bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of induced pluripotent stem cells from Bornean orangutans
Authors: Li Chia-Jung , Chang Chia-Chun , Tsai Li-Kuang , Peng Min , Lyu Wei-Ni , Yu Jane-Fang , Tsai Mong-Hsun , Sung Li-Ying
Published: January 2024

Introduction: Orangutans, classified under the Pongo genus, are an endangered non-human primate (NHP) species. Derivation of induced pluripotent stem cells (iPSCs) represents a promising avenue for conserving the genetic resources of these animals. Earlier studies focused on deriving orangutan iPSCs (o-iPSCs) from Sumatran orangutans (Pongo abelii). To date, no reports specifically target the other Critically Endangered species in the Pongo genus, the Bornean orangutans (Pongo pygmaeus).

Methods: Using Sendai virus-mediated Yamanaka factor-based reprogramming of peripheral blood mononuclear cells to generate iPSCs (bo-iPSCs) from a female captive Bornean orangutan. In this study, we evaluate the colony morphology, pluripotent markers, X chromosome activation status, and transcriptomic profile of the bo-iPSCs to demonstrate the pluripotency of iPSCs from Bornean orangutans.

Results: The bo-iPSCs were successfully derived from Bornean orangutans, using Sendai virus-mediated Yamanaka factor-based reprogramming of peripheral blood mononuclear cells. When a modified 4i/L/A (m4i/L/A) culture system was applied to activate the WNT signaling pathway in these bo-iPSCs, the derived cells (m-bo-iPSCs) manifested characteristics akin to human naive pluripotent stem cells, including high expression levels of KLF17, DNMT3L, and DPPA3/5, as well as the X chromosome reactivation. Comparative RNA-seq analysis positioned the m-bo-iPSCs between human naive and formative pluripotent states. Furthermore, the m-bo-iPSCs express differentiation capacity into all three germlines, evidenced by controlled in vitro embryoid body formation assay.

Discussion: Our work establishes a novel approach to preserve the genetic diversity of endangered Bornean orangutans while offering insights into primate stem cell pluripotency. In the future, derivation of the primordial germ cell-like cells (PGCLCs) from m-bo-iPSCs is needed to demonstrate the further specific application in species preservation and broaden the knowledge of primordial germ cell specification across species.
Platelets promote human macrophages-mediated macropinocytosis of Clostridioides difficile
Authors: Barbero Angela María , Hernández Del Pino Rodrigo Emanuel , Fuentes Federico , Barrionuevo Paula , Pasquinelli Virginia
Published: January 2024

Clostridioides difficile is the main causative agent of hospital-acquired diarrhea and the potentially lethal disease, C. difficile infection. The cornerstone of the current therapy is the use of antibiotics, which is not fully effective. The molecular mechanisms, inflammatory conditions and host-immune responses that could benefit the persistence or elimination of C. difficile remain unclear. Macrophages perform different ways of endocytosis as part of their immune surveillance functions and platelets, classically known for their coagulatory role, are also important modulators of the immune system. The aim of this study was to evaluate the endocytosis of vegetative C. difficile by human macrophages and the involvement of platelets in this process. Our results showed that both macrophages and platelets interact with live and heat-killed C. difficile. Furthermore, platelets form complexes with human monocytes in healthy donor’s fresh blood and the presence of C. difficile increased these cell-cell interactions. Using flow cytometry and confocal microscopy, we show that macrophages can internalize C. difficile and that platelets improve this uptake. By using inhibitors of different endocytic pathways, we demonstrate that macropinocytosis is the route of entry of C. difficile into the cell. Taken together, our findings are the first evidence for the internalization of vegetative non-toxigenic and hypervirulent C. difficile by human macrophages and highlight the role of platelets in innate immunity during C. difficile infection. Deciphering the crosstalk of C. difficile with immune cells could provide new tools for understanding the pathogenesis of C. difficile infection and for the development of host-directed therapies.
Identification of hub genes in heart failure by integrated bioinformatics analysis and machine learning
Authors: Wang Tengfei , Sun Yongyou , Zhao Yingpeng , Huang Jinhe , Huang Ying
Published: January 2024

Objective

To screen feature genes of heart failure patients through machine learning methods, in order to identify characteristic genes driving heart failure and investigate the progression of heart failure

Methods

Heart failure patient samples were downloaded from the public database GEO (Gene Expression Omnibus), including the datasets GSE116250, GSE120895, and GSE59867. GSE116250 and GSE120895 were used as the testing set, while GSE59867 was used as the validation set. LASSO regression analysis and SVM-RFE were utilized to identify feature genes.

Results

Analysis showed that among the differentially expressed genes between normal and heart failure patients, 9 genes were upregulated and 10 genes were downregulated. ROC curve analysis in the training set showed that TAGLN and SGPP2 had AUC values greater than 0.7. Moreover, SDSL and SMTNL2 had even higher AUC values of greater than 0.9. However, further analysis in the validation set showed that only SDSL had an AUC value greater than 0.7. Western blot experiments, RT-PCR, and ISO-induced experiments confirmed that SDSL was highly expressed in heart failure patients and promoted heart failure progression. In addition, SDSL promoted PARP1 expression and knockdown of SDSL expression led to decreased Cleaved-PARP1 expression and reduced cardiomyocyte apoptosis. Conversely, overexpression of SDSL resulted in increased PARP1 expression and myocardial cell apoptosis. These results suggest that elevated expression of SDSL in cardiomyocytes from heart failure patients may be an important factor promoting the occurrence and development of heart failure.

