Advances In Translational Research Research Articles

MicroRNA as a promising molecular biomarker in the diagnosis of breast cancer

Introduction: Breast cancer represents the most prevalent malignancy among women. Recent advancements in translational research have focused on the identification of novel biomarkers capable of providing valuable insights into patient outcomes. Furthermore, comprehensive investigations aimed at discovering novel miRNAs, unraveling their biological functions, and deciphering their target genes have significantly contributed to our understanding of the roles miRNAs play in tumorigenesis. Consequently, these investigations have facilitated the way for the development of miRNA-based approaches for breast cancer prognosis, diagnosis, and treatment. However, conducting a more extensive array of studies, particularly among diverse ethnic groups, is imperative to expand the scope of research and validate the significance of miRNAs. This study aimed to assess the expression patterns of circulating miRNAs in plasma as a prospective biomarker for breast cancer patients within a population primarily consisting of individuals from Black, Indigenous, and People of Color (BIPOC) communities.Methods: We evaluated 49 patients with breast cancer compared to 44 healthy women.Results and discussion: All miRNAs analyzed in the plasma of patients with breast cancer were downregulated. ROC curve analysis of miR-21 (AUC = 0.798, 95% CI: 0.682–0.914, p <0.0001), miR-1 (AUC = 0.742, 95% CI: 0.576–0.909, p = 0.004), miR-16 (AUC = 0.721, 95% CI: 0.581–0.861, p = 0.002) and miR-195 (AUC = 0.672, 95% CI: 0.553–0.792, p = 0.004) showed better diagnostic accuracy in discrimination of breast cancer patients in comparison with healthy women. miR-210, miR-21 showed the highest specificities values (97.3%, 94.1%, respectively). Following, miR-10b and miR-195 showed the highest sensitivity values (89.3%, and 77.8%, respectively). The panel with a combination of four miRNAs (miR-195 + miR-210 + miR-21 + miR-16) had an AUC of 0.898 (0.765–0.970), a sensitivity of 71.4%, and a specificity of 100.0%. Collectively, our results highlight the miRNA combination in panels drastically improves the results and showed high accuracy for the diagnosis of breast cancer displaying good sensitivity and specificity.

Contextual analysis of the first SARS-CoV-2 RNA screening period in nasopharyngeal swabs, 2020-2022: a comparison of two diagnostic tests

Background: exceptionally consistent COVID-19 laboratory diagnostics are crucial for case identification, patient management and contact tracing. The Coronavirus-2019 (COVID-19) pandemic affected over 771.407.825 people up until October 2023, with over 6.9 million deaths. The current process of clinical laboratory consolidation, impacting large geographic areas, presents an opportunity for the efficient and cost-effective implementation of novel laboratory technologies, as well as advancements in translational research and development. The aim of this study was to assess which of the two instruments could offer the most effective support to our laboratory’s activities, minimizing errors during the pre-analytical phase, optimizing human resources, and reducing the Turn-Around-Time (TAT). Materials and Methods: the diagnostic instruments available in the Microbiology laboratory of the Azienda Ospedaliero- Universitaria SS Antonio e Biagio e Cesare Arrigo (AOUAL) were the COBAS 6800 and the ALINITY platforms. Conclusions: the Alinity platform offers clinicians a more user-friendly approach to understanding patient infectivity, compared to the closed Cobas system. It permits clinicians to review curves and access a cumulative Cycle Threshold (Ct), facilitating the hypothesis of acute or initial/final infection stages. This positions Alinity by Abbott as the preferred system over other instruments.

Paradigm shift required for translational research on the brain.

Biomedical research on the brain has led to many discoveries and developments, such as understanding human consciousness and the mind and overcoming brain diseases. However, historical biomedical research on the brain has unique characteristics that differ from those of conventional biomedical research. For example, there are different scientific interpretations due to the high complexity of the brain and insufficient intercommunication between researchers of different disciplines owing to the limited conceptual and technical overlap of distinct backgrounds. Therefore, the development of biomedical research on the brain has been slower than that in other areas. Brain biomedical research has recently undergone a paradigm shift, and conducting patient-centered, large-scale brain biomedical research has become possible using emerging high-throughput analysis tools. Neuroimaging, multiomics, and artificial intelligence technology are the main drivers of this new approach, foreshadowing dramatic advances in translational research. In addition, emerging interdisciplinary cooperative studies provide insights into how unresolved questions in biomedicine can be addressed. This review presents the in-depth aspects of conventional biomedical research and discusses the future of biomedical research on the brain.

