Medicine Research Research Articles

Pyrrolo[2,3-D]Pyrimidines as EGFR and VEGFR Kinase Inhibitors: A Comprehensive SAR Review.

Tyrosine kinases are implicated in a wide array of cellular physiological processes, including cell signaling. The discovery of the BCR-ABL tyrosine kinase inhibitor imatinib and its FDA approval in 2001 paved the way for the development of small molecule chemical entities of diverse structural backgrounds as tyrosine kinase inhibitors for the treatment of various ailments. Two of the most prominent tyrosine kinases as drug targets are the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR), as evidenced by the clinical success of their many inhibitors in the drug market. Among several other physiological roles, EGFR regulates epithelial tissue development and homeostasis, while VEGFR regulates tumor-induced angiogenesis. The pyrrolo[2,3-d]pyrimidine nucleus represents a deaza-isostere of adenine, the nitrogenous base of ATP. The recent introduction of many pyrrolo[2,3-d]pyrimidines to the drug market as tyrosine kinase inhibitors makes them a hot topic in the medicinal chemistry research area at the present time. This review article comprehensively sheds light on the structure-activity relationship (SAR) of pyrrolo[2,3-d]pyrimidines as EGFR and VEGFR tyrosine kinase inhibitors, aiming to provide help medicinal chemists in the design of future pyrrolopyrimidine kinase inhibitors.

Navigating stem cell culture: insights, techniques, challenges, and prospects

Stem cell research holds huge promise for regenerative medicine and disease modeling, making the understanding and optimization of stem cell culture a critical aspect of advancing these therapeutic applications. This comprehensive review provides an in-depth overview of stem cell culture, including general information, contemporary techniques, encountered problems, and future perspectives. The article begins by explaining the fundamental characteristics of various stem cell types, elucidating the importance of proper culture conditions in maintaining pluripotency or lineage commitment. A detailed exploration of established culture techniques sheds light on the evolving landscape of stem cell culture methodologies. Common challenges such as genetic stability, heterogeneity, and differentiation efficiency are thoroughly discussed, with insights into cutting-edge strategies and technologies aimed at addressing these hurdles. Moreover, the article delves into the impact of substrate materials, culture media components, and biophysical cues on stem cell behavior, emphasizing the intricate interplay between the microenvironment and cell fate decisions. As stem cell research advances, ethical considerations and regulatory frameworks become increasingly important, prompting a critical examination of these aspects in the context of culture practices. Lastly, the article explores emerging perspectives, including the integration of artificial intelligence and machine learning in optimizing culture conditions, and the potential applications of stem cell-derived products in personalized medicine. This comprehensive overview aims to serve as a valuable resource for researchers and clinicians, fostering a deeper understanding of stem cell culture and its key role in advancing regenerative medicine and biomedical research.

Challenges in Mathematics Arising from Theoretical and Computational Chemistry

The combination of theoretical chemistry and mathematics represents a significant advancement in science since it has yielded insights into the enigmas surrounding atoms and molecules. The advancement of technology has greatly benefited drug development, leading to significant advancements in both medicine and materials research. This summary discusses innovative methodologies and computational challenges in the expansive domain of theoretical and computational chemistry. Despite the computational challenges associated with the Schrodinger equation and Density Functional Theory (DFT), quantum mechanics offers a basic understanding of the behaviour of molecules and atoms. While MD simulations may not handle long-range interactions and complex configuration spaces, they nonetheless excel at capturing various time scales of molecular behaviour. Nevertheless, the process of transforming abstract notions into computer models for the purpose of solving MD simulations continues to be difficult; statistical mechanics offers a theoretical framework for understanding MD simulations. Data-driven methodologies and machine learning have significantly transformed the perspective of computational chemistry by enabling the observation and comprehension of very complex chemical interactions. We must also address concerns about interpretability, reliability in limited data streams, and system transferability. These challenges expedite the advancement of novel materials, product designs, and pharmaceuticals by leveraging machine learning and integrating it with specialised domain expertise. We used available data from many reputable databases, spanning the time period from 2010 to 2024. It is imperative to prioritise the advancement of multiscale modelling techniques and hybrid quantum-classical tools in order to achieve sufficient mastery over chemical phenomena. Another potential benefit is the use of novel mathematical models to uncover previously unknown patterns and connections in genetic data. The most effective way to tackle mathematical problems is by employing a straightforward approach and engaging in collaboration with experts from other fields. By adopting this approach, we can effectively address significant societal issues and propel advancements in chemistry. Keywords: mathematics, computational, chemistry, theoretical, challenges, quantum mechanics

Health services research in acute pain medicine : Where do we come from in Germany?