Conclusions

Using machine learning methods and experimental validation, it has been demonstrated that SDSL is a driving gene in patients with heart failure, providing a new treatment direction for clinical treatment.
The role of parent-adolescent relationship quality and callous-unemotional traits on sexual prejudice in adolescence
Authors: Bruckner Raffael , Schuster Sarah , Hutzler Florian
Published: January 2024

Sexual prejudice negatively impacts our society and commonly manifests itself in hostile attitudes and aggressive behavior toward people who identify with the LGBTQIA+ community. Adolescents in particular are vulnerable to such negative world views. The present study investigated the impact of the parent-adolescent relationship quality, the potentially associated manifestation of psychopathic personality traits—so-called callous-unemotional (CU) traits—and their relation to sexual prejudice in adolescence. We observed that poor maternal relationship quality in terms of poor communication, lack of trust, and alienation is associated with selfish, cold-hearted personality traits. Moreover, we observed an indirect effect of CU-traits mediating the link between maternal relationship quality and antigay hostile attitudes and behavior. Our findings emphasize the crucial role of attachment in the development of a child's affective personality.
Adaptive linear inversion of Moho topography in the Tibetan Plateau by combining gravity and seismic data
Authors: Yu Hangtao , Chen Haopeng , Xu Chuang , Li Jinbo , Chai Yi , Jian Guangyu , Zhang Hui , Xu Ming , Zhao Qiang , Tu Jun
Published: January 2024

The Tibetan Plateau is a region where the Indian and Asian-European plates collide. A high-precision Moho topography model is important for the study of plate motion and internal tectonics of the Tibetan Plateau. However, previous gravity-based models failed in representing adequately the Moho topography because crustal effects and biases in the inversion parameters were not fully considered. To address these issues, we extracted the gravity effect caused by the crust using wavelet multi-scale analysis, and used an adaptive linear inversion method with available gravity and seismic data to estimate more accurate inversion parameters. With these two improvements, we inverted for a high-precision Moho topography model of the Tibetan Plateau. The results show that the majority of the Tibetan Plateau has a Moho depth of 60–70 km. The Moho depth in the center of the Qaidam Basin is about 50 km, and the Moho topography between the east and west of the basin has obvious undulations. The Moho depth of the Tarim Basin ranges from 38–50 km. While the undulation of Moho is limited in the center of the basin, obvious uplifts are shown in northern and southern basin. The plate driving force between the Tibetan Plateau and the Tarim Basin may be the primary cause of this phenomenon. By comparing the difference with the seismic data, we found that the RMS of our model is 2.8 km smaller than that of the CRUST 1.0 model, which shows that our model is more accurate.
Teaching chemistry in the metaverse: the effectiveness of using virtual and augmented reality for visualization
Authors: Amirbekova Elmira , Shertayeva Nailya , Mironova Ekaterina
Published: January 2024

Introduction

The metaverse is a promising platform for learning that all participants in the teaching and learning process may find appealing. This study aims to investigate the effectiveness of using metaverse-related visualization technologies, such as Virtual Reality (VR) and Augmented Reality (AR), in teaching chemistry.

Methods

The study has an experimental research design and uses the following tools to collect data: Dombrovskaya’s Motivation for Learning Scale, the SAMOAL Questionnaire, and the Self-management Questionnaire. The study sample includes 236 first-year undergraduate students studying chemistry at the Faculty of Natural Sciences.

Results

Results suggest that the integration of immersive VR/AR technologies in chemistry education signifies the beginning of a metaverse transition; the process, however, is in its early stages.

Discussion

The study concludes that immersive VR/AR technologies have an advantage over traditional programs in terms of motivation and competence development. Future research can investigate the impact of VR/AR technologies on students’ anxiety and build a model for predicting student achievements in the metaverse-based chemistry classroom.
Recognising the newcomer: education policy and teaching practices in Norway and England
Authors: Soye Emma , Hilden Per Kristian , Andersen Arnfinn , Watters Charles
Published: January 2024

Education policies in different countries recognise the needs and abilities of newcomer students in different ways, with consequences for their social inclusion and academic progress at school. We highlight the importance of context to debates around the politics of recognition in newcomer education by drawing on qualitative research in Norwegian and English secondary schools. Taylor’s (1994) political theory of “recognition” provides the analytical lens through which we explore how teachers perceive newcomer students to be recognised (or not) in national education policies in each country. We underscore teachers’ agency in responding to these policies through their own politics of recognition at school.
Artistic swimming and school engagement: the mediating role of metacognition and technology
Authors: Merlo Gianluca , Jaforte Luna
Published: January 2024

