Early Stages Of Research Research Articles

Metabolomics profile of selenium-enriched Bacillus subtilis alleviating perfluorohexanoic acid-induced brain damage in Carassius auratus and its response to the intestinal microbial community

Perfluorohexanoic acid (PFHxA), a prevalent industrial pollutant, poses substantial threats to aquatic organisms. Selenium, a vital trace element in animal physiology, has demonstrated detoxifying ability. A recent research focus involves converting inorganic selenium into biological selenium through probiotics to enhance absorption. Our early-stage research found that selenium-rich Bacillus subtilis could ameliorate PFHxA-induced brain damage in Carassius auratus through the microbiota–gut–brain axis, although the metabolic products generated by endogenous substance reactions in Carassius auratus remained unknown. This study investigated how selenium-enriched Bacillus subtilis mitigated PFHxA-induced brain damage in Carassius auratus by examining growth indicators, measuring brain tissue cell apoptosis, and analyzing changes in Carassius auratus brain tissue metabolites using non-targeted metabolomics. In addition, a combined analysis of non-targeted metabolomics and intestinal microbiota was used to explore the alleviating effects of selenium-enriched Bacillus subtilis on PFHxA-induced brain damage in Carassius auratus. The results showed that the bacteria could alleviate PFHxA-inhibited growth and decrease brain tissue cell apoptosis. In the perfluorohexanoic acid group (PFHxA group), 490 differential metabolites were identified, with 257 being upregulated and 233 being downregulated. The levels of harmful metabolites, such as phthalates and ethoxyquin, were significantly increased. Conversely, in the selenium-enriched Bacillus subtilis + perfluorohexanoic acid group (Se + PFHxA group), 1604 differential metabolites were detected, with 409 being upregulated and 1195 being downregulated. The corresponding levels of harmful metabolites were significantly decreased, while the levels of protective metabolites such as L-glutathione were increased. There were significant alterations in the composition of the fish intestinal microbiota due to PFHxA exposure, with selenium-enriched Bacillus subtilis inducing significant changes in the microbial community. These changes were suggested to play a role in mitigating PFHxA-induced toxicity. Overall, our findings highlight the potential of selenium-enriched Bacillus subtilis as an effective supplement in aquaculture for the protection of Carassius auratus against environmental pollutants such as PFHxA, thereby providing valuable insights into complex interactions among diet, gut microbiota, and host metabolism in aquatic organisms exposed to environmental pollutants.

Assessing Environmental Risks during the Drug Development Process for Parasitic Vector-Borne Diseases: A Critical Reflection.

Parasitic vector-borne diseases (VBDs) represent nearly 20% of the global burden of infectious diseases. Moreover, the spread of VBDs is enhanced by global travel, urbanization, and climate change. Treatment of VBDs faces challenges due to limitations of existing drugs, as the potential for side effects in nontarget species raises significant environmental concerns. Consequently, considering environmental risks early in drug development processes is critically important. Here, we examine the environmental risk assessment process for veterinary medicinal products in the European Union and identify major gaps in the ecotoxicity data of these drugs. By highlighting the scarcity of ecotoxicological data for commonly used antiparasitic drugs, we stress the urgent need for considering the One Health concept. We advocate for employing predictive tools and nonanimal methodologies such as New Approach Methodologies at early stages of antiparasitic drug research and development. Furthermore, adopting progressive approaches to mitigate ecological risks requires the integration of nonstandard tests that account for real-world complexities and use environmentally relevant exposure scenarios. Such a strategy is vital for a sustainable drug development process as it adheres to the principles of One Health, ultimately contributing to a healthier and more sustainable world.

