bluuebunny/crossref_metadata_2025 huggingface dataset:
Fieldwork in Zineography
Authors: LeFevre Annie
Published: September 2024

What is a zine? This article—itself a zine—is a meta-analysis of the history of the zine, its evolution, and its ability as a medium to create overlap between social change and artistic and visual production. Through essays, interviews, and illustrations, this article explores zine construction and content, and the legacies of the zine movement and its continuing influence on counterculture and social change. Lastly, this article delves into the continuing creation, circulation and relevance of the zine in the internet age of digitization and social media, and how the crossover in culture between the digital zine and the paper zine translates to both zine creators and their audiences.
Comprehensive examination of intellectual property objects: problematic issues in the context of science and technology development
Authors: Starchenko Olena
Published: September 2024

The article is devoted to the study of a number of problematic aspects related tocomprehensive examinations of intellectual property objects in the context of scienceand technology development.It is established that intellectual property objects created with the help of artificial intelligenceare characterized by a complex legal nature. Thus, a particular work may be entirelygenerated by an artificial intelligence system. In this regard, there is a need to appointcomprehensive examinations for their study in the course of consideration of themerits of cases on the protection of intellectual property rights, within which it will be necessaryto apply both knowledge in the field of intellectual property and technical knowledgerelated to the peculiarities of creating these works.The author identifies the need to adapt existing methods to new intellectual propertyobjects, as well as to develop modern research methods taking into account the specifics ofthe legal nature of such objects. Given the complex legal nature of intellectual property objectscreated with the use of artificial intelligence, the author proposes to appoint a comprehensiveexamination with the involvement of technical specialists.It is noted that a comprehensive examination of intellectual property involves a multi-levelstudy, which, however, forms an interdependent logical sequence of activities of individual experts.In this case, the key is the impossibility of establishing the properties of a particular intellectualproperty object without conducting a study by an expert of another specialization.It is noted that when an intellectual property object has a dualistic legal nature, thereis a need to integrate various areas of knowledge in the field of intellectual property. Despitethe fact that this knowledge relates to the field of intellectual property, such a studywill be complex in its procedural nature.It is summarized that various subtypes of intellectual property expertise may require technicalassistance to solve the tasks assigned to the expert, especially in the context of the developmentof digital technologies and their use for the creation of new intellectual property objects.
Plagiarism and piracy as types of copyright infringement in the creative industries
Authors: Fedorova Nadiya
Published: September 2024

The article examines the concept of violations in the creative industries. It analyses thetypes of infringements that are most common in Ukraine. The main focus is on the analysis ofthe concepts of plagiarism and piracy in Ukrainian legislation and some EU countries.Accordingly, the Laws of Poland and Germany on Copyright and Related Rights do notcontain a definition of plagiarism. Since there is no legal definition of plagiarism, and the phenomenonof plagiarism is quite widespread, the only option for legislative regulation is judicialpractice. In Germany, for example, the concept of plagiarism as an infringement of copyrightapplies not only to literary works but also to works of other art forms. Therefore, byanalogy, it is concluded that plagiarism as an infringement of copyright and/or related rightsin the creative industries is committed not only in the literary or scientific field, but is alsopossible in other art forms, in particular: music, art, choreography, jewellery and costumejewellery, architecture and advertising.The situation is similar with regard to the definition of piracy. In Poland, piracy is usedmainly as a colloquial term. However, it is one of the most common crimes committed onthe Internet. In the German scientific literature, there are different interpretations of theconcept of piracy. Under the German Copyright and Related Rights Act, an author mayprohibit (revoke) the unauthorised posting of his or her work on the Internet. The SwissFederal Law on Copyright and Related Rights provides for a similar provision.However, the purpose of piracy differs from the purpose of plagiarism. In the case ofpiracy, the infringer seeks to gain material benefit and does not intend to create any identificationbetween him or her and the unlawfully used object (pirated film, computer programor database, etc.). In the case of plagiarism, the opposite is true. The infringer wantsconsumers to identify it with the misused intellectual property.Therefore, it is concluded that there is no single, comprehensive and generally accepteddefinition of plagiarism and piracy. The statutory definition of plagiarism and piracy enshrinedin part 2 of Article 53 of the Law differs significantly from the European approachesconsidered.
Search for approaches to the use of artificial intelligence in patent examination
Authors: Mykhailenko Mykhailo
Published: September 2024

