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      Future Science OA 2019 early career researcher issue: foreword

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          Abstract

          LMH/JM: We would like to take this opportunity to welcome our readers to the Future Science OA (FSOA) Early Career Researcher (ECR) Issue. The concept of this issue was born from the understanding that the transition from doctoral studies to academic research can be daunting, with many challenges and hurdles in place. These challenges are not only limited to academic aspects (such as publishing manuscripts and acquiring research funding), but also cover general day-to-day motivation and individual well-being of the researcher. It is important that we understand these difficulties and actively look to support ECRs by providing advice through mentoring schemes and offering opportunities to demonstrate personal/academic capabilities wherever possible (e.g., conference attendance, networking, training courses). The availability of a rich and rewarding experience in the early postdoctoral years will actively encourage researchers to remain in academia (or pursue industrial-based research). This will, in turn, maintain the motivation and passion for research that leads to driving forward the science of the future and establishing personal feelings of self-efficacy and importance within our respective fields. The impact of these complex aspects of psychological health on ECRs cannot be underestimated and, therefore, we should all offer encouragement and recognition in helping promising individuals to flourish. For these reasons, this issue aims to provide advice and support to ECRs from their peers, as well as to offer a platform to publish excellent research that is being performed by developing scientists/researchers. LMH: I am delighted to be involved in this year’s ECR issue. As a researcher who has been recently appointed onto academic tenure, I have experienced first-hand the obstacles and barriers that must be navigated in order to make the big leap into a career of academic research. One of the most difficult aspects of this transition is the realization and acknowledgment that rejection is a major part of our profession. This could be from the interview for that dream job, a submission to a leading journal or that pot of funding that is going to transform your career. While none of these situations is pleasant, we must learn to channel the disappointment to allow for ourselves to develop further and improve for the next opportunities that arise. It is important to remember that you are not the only one. Virtually, all ECRs will have experienced these difficulties, and many of the now internationally successful and leading researchers will have faced these challenges earlier in their career. It is vital that we all remain focussed and confident in our abilities by setting ambitious but realistic targets that can be regularly reassessed. By being conscious and aware that these difficult times will come, we are able to prepare correctly and react in a proactive manner to bring about the best possible outcomes. I would like to wish all ECRs who are reading this the best of luck for your future and encourage you to stay humble but never give up on your dreams. JM: Here at FSOA, we have a number of initiatives to help support ECRs. It is important for us as a publisher to understand the needs and concerns of ECRs who are set to have a big impact in their field. In this special issue, we aimed to include a range of articles touching on what we believe are some of the most important topic areas for ECRs. The issue also features some exciting work led by ECRs. We begin with a selection of interviews from our FS Early Career Research Award (ECRA) winner, Viviana Mucci (University of Antwerp), and finalists, Amy Winship (Monash Biomedicine Discovery Institute), Hannah Wardill (University of Adelaide and the University of Groningen) and Aya Mousa (Monash University). These interviews provide an insight into life as an ECR, what made them chose a career in their field, challenges and outlook to the future [1–4]. The ECRA, supported by FSOA, is an initiative that aims to recognize outstanding, highly talented and motivated researchers within the first 5 years of their first career position (in academia or industry). The winner receives membership to the FSOA early career advisory panel, a webinar to present their work and a monetary prize to support their career, among other things. It is important to include topics that relate to many ECRs. Catherine Rawlins (Universite de Bordeaux) speaks about a very timely topic – mental health and how it can often be neglected in academia [5]. We would like to thank Catherine for writing this very honest and open editorial on such an important subject. Kevin Deighton (Leeds Beckett University) and Javier Gonzalez (University of Bath) follow with an editorial based on the interesting concept ‘Academic Periodization’. Academic periodization is based on concepts used to optimize elite sporting performance, and this may represent an effective approach to help young academics reflect on their working practices in order to meet the demands of their roles [6]. Alistair Moss (University of Edinburgh) discusses both the challenge and importance of finding a mentor who can help to support the career of a young investigator in the editorial ‘See one, do one, teach one’ – finding your mentor in academic medicine’ [7]. In the first of our showcase pieces, guest editor Liam Heaney (Loughborough University) and his colleagues Owen Davies (Loughborough University) and Nicholas Selby (University of Nottingham) have described the potential use of short-chain fatty acids as therapeutic targets and/or biomarkers in renal disease patients in the editorial ‘Gut microbial metabolites as mediators of renal disease: do short-chain fatty acids offer some hope?’ [8]. As the winner of the ECRA, Viviana Mucci was awarded a free accelerated publication in FSOA. This research article on Mal de Debarquement syndrome, specifically aims to evaluate if symptoms change in patients with Mal de Debarquement syndrome during their pregnancy [9]. Viviana also had the opportunity to present her research on the same subject in a webinar organized as part of the ECRA. A group of researchers based at the University of Sydney focus on the complex field of mass spectrometry tissue imaging. O’Rourke et al. provides a visual troubleshooting guide that will act as a reference point for a range of sample preparation mistakes and explanations for unusual or suboptimal data [10]. Heaney also authors the article ‘Probiotics: Current Landscape and Future Horizons’. This review discusses the recent rise in the global market for probiotic supplements, current research and drawbacks alongside the lack of translation from laboratory science to clinical application [11]. LMH/JM: We hope you enjoy reading the articles published in this ECR issue and invite you to contribute to discussion on this topic, and to future issues of FSOA.