This article presents a cross-sectional study that explores the association between artistic swimming and school engagement in a sample of 500 Italian adolescents. The study aimed to examine whether the practice of artistic swimming would foster strategic metacognitive skills. These skills, in turn, were hypothesized to positively influence school engagement and reduce recreational technology use, which could pose a risk to school engagement. The findings revealed that the relationship between artistic swimming and scholastic engagement, encompassing both cognitive and behavioral aspects, was entirely mediated by metacognitive strategies and reduced recreational technology usage. Moreover, students engaged in artistic swimming exhibited significantly higher levels of metacognitive strategies and scholastic engagement compared to their counterparts involved in other sports. The article also addresses the limitations inherent in the cross-sectional design and suggests potential avenues for future research.
Synergistic advancements: fostering collaborative excellence in doctoral education
Authors: Pelser Anna-Marie
Published: January 2024

Doctoral education in Africa is a rigorous journey that demands unwavering commitment from both students and mentors. It involves original research aimed at contributing new knowledge to the academic realm, making it a formidable scholarly pursuit. The pivotal players in this endeavor are the students, their mentors, and the higher education institutions. This paper delves into the strategies and recommendations for enhancing excellence in doctoral education across Africa. One significant approach is fostering entrepreneurship among doctoral students, empowering them to develop businesses and cultivating an innovative culture to broaden their career prospects. Additionally, robust academic support systems play a crucial role, encompassing services like academic writing centers, article writing workshops, and well-structured mentoring programs. These resources bolster research and writing skills, aid in crafting research proposals, and facilitate publishing, thereby boosting students’ self-esteem. International partnerships offer opportunities for academic mobility, through scholarships, exchange programs, and funding. This international exposure fosters cross-cultural understanding and academic excellence. Collaborations, both with academia and industry, enable problem-solving and interdisciplinary research, further enriching the doctoral experience. Exchange programs serve dual purposes by providing funding and ensuring quality standards are met in doctoral programs. These measures collectively contribute to the advancement of excellence in doctoral education in Africa, nurturing a skilled workforce capable of driving innovation and development on the continent. This theoretical paper relies on extensive scrutiny of reputable sources and accredited journals. The findings emphasize the significance of collaborations and academic support systems in achieving academic success, which, in turn, leads to entrepreneurship, job creation, and wealth generation. Adequate funding and motivated supervisors and students are foundational elements for a thriving doctoral program. Overall, these interventions and recommendations pave the way for Africa’s doctoral students to reach their full potential, contributing to the continent’s growth and prosperity.
Teaching advanced statistical methods to postgraduate novices: a case example
Authors: Brown Gavin T. L.
Published: January 2024

Higher degree research students in education are largely underprepared for understanding or employing statistical data analysis methods. This is despite their need to read literature in their field which will indubitably include such research. This weakness may result in students choosing to use qualitative or interpretivist methodologies, even though education data are highly complex requiring sophisticated analysis techniques to properly evaluate the impact of nested data, multi-collinear factors, missing data, and changes over time. This paper describes a research methods course at a research-intensive university designed for students in a thesis-only degree program. The course emphasizes the logic and conceptual function of statistical methods and exposes students to hands-on tutorials in which students are required to conduct analyses with open-access data. The first half of the 12-week course focuses on core knowledge, normally taught in first-year probability and statistics courses. The second half focuses on introducing and modeling advanced statistical methods needed to handle complex problems and data. The course outline is provided along with descriptions of teaching and assessments. This exemplar functions as a potential model of how relative novices in statistical methods can be introduced to a conceptual use of statistical methods to raise the credibility of research.
Disrupted student engagement and motivation: observations from online and face-to-face university learning environments
Authors: Hari Rajan Manisha , Herbert Cristan , Polly Patsie
Published: January 2024

Student engagement is a crucial factor that can influence both the student learning experience and student success. The return to campus learning and teaching after the pandemic highlighted that many university students are still adapting to the shift to full-time online learning from hybrid or full-time on-campus learning and are still experiencing feelings of isolation, anxiety, and uncertainty. As higher education institutions adopt or embed digital methods of teaching and learning with simultaneously moving back to face-to-face learning environments, student feelings of isolation and disengagement are apparent to educators. This “transition,” in our opinion, has affected how learners engage in digital as well as face-to-face environments. Previous studies have highlighted the importance of engagement within an online setting as it brings about new factors for student learning and teaching that were not fully considered before. To address this issue, universities have sharpened the focus on improving student motivation, self-efficacy, and their sense of belonging within their learning community. As educators, it is important for us to understand this period of student disengagement and develop strategies to overcome and support students. We can acknowledge that such challenges are likely to resurface in the future; therefore, it is essential that we are able to provide frameworks to enhance student engagement within higher education. We believe that in creating an effective learning environment, whether it be online or on-campus, educators need to develop intrinsic motivation techniques and collaborative spaces to increase the sense of belonging for students and improve their overall engagement with their learning course content.
Through teachers’ eyes: adaptability and transformations in their practices and relationship with students during COVID-19 pandemic
Authors: Dario Nadia , Mollo Monica , Savarese Giulia , Carpinelli Luna
Published: January 2024

Introduction

This research critically and empirically analyzes the intricate interaction between the transformative impact of the COVID-19 pandemic on the Italian educational system and the quality of the teacher-student relationship. The main focus is on the experiences of Italian educators who had to deal with the upheavals caused by the pandemic within an educational system.