The Constitutional Case Against the Mandatory Vaccine Policy — An Interdisciplinary South African Perspective

In this article, I rethink the perceived/received wisdom of the mandatory vaccine policy which has been punted so ardently, largely uncritically, in South Africa. I investigate whether this line of argument could be justified from a comparative South African constitutional perspective. It became evident in the early stages of my research that the legal perspective is too narrow and constricting to allow for a proper understanding of the puzzle. Following Friedman's suggestion of the schism between Western-based curative medicine and preventive strategies, I employ a critical public health theoretical framework complemented by insights from the social sciences. Given that the vaccine is a product of an outdated paradigm, South Africa's erroneous approach to the pandemic led to disastrous consequences and fared less favourably than the rest of Africa. It is concluded that a mandatory vaccine policy is both unconstitutional and unjustifiable, in the wider view.

“A Comprehensive Review of Anaemia Associated with Hypothyroidism”

Background: Thyroid hormones play a crucial role in erythropoiesis, both directly and indirectly, with reduced secretion potentially causing anaemia—a commonly overlooked symptom of hypothyroidism. By compiling existing data, discussing recent advancements, identifying root causes, and proposing potential treatment options, this work acknowledges the complexity of the issue and aims to serve as a foundational reference for those in the early stages of research or clinical practice. Methods: To comprehend the concept of this disease condition, a number of medical textbooks were consulted. Various search engines, such as PubMed, Google Scholar, Research Gate, Science Direct, Scopus, etc., were cited to explore the recent advancements and obtain data on the topic in question. Later, all the information and data gathered were organised into a review article. Conclusion: Anemia, often referred to as the “haematological mask” of hypothyroidism, can manifest even before hypothyroidism is clinically diagnosed. Hypothyroidism must be considered as a potential cause when confronted with refractory anemia, as its treatment is pivotal for achieving comprehensive and lasting improvements in haematological parameters.

CAR PARKING NEEDS ANALYSIS AT CAMPUS A, JAKARTA STATE UNIVERSITY IN THE CONSTRUCTION PERIOD

Parking is the main supporting facility in the campus environment. Jakarta State University (UNJ) is one of the state universities in the DKI Jakarta province. The increase in the number of UNJ students every year certainly causes an increase in the need for parking, especially on Campus A UNJ as the main campus. Coupled with a construction project in Campus A UNJ, the parking area, especially car parking, is getting narrower. Based on these problems, it is necessary to research parking arrangements at Campus A UNJ. This study aims to determine the need for parking and arrange the car parking area for Campus A UNJ according to the demand for car parking space that existed during the construction period. The parking space arrangement for Campus A UNJ considers UNJ's policy as the manager in allocating parking spaces in the future. Primary data was obtained by conducting a field survey using the number plate survey method and PSU calculation survey while secondary data was obtained from UNJ parking inventory data. Primary data were obtained by conducting field surveys on 29 May-31 May and 8-9 June. The results showed that the value of the need for car parking in 2023 was 367 PSU cars, while the number of parking lots available at Campus A UNJ was 389 PSU. The peak day occurs on Tuesday 30 May 2023 and the peak hour for parking accumulation occurs at 13.00-14.00 WIB. With a parking index close to 100%, this can make it difficult for drivers to find an empty parking space, especially considering the pattern of car parking in the UNJ campus A parking area rotates in one direction so that the opportunity to find an empty parking space during peak parking hours only has a one-time or one-time chance. parking spaces at peak parking hours only have a one-time chance or the driver must first exit the parking lot and then enter again to find an empty parking space. The arrangement of car parking modeling will also be presented in this article. It is hoped that the results of this early-stage research can provide an overview and recommendations on parking management methods at Campus A UNJ.

The rise of nanomechanical biomarkers: how cell and tissue mechanics can help medicine?