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          Gut microbial metabolites as mediators of renal disease: do short-chain fatty acids offer some hope?

          One in ten people worldwide have chronic kidney disease (CKD), which can progress to end-stage renal disease (ESRD) and increase cardiovascular risk [1]. CKD is defined in the “Kidney Disease: Improving Global Outcomes” guidelines as abnormalities of kidney structure or function present for >3 months that have implications for health; the criteria include a reduced glomerular filtration rate, presence of albuminuria or abnormalities of kidney structure [2]. CKD is a major health concern and consumes considerable resource, with CKD-associated costs in England estimated at £1.45 billion per annum [3]. CKD has a number of different causes but there are common underlying disease mechanisms, in particular fibrosis, inflammation and hypoxia [4]. Current therapies are nonspecific and do not directly target these mechanisms. Their ineffectiveness is evident by the many patients who progress relentlessly to renal failure, whereas the high number of failed clinical trials stresses the need for a paradigm shift. Therefore, an improved knowledge and assessment of etiological factors would facilitate personalized medicine approaches by determining individual patient risk, as well as targeting of and assessing response to therapies. One potential target is the metabolic relationship between the gut microbiome and host. Increasing evidence suggests that the gut microbiome plays an important role in homeostasis, health and disease [5]. Bacteria, as living organisms, require nutrients and energy sources to function. This demand is met via internal metabolism and often leads to the release of metabolic by-products. Importantly, these molecules cross the intestinal wall and thus enter the human circulatory system. Host diet plays a major role in bacterial metabolism, with the breakdown of dietary molecules to potentially harmful metabolites shown to associate with the development or progression of multiple diseases [5]. Renal disease patients are at a high risk of a build-up of these metabolites due to declining capabilities for systemic metabolite clearance. This build-up can lead to negative effects on host health and demonstrates an indirect effect of the gut microbiome on disease status. For instance, gut bacterial fermentation of amino acids tyrosine and tryptophan increases circulating levels of uremic toxins such as p-cresol (and its sulfated form) and indoxyl sulfate [6], which have been shown to be associated with progressive CKD [7,8]. Importantly, elevated levels of these metabolites have been associated with disease progression and adverse outcomes in CKD and ESRD patients [7,9,10]. In addition, trimethylamine N-oxide (TMAO) is a downstream marker of gut microbial metabolism of dietary trimethylamine-containing molecules (such as betaine, choline and L-carnitine) that has demonstrated negative mechanistic effects in models of atherosclerosis and pressure overload-induced heart failure [11,12]. Furthermore, elevated TMAO levels measured in patients with cardiovascular disease have shown strong associations with increased risk of adverse outcomes including death and rehospitalization [13,14]. Circulating TMAO levels have also been investigated in CKD, albeit to a lesser extent to date. Increased levels of TMAO have been shown to accelerate renal fibrosis in a C57BL/6J mouse model that is relatively resistant to kidney injury [15]. There are some suggestions that TMAO may also have functions as a biomarker of kidney disease, with 30-fold elevations documented in ESRD patients and elevated risk of adverse events in patients at CKD stages 3–5 that have high levels of TMAO [15–17]. However, not all metabolites produced as by-products of bacterial metabolism are associated with negative pathophysiological processes and poor clinical outcomes. In contrast to the evidence shown for uremic toxins and TMAO, short-chain fatty acids (SCFAs) are a