Brain on Fire: How Brain Infection and Neuroinflammation Drive Worldwide Epilepsy Burden

Roughly 80% of the global burden of epilepsy resides in low- and middle-income countries (LMICs; WHO, 2022). Despite numerous new therapies for the treatment of epilepsy, the number of patients who remain resistant to available medications is unchanged. Additionally, no therapy has yet been clinically proven to prevent or attenuate the development of epilepsy in at-risk individuals. Unfortunately, access to next generation therapies in LMICs is low, the stigma associated with epilepsy remains high, and access to adequate resources is unchanged. Thus, the global epilepsy burden disproportionately falls on LMICs such that strategies to conscientiously integrate global epilepsy risk factors into preclinical research may meaningfully advance 21st century epilepsy therapies. Brain infections are one of the main risk factors for epilepsy in resource-poor settings. Further, both infection- and autoimmune-associated encephalitis contribute to worldwide epilepsy risk and remain relatively understudied. For example, clinical SARS CoV-2 infection can induce rare instances of encephalopathy and acute seizures. Among viruses known to cause acute brain infection, enteroviruses increase risk for encephalitis-induced epilepsy, but are not associated with risk for other neurodevelopmental disorders (eg, autism spectrum or attentional deficit hyperactivity disorders). Naturally occurring models of viral infection-induced epilepsy therefore provide an exquisite opportunity to uncover novel contributors to epileptogenesis. Moreover, the convergent neuroinflammatory pathways that are associated with viral infection-induced encephalitis and autoimmune encephalitis reflect an untapped therapeutic opportunity to meaningfully reduce the global burden of epilepsy. This review summarizes the latest advances in translational research integrating encephalitis-induced seizure and epilepsy models, in tandem with progress in clinical diagnosis of inflammation and virally mediated epilepsy. This improved awareness of the shared biological underpinnings of epileptogenesis following brain infection or autoimmune encephalitis is anticipated to beneficially impact the global burden of epilepsy.

How to optimize the immune checkpoint blockade therapy for cancers?

Abstract The realm of cancer therapy has been profoundly altered with the emergence of immune checkpoint blockade (ICB) therapy, providing improved survival prospects for many patients with some cancers. However, the challenge of achieving efficient or sustained therapeutic benefits underscores the critical imperative to optimize ICB strategies. This review elucidates the pivotal role of predictive biomarkers in optimizing precision ICB therapy, deciphering the intricate dynamics associated with the response heterogeneity. Furthermore, it critically examines the application of nanotechnology-driven drug delivery as a promising avenue to amplify ICB efficacy, facilitating controlled and targeted drug release. Recognizing the comprehensive and dynamic interplay among tumor cells, immune cells, and stromal cells has catalyzed the transformative advances in reverse translational research. This approach enables researchers to gain insights into the underlying mechanisms of ICB therapy, therapeutic responses, and resistance mechanisms. The convergence of predictive biomarkers, revolutionary nanotechnology, and reverse translational research emerges as an indispensable focal point, propelling the frontiers of precision oncology within the complex landscape of ICB therapy.

Lung Organoids: Systematic Review of Recent Advancements and its Future Perspectives.

Organoids are essentially an in vitro (lab-grown) three-dimensional tissue culture system model that meticulously replicates the structure and physiology of human organs. A few of the present applications of organoids are in the basic biological research area, molecular medicine and pharmaceutical drug testing. Organoids are crucial in connecting the gap between animal models and human clinical trials during the drug discovery process, which significantly lowers the time duration and cost associated with each stage of testing. Likewise, they can be used to understand cell-to-cell interactions, a crucial aspect of tissue biology and regeneration, and to model disease pathogenesis at various stages of thedisease. Lung organoids can be utilized to explore numerous pathophysiological activities of a lung since they share similarities with its function. Researchers have been trying to recreate the complex nature of the lung by developing various "Lung organoids" models.This article is a systematic review of various developments of lung organoids and their potential progenitors. It also covers the in-depth applications of lung organoids for the advancement of translational research. The review discusses the methodologies to establish different types of lung organoids for studying the regenerative capability of the respiratory system and comprehending various respiratory diseases.Respiratory diseases are among the most common worldwide, and the growing burden must be addressed instantaneously.Lung organoids along with diverse bio-engineering tools and technologies will serve as a novel model for studying thepathophysiology of various respiratory diseasesand fordrug screening purposes.