Inventions are the key foundation of innovation. When a new technology is introduced to themarket, society benefits both directly, as it enables us to do things that were previously impossible,and indirectly, in terms of the economic opportunities that arise, such as business developmentand employment. Currently, the only way to obtain proper legal protection for an inventionis through patent registration. Delays in obtaining a patent can significantly hinder thebusiness and innovation processes of any country. Given the increasing number of patent applicationsin Ukraine and globally, it is important to study methods for optimizing the patent examinationprocess. This article addresses the issue of the steadily increasing number of patentapplications by exploring the use of artificial intelligence (AI) technologies in the patent examinationprocess. It examines the relevance, methods, and outcomes of using AI technologies ineconomically developed countries, with particular attention to the cooperation between the NationalInstitute of Industrial Property of Brazil and the American Chemical Society.On September 4, 2020, these organizations signed a Technical Cooperation Agreementaimed at testing and optimizing patent examination processes using AI technologies. This cooperationhas demonstrated convincingly positive results in optimizing patent examinationprocesses with AI. The article also analyses the content of Ukraine's «Rules for Examinationof Applications for Invention and Utility Model Applications» and identifies the stages atwhich the use of AI technologies is possible and appropriate, considering the importance ofprocess optimization and speeding up patent application examinations. As a result of thestudy, it is recommended that the national patent office begin developing and implementingAI technologies in the patent application examination process. This will help accelerate theexamination of patent applications and, consequently, stimulate innovation in Ukraine.
Law of Ukraine on Palliative Care: to be or not to be
Authors: Senyuta Iryna
Published: September 2024

The author has conducted an analysis of the laws on palliative care acting in foreign countries:(Italy, Spain, Germany, Slovakia, France), determined their peculiarities, which areconcordant for a national law, the necessity of which has grown in Ukraine. In particular, thegiven peculiarities include: 1) a value-oriented focus of the laws (quality of life, informed consentetc.); 2) the litmus paper — the confirmation of human dignity, anchored in the internationalstandards; 3) the struggle for life «in the boundaries»; 4) an appropriate pain relief as akey algorithm of medical assistance; 5) the foundations of the law constitute a conceptual-categoricalapparatus.The author has formed a mosaic of the strategy of a special law through the prism of a preambula,the definitive-categorial apparatus and the principles, as well as the author's view ofthe content of the act. The author hallmarked that the structure of the domestic palliativecare law should contain, inter alia: the legal status of palliative patients, the legal representativesof palliative patients, the members of their families, as well as the legal status of medicalemployees, which fulfill the provision of palliative care. The author outlined, that amongthe rights of palliative patients, the following possibilities should be concordant to be included:the refusal from medical interventions, an advance directive, the respect to human dignity,obtaining medical information and the refusal of obtaining it, right to autonomy and voluntaryinformed consent to a medical intervention. The author underlined that the palliativecare law should contain a distinct chapter, dedicated to the peculiarities of providing palliativecare to children, as specific subjects of receiving such care. The author focused the attentionto the fact that distinct chapters would have to regulate the legal status of palliative careproviders and their interaction, and contain the division of powers, since the interdisciplinarityof the sphere would combine two institutions of the Ministry of Health of Ukraine and theMinistry of Social Policy of Ukraine, various institutions and establishments.The author justified the necessity of determining the key definition of the research sphereprecisely as palliative care, without the hospice one.
Temporal restriction of biomedical research on human embryos created in vitro
Authors: Shyshko Ihor
Published: September 2024

The article is devoted to the study of temporal limitation of biomedical research ofhuman embryos created in vitro. The author has investigated various models of settingtemporal restrictions, in particular, the most widespread in the world model of 14 daystemporal limitation. The article examines the validity of various models of temporal limitations(in particular, models that provide for temporal limitation of 7 days, 14 days, 28days) and their ability to maintain a balance between protection of a human embryo, interestsof a human, society, state, and science.Having studied the practice of establishing temporal limitations in various countries,including Switzerland, the Czech Republic, the United Kingdom, and the Netherlands, theauthor reached a conclusion. The research focused on issues related to the status of thehuman embryo and the scientific potential of studying embryos created in vitro more than14 days since their creation. The author concluded that the existing models, particularlythe 14-day rule, do not maintain a balance of interests. Therefore, it is necessary to establisha model that provides for multiple temporal limitations. The author has proposed atwo-level model of temporal limitation. The first level provides for the possibility of cultivatinga human embryo created in vitro up to the 14th day of its development from themoment of creation and carrying out biomedical research of such embryos up to the 14thday of their development from the moment of creation. The second level, which in exceptionalcases and in the presence of stricter conditions provides for the possibility of cultivatinga human embryo created in vitro up to the 28th day of its development from themoment of creation and carrying out biomedical research of such embryos up to the 28thday of their development from the moment of creation. Such a model is a compromise andwill ensure the balance between proper protection of a human embryo and interests of aperson, society, state, and science.
Eco-innovación en cooperativas y empresas de capital industriales: un análisis comparativo
Authors: Basterretxea Imanol , Fernández-Sainz Ana , Gutiérrez-Goiria Jorge , Santos-Larrazabal Josu
Published: September 2024