bacterial-mediated classification of metabolites that have been associated with protective effects. SCFAs are aliphatic carboxylic acids of low carbon number (C2–6) that are produced following fermentation of dietary fiber or via protein catabolism (creating branch-chained forms), with acetate (C2), propionate (C3) and butyrate (C4) the predominant contributors to total SCFA content [18]. SCFAs have been shown to bind to G protein-coupled receptors to beneficially modulate immunity, blood pressure, inflammation, as well as fibrotic and epigenetic factors in models of kidney disease [18]. Animal and cell line supplementation studies have shown that SCFAs can ameliorate some of the progressive factors thought to underpin CKD progression through the blunting of fibrotic and inflammatory responses. Specifically, butyrate is known to reduce the production of the pro-fibrotic cytokine TGF-β1 in renal epithelial cells [19,20], as well as decreasing the expression of both pro-inflammatory (e.g., NF-κB) and pro-oxidative stress pathways (e.g. eNOS) [20,21]. Protective effects of SCFAs on fibrotic factors have included the suppression of TNF-α stimulated MCP-1 expression (observed for acetate, propionate and butyrate [22]), and the acetate-induced inhibition of NOX2 signaling through the attenuation of histone deacetylase activity in T cells following sepsis-induced kidney injury [23]. In an animal model of acute kidney injury (mice that underwent bilateral renal ischemia-perfusion), Andrade-Oliveira et al. [24] assessed the impact of acetate, propionate and butyrate on renal function following ischemia and supplementation with any one of the SCFAs ameliorated the degree of renal injury. Outcomes included reduced serum creatinine levels, blunted pro-inflammatory cytokine/chemokine production and decreased necrotic scores in kidney tubular epithelial cells. These effects were most prominent following acetate supplementation and were also observed when acetate-producing bacteria were given by daily gavage in place of chemical supplementation. Furthermore, it has been shown that the feeding of a diet high in fermentable fibrous material (e.g., amylose maize resistant starch or HAMRS2) mimics the beneficial effects of ameliorating kidney disease in a similar way as observed with SCFA supplementation (reduced declines in renal function, less interstitial fibrosis and tubular damage, and reduced activation of inflammatory and fibrotic pathways) [25]. Alongside these clinical improvements, high-fiber diets induce changes in circulating gut metabolites through the upregulation of SCFA production and decreases in p-cresol, indoxyl sulfate and TMAO [26,27]. This demonstrates a multimetabolite interaction between the metabolic processes of the gut bacteria and host health, with potential application of promising nutritional strategies to elevate bacterial SCFAs, reduce build-up of uremic toxins and subsequently improve disease characteristics. Despite the potential benefits documented with SCFA supplementation, findings are predominantly restricted to in vitro and in vivo models of renal disease. Importantly, there is a current lack of clinical research investigating the potential of circulating SCFA measurements to serve as biomarkers in diagnosis, prognosis and therapeutic monitoring of renal patients. Further study would therefore seem warranted. The routine clinical measurement of systemically absorbed gut SCFAs offers the potential to develop clinical risk stratification tools that may then lead to targeted treatments to slow CKD progression. This could be in the format of dietary (e.g., high-fiber), medicinal (e.g., SCFA supplementation) or biological (e.g., probiotics) interventions. Further research in this area will provide insight on whether increasing circulating SCFAs provide any direct clinical benefit, which ultimately could result in a new therapeutic approach for people with CKD.
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            Pilot study on patients with Mal de Debarquement syndrome during pregnancy