The rise of nanomechanical biomarkers: how cell and tissue mechanics can help medicine? “MechaDynA” develops two novel nanotools to allow force measurements on living cells. The goal is to obtain a complete, multi-scale picture of the physics of leucocyte adhesion. Technologically, it will establish two nanotools for force measurements on living cells covering the widest temporal range. This will open the door to unexplored physical phenomena in cell biology, biological physics and soft condensed matter. Biomedically, the expected outcomes will provide a mechanistic description of the physics of leucocyte immune response that may lead to better diagnosis and therapeutics. “Phys2BioMed” aims to identify biomechanical markers for the early detection of disease. The objective is to create an interdisciplinary research training network for early-stage researchers on the application of physical tools for the mechanical phenotyping of cells and tissues applied to early diagnostics. The network merged training from fields such as nanotechnology, physics, biology and medicine, defining the main features of new-generation instrumentation optimised for the mechanical phenotyping of clinical samples.

Facilitating research ethics in qualitative research through doctoral supervision in the context of European Commission funding

The increasing need for innovative research driven by rapid global changes gives doctoral supervisors of early-stage researchers a significant role in facilitating the ethical conduct of qualitative research. In the context of European Commission funding, the demands of research ethics and integrity place a tremendous responsibility on the supervisors of early-stage researchers involved in cross-national projects. This document study seeks to illuminate the role of the supervisors in facilitating research ethics in these projects. Specifically, we describe and discuss the supervisor role associated with five approaches to doctoral supervision of qualitative research, namely those described as ‘Functional’, ‘Enculturation’, ‘Critical thinking’, ‘Emancipation’ and ‘Developing a quality relationship’. The main challenges for supervisors of cross-national research projects are the cultural and linguistic mobilisation of ethical principles in qualitative research processes and the management of the future use of open data. The results from this study have implications for planning and conducting cross-national studies within research involving human participants. These results can guide supervisors in the codification and mobilisation of ethical qualitative research in practice.

Patterns of dissertation dissemination: publication-based outcomes of doctoral theses in the social sciences

AbstractDissemination of knowledge through the publication of findings is a cornerstone of the academic research system. Doctoral dissertations document the findings made by early-stage researchers during their doctoral studies. However, prior research suggests that dissertations may not be effective in disseminating these findings to the broader community of researchers. We study how knowledge documented in doctoral dissertations is disseminated. Specifically, we investigate which dissertation characteristics and institutional factors are related to the number of journal publications based on these dissertations and the number of citations that these publications receive. Our analysis uses a random sample of doctoral dissertations from German universities in economics, political science, and sociology. We find that “cumulative” dissertations—dissertations consisting of a number of separate articles—are turned into three times more publications which receive three times more citations than monographic dissertations. We also find explorative evidence that dissertations written in English and empirical dissertations have higher publication-based outcomes. We conclude that a policy allowing doctoral candidates to write their dissertations in a cumulative format provides them with an opportunity to share the results of their research through publications in peer-reviewed journals.

Biopolymer Composite Materials in Oil and Gas Sector

In the oil and gas industry, the demand for alternative materials is rising due to corrosion and the desire to reduce costs through weight reduction. Polymer composites are gaining attention for their corrosion resistance, favourable strength-to-weight ratio, and cost-effectiveness. The biopolymer composite is projected to have an output worth $4.95 billion between 2021 and 2025 and growth at a 5.38% compound annual growth rate. This review focuses on exploring the potential of natural fibres as reinforcement for biofibre polymer composite pipes in oil and gas, highlighting their ecofriendliness, biodegradability, and cost-efficiency. The paper assesses biopolymer composite pipes’ development, challenges, and applications, particularly those using continuous basalt and banana fibres. While basalt fibre has found field applications, banana fibre-reinforced polymer composites are still in the early research stages. Despite significant oil and gas industry players already endorsing polymer composites, further research is needed for biopolymer composites to address challenges like compatibility, environmental impact, standardisation, long-term durability, production processes, and regulatory acceptance. Advancing biocomposite research and exploring new research opportunities are essential for engineering advancements and advanced materials.

Exploring the relationships between human consumption and environmental pressure: A case study of the Yangtze river economic zone in China.