Up to the early 2000s the need for optimization in the treatment of acute pain in hospitals was highlighted. Only afew successes were achieved in the optimization process. As the acute pain care in Germany remained persistently unsatisfactory, the first health services research projects in pain medicine were initiated. These were intended to achieve improvements in patient care. To illustrate the beginnings of health services research in the field of pain medicine in Germany the research projects "Pain-free hospital" and "Action alliance pain-free City of Münster" as well as the certification initiative Certkom are described. An analysis of the current state of pain care for patients and interdisciplinary pain management, the derivation of optimization measures, their implementation and subsequent evaluation were carried out in all the projects presented in the sense of acomplex intervention. All the projects could achieve improvements in patient care through asystematic survey of the current situation, targeted planning and the introduction of optimization measures. Corresponding evaluations could demonstrate these results. The systematic approach in the projects with the collation of scientific data in real-life care has achieved optimization in acute pain management. The foundations were laid for further healthcare research in pain treatment in Germany; however, the projects also revealed limitations in the inclusion of vulnerable patient groups.

VARIATIONS IN VOLATILE OIL CONSTITUENTS OF ECHINOPS SPECIES GROWING IN THE MIDDLE EAST AND THE MEDITERRANEAN REGIONS: MINI REVIEW

The genus Echinops of the family Asteraceae has commonly been a subject of interest because its members have various chemical constituents and crucial pharmacological activities of great medicinal importance over the last decade (2010-2023). Therefore, this genus has attracted serious research in pharmacognosy and herbal medicine. Detailed studies revealed that Echinops species contain numerous bioactive compounds, such as sesquiterpene lactones, essential oils, flavonoids, and polyacetylenic aliphatic acids, largely in plant parts that are important for therapeutic use. These bioactive constituents have been associated with a wide diversity of pharmacological activities such as anti-inflammatory, antimicrobial, and cytotoxic underlined while proceeding to show some antioxidant activity and even hepatoprotective action of the genus, hence encouraging the further development of novel therapeutic agents. Most of these activities have been studied both in vitro and in vivo to establish their underlying effects. This will help us evaluate pharmacological properties attributed to the genus Echinops and pave the way for future studies to validate traditional uses and optimize extraction methods and their clinical applications. This work highlighted the position of Echinops species in Mediterranean areas, especially essential oils as a source of bioactive compounds useful in the well-being of humans and its variation concerning several factors. It has reaffirmed the place of natural products in drug discovery and development.

Open science practices among authors published in complementary, alternative, and integrative medicine journals: An international, cross-sectional survey.

Open science practices aim to increase transparency in research and increase research availability through open data, open access platforms, and public access. Due to the increasing popularity of complementary, alternative, and integrative medicine (CAIM) research, our study aims to explore current open science practices and perceived barriers among CAIM researchers in their own respective research articles. We conducted an international cross-sectional online survey that was sent to authors that published articles in MEDLINE-indexed journals categorized under the broad subject of "Complementary Therapies" or articles indexed under the MeSH term "Complementary Therapies." Articles were extracted to obtain the names and emails of all corresponding authors. Eight thousand seven hundred eighty-six researchers were emailed our survey, which included questions regarding participants' familiarity with open science practices, their open science practices, and perceived barriers to open science in CAIM with respect to participants' most recently published article. Basic descriptive statistics was generated based on the quantitative data. The survey was completed by 292 participants (3.32% response rate). Results indicate that the majority of participants were "very familiar" (n = 83, 31.68%) or "moderately familiar" (n = 83, 31.68%) with the concept of open science practices while creating their study. Open access publishing was the most familiar to participants, with 51.96% (n = 136) of survey respondents publishing with open access. Despite participants being familiar with other open science practices, the actual implementation of these practices was low. Common barriers participants experienced in implementing open science practices include not knowing where to share the study materials, where to share the data, or not knowing how to make a preprint. Although participants responded that they were familiar with the concept of open science practices, the actual implementation and uses of these practices were low. Barriers included a lack of overall knowledge about open science, and an overall lack of funding or institutional support. Future efforts should aim to explore how to implement methods to improve open science training for CAIM researchers.