            Aim: To evaluate if patients with Mal de Debarquement syndrome (MdDS) demonstrate different symptom levels or symptom type during pregnancy. Materials & methods: 18 MdDS patients that were or had been pregnant during their condition were recruited to complete a retrospective online questionnaire. Respondents answered questions regarding their basic clinical data, diagnosis, triggers and differences in symptom level and symptom type during pregnancy and before pregnancy. Results: A total of 81.3% reported that their symptoms were reduced during pregnancy compared with before pregnancy. Respondents also reported a different perception of motion and experienced less dizziness while being pregnant. Conclusion: The physiological changes that occur during pregnancy improve the symptoms of patients with MdDS, and this is potentially attributable to the rise in estrogen and progesterone.
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              The ivory tower of academia and how mental health is often neglected

              Whether you are in the thick of graduate school or a tenured professor struggling to obtain the next grant, the truth is, academia operates in a culture of extreme competitiveness. I am certainly not the first person to make the ‘ivory tower’ metaphor when describing the academic environment. Even in the best departments, egos run unchecked and many are not held accountable for their actions on how they treat their students, colleagues and collaborators. Increasing competitiveness for grants and publications, the privatization of universities, a decline in tenured faculty positions, low pay and minimal benefits are just some of the stressors academics face [1]. With all of this, it is no wonder that mental health is a serious issue in academia and it is imperative that we talk honestly about how it is affecting the scientific enterprise. As someone who has recently obtained their PhD, I can say with certainty that I had a great graduate education at a top school; I was able to attend conferences, published a few papers and had access to excellent training and instrumentation that prepared me well for my current postdoctoral position. However, I cannot deny that for a majority of graduate school I was depressed and struggled with mental health issues along with job related issues (e.g., switching advisors and sexual harassment). Anxiety and depression can affect anyone and graduate students are particularly vulnerable; an article in C&EN News reported on the suicide of a graduate student and highlighted how easily mental health can decline while pursuing a PhD [2]. In 2018, there was a published study in Nature which found that 40% of the 2279 students surveyed around the world had anxiety and depression scores in the moderate to severe range [3]. Graduate students are placed in a tenuous position with the duality of being both a student and an employee. You are expected to teach courses and conduct lab work for which the university profits, but when it comes to matters regarding benefits, pay and other job-related support, you are treated like a student. Moreover, there is no regulation of the number of hours students work, vacation time and how you are treated by your superiors. In USA, much to the chagrin of neoliberal universities, there has been an increase of graduate students unionizing to improve their quality of life and to take some control over their working conditions [4]. Many of the mental health challenges faced in graduate school carry over into the behaviors and methods of future academics; thus, the vicious cycle continues. After completing a PhD, moving to a new institution and starting a new position in academia, these problems do not go away. Academics are notorious for having competitions on who is suffering the most. There are countless stories of late hours, working through weekends and not taking vacations, all under the guise that the work being done is more noble than nonacademics. The fallout of this is poor physical and mental health and a deterioration of one’s personal life. Friendships, family and social life all fall by the wayside and you lose sight of who you are as a person outside of your position. Academia is built on the exploitation of often well-meaning academics, but the higher you rise, the greater the workload, the greater the pressure and the greater the fall. What is worse, if you try to achieve the sought-after work–life balance, you are seen as not working hard enough and judged by your colleagues. In my efforts to avoid this, I volunteered with my local section of the American Chemical Society since the beginning of my PhD, which gave me a nonlab work related outlet, helping me develop skills and make new friends and contacts. Naturally, I was criticized by my colleagues for not being committed enough to my lab work, but it was the best decision I made and ensured I had marketable skills outside of the ivory tower. There are many things that have make success in academia difficult and too many to fit in one article; for instance, I have not addressed the additional challenges that people of color, LGBTQ+ and single parents face. Although this article is from a heterosexual, white and American perspective, it is still my hope that if these experiences resonate with you and you are struggling, that you seek help. It was through the support of friends, family and my therapist that I was able to complete my degree and manage the mental load of graduate school a bit better. I want to close this editorial with my perspective now that I am looking back at graduate school a few months into my new position. I moved from USA to France which has its challenges in addition to making the transition from a graduate student to a postdoc. Already I see an improvement in my productivity now that I am in a healthier work environment where work/life balance is achievable and encouraged. The system is flawed and unjust, but we as individuals can do our part to change the toxic work environment for the next generation. We have to make efforts going forward not to be complicit in the exploitation of our fellow colleagues and the people we mentor. If you are questioning your future career in academia, I highly recommend the book ‘The Professor is In’ by Dr Karen Kelsky who gives a frank and honest assessment of what a career as an academic is really like [5]. Although the academic system is tough to navigate and positive change in the ivory tower has a long way to go, take charge of what you can control such as your own happiness and mental health.
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                Author and article information

                Journal
                Future Sci OA
                Future Sci OA
                FSOA
                Future Science OA
                Future Science Ltd (London, UK )
                2056-5623
                April 2019
                03 May 2019
                : 5
                : 4
                : FSO393
                Affiliations
                [1 ]School of Sport, Exercise & Health Sciences, Loughborough University, Loughborough, LE11 3TU, UK
                [2 ]Future Science Group
                Author notes
                [* ]Author for correspondence: j.martin@ 123456future-science.com
                Author information
                https://orcid.org/0000-0002-8791-0167
                Article
                10.4155/fsoa-2019-0039
                6511919
                2382fd0e-4fed-4f21-b252-1f8253e602c4
                © 2019 Future Science Ltd

                This work is licensed under the Creative Commons Attribution 4.0 License

                History
                : 25 March 2019
                : 25 March 2019
                : 03 May 2019
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                Pages: 3
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