It is crucial to decouple and coordinate human consumption and its environmental pressure for achieving sustainable development. As an important aspect of United Nations Sustainable Development Goal (SDG12), sustainability on material consuming is still in its early stages of research. To address the research gap in sustainable consumption of vegetation net primary productivity (NPP), this study analyzed the spatio-temporal dynamics of human consumption and environmental pressure in the Yangtze River Economic Zone (YREZ) using consumption-based HANPP (cHANPP) and Human Appropriation of Net Primary Production (HANPP) as indicators. Later, we measured their decoupling relationship using Tapio decoupling approach. We found that distribution of HANPP and cHANPP were regionally separated, with the former mainly concentrated in the middle and upper reaches provinces, while the latter concentrated in the lower reach provinces. From 2004 to 2019, the relationship between HANPP and cHANPP changed from strong negative decoupling to weak decoupling in the YREZ. Furthermore, the relationship was differed among different regions. As a whole, developing regions showed a weak decoupling state, experiencing an increase in environmental pressure (i.e., HANPP) alongside increased human consumption (i.e., cHANPP). In contrast, developed regions showed a strong decoupling state, experiencing a decrease in environmental pressure (i.e., HANPP) alongside increased human consumption (i.e., cHANPP). Our study highlights that different countermeasures should be formulated by regions according to their own situation to realize sustainable regional development.

Collaborative Learning of Ph.D. Candidates in Design on Emerging Scenarios in Scientific Publication

The article describes a collaborative learning process aimed at introducing early stage researchers in design to a non-hegemonic approach to design knowledge production and publications. Four co-creation sessions has been held in the context of Prode project, engaging phd students in design to take in account emerging issues in scientific publishing. In specific an innovative Living publication lifecycle has been introduced (supporting an iterative model for publications) and the relative Living publications scenario (including Augmented publications; Collective authoring; Evolving publications; Publications reuse) has been used to discuss and disrupt traditional publication patterns and envision beyond the “article” format, new typologies of (not only textual) research products and new forms of dissemination, to meet the challenges of an impactful design education. The context of change of scientific publication and hypothesis underlying the paper have been discussed elsewhere (Lupo, 2022; Lupo, 2023). For the purpose of this article, the focus is the training of early stage researchers, in order to make them aware of the potentiality of plurality and diversity of design knowledge publication. The collaborative approach and tools adopted eased the empowering of the PhD students through brainstorms, role plays and hands-on tests.

Demonstration of a robust high cell density transient CHO platform yielding mAb titers of up to 2 g/L without medium exchange.

Biopharmaceuticals like therapeutic monoclonal antibodies (mAbs) and other derived proteins are popular for treating various diseases. Transient gene expression (TGE) is typically used as a fast yet efficient method to generate moderate amounts of material. It has been used to support early stage research and discovery processes. Introduction of a robust high yielding and predictive TGE platform in Chinese hamster ovary (CHO) is crucial. It maintains the consistency in cell lines and processes throughout the early drug discovery and downstream manufacturing processes. This helps researchers to identify the issues at an early stage for timely resolution. In this study, we have demonstrated a simple high-titer platform for TGE in CHO based on a dilution process of seeding cells. We achieved titers ranging from 0.8 to 1.9 g/L for eight model mAbs at three scales (1, 30, 100 mL) in 10 days using our new platform. The ability to seed by dilution significantly streamlined the process and dramatically enhanced platform throughput. We observed a modest reduction in titer ranging from 11% to 28% when cells were seeded using dilution compared to when cells were seeded using medium exchange. Further studies revealed that carry over of spent medium into transfection negatively affected the DNA uptake and transcription processes, while the translation and secretion was minimally impacted. In summary, our transient CHO platform using cells prepared by dilution at high densities can achieve high titers of up to 1.9 g/L, which can be further improved by targeting the bottlenecks of transfection and transcription.