Aim

The primary purpose of this study is to explore (a) how did teachers’ educational practices change during the first lockdown and (b) how did the teacher-student relationship evolve during the first lockdown from the teachers’ point of view.

Methods

The study uses a qualitative approach through semi-structured interviews and diary collection (conducted via platforms). Participants are Italian primary and secondary school teachers aged between 25 and 60.

Results

In this study, the thematic analysis of the content of the interviews and diaries reveals: the initial responses of educators, the transition to distance learning, the challenges and potential of virtual education, the students’ evaluation, future perspectives, and the topic of the relationship with students (particularly addressed in the diaries).

Discussion

By delving into the transformation of the teacher-student relationship under extraordinary circumstances, this research enriches the discourse on its quality, capturing the psychological nuances of learning-teaching experiences, and uncovers the multifaceted transformations in teaching methodologies, tools, and assessments.
Case report: Sagliker syndrome in the patient with recurrent tertiary hyperparathyroidism due to intrathyroidal parathyroid carcinoma
Authors: Salimkhanov Rustam , Bondarenko Ekaterina , Eremkina Anna , Bibik Ekaterina , Kim Ekaterina , Begova Kamila , Kim Ilya , Kuznetsov Sergey , Mokrysheva Natalia
Published: January 2024

Sagliker syndrome (SS) is an extremely rare disorder that manifests in patients with advanced chronic kidney disease (CKD) undergoing programmed hemodialysis as a renal replacement therapy. Treatment of secondary hyperparathyroidism (SHPT) in these patients is still challenging. The main clinical manifestations of SS include craniofacial and fingertip deformities, dental anomalies, gingival hyperplasia, short stature, hearing loss, neurological and psychiatric impairment. The etiology and pathogenesis of SS in patients with SHPT require further clarification. However, mutations in the GNAS1, FGF23, and FGFR3 genes were described in some patients, suggesting a possible role of genetic predisposition to the syndrome. The preferred therapeutic approach for SS is surgery, but the volume of the operation is debated. The main surgical strategies include total, subtotal parathyroidectomy, or total parathyroidectomy with autotransplantation of the parathyroid gland (PG). Unfortunately, parathyroidectomy does not contribute to the regression of significant skeletal deformities. We present a unique clinical case of a patient with classical features of SS, recurrent tertiary hyperparathyroidism (THPT) after total parathyroidectomy due to intrathyroidal parathyroid carcinoma (PC).
Study on multi-cluster fracturing simulation of deep reservoir based on cohesive element modeling
Authors: Wu Jianfa , Wu Mingyang , Guo Yintong , Huang Haoyong , Zhang Zhen , Zhong Guanghai , Gui Junchuan , Lu Jun
Published: January 2024

With the depletion of conventional reservoir development, reservoir fracturing under deep high geo-stress and high geo-stress difference conditions is receiving increasing attention. Deep reservoirs typically require multi-cluster fracturing to achieve efficient reservoir transformation and development. In this paper, considering the relevant geological parameters of a certain reservoir in the southwest, three-dimensional multi-cluster reservoir fracturing models were established based on cohesive element modeling. Then, the propagation law of artificial fractures in reservoirs under the influence of the different number of fracturing clusters, injection displacement, and Young’s modulus in different regions of the 60 m fracturing well section is analyzed, and the quantitative law of parameters such as fracture length, maximum fracture width, injection point fracture width, fracture area, and tensile failure ratio during multi-cluster fracturing construction, as well as the propagation law of fracture morphology are revealed. The simulation results show that using multi-cluster fracturing can significantly improve the effectiveness of reservoir reconstruction, but as the number of fracturing clusters increases, it is also easy to form some small opening artificial fractures. These small opening artificial fractures may not be conducive to the transportation of proppants and fluids. During single cluster fracturing, the interface stiffness and rock Young’s modulus have a significant impact on the propagation of artificial fractures in the reservoir. As the number of fracturing clusters increases, the competition between artificial main fractures expands significantly, which may reduce the impact of interface stiffness and rock Young’s modulus. The fluid injection rate has a significant impact on reservoir fracturing, and in the same area, using high displacement injection can significantly increase the volume of reservoir reconstruction. This study can provide some reference for multi-cluster fracturing construction in deep reservoirs.
Unlocking the power of public awareness: paving the way for sustainable wetland management in Anzali, Iran
Authors: Allahyari Mohammad Sadegh , Marzban Soroush , Gonzalez-Ollauri Alejandro , Nazari Elham , Ben Hassen Tarek , Surujlal Jhalukpreya
Published: January 2024

