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The role of human microbiota in cancer initiation and progression is recognized in recent years. In order to investigate the interactions between cancer cells and microbes, a systematic analysis using various emerging techniques is required. Owing to the label-free, non-invasive and molecular fingerprinting characteristics, vibrational spectroscopy is uniquely suited to decode and understand the relationship and interactions between cancer and the microbiota at the molecular level. In this review, we first provide a quick overview of the fundamentals of vibrational spectroscopic techniques, namely Raman and infrared spectroscopy. Next, we discuss the emerging evidence underscoring utilities of these spectroscopic techniques to study cancer or microbes separately, and share our perspective on how vibrational spectroscopy can be employed at the intersection of the two fields. Finally, we envision the potential opportunities in exploiting vibrational spectroscopy not only in basic cancer-microbiome research but also in its clinical translation, and discuss the challenges in the bench to bedside translation.

Background Paraplegia remains one of the most devastating complications of descending and thoracoabdominal aortic repair. The aim of this review is to outline the current state of art in the rapidly developing field of spinal cord injury research. Methods A review of PubMed and Web of Science databases was performed using the following terms and their combinations: spinal cord, injury, ischemia, ischemia-reperfusion, ischemic spinal cord injury, paraplegia, paraparesis. Articles published before July 2019 were screened and included if considered relevant. Results The review focuses on the topic of spinal cord injury and the developments concerning methods of monitoring, diagnosing, and preventing spinal cord injury. Conclusions Translation of novel technologies from bench to bedside and into everyday clinical practice is challenging; however, each of the developing areas holds great promise in spinal cord injury prevention.

Background: The development of cancer drugs is among the most focused “bench to bedside activities” to improve human health. Because of the amount of data publicly available to cancer research, drug development for cancers has significantly benefited from big data and Artificial Intelligence (AI). In the meantime, challenges, like curating the data of low quality, remain to be resolved. Objective: This review focused on the recent advancements in and challenges of AI in developing cancer drugs. Method: We discussed target validation, drug repositioning, de novo design, and compounds' synthetic strategies. Results and Conclusion: AI can be applied to all stages during drug development, and some excellent reviews detailing the applications of AI in specific stages are available.

Pharmaceutical nanotechnology research is focused on smart nano-vehicles, which can deliver active pharmaceutical ingredients to enhance their efficacy through any route of administration and in the most varied therapeutical application. The design and development of new nanopharmaceuticals can be very laborious. In recent years, the application of mathematics, statistics and computational tools is emerging as a convenient strategy for this purpose. The application of Quality by Design (QbD) tools has been introduced to guarantee quality for pharmaceutical products and improve translational research from the laboratory bench into applicable therapeutics. In this review, a collection of basic-concept, historical overview and application of QbD in nanomedicine are discussed. A specific focus has been put on Response Surface Methodology and Artificial Neural Network approaches in general terms and their application in the development of nanomedicine to monitor the process parameters obtaining optimized system ensuring its quality profile.

Pre-clinical models of disease have long played important roles in the advancement of new treatments. However, in traumatic brain injury (TBI), despite the availability of numerous model systems, translation from bench to bedside remains elusive. Integrating clinical relevance into pre-clinical model development is a critical step toward advancing therapies for TBI patients across the spectrum of injury severity. Pre-clinical models include in vivo and ex vivo animal work-both small and large-and in vitro modeling. The wide range of pre-clinical models reflect substantial attempts to replicate multiple aspects of TBI sequelae in humans. Although these models reveal multiple putative mechanisms underlying TBI pathophysiology, failures to translate these findings into successful clinical trials call into question the clinical relevance and applicability of the models. Here, we address the promises and pitfalls of pre-clinical models with the goal of evolving frameworks that will advance translational TBI research across models, injury types, and the heterogenous etiology of pathology.