Quality and applicability of cadaveric donor eyes for molecular biology research: An Indian experience.

Human ocular tissue banking plays an important part in the advancement of translational research for identifying the molecular processes involved in disease etiology and pathogenesis. Timely obtaining a good-quality ocular tissue from a cadaveric donor is exceedingly difficult, especially in remote areas, with a variable transportation time (within 12-24 h), raising concerns about RNA quality and its subsequent applications. Therefore, we assessed the utility of retinal tissues from cadaver donor and enucleated eyes based on the RNA quality and gene expression by real-time polymerase chain reaction (PCR). Prospective study. Retina tissues were separated from the donor/enucleated eyes received in the eye bank within 24 h of death (n = 15) and within an hour from OR (n = 3), respectively, and stored immediately at -80 degree. RNA was isolated using trizol, and the quantity and quality were assessed using Qubit and agarose gel electrophoresis, respectively. QPCR was performed for measuring the expression of different retinal-specific genes. The cellular viability of the retina was assessed by establishing explant primary cell cultures. The data were calculated as an average of normalised Ct values ± standard error of the mean. RNA obtained from cadaveric tissues despite being partially degraded showed a uniform strong gene expression of several retinal-specific genes such as PAX6, RHO, TUBB3, CRX, and ALDH1L1. The primary cultures established from cadaveric tissues showed viable cells. The cadaver donor tissues collected within 24 hours of death can be effectively utilized for gene expression profiling.

Call for Papers: New Perspectives and Advances in Translational Pain Research

Call for Papers: New Perspectives and Advances in Translational Pain Research

Chitooligosaccharide and Its Derivatives: Potential Candidates as Food Additives and Bioactive Components.

Chitooligosaccharide (CHOS), a depolymerized chitosan, can be prepared via physical, chemical, and enzymatic hydrolysis, or a combination of these techniques. The superior properties of CHOS have attracted attention as alternative additives or bioactive compounds for various food and biomedical applications. To increase the bioactivities of a CHOS, its derivatives have been prepared via different methods and were characterized using various analytical methods including FTIR and NMR spectroscopy. CHOS derivatives such as carboxylated CHOS, quaternized CHOS, and others showed their potential as potent anti-inflammatory, anti-obesity, neuroprotective, and anti-cancer agents, which could further be used for human health benefits. Moreover, enhanced antibacterial and antioxidant bioactivities, especially for a CHOS-polyphenol conjugate, could play a profound role in shelf-life extension and the safety assurance of perishable foods via the inhibition of spoilage microorganisms and pathogens and lipid oxidation. Also, the effectiveness of CHOS derivatives for shelf-life extension can be augmented when used in combination with other preservative technologies. Therefore, this review provides an overview of the production of a CHOS and its derivatives, as well as their potential applications in food as either additives or nutraceuticals. Furthermore, it revisits recent advancements in translational research and in vivo studies on CHOS and its derivatives in the medical-related field.

Advances in translational research of the rare cancer type adrenocortical carcinoma.

Adrenocortical carcinoma is a rare malignancy with an annual worldwide incidence of 1-2 cases per 1 million and a 5-year survival rate of <60%. Although adrenocortical carcinoma is rare, such rare cancers account for approximately onethird of patients diagnosed with cancer annually. In the past decade, there have been considerable advances in understanding the molecular basis of adrenocortical carcinoma. The genetic events associated with adrenocortical carcinoma in adults are distinct from those of paediatric cases, which are often associated with germline or somatic TP53 mutations and have a better prognosis. In adult primary adrenocortical carcinoma, the main somatic genetic alterations occur in genes that encode proteins involved in the WNT-β-catenin pathway, cell cycle and p53 apoptosis pathway, chromatin remodelling and telomere maintenance pathway, cAMP-protein kinase A (PKA) pathway or DNA transcription and RNA translation pathways. Recently, integrated molecular studies of adrenocortical carcinomas, which have characterized somatic mutationsand the methylome as well as gene and microRNA expression profiles, have led to a molecular classification of these tumours that can predict prognosis and have helped to identify new therapeutic targets. In this Review, we summarize these recent translational research advances in adrenocortical carcinoma, which it is hoped could lead to improved patient diagnosis, treatment and outcome.