The Anzali Wetland, located in the Guilan Province of Iran, is a vital ecosystem with significant ecological value. However, it faces numerous environmental challenges due to pollution, habitat degradation, and unsustainable resource use. This paper aims to assess the awareness and perceptions of local communities regarding the Anzali Wetland, Iran, and its management and how these factors might influence the implementation of the CEPA program. A quantitative survey based on a structured questionnaire was designed and administered to local communities within the wetland’s watershed. The data were analyzed using descriptive statistics. The results indicate that local communities have limited knowledge about the wetland, often associating it solely with Anzali Lagoon. Despite this lack of awareness, most participants recognize the wetland’s importance in conserving wildlife. Further, participants identified domestic and industrial wastewater pollution as the most significant threat to the wetland. Additionally, education at the school level, the Internet, and virtual networks were perceived as effective means of raising awareness among the local population. The study highlights the importance of increasing public participation and interaction among different social groups to enhance awareness of the wetland’s value and environmental issues. It also emphasizes the need for coordinated efforts among stakeholders in wetland management and policy-making, including government agencies and civil organizations. By examining the significance of public awareness in the Iranian context, the study provides unique insights into wetland conservation efforts in a specific geographical and ecological setting. Furthermore, by considering the perceptions and opinions of these stakeholders, the study offers a holistic understanding of the diverse perspectives and interests related to wetland conservation, which adds depth and richness to the analysis.
Adsorption of particulate matter and uptake of metal and non-metal elements from PM in leaves of Pinus densiflora and Quercus acutissima: a comparative study
Authors: Lee Jongkyu , Kwak Myeong Ja , Woo Su Young
Published: January 2024

Trees can serve as effective biofilters of Particulate matter (PM) pollution, making them valuable for managing air pollution and promoting public health. Leaves of trees can reduce PM through absorption, adsorption, and fallout mechanisms, which are influenced by species-specific characteristics and environmental factors. Although several studies have explored the impact of various leaf characteristics on their ability to adsorb PM from field conditions, few have been conducted in controlled chambers to analyze the adsorption of PM on leaf surfaces and the uptake of metal and non-metal elements from PM on leaves. To fill these knowledge gaps, this study investigated the PM adsorption and leaf characteristics of two different tree species, Pinus densiflora (an evergreen coniferous species) and Quercus acutissima (a deciduous broad-leaved species) under controlled conditions in a PM exposure chamber with a target concentration of 300 μg m−3. The main aim of this study was to measure and compare the rate of PM component (metal and non-metal elements) uptake in two species and investigate the leaf characteristics that contribute to PM adsorption. We investigated the relationship between PM adsorption and physiolog, micro-morphology, and chemical properties of the leaf surface in two species. This study used a Pearson’s correlation analysis and a principal component analysis (PCA) to evaluate correlation between PM adsorption and leaf characteristics and uptake of metal/non-metal elements in PM on leaves. This result showed that leaf characteristics such as stomatal size, leaf roughness, and wax content played a crucial role in PM10 adsorption, while physiological factors like transpiration and leaf boundary layer conductance were identified as important determinants of PM2.5 adsorption on plant leaves. It also observed significant variations in the uptake of aluminum, iron, magnesium, phosphorus, and sulfur. This study not only advances our understanding of the mechanisms behind PM adsorption by tree leaves but also underscores the importance of selecting appropriate tree species based on their leaf characteristics for urban forestry and green infrastructure projects. The ability to strategically use tree species for PM pollution mitigation highlights a practical approach to enhancing environmental sustainability and public health.
Heterogeneity and subtypes of CD4+ regulatory T cells: implications for tumor therapy
Authors: Lin Hanqing , Xu Yuanteng , Lin Chang
Published: January 2024

In the conventional view, CD4+ regulatory T cell (Treg) represents a subset of lymphocytes that involve the perception and negative regulation of the immune response. CD4+Treg plays an important role in the maintenance of immune homeostasis and immune tolerance. However, recent studies have revealed that CD4+Treg do not suppress the immune response in some diseases, but promote inflammatory injury or inhibit tissue remodeling, suggesting the functional heterogeneity of CD4+Treg. Their involvement in tumor pathogenesis is more complex than previously understood. This article reviews the relevant research on the heterogeneity of CD4+Treg, subtype classification, and their relationship with tumor therapy.
H2-O deficiency promotes regulatory T cell differentiation and CD4 T cell hyperactivity
Authors: Welsh Robin A. , Song Nianbin , Park Chan-Su , Peske J. David , Sadegh-Nasseri Scheherazade
Published: January 2024

Regulatory T cells (Treg) are crucial immune modulators, yet the exact mechanism of thymic Treg development remains controversial. Here, we present the first direct evidence for H2-O, an MHC class II peptide editing molecular chaperon, on selection of thymic Tregs. We identified that lack of H2-O in the thymic medulla promotes thymic Treg development and leads to an increased peripheral Treg frequency. Single-cell RNA-sequencing (scRNA-seq) analysis of splenic CD4 T cells revealed not only an enrichment of effector-like Tregs, but also activated CD4 T cells in the absence of H2-O. Our data support two concepts; a) lack of H2-O expression in the thymic medulla creates an environment permissive to Treg development and, b) that loss of H2-O drives increased basal auto-stimulation of CD4 T cells. These findings can help in better understanding of predispositions to autoimmunity and design of therapeutics for treatment of autoimmune diseases.
Tailoring a One Health course for an established non-One Health graduate program in Brazil
Authors: Magalhaes Tereza , Barreto Ana , Mesquita-Silva Jamerson , Serravalle Kamile M. L. , Valente de Andrade Marcela , Gomes Rita C. L. , Nazaré Romero J. , Calado Rosa M. G. A. , Ribeiro Guilherme S. , Kitron Uriel
Published: January 2024