The increasing development in computational technology has allowed the use of numerical modeling and analysis to investigate the mechanical behavior of single human vertebra. Among the several approaches, computed tomography (CT)-based finite element (FE) modeling has been widely used and validated in vitro, reaching different levels of accuracy. Recently, the CT-based FE modeling of the single human vertebra has been applied to clinical cohorts of patients to estimate the vertebral mechanical competence in healthy and pathological conditions, such as osteoporosis and metastasis, as well as to evaluate the efficacy of drug treatments. The ultimate aim is to obtain a comprehensive understanding of the mechanical behavior of vertebra and thus translate the computational technology from bench to bedside to develop accurate clinical tools for the clinical practice to improve diagnosis and prevention of fracture and assess the efficacy of treatments. Different key aspects have been included in the FE modeling approaches. As such, this work aims to furnish a comprehensive state of the art for the FE modeling of the single vertebra, focusing on geometrical and constitutive aspects, as well as boundary conditions. An overview of the main results obtained have been furnished. Finally, limitations of single human vertebra models and possible future research directions have been highlighted.

Translation of the stem cell investigation from the bench to bedside opens up new therapeutic options for many patients, especially those with chronic diseases that do not respond to conventional therapies. Although stem cell research has progressed very fast, its clinical applications are still slow. To overcome this problem in Iran, along with the rest of the world, the Ministry of Health and Medical Education (MOHME) has established the Cellular Medicine and Infertility Department (CMID) under the Curative Affairs Deputy of MOHME. The CMID provides independent guidance, guidelines, and decision on Cell Therapy & Regenerative Medicine (CTRM) services in the therapeutic centers. In early 2018, the CMID found a mission to prepare a guideline for the CTRM services in public or private therapeutic centers. The preliminary draft of the guideline was written by the experts involved in the basic sciences or clinical fields of the CTRM. The preliminary draft was reviewed by a large group of experts from regulatory bodies, juristic, national ethics committee members, clinicians, and basic scientists. After several revisions, the finalized guideline was announced by the Minister of Health on 19 November 2018 as “The National guideline for the Establishment and Operation of Cell Therapy and Regenerative Medicine Departments in the Public, Public-Non-governmental, and Private therapeutic centers.” This guideline serves as a basis for all CTRM services in the therapeutic center of the country. This guideline which was drafted in 13 articles and 21 notes will have strict oversight of cell therapy centers, will stop the abuser centers, and will pave the way for cell-based therapies in the country. We are at an exciting stage in this program, but certainly, our progress to the international stage will be fast with a significant impact. In Iran, the Ministry of Health and Medical Education (MOHME) has established the Cellular Medicine and Infertility Department (CMID) under the Curative Affairs Deputy of MOHME. The CMID provides independent guidance, guidelines, and decision on the Cell Therapy & Regenerative Medicine (CTRM) services in the therapeutic centers. In November 2018, “The National guideline for the Establishment and Operation of Cell Therapy and Regenerative Medicine Departments in the Public, Public-Non-governmental, and Private therapeutic centers” was declared by the CMID. This guideline serves as a basis for all CTRM services in the therapeutic center of the country and will have strict oversight of cell therapy centers.

The development of CRISPR-derived genome editing technologies has enabled the precise manipulation of DNA sequences within the human genome. In this review, we discuss the initial development and cellular mechanism of action of CRISPR nucleases and DNA base editors. We then describe factors that must be taken into consideration when developing these tools into therapeutic agents, including the potential for unintended and off-target edits when using these genome editing tools, and methods to characterize these types of edits. We finish by considering specific challenges associated with bringing a CRISPR-based therapy to the clinic, including manufacturing, regulatory oversight, and considerations for clinical trials that involve genome editing agents.

Relapsed and refractory multiple myeloma (RRMM) presents a therapeutic challenge due to the development of drug resistance. Panobinostat is an oral histone deacetylase inhibitor (HDACi) that affects multiple cellular pathways and has demonstrated the ability to resensitize refractory-multiple myeloma cells in preclinical studies, as well as in patients with RRMM in clinical trials. Synergy of panobinostat with a number of different classes of antimyeloma drugs (proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies) has also been shown. Panobinostat is a promising HDACi for the treatment of multiple myeloma. Here, we present a comprehensive review of preclinical and clinical studies of panobinostat.