Keeping the health of our home planet in mind as we do research

ABSTRACT Climate change stood out as an important ethical issue that is contemplated, at least among early-stage researchers, in Buedo and colleagues’ collected views on ethical issues in preclinical research. It is about time that all scientists and researchers, young or old, to stand to be accountable for our contributions toward environmental crises in our work, and conversely to think about how these crises could be mitigated by our research.

“Nutrient–fungi–host” tripartite interaction in cancer progression

AbstractThe human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer‐related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue‐resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside.

Enhancing diaphragmatic defect repair and regeneration: How biomaterials leading the way to progress?

AbstractPhysicians encounter significant challenges in dealing with large diaphragmatic defects in both pediatric and adult populations. Diaphragmatic hernias, such as Morgagni, Bochdalek, and Hiatus hernias, can result in congenital lesions that are often undiagnosed until the appearance of symptoms (bleeding, anemia, and acid reflux). Therefore, substantial potential exists for developing tissue‐engineered constructs as novel therapeutic options in clinics. Recent research indicates promising mid‐term performance for both natural and synthetic materials. However, studies exploring their application in diaphragm regeneration are limited and remain in the early research stages. Additionally, further investigation is required to address the constraints in human tissue supply for clinical implementation. This article comprehensively reviews the role of biomaterials in diaphragmatic tissue repair and regeneration. It emphasizes biomaterials, including biomimetic polymers used in technological solutions. This summary will enable researchers to critically assess the capability of existing natural biomaterials as essential tissue‐engineered patches for clinical use.

Design and development of high-dose bioactive oil-loaded transdermal patch with the aid of natural waste as an adsorbent- optimization with SeDeM-SLA tool

PurposeRheumatoid arthritis (RA) is an autoimmune disease that affects joints significantly. Its prevalence varies globally, with more impact on females than males. Presently it is treated using NSAIDs which unfortunately show significant adverse effects on the liver and renal system after long-term use. Conventional topical use of bioactive oils like ginseng oil is one of the best natural options to treat RA, but poor retention time has limited its usefulness. By considering the involvement of ginseng oil in managing RA and the associated limitations, the proposed study investigated the impact of the transdermal patch prepared by ginseng oil loaded-natural biocompatible adsorbent in treating RA. MethodAt early stage of research, the flow property of ginseng oil-loaded adsorbent was optimized by using advanced technology, viz. Brookfield powder flow tester and SeDeM model. In the lateral stage, the transdermal patches of oil-loaded adsorbent were prepared by variable concentrations of HPMC and PEG using the solvent casting method. Prepared patches were evaluated for various parameters. ResultOptimized patch showed average thickness, average weight, folding endurance, tensile strength, and moisture content as 0.38 ± 0.10 mm, 0.215 ± 0.41 gm/ 2 sq. inch, 145 ± 0.20, 3.370 ± 0.16 MPA/mm and 3.770 ± 0.81 %, respectively, along with satisfactory skin adherence property. In vitro diffusion study showed increased ginseng oil release from the prepared patch at a specific interval of up to 10 h, and then release diminished. ConclusionAnti-inflammatory test and measurement of cytokines levels (IL-6 and TNF-α) on male Wistar rats showed a significant reduction in paw edema and notable control on the cytokines level compared to a conventional approach.

More ethics in the laboratory, please! Scientists’ perspectives on ethics in the preclinical phase

ABSTRACT In recent years there have been calls to improve ethics in preclinical research. Promoting ethics in preclinical research should consider the perspectives of scientists. Our study aims to explore researchers’ perspectives on ethics in the preclinical phase. Using interviews and focus groups, we collected views on ethical issues in preclinical research from experienced (n = 11) and early-stage researchers (ESRs) (n = 14) working in a gene therapy and regenerative medicine consortium. A recurring theme among ESRs was the impact of health-related preclinical research on climate change. They highlighted the importance of strengthening ethics in relations within the scientific community. Experienced researchers were focused on technicalities of methods used in preclinical research. They stressed the need for more safeguards to protect the sensitive personal data they work with. Both groups drew attention to the importance of the social context of research and its social impact. They agreed that it is important to be socially responsible – to be aware of and be sensitive to the needs and views of society. This study helps to identify key ethical challenges and, when combined with more data, can ultimately lead to informed and evidence-based improvements to existing regulations.