We present a study of the tailoring of a One Health (OH) course for its integration into an established non-OH graduate program at a large public university in Brazil. The graduate program focuses on topics such as environmental resource management, impacts on ecosystems, precariousness of the work environment and relationships, workers’ health, social determinants of health, and public policies. Tailoring the OH syllabus involved addressing broader OH concepts, condensing or adapting aspects of infectious diseases, covering non-infectious disease OH topics, and linking OH aspects to ongoing projects in the program. Despite the small class size, students brought diverse backgrounds, significantly enriching discussions. The course was offered in a longer (51 contact hours) and a shorter format (34 contact hours), both of which worked well within a lecture- and discussion-based structure. The extended format allowed more time for student activities and in-depth discussions. The multisectoral and transdisciplinary nature of lectures played a critical role in the course’s success. This information may prove valuable for those designing OH courses for implementation in diverse settings, with the ultimate goal of disseminating OH concepts, fostering discussions, and facilitating the development and implementation of OH approaches in groups not typically exposed to this concept.
Transcolonoscopic spraying formalin solution for hemorrhagic radiation proctitis: a retrospective analysis
Authors: Huang Kun , Zhao Xiaolin , Yu Jiufei , Cheng Jianping , Wu Lili
Published: January 2024

Background

Radiation proctitis is a common complication that occurs as a result of radiation therapy used to treat pelvic malignancies. The most common and bothersome symptom resulting from radiation proctitis is rectal bleeding, which can be persistent or recurrent. This study aimed to review our experience and evaluate the efficacy and safety of transcolonoscopic spraying of formalin solution in patients with hemorrhagic radiation proctitis.

Methods

A total of 37 patients with hemorrhagic radiation proctitis, aged between 48 and 79 years (mean age 62.56 ± 8.48 years), were divided into three cohorts based on the severity of radiation injury. Under direct endoscopic vision, a 4% formalin solution was applied directly to the rectal hemorrhagic mucosa. The patients were followed for a period of over 6 months after receiving treatment, during which the therapeutic effectiveness and occurrence of complications were observed.

Results

The study resulted in an overall response rate of 89.2% among all patients. The response rates for patients with grades 1–3 were 100, 100, and 66.7%, respectively. Notably, the rate of response among patients with grade 3 radiation injury was significantly lower compared to those with grades 1–2 (p = 0.009). Mild adverse reactions, such as anal pain and tenesmus, were reported in a small number of patients but could be alleviated without any intervention.

Conclusion

The endoscopic application of formalin solution for the treatment of hemorrhagic radiation proctitis has shown a significant effect, particularly in patients with grades 1–2 radiation injury. The observed effect is superior to that observed in patients with grade 3 radiation injury.
Appropriateness of specialized care referrals for LBP: a cross-sectional analysis
Authors: Mathieu Janny , Robert Marie-Ève , Châtillon Claude-Édouard , Descarreaux Martin , Marchand Andrée-Anne
Published: January 2024

Background

Low back pain (LBP) accounts for a significant proportion of primary care visits. Despite the development of evidence-based guidelines, studies point to the inefficient use of healthcare resources, resulting in over 60.0% of patients with LBP being referred to spine surgeons without any surgical indication. Centralized waiting lists (CWLs) have been implemented to improve access to specialized care by managing asymmetry between supply and demands. To date, no study has provided data on patients’ clinical profiles and referral patterns to medical specialists for LBP in the context of a publicly funded healthcare system operating a prioritization model. The objective of this study was to evaluate the appropriateness of specialized care referrals for LBP after the implementation of a CWL.

Methods

A retrospective cross-sectional analysis of 500 randomly selected electronic health records of patients who attended the outpatient neurosurgery clinic of the administrative Mauricie-et-Centre-du-Québec region was performed. Inclusion criteria were neurosurgery consultation referrals for adults ≥18 years suffering from a primary complaint of LBP, and performed between September 1st, 2018, and September 1st, 2021. Data relevant for drawing a comprehensive portrait of patients referred to the neurosurgery service and for judging referrals appropriateness were manually extracted.

Results

Of the 500 cases analyzed, only 112 (22.4%) were surgical candidates, while 221 (44.2%) were discharge from the neurosurgery service upon initial assessment. Key information was inconsistently documented in medical files, thus preventing the establishment of a comprehensive portrait of patients referred to the neurosurgery service for LBP. Nevertheless, over 80.0% of referrals made during the study period were deemed inappropriate. Inappropriate referrals were characterized by higher proportion of patients symptomatically improved, presenting a back-dominant chief complaint, exhibiting no objective neurological symptoms, and diagnosed with non-specific LBP.