El estudio examina la ecoinnovación en cooperativas y empresas de capital, analizando sus factores impulsores. Tras evaluar respuestas de 718 establecimientos industriales vascos, incluyendo 57 cooperativas, se concluye que los principios cooperativos no aseguran el éxito en ecoinnovación. La voluntariedad de la ecoinnovación no es más relevante en las cooperativas, siendo las presiones regulatorias y fuerzas del mercado los principales impulsores. A pesar de enfrentar mayores limitaciones, las cooperativas logran beneficios medioambientales similares. Los resultados refuerzan la importancia de las políticas públicas para una efectiva transición ecológica. Así mismo, instan a reevaluar con evidencia empírica algunos postulados de la literatura de la economía social.
Una A ‘Transformation Compass’ for Social and Solidarity Economy Initiatives in their Transition towards Postgrowth
Authors: Atutxa Ordeñana Ekhi , Damborenea Iglesias Mario , Mendizabal Leiñena Xabier
Published: September 2024

The current climate crisis and global inequalities trigger intense debates on the need of achieving socioecological transitions towards environmentally and socially just scenarios. In this context, the Social and Solidarity Economy and Postgrowth paradigms could play a major role in leading these transitions. The strong convergence between their principles opens the door for this article’s main contribution: a ‘Transformation Compass’. This tool allows Social and Solidarity Economy initiatives to approach a post-growth economy through a well-defined matrix, which incorporates Hinton’s (2021) characterization of postgrowth businesses. In addition, this Compass helps to assess the factors and dimensions that affect different initiatives during this process.
Aportaciones de la biomimética a la Economía Solidaria: integrar soluciones provenientes de la naturaleza
Authors: Chavarri Reinalina , Morales Sánchez Rafael
Published: September 2024

La necesidad de cambiar el paradigma socioeconómico actual requiere plantearse qué sistemas están en condiciones de facilitar la transición hacia una economía más sostenible medioambientalmente y equitativa socialmente. El objetivo de este artículo teórico es evaluar la capacidad de la Economía Solidaria para conducir hacia una transición socioecológica justa. La metodología utiliza es aplicar la caracterización que hace la biomimética de los sistemas maduros. Las conclusiones que se extraen del análisis son que los principios que rigen la Economía Solidaria la convierten en un modelo de referencia para generar estructuras, procesos y organizaciones sostenibles, inclusivas, equitativas y de calidad, al servicio de las necesidades de las personas y vinculadas al territorio.
The management of exercise-induced anaphylaxis in a Chinese child with biologics: a case report
Authors: Jiang Nannan , Xiang Li , Huang Huijie , Zhang Xudong
Published: September 2024

Exercise-induced anaphylaxis (EIA) is a rare and potentially life-threatening disorder. In difficult to control and refractory cases of EIA, biologics such as omalizumab and dupilumab have shown promise, with documented successful outcomes. Here, we present a case of EIA with lipid transfer protein (LTP) sensitization successfully treated with omalizumab with long-term follow-up. A 12-year-old girl presented to our allergy department because of recurrent episodes of EIA, with no specific food ingestion before exercise. Allergen testing revealed sensitization to weed pollens, particularly mugwort (76.1 kUA/L) and Alternaria alternata (10.8 kUA/L). Allergen component testing indicated sensitization to LTP components from mugwort Art v 3 (49.9 kUA/L), wheat Tri a 14 (2.03 kUA/L), and peach Pru p 3 (11.5 kUA/L), with a negative result for omega-5 gliadin. Despite initial prophylactic treatment with budesonide–formoterol (80/4.5 μg) and cetirizine (10 mg) before exercise, the patient still experienced EIA; she was then recommended for dupilumab therapy (an initial dose of 600 mg, followed by 300 mg every 2 weeks for six doses). However, even while undergoing dupilumab therapy, she suffered two anaphylactic episodes after running 800–1,000 m. With the patient's consent, a trial of omalizumab was initiated (injections of 300 mg every 4 weeks). After 2 months of omalizumab therapy, the patient showed significant improvement. She had been engaging in physical exercise three times a week and experienced a mild episode of urticaria. There were no further episodes of anaphylaxis or emergency room visits. By the fourth month of omalizumab treatment, she was able to consume food normally even just before exercising and had returned to her full activity level without any restrictions. This case presents the first successful off-label use of omalizumab in the prevention of EIA in the Chinese population. It is concluded that omalizumab may be helpful in resolving EIA symptoms, as evidenced by this case of successful long-term use.
DCAF2 is essential for the development of uterine epithelia and mouse fertility
Authors: Yang Man , Wang Kaixuan , Zhang Liang , Zhang Hongya , Zhang Cong
Published: September 2024

Introduction

The successful outcome of a pregnancy depends on the proper functioning uterine epithelium. DNA damage binding protein 1 and cullin 4-associated factor 2 (DCAF2), a conserved substrate receptor for the cullin 4-RING E3 ubiquitin ligase (CRL4) complex, is essential for maintaining genome stability by facilitating ubiquitin-mediated degradation of substrates.