Recent progress in regenerative therapy for damaged salivary glands: From bench to bedside.

For functional restoration of salivary glands (SGs) injured by radiation therapy or Sjögren's syndrome (SS), various experimental approaches, such as gene therapy, tissue engineering, and cell-based therapy, have been proposed. This narrative review summarized recent progresses in research using cell-based therapies, including promising trials that could lead to bench-to-clinic applications. A literature review based on PubMed publications in the last two decades was performed to summarize progresses in cell-based therapies for SG dysfunction. Over 100 experimental studies have shown the therapeutic potential of several types of cells, such as SG stem cells and mesenchymal stem cells, as well as effectively conditioned mononuclear cells, in both radiation injury and SS animal models. These therapies affect to slow fibrosis progression and stimulate tissue regeneration in atrophic glands. However, to date, only a total of seven studies have been developed to the stage of clinical study, showing the safety and preliminary efficacy. To lead the radical effectiveness expected in cell-based therapy, advances in reverse translational research and in innovative experimental research, based on the findings of recent clinical studies, will be critical in the next decade.

Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.

Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations. A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms "venous malformation," "lymphatic malformation," "lymphaticovenous malformation," "genetic variant," "genetic mutation," "endothelial cells," and "animal model." Relevant publications were reviewed and summarized. The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments. Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features.

Advances in basic and translational research in atrial fibrillation.

Atrial fibrillation (AF) is a very common cardiac arrhythmia with an estimated prevalence of 33.5 million patients globally. It is associated with an increased risk of death, stroke and peripheral embolism. Although genetic studies have identified a growing number of genes associated with AF, the definitive impact of these genetic findings is yet to be established. Several mechanisms, including electrical, structural and neural remodelling of atrial tissue, have been proposed to contribute to the development of AF. Despite over a century of exploration, the molecular and cellular mechanisms underlying AF have not been fully established. Current antiarrhythmic drugs are associated with a significant rate of adverse events and management of AF using ablation is not optimal, especially in cases of persistent AF. This review discusses recent advances in our understanding and management of AF, including new concepts of epidemiology, genetics and pathophysiological mechanisms. We review the current status of antiarrhythmic drug therapy for AF, new potential agents, as well as mechanism-based AF ablation. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Unveiling the vulnerabilities of synthetic lethality in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most invasive molecular subtype of breast cancer (BC), accounting for about nearly 15% of all BC cases reported annually. The absence of the three major BC hormone receptors, Estrogen (ER), Progesterone (PR), and Human Epidermal Growth Factor 2 (HER2) receptor, accounts for the characteristic "Triple negative" phraseology. The absence of these marked receptors makes this cancer insensitive to classical endocrine therapeutic approaches. Hence, the available treatment options remain solemnly limited to only conventional realms of chemotherapy and radiation therapy. Moreover, these therapeutic regimes are often accompanied by numerous treatment side-effects that account for early distant metastasis, relapse, and shorter overall survival in TNBC patients. The rigorous ongoing research in the field of clinical oncology has identified certain gene-based selective tumor-targeting susceptibilities, which are known to account for the molecular fallacies and mutation-based genetic alterations that develop the progression of TNBC. One such promising approach is synthetic lethality, which identifies novel drug targets of cancer, from undruggable oncogenes or tumor-suppressor genes, which cannot be otherwise clasped by the conventional approaches of mutational analysis. Herein, a holistic scientific review is presented, to undermine the mechanisms of synthetic lethal (SL) interactions in TNBC, the epigenetic crosstalks encountered, the role of Poly (ADP-ribose) polymerase inhibitors (PARPi) in inducing SL interactions, and the limitations faced by the lethal interactors. Thus,the future predicament of synthetic lethal interactions in the advancement of modern translational TNBC research is assessed with specific emphasis on patient-specific personalized medicine.