Comprehensive characterization of active components in Salvia miltiorrhiza using polarity-partitioned two-dimensional liquid chromatography coupled with mass spectrometry

Salvia miltiorrhiza, a widely used traditional Chinese medicine, contains a complex matrix of hydrophobic diterpenoids and hydrophilic phenolic acids, presenting significant challenges in comprehensive analysis. In this study, an online polarity-partitioned two-dimensional liquid chromatography coupled with mass spectrometry (2D-LC-MS) method was developed for comprehensive analysis of both lipophilic and hydrophilic active components in Salvia miltiorrhiza. The method integrated hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography (RPLC), facilitating the efficient separation of compounds across a wide range of polarities. An online dilution strategy was implemented, minimizing sample loss and enhancing the method's utility for quality control and chemical characterization of complex herbal matrices. Compared with other LC methods, this approach significantly improved analyte coverage, resolution, and analysis efficiency. Under optimal conditions, 150 active components were successfully identified, including 33 compounds newly discovered in Salvia miltiorrhiza. Additionally, the validated online method was applied to the quantitative determination of 16 quality markers of Salvia miltiorrhiza from different sources. The results demonstrated the online method's potential as a superior alternative to existing techniques, offering broader applicability in traditional Chinese medicine research.

APPLICATION OF GENETICALLY MODIFIED INDUCED PLURIPOTENT STEM CELL LINES IN ARTICULAR CARTILAGE TISSUE ENGINEERING

The restoration of hyaline cartilage poses a complex clinical and scientific challenge due to its low regenerative potential. Joint cartilage injuries contribute to the development of osteoarthritis and, as a consequence, loss of joint function, and subsequent disability. Surgical approaches such as mosaic chondroplasty and microfracture are applicable only to relatively small defects and are unsuitable for patients with degenerative cartilage conditions. Developing of cell therapies using chondrocytes differentiated from induced pluripotent stem cells (iPSCs) is a promising direction for joint cartilage tissue reconstruction. iPSCs have high proliferative activity, allowing the generation of autologous cells in the amount required to restore an individual’s articular defect. The CRISPR-Cas genome editing technology, based on the bacterial adaptive immune system, enables genetic modification of iPSCs to produce progenitor cells with specific characteristics and properties. This review contains scientific studies of highly specialized focus on combining iPSC and CRISPR-Cas technologies for research in cartilage regenerative medicine. We have compiled articles over the past twelve years, since CRISPR-Cas became available to the world community. Currently, for the field of regenerative medicine of articular cartilage CRISPR-Cas is used to increase the effectiveness of chondrogenic differentiation of iPSCs and to obtain a chondroprogenitor population with a high homogeneity. Additionally, deletion of a sequence of pro-inflammatory cytokine receptors is conducted to produce inflammation-resistant tissue. Finally, knockout of major histocompatibility complex components allows the creation of hypoimmunogenic chondrocytes. These approaches contribute to the development of personalized medicine and may, in the long term, lead to improved quality of life for the global population.