Parathyroid hormone and vitamin D are essential endocrine regulators primarily responsible for maintaining calcium and phosphate homeostasis. Parathyroid hormone is responsible for the activation of vitamin D and forms a self-regulating negative feedback loop in response to changes in calcium and phosphate serum concentrations. This review discusses the synthesis, mechanisms of action the cellular and genomic targets of parathyroid hormone and vitamin D in both ‘calcaemic’ and ‘non-calcaemic’ scenarios. It will also discuss the clinical ramifications of disorders of the parathyroid hormone and vitamin D axis and the main considerations the orthopaedic surgeon should appreciate when treating their patients.

Advances in research have transformed the management of melanoma in the past decade. In parallel, patient advocacy has gained traction, and funders are increasingly prioritizing patient and public involvement. Here we discuss the ways in which patients and the public can be engaged in different stages of the research process, from developing, prioritizing and refining the research question to preclinical studies and clinical trials, then finally to ongoing research in the clinic. We discuss the challenges and opportunities that exist at each stage in order to ensure that a representative population of patients and the public contribute to melanoma research both now and in the future.

Atherosclerotic vascular calcification contributes to increased risk of death in patients with cardiovascular diseases. Assessing the type and severity of inflammation is crucial in the treatment of numerous cardiovascular conditions. IL-1β, a potent proinflammatory cytokine, plays diverse roles in the pathogenesis of atherosclerotic vascular calcification. Several large-scale, population cohort trials have shown that the incidence of cardiovascular events is clinically reduced by the administration of anti-IL-1β therapy. Anti-IL-1β therapy might reduce the incidence of cardiovascular events by affecting atherosclerotic vascular calcification, but the mechanism underlying this effect remains unclear. In this review, we summarize current knowledge on the role of IL-1β in atherosclerotic vascular calcification, and describe the latest results reported in clinical trials evaluating anti-IL-1β therapies for the treatment of cardiovascular diseases. This review will aid in improving current understanding of the pathophysiological roles of IL-1β and mechanisms underlying its activity.

Neuroinflammation is one of the host defensive mechanisms through which the nervous system protects itself from pathogenic and or infectious insults. Moreover, neuroinflammation occurs as one of the most common pathological outcomes in various neurological disorders, makes it the promising target. The present review focuses on elaborating the recent advancement in understanding molecular mechanisms of neuroinflammation and its role in the etiopathogenesis of various neurological disorders, especially Alzheimer's disease (AD), Parkinson's disease (PD), and Epilepsy. Furthermore, the current status of anti-inflammatory agents in neurological diseases has been summarized in light of different preclinical and clinical studies. Finally, possible limitations and future directions for the effective use of anti-inflammatory agents in neurological disorders have been discussed.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Heart attack and stroke cause irreversible tissue damage. The currently available treatment options are limited to “damage-control” rather than tissue repair. The recent advances in nanomaterials have offered novel approaches to restore tissue function after injury. In particular, carbon nanomaterials (CNMs) have shown significant promise to bridge the gap in clinical translation of biomaterial based therapies. This family of carbon allotropes (including graphenes, carbon nanotubes and fullerenes) have unique physiochemical properties, including exceptional mechanical strength, electrical conductivity, chemical behaviour, thermal stability and optical properties. These intrinsic properties make CNMs ideal materials for use in cardiovascular theranostics. This review is focused on recent efforts in the diagnosis and treatment of heart diseases using graphenes and carbon nanotubes. The first section introduces currently available derivatives of graphenes and carbon nanotubes and discusses some of the key characteristics of these materials. The second section covers their application in drug delivery, biosensors, tissue engineering and immunomodulation with a focus on cardiovascular applications. The final section discusses current shortcomings and limitations of CNMs in cardiovascular applications and reviews ongoing efforts to address these concerns and to bring CNMs from bench to bedside., Graphical abstract Image 1, Highlights • Unique properties of the carbon nanomaterials (CNM) for cardiovascular theranostics. • Applications of CNMs for cardiovascular medicine as drug carriers, biosensors, cardiac tissue engineering constructs and immunomodulation. • Limitations of CNMs in cardiovascular theranostics applications. • Strategies to mitigate the challenges to bring CNMs from bench to bedside for cardiovascular theranostics.