Conclusion

This study reveals a significant proportion of inappropriate referrals to specialized care for LBP. Further research is needed to better understand the factors that prompt referrals to medical specialists for LBP, and the criteria considered by neurosurgeons when selecting the appropriate management strategy. Recent studies suggest that triaging approaches led by musculoskeletal experts may improve referral appropriateness to specialized care.
Surveillance of high-risk early postsurgical patients for real-time detection of complications using wireless monitoring (SHEPHERD study): results of a randomized multicenter stepped wedge cluster trial
Authors: Posthuma Linda M. , Breteler Martine J. M. , Lirk Philipp B. , Nieveen van Dijkum Els J. , Visscher Maarten J. , Breel Jennifer S. , Wensing Carin A. G. L. , Schenk Jimmy , Vlaskamp Lyan B. , van Rossum Mathilde C. , Ruurda Jelle P. , Dijkgraaf Marcel G. W. , Hollmann Markus W. , Kalkman Cor J. , Preckel Benedikt
Published: January 2024

Background

Vital signs measurements on the ward are performed intermittently. This could lead to failure to rapidly detect patients with deteriorating vital signs and worsens long-term outcome. The aim of this study was to test the hypothesis that continuous wireless monitoring of vital signs on the postsurgical ward improves patient outcome.

Methods

In this prospective, multicenter, stepped-wedge cluster randomized study, patients in the control group received standard monitoring. The intervention group received continuous wireless monitoring of heart rate, respiratory rate and temperature on top of standard care. Automated alerts indicating vital signs deviation from baseline were sent to ward nurses, triggering the calculation of a full early warning score followed. The primary outcome was the occurrence of new disability three months after surgery.

Results

The study was terminated early (at 57% inclusion) due to COVID-19 restrictions. Therefore, only descriptive statistics are presented. A total of 747 patients were enrolled in this study and eligible for statistical analyses, 517 patients in the control group and 230 patients in the intervention group, the latter only from one hospital. New disability at three months after surgery occurred in 43.7% in the control group and in 39.1% in the intervention group (absolute difference 4.6%).

Conclusion

This is the largest randomized controlled trial investigating continuous wireless monitoring in postoperative patients. While patients in the intervention group seemed to experience less (new) disability than patients in the control group, results remain inconclusive with regard to postoperative patient outcome due to premature study termination.

Clinical trial registration

ClinicalTrials.gov, ID: NCT02957825.
High-throughput screening identification of novel immunomodulatory combinations for the generation of tolerogenic dendritic cells
Authors: Jia Sihan , Kim Jeremiah , Esser-Kahn Aaron Palmer , Deak Peter
Published: January 2024

Introduction

Tolerogenic Dendritic Cells (tolDCs) have an exceptional promise as a potential therapy for autoimmune disease and transplantation rejection. TolDCs are a unique phenotype of antigen presenting cells (APCs) that can influence naïve T cells into antigen specific T regulatory cells (Tregs), which can re-establish tolerance against auto/allo-antigens in the long term. Despite their promise, tolDCs have not found clinical success. Most strategies seek to generate tolDCs ex vivo by differentiating naïve dendritic cells (DCs) with immunosuppressive agents. Recently, we developed a tolDC generation strategy, which we call Push/Pull Immunomodulation (PPI). In PPI, DCs are treated with combinations of toll-like-receptor (TLR) agonists and immunomodulatory agents, which generate more robust, Treg-inducing tolDCs than previous strategies. Here, we seek to identify more potent and clinically viable PPI formulations using data from a high-throughput screening project.

Methods

Over 40,000 combinations of pathogen-associated molecular patterns (PAMPs) and immunomodulatory small molecules were screened using a modified murine macrophage line, RAW dual cells, to observe the effect of these combinations on two major immune regulatory transcription factors, NF-κB and IRF. Combinations were further screened for inflammatory cytokine activity using a human monocyte cell line, THP-1, then on murine DCs. Leading candidates were co-cultured with T cells to assess antigen specific T cell responses.

Results

From this data, we identified 355 combinations that showed low or moderate IRF activity, low NF-κB activity, low inflammatory cytokine generation and good viability: all hallmarks of tolerogenic potential. We further screened these 355 combinations using bone marrow derived DCs (BMDCs) and identified 10 combinations that demonstrated high IL-10 (tolerogenic) and low TNF-α (inflammatory) secretion. After further optimizing these combinations, we identified two combinations that generate robust tolDCs from BMDCs ex vivo. We further show that these PPI-tolDCs can also generate antigen specific Tregs but do not increase overall Treg populations.

Discussion

These second-generation PPI formulations have significant potential to generate robust tolDCs and strong antigen specific Tregs.
Automatic diagnosis of Parkinson’s disease using artificial intelligence base on routine T1-weighted MRI
Authors: Li Chang , Hui Dongming , Wu Faqi , Xia Yuwei , Shi Feng , Yang Mingguang , Zhang Jinrui , Peng Chao , Feng Junbang , Li Chuanming
Published: January 2024

Background

Parkinson’s disease (PD) is the second most common neurodegenerative disease. An objective diagnosis method is urgently needed in clinical practice. In this study, deep learning and radiomics techniques were studied to automatically diagnose PD from healthy controls (HCs).