Methods

To better understand the physiological role of DCAF2 in female reproduction, we conducted a study using mice with conditional knockout (cKO) of DCAF2 in the uterus using the progesterone receptor Cre (PgrCre/+) mouse model.

Results

Our results showed the cKO mice were completely infertile, despite having ovarian function. The cKO mice exhibited severely thin uteri, demonstrating notable defects in both the uterine epithelium and a lack of glands. In addition, there were impaired proliferation and differentiation of epithelial cells in the cKO mice, ultimately resulting in failed implantation. Moreover, through deciphering the uterine transcriptome of cKO mice, we revealed crucial differentially expressed genes associated with steroid signaling. Further experiments have demonstrated cKO mice exhibit elevated uterine PGR signaling and reduced estrogen receptor signaling, although the levels of progesterone and estrogen remained unaltered. These alterations may contribute to defects in epithelium.

Discussion

Overall, our findings highlight a previously unrecognized but indispensable role for DCAF2 in the development of uterine luminal and glandular epithelium by orchestrating PGR and estrogen receptor responses. Its deficiency in the uterus leads to mouse infertility.
The impact of extent and variety in active learning methods across online and face-to-face education on students’ course evaluations
Authors: Beimel Dizza , Tsoury Arava , Barnett-Itzhaki Zohar
Published: September 2024

Introduction

In recent years, numerous studies have compared traditional face-to-face (F2F) learning on campus with online learning, seeking to establish how the learning environment (online vs. F2F) affects outcomes such as student satisfaction and achievement. In a separate line of research, scholars have examined various facets of active learning—an approach that makes use of interactive learning methods—separately in online and F2F environments. However, few studies have compared the effects of active learning in classes taught online vs. F2F. The present study addresses this gap. It follows an earlier study in which we examined the effects of active learning in an online environment, particularly how the extent and variety of interactive teaching methods used affect students’ course evaluations (overall evaluations and perceived clarity of the teaching).

Methods

The present study repeats the setup of that previous study in a F2F environment, allowing us both to gain new insights into the effects of active learning in this context and to directly compare the examined outcomes in F2F vs. online learning.

Results

The results reveal consistent trends in both studies: more extensive and more varied use of interactive learning methods improves overall student evaluations and perceptions of the clarity of teaching in the course. Crucially, minimal use of interactive teaching methods results in notably lower student evaluations and perceptions of teaching clarity in F2F settings compared to online classes.

Discussion

The findings highlight the essential need for instructors to adopt diverse interactive methods in F2F environments to improve educational outcomes and reinforce the effectiveness of active learning.
Whole body vibration therapy and diabetes type 2: a systematic review and meta-analysis
Authors: Fabregat-Fernández Juan , Rodríguez-Pérez Vicente , Llamas-Ramos Rocío , López-Rodríguez Ana Felicitas , Cortés-Rodríguez María , Llamas-Ramos Inés
Published: September 2024

Background

Vibration platforms have demonstrated systemic effects generated by the use of mechanical vibrations, which are similar to those of any physical activity. The effect that whole body vibration (WBV) generates on the organism could be recommended in Diabetes Mellitus 2 (DM 2) patients.

Objective

To systematically review and meta-analyze the available evidence on the effects of WBV on glycemic control in patients with DM 2

Material and methods

Exhaustive bibliographic searches were carried out until October 2023 in different biomedical portals and databases: Public Medline (PubMed), Scientific Electronic Library Online (SciELO), VHL Regional Portal, Cochrane Central and Latin American and Caribbean Literature in Health Sciences (LILACS). Randomized clinical trials based on the effects of Whole Body Vibration on glycosylated hemoglobin levels, with control group and participants were non-insulin dependent were the inclusion criteria. Two reviewers extracted data independently. A third reviewer was available for discrepancies.

Results

Six articles with 223 participants met the criteria and were included in the systematic review; only four of them met the criteria to be part of the meta-analysis. This meta-analysis reveals a positive and significant effect size (μ ê=0.5731), indicating a substantial difference between the groups studied. Although there is some variability between studies (heterogeneity of 30.05%), the overall direction of the effects is consistent. These findings conclusively suggest the presence of a significant influence of the variable evaluated, underscoring the robustness and consistency of the relationship observed in the literature reviewed.

Conclusion

There are no conclusive results due to the lack of data for some variables, which prevents comparison; but WBV may be an effective therapy to improve glycemic control in DM 2 patients. More studies with more patients and longer follow-up are needed.
Case report: A novel FBXW7 gene variant causes global developmental delay
Authors: Wang Yu , Ma Xiaoping , Li Hua , Dai Yanrui , Wang Xiaochen , Liu Li
Published: September 2024

Objective: To investigate a case of neurodevelopmental disorder caused by mutation of FBXW7.