Spinal acrylic bone cements (ABCs) are used clinically for percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) to treat osteoporotic vertebral compression fractures. Product translation of spinal ABC products followed the design control processes including design verification and validation. The bench to bedside translation of the first Chinese spinal ABC product (Alliment®, namely Alliment Cement) approved by National Medical Products Administration of China was investigated and another commercial product served as the control (Osteopal®V, namely Osteopal V Cement). Results of non-clinical bench performance verification tests of compression, bending and monomer release showed that the newly marketed Alliment Cement is similar to the Osteopal V Cement with properties of both meeting the criteria specified by standards. The Alliment Cement demonstrated good biocompatibility during the 26 weeks’ bone implantation test. Porcine cadaver validation tests further revealed that the Alliment Cement satisfied the needs for both PVP and PKP procedures. A post-approval, retrospective clinical investigation further demonstrated the safety and efficacy of the Alliment Cement, with a significant reduction of pain and the improved stability of the fractured vertebral bodies. A successful translation of biomaterial medical products needs close collaborations among academia, industry, healthcare professionals and regulatory agencies., Graphical abstract Image 1, Highlights • Bench-to-bedside research of the first Chinese spinal acrylic bone cement product. •Pre- & clinical investigations demonstrate the product's safety and efficacy. •Translation of biomaterial medical products follows regulated processes.

Uterine fibroids (leiomyomas) are noncancerous growths that can have deleterious effects on the health and quality of life for millions of women. Attempts to better understand the factors that influence prevalence and disparities associated with fibroids have been made; however, significant knowledge gaps continue to persist, which hinder care for individuals living with fibroids. The Society for Women's Health Research convened an interdisciplinary Uterine Fibroids Working Group to review the current state of knowledge about uterine fibroids and recommend areas in which to prioritize efforts to address research gaps and improve diagnosis, treatment, and access to care for patients with this chronic disease. Throughout a 2-day roundtable meeting, participants discussed updates on key literature, research, clinical practice, and public health data on uterine fibroids. Overarching themes and recommendations were identified and determined by consensus agreement of the participants at the conclusion of the meeting. Systematic studies of the etiology and pathology of uterine fibroids are needed to address important knowledge gaps and unmet clinical needs regarding the multifaceted management of fibroids and their effects on overall health and quality of life. The Working Group recommends addressing key deficits within the spheres of research, clinical care, and federal policy. Immediate needs include increasing research investment, improving fibroid assessment using pelvic imaging, implementing longitudinal study designs, addressing factors that contribute to disease disparities (especially among women of color), developing fertility-friendly treatment options, expanding awareness and education beyond gynecologic specialists, and advancing personalized patient care through shared decision-making approaches.

Myeloid malignancies, stemming from a somatically mutated hematopoietic clone, can cause a wide variety of clinical consequences, including pancytopenia in myelodysplastic syndrome, overproduction of three myeloid lineages in myeloproliferative neoplasm, and the rapid growth of immature hematopoietic cells in acute myeloid leukemia (AML). It is becoming clear that inflammation is a hallmark feature of clonal myeloid conditions, ranging from clonal hematopoiesis of indeterminate potential to AML. Fundamental findings from laboratory research on inflammation in myeloid malignancies has potential implications for diagnosis, prognostication, and treatment in these diseases. In this review, we highlighted some pertinent basic science findings regarding the role of inflammation in myeloid malignancies and speculated how these findings could impact the clinical care of patients.

Neurosurgeons represent 0.5% of all physicians and currently face a high burden of disease. Physician-scientists are essential to advance the mission of National Academies of Science (NAS) and National Institutes of Health (NIH) through discovery and bench to bedside translation. We investigated trends in NIH neurosurgeon-scientist funding over time as an indicator of physician-scientist workforce training. We used NIH Research Portfolio Online Reporting Tools (RePORTER) to extract grants to neurosurgery departments and neurosurgeons from 1993 to 2017. Manual extraction of each individual grant awardee was conducted. After adjusting for U.S. inflation (base year: 1993), NIH funding to neurosurgery departments increased yearly (P