Molecular docking and ADME evaluation of plant-based bioactive molecules targeting nonsense-mediated mRNA decay pathway factors to modulate tumorigenesis

Cancer is a global health challenge that requires continuous efforts to discover effective anticancer drugs. Phytochemicals are compounds found in plants that often have medicinal properties. They possess a wide range of bioactive properties, including anticancer activity. Their multiple mechanisms of action in different physiological processes in humans make them promising candidates in the anticancer therapeutics development. The presence of these compounds makes plants valuable resources for traditional medicine and modern pharmaceutical research as well. Natural products from plants and marine sources are being used to find new anticancer agents. In humans, different cellular pathways are involved in the tumorigenesis process. Many studies have shown the role of the nonsense-mediated mRNA decay (NMD) pathway in the process of tumorigenesis. This NMD pathway is controlled by multiple proteins. In this study, we conducted a molecular docking analysis of 50 phytochemicals against the human NMD factor up-frameshit2 (UPF2) protein. The results of the molecular docking experiment and ADME properties indicate that 4 of these molecules (Genistein, Trihydroxyflavone, Baicalein and Epigallocatechin) have the potential to modulate the NMD pathway. Furthermore, these molecules comply with Lipinski's rule of five. The effects of these 4 phytochemicals may be further evaluated using in vitro and in vivo methods for novel anticancer therapeutic development.

Construction of Aryl Azide‐ and Triazole‐Based Unnatural Amino Acid Motifs via the Pd(II)‐Catalyzed C(sp3)−H Arylation

AbstractThis paper reports a method for the synthesis of examples of aryl azide‐ and triazole moiety‐based unnatural amino acid motifs using the Pd(II)‐catalyzed arylation of the prochiral C(sp3)−H bonds of carboxamides of amino acids as one of the key transformations. Synthesis of racemic and enantioenriched aryl azide‐based unnatural amino acid motifs including, norvaline, leucine, norleucine, phenylalanine, 2‐aminobutyric acid, 2‐aminooctanoic acid, and non‐α‐amino acid derivatives were shown. Additionally, we attempted the synthesis of triazole moiety‐installed norvaline, leucine, norleucine, phenylalanine, 2‐aminobutyric acid, 2‐aminooctanoic acid, and non‐α‐amino acid derivatives via the Cu‐catalyzed Click reaction. We also demonstrated the removal of the protecting groups and the synthesis of free amino group‐containing aryl azide‐ or triazole‐based unnatural amino acid motifs and peptides. Generally, azide moiety‐containing unnatural amino acid motifs are important molecular tools in chemical biology. Furthermore, aryl azide‐ and triazole moiety‐containing unnatural amino acid scaffolds are notable substrates in medicinal chemistry and drug discovery research. Accordingly, this work contributes to enriching the library of aryl azide‐ and triazole‐based unnatural amino acid derivatives.

A Protocol for a Bibliometric Analysis of Traditional, Complementary, and Integrative Medicine Research Preprints

Background: Traditional, complementary, and integrative medicine (TCIM) has witnessed significant growth in interest globally. Despite its popularity, TCIM research encounters numerous challenges including funding, methodological issues, and risk of bias. Preprints (scientific manuscripts openly accessible before formal peer review) present a potential solution, and understanding the characteristics and impact of TCIM preprints could offer valuable insights.Methods: A bibliometric analysis will be conducted on all TCIM-related preprints, since inception, and posted on preprint servers with TCIM subject filters. Preprints will be sourced from servers listed in the Accelerating Science and Publication in Biology directory which allow filtering by TCIM-related categories. The preprint server and URLs, preprint server’s disciplinary scope, ownership type, screening processes, external content indexing, permanence of content, preservation of content, and comments will be extracted. The number of TCIM-related preprints yielded, and which TCIM-related term each preprint server uses will be noted. Data will be extracted from each eligible preprint: preprint server, title, DOI, preprint posted date, status of preprint, journal of final publication, final publication date, type of preprint, abstract of preprint, authors, author affiliation(s), country of corresponding author, funders, number of views, number of downloads, number of comments, number of citations, number of versions, and keywords. Descriptive statistics will be used to summarize the bibliometric characteristics, and trend analysis will identify publication patterns over time.Conclusion: This protocol was developed for a study to identify trends in TCIM research dissemination, and contribute to a better understanding of how preprints are being used to advance the field

The Theoretical and Practical Research of Traditional Chinese Medicine in the Prevention and Treatment of Sarcopenia