Methods: Clinical data were collected from the patient, trio-WES (whole-exome sequencing) was performed on the patient and his parents (trio), and the results were verified by Sanger sequencing. RESULTS: The patient was a 2-year and 1-month old male who presented with facial dysmorphism (prominent forehead, ocular hypertelorism, and low nasal bridge), global developmental delay, language impairment, hypertonia, labial hemangioma, hydrocele, and overgrowth. The trio-WES confirmed that the child had a pathogenic de novo FBXW7 gene variant, c.1612C>T (p.G1n538*), a heretofore unreported locus.

Conclusion: This case of developmental delay, hypotonia, and impaired language (OMIM: #620012) related to a mutation in FBXW7, is a rare genetic disorder, newly identified in recent years, and seldom reported. The presence of hypertonia, labial hemangioma, and hydrocele in this child suggests significant phenotypic heterogeneity of the disease, and the discovery of new mutant loci enriches the spectrum of pathogenic variants of the disease.
Machine learning to predict distant metastasis and prognostic analysis of moderately differentiated gastric adenocarcinoma patients: a novel focus on lymph node indicators
Authors: Yang Kangping , Wu Jiaqiang , Xu Tian , Zhou Yuepeng , Liu Wenchun , Yang Liang
Published: September 2024

Background

Moderately differentiated gastric adenocarcinoma (MDGA) has a high risk of metastasis and individual variation, which strongly affects patient prognosis. Using large-scale datasets and machine learning algorithms for prediction can improve individualized treatment. The specific efficacy of several lymph node indicators in predicting distant metastasis (DM) and patient prognosis in MDGA remains obscure.

Methods

We collected data from MDGA patients from the SEER database from 2010 to 2019. Additionally, we collected data from MDGA patients in China. We used nine machine learning algorithms to predict DM. Subsequently, we used Cox regression analysis to determine the risk factors affecting overall survival (OS) and cancer-specific survival (CSS) in DM patients and constructed nomograms. Furthermore, we used logistic regression and Cox regression analyses to assess the specific impact of six lymph node indicators on DM incidence and patient prognosis.

Results

We collected data from 5,377 MDGA patients from the SEER database and 109 MDGC patients from hospitals. T stage, N stage, tumor size, primary site, number of positive lymph nodes, and chemotherapy were identified as independent risk factors for DM. The random forest prediction model had the best overall predictive performance (AUC = 0.919). T stage, primary site, chemotherapy, and the number of regional lymph nodes were identified as prognostic factors for OS. Moreover, T stage, number of regional lymph nodes, primary site, and chemotherapy were also influential factors for CSS. The nomograms showed good predictive value and stability in predicting the 1-, 3-, and 5-year OS and CSS in DM patients. Additionally, the log odds of a metastatic lymph node and the number of negative lymph nodes may be risk factors for DM, while the regional lymph node ratio and the number of regional lymph nodes are prognostic factors for OS.

Conclusion

The random forest prediction model accurately identified high-risk populations, and we established OS and CSS survival prediction models for MDGA patients with DM. Our hospital samples demonstrated different characteristics of lymph node indicators in terms of distant metastasis and prognosis.
MiR-146a-5p engineered hucMSC-derived extracellular vesicles attenuate Dermatophagoides farinae-induced allergic airway epithelial cell inflammation
Authors: Liu Jiaxi , Xu Zuyu , Yu Jinyan , Zang Xiao , Jiang Shangde , Xu Shuyue , Wang Wei , Hong Shanchao
Published: September 2024

Introduction

Allergic asthma is prevalent in children, with Dermatophagoides farinae as a common indoor allergen. Current treatments for allergic airway inflammation are limited and carry risks. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show promise as a cell-free therapeutic approach. However, the use of engineered MSC-EVs for D. farinae-induced allergic airway epithelial cell inflammation remains unexplored.

Methods

We generated miR-146a-5p-engineered EVs from human umbilical cord mesenchymal stem cells (hucMSCs) and established D. farinae-induced mouse and human bronchial epithelial cell allergic models. Levels of IL-1β, IL-18, IL-4, IL-5, IL-6, IL-10, IL-33, TNF-α and IgE were detected using ELISA. The relative TRAF6 and IRAK1 mRNA expression was quantified using qPCR assay and the NLRP3, NF-κB, IRAK1 and TRAF6 protein expression was determined using Western blotting. The regulatory effect of IRAK1 and TRAF6 by miR-146a-5p was examined using a dual luciferase reporter assay, and the nuclear translocation of NF-κB p65 into 16-HBE cells was evaluated using immunofluorescence assay.

Results

Treatment with hucMSC-EVs effectively reduced allergic inflammation, while miR-146a-5p engineered hucMSC-EVs showed greater efficacy. The enhanced efficacy in alleviating allergic airway inflammation was attributed to the downregulation of IRAK1 and TRAF6 expression, facilitated by miR-146a-5p. This downregulation subsequently led to a decrease in NF-κB nuclear translocation, which in turn resulted in reduced activation of the NLRP3 inflammasome and diminished production of inflammatory cytokines, including IL-6, TNF-α, IL-1β and IL-18.