Introduction: Cardiac arrest outside medical center is a major cause of death. The survival rates ranges from 5 percent to 35 percent. In patients who are initially resuscitated, anoxic neurologic injury is the prime cause of morbidity and mortality, besides hazards in multiple organs as the kidneys, for example. Induced hypothermia has proven to improve the prognosis after resuscitation from cardiac arrest. Objective: To demonstrate in experiments where induced mild hypothermia has been able to reduce ischemic and inflammatory damage in animal’s brains and consequently the multiplicity of the other organs. Methods: Experiments were carried out with rabbits and rats when mild hypothermia was induced in order to demonstrate its neuroprotective properties. Results: Induced mild hypothermia demonstrated to be able to reduce the deleterious effects caused by brain ischemia and brain inflammation. Conclusions: Hypothermia may be helpful in reducing the ischemic process as well as in reducing the inflammatory cascade caused by ischemia. We believe that induced hypothermia improves prognosis after resuscitation from cardiac arrest reinforcing the application of mild hypothermia in cases of cerebral ischemia mainly after cardiac arrest.

Peripheral arterial disease is a growing worldwide problem with a wide spectrum of clinical severity and is projected to consume >$21 billion per year in the United States alone. While vascular researchers have brought several therapies to the clinic in recent years, few of these approaches have leveraged advances in high-throughput discovery screens, novel translational models, or innovative trial designs. In the following review, we discuss recent advances in unbiased genomics and broader omics technology platforms, along with preclinical vascular models designed to enhance our understanding of disease pathobiology and prioritize targets for additional investigation. Furthermore, we summarize novel approaches to clinical studies in subjects with claudication and ischemic ulceration, with an emphasis on streamlining and accelerating bench-to-bedside translation. By providing a framework designed to enhance each aspect of future clinical development programs, we hope to enrich the pipeline of therapies that may prevent loss of life and limb for those with peripheral arterial disease.

Over the past couple of decades, accumulating evidence has shown that structural and functional abnormalities of coronary microvasculature are highly prevalent, associated with adverse clinical outcomes in patients with various cardiovascular diseases. The term coronary microvascular dysfunction (CMD) has been coined to refer to this clinical condition and is increasingly recognized as an important clinical entity in many clinical settings. The potential mechanisms of CMD appear to be heterogenous, including enhanced coronary vasoconstrictive reactivity at microvascular level, impaired endothelium-dependent and independent coronary vasodilator capacities, and increased coronary microvascular resistance secondary to structural factors. Recent experimental and clinical studies have highlighted emerging modulators of vascular functions, vital insight into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will briefly review the current progress on pathophysiology, molecular mechanisms, and clinical management of CMD from bench to bedside.

The summation of 20 years of biological studies and the comprehensive analysis of more than 1000 multiple myeloma genomes with data linked to clinical outcome has enabled an increased understanding of the pathogenesis of multiple myeloma in the context of normal plasma cell biology. This novel data have facilitated the identification of prognostic markers and targets suitable for therapeutic manipulation. The challenge moving forward is to translate this genetic and biological information into the clinic to improve patient care. This review discusses the key data required to achieve this and provides a framework within which to explore the use of response-adapted, biologically targeted, molecularly targeted, and risk-stratified therapeutic approaches to improve the management of patients with multiple myeloma.

Bempedoic acid is a first-in-class, oral, inhibitor of cholesterol biosynthesis that is approved for use in patients with atherosclerotic cardiovascular disease (ASCVD) and for primary prevention in individuals with heterozygous familial hypercholesterolemia (HeFH) by the United States Food and Drug Administration. Pooled data from the phase III clinical trials, CLEAR Harmony and CLEAR Wisdom, have demonstrated the safety and efficacy of bempedoic acid with regard to lowering of low-density lipoprotein cholesterol (LDL-C) in patients with HeFH as an adjunct or alternative to currently existing lipid-lowering therapies. CLEAR Outcomes is a cardiovascular outcomes trial that is currently underway that will provide additional insight as to where bempedoic acid will fit into treatment regimens among the non-statin lipid-lowering therapy options. Patients who might particularly benefit from bempedoic acid are those with HeFH and those unable to take adequate doses of statins or take any statin therapy altogether who need additional LDL-C lowering. In this review, we will discuss the profile of bempedoic acid from its design, development, and its place in therapy for the management of LDL-C for the purposes of ASCVD prevention.