka , Puchmajerová Alena , Vik Viktor , Krátká Zuzana , Thon Vojtěch
Published: December 2024

Background

Primary ciliary dyskinesia (PCD) is a heterogenous disease caused by mutations of miscellaneous genes which physiologically play an important role in proper structure and/or function of various cellular cilia including sperm flagella. Besides male infertility, the typical phenotypes, based on decreased mucociliary clearance, are lifelong respiratory issues, i.e., chronic bronchitis leading to bronchiectasis, chronic rhinosinusitis, and chronic otitis media. Moreover, since motile cilia are important during embryological development in the sense of direction of gut rotation, 50% of affected individuals develop situs inversus – so-called Kartagener’s syndrome.

Case presentation

We present two cases of PCD as a rare cause of male infertility.

Conclusions

Primary ciliary dyskinesia should be suspected in infertile males having (sub)normal sperm concentration values with persistent zero motility together with patient’s and/or family history of respiratory symptoms like bronchiectasis, chronic cough, rhinitis, recurrent sinusitis, and otitis media. Due to more than 50 identified mutations until now, the causal mechanism of male infertility is miscellaneous and not in all cases known in detail. Besides impaired sperm motility, other mechanisms significantly decreasing efficacy of assisted reproduction techniques play a pivotal role. Thus, proper diagnostic work-up including, among others, sperm DNA fragmentation, is mandatory to avoid ineffective treatment burden.
Robustness assessment of regressions using cluster analysis typologies: a bootstrap procedure with application in state sequence analysis
Authors: Roth Leonard , Studer Matthias , Zuercher Emilie , Peytremann-Bridevaux Isabelle
Published: December 2024

Background

In standard Sequence Analysis, similar trajectories are clustered together to create a typology of trajectories, which is then often used to evaluate the association between sequence patterns and covariates inside regression models. The sampling uncertainty, which affects both the derivation of the typology and the associated regressions, is typically ignored in this analysis, an oversight that may lead to wrong statistical conclusions. We propose utilising sampling variation to derive new estimates that further inform on the association of interest.

Methods

We introduce a novel procedure to assess the robustness of regression results obtained from the standard analysis. Bootstrap samples are drawn from the data, and for each bootstrap, a new typology replicating the original one is constructed, followed by the estimation of the corresponding regression models. The bootstrap estimates are then combined using a multilevel modelling framework that mimics a meta-analysis. The fitted values from this multilevel model allow to account for the sampling uncertainty in the inferential analysis. We illustrate the methodology by applying it to the study of healthcare utilisation trajectories in a Swiss cohort of diabetic patients.

Results

The procedure provides robust estimates for an association of interest, along with 95% prediction intervals, representing the range of expected values if the clustering and associated regressions were performed on a new sample from the same underlying distribution. It also identifies central and borderline trajectories within each cluster. Regarding the illustrative application, while there was evidence of an association between regular lipid testing and subsequent healthcare utilisation patterns in the original analysis, this is not supported in the robustness assessment.

Conclusions

Investigating the relationship between trajectory patterns and covariates is of interest in many situations. However, it is a challenging task with potential pitfalls. Our Robustness Assessment of Regression using Cluster Analysis Typologies (RARCAT) may assist in ensuring the robustness of such association studies. The method is applicable wherever clustering is combined with regression analysis, so its relevance goes beyond State Sequence Analysis.
Replacing serum with dried blood microsampling for pharmacokinetics, viral neutralisation and immunogenicity bioanalysis supporting future paediatric development of RSM01, a candidate respiratory syncytial virus neutralising monoclonal antibody
Authors: White Joleen T. , Terstappen Jonne , Levi Micha , Radivojevic Andrijana , Noble Robert , Anderson Aparna B. , Wise-Blackman Gwendolyn , Dunne Michael W.
Published: December 2024

Background

Virus neutralising antibodies in serum are considered key correlates of protection for vaccines and monoclonal antibodies against respiratory syncytial virus (RSV). RSM01 is a novel, highly-potent, half-life-extended and fully-human monoclonal antibody candidate targeting the RSV prefusion F protein. Currently in Phase 1 development, RSM01 is primarily being developed to potentially provide an effective and affordable RSV prevention strategy in low- and middle-income countries. To evaluate the ability of dried blood collection to generate data sets and conclusions comparable to serum collection, we compared pharmacokinetics (PK) of RSM01, immunogenicity, and virus neutralisation for dried capillary blood samples with serum samples.

Methods

RSM01 PK, anti-drug antibodies (ADA), and RSV-neutralising antibodies from the Phase 1 trial were analyzed and compared between matched serum and dried blood samples. Deming regression analysis was performed using baseline-corrected values to evaluate correlation between measurements in liquid serum versus dried blood.

Results

The analysis showed good correlation (R2 > 0.95) between individual RSM01 concentrations measured in both serum and capillary blood. Analysis of RSM01 PK parameters in capillary blood yielded equivalent conclusions as from serum. A strong correlation (R2 > 0.95) was observed between RSV neutralising activity measured in both serum and capillary blood. In addition, RSV neutralising activity was correlated with RSM01 concentrations in both serum and capillary blood data sets. For ADA, individual sample results had 96% agreement (290/302) and overall participant ADA status had 93% agreement (52/56).

Conclusions

Both RSM01 concentrations and RSV neutralising activity showed a strong correlation between the serum and blood measurements. ADA measurements also had an agreement of > 90% for individual samples and overall participant status. Our results demonstrate that dried blood is a suitable specimen type for collection and evaluation in the RSM01 clinical development program and shows promise as a useful approach to reduce patient burden in clinical trials, particularly for infants in low- and middle-income countries.

Trial Registration

Clinicaltrials.gov NCT05118386 November 12, 2021.
DKI and 1H-MRS in angiogenesis evaluation of soft tissue sarcomas: a prospective clinical study based on MRI-pathology control method
Authors: Han Wubing , Xin Cheng , Wang Zeguo , Wang Fei , Cheng Yu , Yang Xingrong , Zhou Yangyun , Liu Juntong , Yu Wanjiang , Wang Shaowu
Published: December 2024

Background

The vascular endothelial growth factor (VEGF) and microvessel density (MVD) have been widely employed as angiogenesis indicators in the diagnosis and treatment of soft tissue sarcomas. While diffusion kurtosis imaging (DKI) and proton magnetic resonance spectroscopy (1H-MRS) imaging hold potential in assessing angiogenesis in other tumors, their reliability in correlating with angiogenesis in soft tissue sarcomas remains uncertain, contingent upon accurately acquiring the region of interest (ROI).

Methods

23 patients with soft tissue sarcomas (STSs) confirmed by pathology were selected, underwent DKI and 1H-MRS at 3.0T MRI. The DKI parameters mean diffusivity (MD), mean kurtosis (MK), kurtosis anisotropy (KA), and 1H-MRS parameters choline (Cho), lipid/lactate (LL) were measured by two radiologists. Two pathologists obtained pathological slices using a new sampling method called MRI-pathology control and evaluated VEGF and MVD in the selected regions. Correlations between MRI parameters and angiogenesis markers were assessed by Person or Spearman tests.

Results

The DKI parameters MD and KA, and the 1H-MRS parameters Cho and LL, have varying degrees of correlation with the expression levels of VEGF and MVD. Among them, Cho exhibits the strongest correlation (r = 0.875, P < 0.001; r = 0.807, P < 0.001).

Conclusion

Based on this preliminary clinical studies, DKI and 1H-MRS parameters are correlated with angiogenesis markers obtained through the “MRI-pathology control” method.