Conclusion

Our study underscores the potential of miR-146a-5p engineered hucMSC-EVs as a cell-free therapeutic strategy for D. farinae-induced allergic airway inflammation, offering a promising avenue for boosting anti-inflammatory responses.
Robust and persistent B-cell responses following SARS-CoV-2 vaccine determine protection from SARS-CoV-2 infection
Authors: Byrne Joanne , Gu Lili , Garcia-Leon Alejandro , Gaillard Colette Marie , Saini Gurvin , Alalwan Dana , Tomás-Cortázar Julen , Kenny Grace , Donohue Sean , Reynolds Bearach , O’Gorman Tessa , Landay Alan , Doran Peter , Stemler Jannik , Koehler Philipp , Cox Rebecca Jane , Olesen Ole F. , Lelievre Jean-Daniel , O’Broin Cathal , Savinelli Stefano , Feeney Eoin R. , O’Halloran Jane A. , Cotter Aoife , Horgan Mary , Kelly Christine , Sadlier Corrina , de Barra Eoghan , Cornely Oliver A. , Gautier Virginie , Mallon Patrick WG ,   All Ireland Infectious Diseases cohort study and VACCELERATE consortium
Published: September 2024

Introduction

A clear immune correlate of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been defined. We explored antibody, B-cell, and T-cell responses to the third-dose vaccine and relationship to incident SARS-CoV-2 infection.

Methods

Adults in a prospective cohort provided blood samples at day 0, day 14, and 10 months after the third-dose SARS-CoV-2 vaccine. Participants self-reported incident SARS-CoV-2 infection. Plasma anti–SARS-CoV-2 receptor-binding domain (RBD) and spike-subunit-1 and spike-subunit-2 antibodies were measured. A sub-study assessed SARS-CoV-2–specific plasma and memory B-cell and memory T-cell responses in peripheral blood mononuclear cells by enzyme-linked immunospot. Comparative analysis between participants who developed incident infection and uninfected participants utilised non-parametric t-tests, Kaplan–Meier survival analysis, and Cox proportional hazard ratios.

Results

Of the 132 participants, 47 (36%) reported incident SARS-CoV-2 infection at a median 16.5 (16.25–21) weeks after the third-dose vaccination. RBD titres and B-cell responses, but not T-cell responses, increased after the third-dose vaccine. Whereas no significant difference in day 14 antibody titres or T-cell responses was observed between participants with and without incident SARS-CoV-2 infection, RBD memory B-cell frequencies were significantly higher in those who did not develop infection [10.0% (4.5%–16.0%) versus 4.9% (1.6%–9.3%), p = 0.01]. RBD titres and memory B-cell frequencies remained significantly higher at 10 months than day 0 levels (p < 0.01).

Discussion

Robust antibody and B-cell responses persisted at 10 months following the third-dose vaccination. Higher memory B-cell frequencies, rather than antibody titres or T-cell responses, predicted protection from subsequent infection, identifying memory B cells as a correlate of protection.
CCL4 as a potential serum factor in differential diagnosis of central nervous system inflammatory diseases and gliomas
Authors: Lyu Tian-Jie , Wang Jia , Zhao Fengmao , Sun Ke , Zhao Zheng , Tian Runfa , Guo Zhendong , Wang Haoran , Zhao Xin , Ma Wenping , Zhang Mingshan , Xu Wangshu
Published: September 2024

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20–0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes.
Flow-weighted sourcing of freshwater runoff from Pacific-draining continental and coastal basins in south-western Patagonia (41-56° S): characterizing regional inputs to Chilean fjords
Authors: Moreno-Meynard Paulo , Artal Osvaldo , Torres Rodrigo , Reid Brian
Published: September 2024

Global estimates of the supply of dissolved and suspended materials to the ocean, in order to be relevant at either political or ecological scales, belie a finer-scale analysis necessary for understanding specific terrestrial-marine interactions. This is especially true for continental runoff to the marine critical zone of inland fjords and channels, where mechanisms, drivers, and predictions need to be elaborated in the context of changing land use and shifting climate forcing. In fjords in south-western Patagonia, runoff from small coastal and large continental basins (~310 x103 km2), sourced from a diverse geography and wide climatic gradient (<150 – 6,000+ mm/year), correspond with a very low density of hydrological and water quality observations. Based on the recently developed regional runoff model (FLOW), we estimated the coastal freshwater discharges and characterized flow-weighted sourcing (land use-cover type, climate, glaciers/geology, and soil province) for Pacific drainages from 41° to 56° south latitude. An estimated 692 km3/year (mean across 1979-2018), or 2% of worldwide total, is more than 85% of previous estimates for the much larger Pacific South American input. Based on limited water quality observations and inference from runoff sourcing, we predict general patterns of export for four groups of continental resources important for marine productivity, including: significant regional variation in flow seasonality, a N-S gradient in declining input of silicic acid and increased glacial input of sediment and iron, and potential shift in dissolved organic matter input sources from rainforest (potentially labile) to peatlands (refractory). Finally, we emphasize the temporal and spatial consequences of near-reference condition river runoff for marine ecosystem productivity and function in the Patagonian fjords, with specific recommendations for water quality standards and sustained monitoring for coupled river and marine ecosystems.
Elevated serum albumin-to-creatinine ratio as a protective factor on clinical outcomes among critically ill patients with sepsis: a retrospective study
Authors: Hu Zhenkui , Song Chao , Zhang Jinhui
Published: September 2024