Harnessing the power of RNA therapeutics in treating ischemic heart failure: the TRAIN-HEART story.

Ischemic heart disease (IHD) is one of the world's foremost killers, accounting for 16% of all deaths worldwide. IHD is the main cause of heart failure (HF), as it leads to pathological changes in the heart, improper pumping function and eventual death. Therapeutic interventions usually follow a systemic general strategy for all heart failure subtypes due to the lack of a deep understanding of the disease mechanisms. Hence, HF and IHD therapeutics need groundbreaking concepts to guide the development of a new therapeutics class that tackles the disease at a molecular level. The TRAIN-HEART consortium, a Marie Skłodowska-Curie Actions Innovative Training Network (MSCA-ITN) funded by the European Commission, was established with the goal of filling that gap and developing RNA-based cardiovascular therapeutics. Created in the context of the Horizon 2020 research and innovation program, TRAIN-HEART comprises three key work packages (WPs) focusing on the pathogenesis of heart disease (WP1), the therapeutic potential of RNA therapeutics (WP2), and the development of new efficient delivery systems (WP3). Fifteen international early stage researchers (ESRs) from multiple complementary scientific disciplines were recruited to collaborate with a network of PIs from nine academic and eight non-academic partners in various disciplines to fully harness their collective potential for the betterment of HF treatment. This article provides an overview of the benefits of being part of an MSCA-ITN, with its different training and networking opportunities, maximizing ESRs' potential and broadening collaborative research possibilities. Finally, it describes what was like to do a PhD during the COVID-19 pandemic, with all the uncertainty and concern attached to it. Luckily, TRAIN-HEART stood out as a proactive network, finding new initiatives and alternatives to promote scientific and personal development. By bringing together leading academic teams, (biotech) companies, and highly motivated researchers, TRAIN-HEART is expanding scientific horizons and accelerating future development of effective RNA-based therapies to treat IHD.

International collaboration of early-stage researchers in nursing science: A discussion paper

Nursing is a global profession and international collaboration of early-stage researchers (ESRs) builds their capacity as future nursing scientists. This discussion paper focuses on international collaboration of ESRs in nursing science. The aim of this paper was to clarify the optimal collaboration forms and identify challenges and recommendations for supporting individual researchers and organisations to strengthen international collaboration for the ESR phase. The paper is based on previous literature and authors’ experiences in the collaboration between two countries by the Baltic Sea, Estonia and Finland. In future, more discussion is needed on how to establish international partnerships and collaboration in researcher career building globally: expanded and long-term collaboration is needed to develop nursing science but also to improve nursing care, patient outcomes and, finally, to benefit society.

Extremely Large-Scale MIMO: Fundamentals, Challenges, Solutions, and Future Directions

Extremely large-scale multiple-input-multipleoutput (XL-MIMO) is a promising technology to empower the next-generation communications. However, XL-MIMO, which is still in its early stage of research, has been designed with a variety of hardware and performance analysis schemes. To illustrate the differences and similarities among these schemes, we comprehensively review existing XL-MIMO hardware designs and characteristics in this article. Then, we thoroughly discuss the research status of XL-MIMO from "channel modeling", "performance analysis", and "signal processing". Several existing challenges are introduced and respective solutions are provided. We then propose two case studies for the hybrid propagation channel modeling and the effective degrees of freedom (EDoF) computations for practical scenarios. Using our proposed solutions, we perform numerical results to investigate the EDoF performance for the scenarios with unparallel XL-MIMO surfaces and multiple user equipment, respectively. Finally, we discuss several future research directions.