Sarcopenia, as an age-related skeletal muscle mass and strength decline in the elderly syndrome, seriously affects the quality of life of patients. In recent years, with the aggravation of aging in China, the incidence of sarcopenia is gradually increasing. The research on sarcopenia in traditional Chinese medicine is also deepening, and relatively rich experience and results have been achieved. This paper summarizes and expounds the theoretical research and intervention methods of traditional Chinese medicine for sarcopenia by combing the relevant literature. The purpose of this paper is to discuss the current status of its theoretical research and to look forward to the future development trend, so that the etiology and mechanism of sarcopenia in TCM can be further explored and the treatment plan can be optimized, and more possibilities for the treatment of sarcopenia in TCM can be provided in the future research.

Digital health and some thematic shifts in bioethics in academic publications after the pandemic

Abstract Background Digital health (DH) presents vast opportunities, but also dynamic shift in viewpoints, which is reflected in academic works. Since DH concerns patient data, a major issue is complying with the bioethical principles, and ensuring patients’ privacy and security. The aim of this research is to explore avenues, in which ethics and privacy are reflected in DH, especially in terms of research, legislation, artificial intelligence (AI) and blockchain applications in medicine and public health. Methods Literature search for full text publications in PubMed, Scopus and ScienceDirect focused on ethics and privacy in DH in the period 2019-2023 found 325 articles in English authored by academicians. Six thematic categories were identified: ethics (fundamental principles; ethics in using novel DH tools); privacy (in use of apps/wearables; as a challenge/barrier to DH interventions/technologies); ethics/privacy in: DH research (data gathering, use, sharing); policy and legislation (for DH applications); AI and blockchains (in medicine and public health). Results Articles were from 32 countries: USA-24.3%; UK-13.5%; Germany-7.7%; Canada-7.4%; Australia-6.7%; Netherlands, Italy, Switzerland-4.7% each; China, India-3.0% each and 20.3% from 22 other countries; 86.5% in medical/DH journals. Only 10.2% were published in 2019; 17.8% - 2020; 19.4% - 2021; 27.1% - 2022 and 25.5% - 2023. Privacy was discussed in 26.5%; ethics-23.7%; research-19.4%; AI-15.1%; policy and legislation-9.5% and blockchains-5.5% of the articles. The publication activity of all six categories increased after the unfold of the pandemic in 2020. In 2023 publications for ethics (13%), privacy (5.8%) and research (6.3%) decreased; for legislation (12.9%), AI (14.3%) and blockchains in healthcare (16.8%) increased. Conclusions The pandemic and its aftermath present a change in academic interest. Traditional ethical fundaments in DH slightly lose position in favor of top notch technologies and apt legislation. Key messages • The pandemic and modern technologies enforced new digital health applications. Further research will reveal the needs of AI and blockchain applications respecting privacy and the ethical principles. • Besides existing legislation and regulations, in order to catch up with the dynamic developments in DH, the legal base needs to become more flexible. Technologies change, privacy importance does not.

Issues of social justice in the development of personalised therapy for paediatric SIRS patients

Abstract Background Systemic Inflammatory Response Syndrome (SIRS) is an often-emergent condition, which lacks specific diagnostic tools. Personalised therapy could fill this gap but as every new technology, it raises issues of social justice. Our report aims at identification and analysis of social justice implications within the bigger ERA PerMed funded project of development of tailored immunotherapy for paediatric SIRS patients (TIPS) coordinated by Prof. Catharina Schütz from Technic University Dresden. Methods Qualitative research methodology thought 10 semi-structured interviews. Systematic literature review grounded the interview questionnaire. Transcripts were subjected to thematic analysis by two independent researchers. Results Social justice was seen as equal chances of inclusion of different population groups in research. Socioeconomic differences were perceived as a challenge to ensure justice across various populations (N = 7). Two interviewees saw discrimination as inherent to precision medicine, which is focused on personalised treatment. Two experts viewed the exclusion of specific patients’ groups as an unsolvable problem, that only advocates for the inclusion of as many patients as possible. On the opinion of six experts individual and ethnocultural factors may influence outcomes in personalised treatment, especially considering the small sample size and the diverse populations. One medical expert, on the contrary, perceived no significant challenges associated with the heterogeneity of patients. Whether socioeconomic injustices should be addressed by guidelines and how these correspond to the rights of the patient were further discussed. Conclusions The issues of social justice accompany research in personalised medicine, including SIRS. In general, there is sensitivity to this issue, but current guidelines are too vague. As with other ethical problems, so with social justice we seem to have a rethinking of the concept, that needs further study. Key messages • In the context of SIRS personalised therapy research, there is a sensitivity to the issue of social justice, but no consensus how to ensure it. • Issues of social justice are often boiled down to equal chances of inclusion in research and equal access to treatment. In the case of personalised therapy, there seems to be more to it.