Background

The aim of this study was to examine the prognostic significance of serum albumin-to-creatinine ratio (ACR) in critically ill patients with sepsis.

Methods

This retrospective study analyzed sepsis cases admitted to the Affiliated Hospital of Jiangsu University between January 2015 and November 2023. The patients were divided into four groups based on their ACR upon admission to the intensive care unit (ICU). Laboratory data were collected at the time of ICU admission, and the primary outcome measure was in-hospital all-cause mortality. Kaplan–Meier survival curves were generated to illustrate the differences in 30−/60-day mortality among the various groups. Multivariate Cox regression models and restricted cubic splines (RCS) were utilized to explore the association between ACR and all-cause mortality in sepsis patients. Subgroup analyses were conducted to examine the impact of other covariates on the relationship between ACR and all-cause mortality.

Results

A total of 1,123 eligible patients were included in the study, with a median ACR of 0.169. The in-hospital mortality rate was 33.7%, the ICU mortality rate was 31.9%, and the 30-day mortality rate was 28.1%. Kaplan–Meier survival analysis demonstrated that patients with higher ACR had a significantly lower risk of 30−/60-day mortality (log-rank p < 0.001). Multivariable Cox proportional hazards analyses revealed that ACR was an independent predictor of in-hospital death (HR: 0.454, 95% CI 0.271–0.761, p = 0.003), ICU death (HR: 0.498, 95% CI 0.293–0.847, p = 0.010), and 30-day death (HR: 0.399, 95% CI 0.218–0.730, p = 0.003). For each 1-unit increase in ACR, there was a 1.203-fold decrease in the risk of death during the hospital stay. The RCS curve illustrated a non-linear negative correlation between ACR and in-hospital mortality (p for non-linear =0.018), ICU mortality (p for non-linear =0.005), and 30-day mortality (p for non-linear =0.006). Sensitivity analysis indicated consistent effect sizes and directions in different subgroups, confirming the stability of the results.

Conclusion

Low ACR levels were identified as independent risk factors associated with increased in-hospital, ICU, and 30-day mortality in sepsis patients. ACR can serve as a significant predictor of the clinical outcome of sepsis.
Comparison of ustekinumab, infliximab and combination therapy in moderately to severely active ulcerative colitis – a study protocol of a randomized, multicenter, head-to-head COMBO-UC trial
Authors: Talar-Wojnarowska Renata , Fabisiak Adam , Zatorski Hubert , Płoszka Katarzyna , Błaziak Katarzyna , Fendler Wojciech , Rydzewska Grażyna , Małecka-Wojciesko Ewa , Eder Piotr
Published: September 2024

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a complex etiology that affects the large intestine. Characterized by chronic, bloody diarrhea, UC can lead to severe complications, including an increased risk of colorectal cancer. Despite advancements in conservative treatment, including biologics like anti-TNF agents and ustekinumab (UST), many patients do not achieve full remission. Dual targeted therapy (DTT) combining infliximab (IFX) and UST is a promising approach to improve treatment outcomes.

Methods

This prospective, randomized, multicenter, head-to-head controlled trial will evaluate the efficacy and safety of UST, IFX, and combination therapy (UST + IFX) in 172 patients with moderate to severe active UC across eight gastroenterology centers in Poland. The study includes a 14–16 week remission induction period followed by a 52-week maintenance phase. Patients will be randomly assigned to one of three treatment arms: IFX monotherapy, UST monotherapy, or IFX + UST combination therapy. Primary endpoint is clinical and endoscopic remission post-induction. Secondary endpoints include clinical response, biochemical remission, histological remission, and quality of life assessments using the Inflammatory Bowel Diseases Questionnaire and 36-Item Short Form Survey. Safety will be monitored through adverse event and serious adverse event reporting.