Methods

155 PD patients and 154 HCs were randomly divided into a training set (246 patients) and a testing set (63 patients). The brain subregions identification and segmentation were automatically performed with a VB-net, and radiomics features of billateral thalamus, caudatum, putamen and pallidum were extracted. Five independent machine learning classifiers [Support Vector Machine (SVM), Stochastic gradient descent (SGD), random forest (RF), quadratic discriminant analysis (QDA) and decision tree (DT)] were trained on the training set, and validated on the testing. Delong test was used to compare the performance of different models.

Results

Our VB-net could automatically identify and segment the brain into 109 regions. 2,264 radiomics features were automatically extracted from the billateral thalamus, caudatum, putamen or pallidum of each patient. After four step of features dimensionality reduction, Delong tests showed that the SVM model based on combined features had the best performance, with AUCs of 0.988 (95% CI: 0.979 ~ 0.998, specificity = 91.1%, sensitivity =100%, accuracy = 89.4% and precision = 88.2%) and 0.976 (95% CI: 0.942 ~ 1.000, specificity = 100%, sensitivity = 87.1%, accuracy = 93.5% and precision = 88.6%) in the training set and testing set, respectively. Decision curve analysis showed that the clinical benefit of the line graph model was high.

Conclusion

The SVM model based on combined features could be used to diagnose PD with high accuracy. Our fully automatic model could rapidly process the MRI data and distinguish PD and HCs in one minute. It greatly improved the diagnostic efficiency and has a great potential value in clinical practice to help the early diagnosis of PD.
Associations of traditional Chinese medicine body constitution and all-cause mortality in patients with type 2 diabetes mellitus: a prospective cohort study of a Taiwanese medical center
Authors: Lee Cheng-Hung , Su Yi-Chang , Lin Shih-Yi , Lee I-Te , Tsai Chia-I , Li Tsai-Chung
Published: January 2024

Introduction

The objective of this study was to investigate associations between baseline body constitutions (BCs) in traditional Chinese Medicine (TCM) and all-cause mortality in Chinese individuals with type 2 diabetes.

Methods

A total of 887 individuals with type 2 diabetes who were enrolled in managed care in 2010 were included. These individuals were followed up until 2015, and their mortality status was determined through the use of Taiwan National Death Datasets. At baseline, BC status of participants, including Yin deficiency, Yang deficiency, and phlegm stasis, was assessed using a well-developed Body Constitutions Questionnaire. Hazard ratios (HR) were calculated using a multivariate Cox proportional hazards model.

Results

During 6807.2 person-years of follow-up of 887 participants, with an average follow-up period of 7.7 years, a total of 190 individuals died, resulting in an incidence density of 0.0279 person-years. Yin deficiency was associated with all-cause mortality (HR, 95% CI: 1.39, 1.02–1.90). This study indicates that individuals diagnosed with Yin deficiency in TCM, characterized by symptoms such as thirst, reduced urine volume, hard stool, and hot flushes, had a 39% higher risk of all-cause mortality.

Discussion

The findings may provide information for TCM practitioners on tailoring treatment plans for persons with type 2 diabetes. No conclusive statements can be made on the basis of the preliminary data presented here. Controlled prospective studies are warranted.
The role of the Notch signalling pathway in the pathogenesis of ulcerative colitis: from the perspective of intestinal mucosal barrier
Authors: Ning Hang , Liu Jiemin , Tan Jiaqian , Yi Mengni , Lin Xiaoyuan
Published: January 2024

Ulcerative colitis is a common digestive disorder worldwide, with increasing incidence in recent years. It is an urgent problem to be solved, as it seriously affects and threatens the health and life of the global population. Studies have shown that dysfunction of the intestinal mucosal barrier is a critical pathogenic factor and molecular basis of ulcerative colitis, and some scholars have described it as a “barrier organ disease.” While the Notch signalling pathway affects a series of cellular processes, including proliferation, differentiation, development, migration, and apoptosis. Therefore, it can regulate intestinal stem cells, CD4+ T cells, innate lymphoid cells, macrophages, and intestinal microbiota and intervene in the chemical, physical, immune, and biological mucosal barriers in cases of ulcerative colitis. The Notch signalling pathway associated with the pathogenesis of ulcerative colitis has distinct characteristics, with good regulatory effects on the mucosal barrier. However, research on ulcerative colitis has mainly focused on immune regulation, anti-inflammatory activity, and antioxidant stress; therefore, the study of the Notch signalling pathway suggests the possibility of understanding the pathogenesis of ulcerative colitis from another perspective. In this article we explore the role and mechanism of the Notch signalling pathway in the pathogenesis of ulcerative colitis from the perspective of the intestinal mucosal barrier to provide new targets and theoretical support for further research on the pathogenesis and clinical treatment of ulcerative colitis.