AI-driven ethical issues in the development of personalised therapy for pediatric SIRS patients

Abstract Background Systemic Inflammatory Response Syndrome (SIRS) is a rare disease often presenting emergency. While the aetiology varies, current diagnostic criteria do not allow differentiation. Hopes are placed on OMICs research and development of Artificial intelligence (AI) algorithms for personalised disease management. Our report aims at identification and analysis of AI-driven ethical issues within the bigger ERA PerMed funded project of development of tailored immunotherapy for paediatric SIRS patients (TIPS) coordinated by Prof. Catharina Schütz from Technic University Dresden. Methods Systematic literature review followed by qualitative research methodology. Ten experts with different backgrounds were interviewed. Subsequent thematic analysis was performed by two independent researchers. Results Experts were on the opinion that AI can lead to a depart from individual approach in the medicine, as the physician may be induced to only act based on algorithms that are more or less representative (N = 2). Interviewees were aware that AI can lead to changes in the assessment of reality, as it is dependent on data quality (N = 4). AI-aided decision-making might be useful for special therapeutic situations, although it may not always capture the subtleties of individual situations (N = 2). Positive implications of AI were significantly more emphasised, though current frameworks were perceived as more limiting than enabling. Conclusions Personalised therapy is making its first steps while the ethical apprehensions has already been there with a strong emphasis on precautionary principle and resulting limitations on the application of AI-algorithms. The multifaceted nature of the AI-driven ethical issues in personalised medicine research requires an interdisciplinary discourse, strengthened ethics training of all professionals involved in the technology development and more active involvement of physicians in the shaping of AI. Key messages • AI algorithms promise therapeutic benefits, not achievable by other means, for specific categories of vulnerable pediatrics patients. • The multifaceted nature of the AI-driven ethical issues in personalised medicine research requires an interdisciplinary discourse and further ethics training of all stakeholders.

Pharmacometrics in obstetrics and maternal-fetal medicine research: Bridging gaps in maternal and fetal pharmacology.

Pharmacometrics in obstetrics and maternal-fetal medicine research: Bridging gaps in maternal and fetal pharmacology.

The recent history and near future of digital health in the field of behavioral medicine: an update on progress from 2019 to 2024.

The field of behavioral medicine has a long and successful history of leveraging digital health tools to promote health behavior change. Our 2019 summary of the history and future of digital health in behavioral medicine (Arigo in J Behav Med 8: 67-83, 2019) was one of the most highly cited articles in the Journal of Behavioral Medicine from 2010 to 2020; here, we provide an update on the opportunities and challenges we identified in 2019. We address the impact of the COVID-19 pandemic on behavioral medicine research and practice and highlight some of the digital health advances it prompted. We also describe emerging challenges and opportunities in the evolving ecosystem of digital health in the field of behavioral medicine, including the emergence of new evidence, research methods, and tools to promote health and health behaviors. Specifically, we offer updates on advanced research methods, the science of digital engagement, dissemination and implementation science, and artificial intelligence technologies, including examples of uses in healthcare and behavioral medicine. We also provide recommendations for next steps in these areas with attention to ethics, training, and accessibility considerations. The field of behavioral medicine has made meaningful advances since 2019 and continues to evolve with impressive pace and innovation.

Pilocarpine in the Treatment of Presbyopia: Progress, Issues, and Future Prospects.