Discussion

This trial aims to determine whether combining IFX and UST can achieve higher remission rates and better long-term outcomes compared to monotherapy. The results could provide crucial insights into the optimal use of biologic agents in UC treatment, potentially establishing DTT as a standard therapy. The study’s design, including extensive follow-up and robust endpoint measures, will contribute to understanding the therapeutic potential and safety profile of this combination therapy.
Recent developments in intranasal drug delivery of nanomedicines for the treatment of neuropsychiatric disorders
Authors: Kisku Anglina , Nishad Ambresh , Agrawal Saurabh , Paliwal Rishi , Datusalia Ashok Kumar , Gupta Gaurav , Singh Sachin Kumar , Dua Kamal , Sulakhiya Kunjbihari
Published: September 2024

Neuropsychiatric disorders are multifaceted syndromes with confounding neurological explanations. It includes anxiety, depression, autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, Tourette’s syndrome, delirium, dementia, vascular cognitive impairment, and apathy etc. Globally, these disorders occupy 15% of all diseases. As per the WHO, India has one of the largest populations of people with mental illnesses worldwide. The blood-brain barrier (BBB) makes it extremely difficult to distribute medicine to target cells in the brain tissues. However, it is possible through novel advancements in nanotechnology, molecular biology, and neurosciences. One such cutting-edge delivery method, nose-to-brain (N2B) drug delivery using nanoformulation (NF), overcomes traditional drug formulation and delivery limitations. Later offers more controlled drug release, better bioavailability, improved patient acceptance, reduced biological interference, and circumvention of BBB. When medicines are delivered via the intranasal (IN) route, they enter the nasal cavity and go to the brain via connections between the olfactory and trigeminal nerves and the nasal mucosa in N2B. Delivering phytochemical, bioactive and synthetic NF is being investigated with the N2B delivery strategy. The mucociliary clearance, enzyme degradation, and drug translocations by efflux mechanisms are significant issues associated with N2B delivery. This review article discusses the types of neuropsychiatric disorders and their treatment with plant-derived as well as synthetic drug-loaded NFs administered via the IN-delivery system. In conclusion, this review provided a comprehensive and critical overview of the IN applicability of plant-derived NFs for psychiatric disorders.
Screening and identification of the hub genes in severe acute pancreatitis and sepsis
Authors: Yang Si-Jiu , Luo Yan , Chen Bao-He , Zhan Ling-Hui
Published: September 2024

Background

Severe acute pancreatitis (SAP) is accompanied with acute onset, rapid progression, and complicated condition. Sepsis is a common complication of SAP with a high mortality rate. This research aimed to identify the shared hub genes and key pathways of SAP and sepsis, and to explore their functions, molecular mechanism, and clinical value.

Methods

We obtained SAP and sepsis datasets from the Gene Expression Omnibus (GEO) database and employed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to identify the shared differentially expressed genes (DEGs). Functional enrichment analysis and protein–protein interaction (PPI) was used on shared DEGs to reveal underlying mechanisms in SAP-associated sepsis. Machine learning methods including random forest (RF), least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) were adopted for screening hub genes. Then, receiver operating characteristic (ROC) curve and nomogram were applied to evaluate the diagnostic performance. Finally, immune cell infiltration analysis was conducted to go deeply into the immunological landscape of sepsis.

Result

We obtained a total of 123 DEGs through cross analysis between Differential expression analysis and WGCNA important module. The Gene Ontology (GO) analysis uncovered the shared genes exhibited a significant enrichment in regulation of inflammatory response. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the shared genes were primarily involved in immunoregulation by conducting NOD-like receptor (NLR) signaling pathway. Three machine learning results revealed that two overlapping genes (ARG1, HP) were identified as shared hub genes for SAP and sepsis. The immune infiltration results showed that immune cells played crucial part in the pathogenesis of sepsis and the two hub genes were substantially associated with immune cells, which may be a therapy target.

Conclusion

ARG1 and HP may affect SAP and sepsis by regulating inflammation and immune responses, shedding light on potential future diagnostic and therapeutic approaches for SAP-associated sepsis.
Primary cilia in Parkinson’s disease: summative roles in signaling pathways, genes, defective mitochondrial function, and substantia nigra dopaminergic neurons
Authors: Tian Zijiao , Zhang Yixin , Xu Jing , Yang Qianwen , Hu Die , Feng Jing , Gai Cong
Published: September 2024

Primary cilia (PC) are microtubules-based, independent antennal-like sensory organelles, that are seen in most vertebrate cells of different types, including astrocytes and neurons. They send signals to cells to control many physiological and cellular processes by detecting changes in the extracellular environment. Parkinson’s disease (PD), a neurodegenerative disease that progresses over time, is primarily caused by a gradual degradation of the dopaminergic pathway in the striatum nigra, which results in a large loss of neurons in the substantia nigra compact (SNpc) and a depletion of dopamine (DA). PD samples have abnormalities in the structure and function of PC. The alterations contribute to the cause, development, and recovery of PD via influencing signaling pathways (SHH, Wnt, Notch-1, α-syn, and TGFβ), genes (MYH10 and LRRK2), defective mitochondrial function, and substantia nigra dopaminergic neurons. Thus, restoring the normal structure and physiological function of PC and neurons in the brain are effective treatment for PD. This review summarizes the function of PC in neurodegenerative diseases and explores the pathological mechanisms caused by PC alterations in PD, in order to provide references and ideas for future research.