Presbyopia is a common age-related visual impairment. With the aging of the population, the incidence of presbyopia is increasing globally, becoming a worldwide public health concern. Treatment options for presbyopia include optical lens correction, surgical intervention, and pharmacological therapy. Pharmacological treatments for presbyopia are non-invasive, reversible, and have emerged over the past decade. Following the US Food and Drug Administration's approval of 1.25% pilocarpine for presbyopia, the use of pilocarpine and its compound formulations has gained increased attention, with some drugs entering clinical phase II/III trials ( www.clinicaltrials.gov ). Therefore, this article primarily describes and analyzes the progress of research on the use of pilocarpine and its compound formulations for presbyopia, as well as the challenges that remain to be addressed. The optimal dosage form, the optimal concentration, the long-term safety, and patient compliance should be further explored, and there is a lack of multi-center evidence-based medicine research to support it. The aim of this article is to provide a reference for researchers to conduct further in-depth investigations in this area.

A systematic review protocol of injuries and illness across all the competitive cycling disciplines, including track cycling, mountain biking, road cycling, time trial, cyclocross, gravel cycling, BMX freestyle, BMX racing, e-sport, para-cycling and artistic cycling

IntroductionThe sport of cycling has witnessed phenomenal growth over the past decade. Globally, over 200 million television hours across five continents watched the recent inaugural World Championships in Glasgow, in 2023. The Union Cycliste Internationale (UCI), the world cycling governing body, has highlighted its mission to “promote and support research in cycling epidemiology and medicine, especially for the benefit of lesser-known disciplines” within its 2030 Agenda. This paper outlines a proposed protocol to conduct a systematic review that comprehensively analyses and synthesises the existing literature about cycling-related injuries and illness across all competitive disciplines.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines will be followed through each stage of this systematic review. Cycling is an umbrella term used for many individual disciplines. Investigation of all types of injuries and/or illnesses sustained during training and/or competition among competitive athletes across all disciplines will be included in this review. A computerised, systematic literature search will be conducted in electronic databases MEDLINE, Scopus, Embase, and Cochrane Library. Independent screening by two reviewers in a two-step process: title/abstract screening followed by full-text review. The reference lists of included articles will be searched to identify any other potentially relevant articles. Narrative synthesis and tabular/charted presentation of the extracted data will be included.DiscussionThis protocol paper outlines the methodology to conduct a systematic review of injuries and illness across all competitive cycling disciplines. The aims of outlining this systematic review protocol are to aid research transparency, help reduce publication bias, prevent selective publication, and prevent the selective reporting of results. Future systematic reviews based on the proposed protocol will summarise the known prevalence, incidences, locations and burden of injury and illness across the sport of cycling.Trial RegistrationThis study has been registered with the PROSPERO International Prospective Register of Systematic Reviews (registration number CRD42024502703).

New Occurrence of Nigrospora oryzae Causing Leaf Blight in Ginkgo biloba in China and Biocontrol Screening of Endophytic Bacteria

Ginkgo biloba is a multifunctional composite tree species that has important ornamental, economic, medicinal, and scientific research value. In October 2023, the foliage of G. biloba on the campus of Nanjing Forestry University exhibited leaf blight. Black-brown necrotic spots were observed on a large number of leaves, with a disease incidence of 86%. After isolating a fungus from symptomatic leaves, pathogenicity was tested to satisfy Koch’s postulates. Using morphological features and multi-gene phylogenetic analyses of an internal transcribed spacer (ITS), elongation factor 1-alpha (EF1-α), and beta-tubulin (β-tub), the isolates YKB1-1 and YKB1-2 were identified as Nigrospora oryzae. N. oryzae was previously reported as an endophyte of G. biloba. However, this study shows it to be pathogenic to G. biloba, causing leaf spots. Two endophytic bacteria were isolated from asymptomatic leaves of diseased G. biloba trees, and their molecular identification was performed using 16S ribosomal DNA (16S rDNA). GBB1-2 was identified as Bacillus altitudinis, while GBB1-5 was identified as Bacillus amyloliquefaciens. The screening and verification of endophytic bacteria provide a new strategy for the control of N. oryzae.