Abstract 4185: Inclusive basic and advanced translational laboratory research competencies for research in cancer biology and therapeutics

Abstract Our Laboratory was established in 1994 at Univ. of Pennsylvania. Lab members demonstrated initial competencies by performing cell culture, western blots, immunofluorescence, and flow cytometry showing induction of p53/p21(WAF1) in cells treated with chemotherapy. Years later, our Laboratory of Translational Oncology &amp; Experimental Cancer Therapeutics moved to Penn State Univ., Fox Chase Cancer Center/Temple Univ. and then Brown Univ. By 2020, with desire for inclusiveness (everyone succeeds), scientific rigor/reproducibility mandated by NIH, and as a training and mentoring activity (lab scientists/trainees/students mentoring others at High School level and beyond), we established a process for onboarding and training new cancer researchers. By Fall of 2022, there were 17 current Brown University undergraduate students (10 receiving research credit and 7 not receiving credit), HS students, 7 graduate students (PhD, masters, MD/PhD), and 6 medical students working with collaborating faculty at our laboratory at Brown’s Legorreta Cancer Center. After completion of biosafety training, and required trainings such as by IACUC, new lab members complete basic competencies in cell culture, cell viability, and western blot analysis that include technical, presentation quality output, and quantitative/statistical rigor to satisfy current standards for journal publication. For cell culture this includes pathogen free conditions, authentication, attention to details of routine procedures, documentation of morphology, freezing, thawing, passaging, seeding density, and managing cell populations to not run out of cells. Cell viability assessment includes attention to culture conditions, synergy analysis, data robustness, and presentation, and for western blots attention to quality of blots, protein quantification, loading, labeling, antibody specificity and sensitivity controls, presentation at 2022 standards, conventions for splicing, and issues with reproducibility including biological replicates, and generalizability. Additional and advanced competencies include RT-PCR, long-term colony assays, 3-D cultures (spheroids, organoids), transfection (overexpression, knockdown, CRISPR), co-culture and triculture with immune cells and fibroblasts, cytokine profiling, in vivo studies, in vivo imaging, immunohistochemistry, flow cytometric analysis, single cell techniques, viral infection, circulating tumor cell isolation, blood immune and cytokine analysis, and work with transgenic organoids and inducible cancer predisposing alleles. Modeling the tumor microenvironment, relevance to human cancer and translational directions are emphasized. Shared online lab resources, protocols, practices, videos, and manuscripts are available for lab members. The framework herein may be of interest to others involved in similar training programs. Citation Format: Wafik S. El-Deiry, Andrew George, Francesca Di Cristofano, Praveen Srinivasan, Lindsey Carlsen, Kelsey E. Huntington, Arielle De La Cruz, Leiqing Zhang, Marina Hahn, Shuai Zhao, Attila Seyhan, Bradley D. DeNardo, Aaron W. Maxwell, Dae Hee Kim, Alex Raufi, Hina Khan, Stephanie L. Graff, Don S. Dizon, Christopher Azzoli, Abbas E. Abbas, Roxanne Wood, Rishi R. Lulla, Howard P. Safran, Benedito A. Carneiro, Arunasalam Navaraj, Xiaobing Tian, Shengliang Zhang, Lanlan Zhou. Inclusive basic and advanced translational laboratory research competencies for research in cancer biology and therapeutics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4185.

ERS International Congress 2022: highlights from the Interstitial Lung Diseases Assembly.

This article contains a selection of scientific highlights in the field of interstitial lung diseases (ILDs) presented at the hybrid European Respiratory Society International Congress 2022. Early Career Members of Assembly 12 summarise recent advances in translational and clinical research in idiopathic interstitial pneumonias, ILDs of known origin, sarcoidosis and other granulomatous diseases, and rare ILDs. Many studies focused on evaluation of diagnostic and prognostic (bio)markers, and novel pharmacological and nonpharmacological treatment options for different ILDs. In addition, new insights in clinical, physiological and radiological features of various rare ILDs were presented.

New developments in targeted therapy for metastatic colorectal cancer.

Colorectal cancer (CRC) is the second most lethal cancer worldwide and the prognosis of metastatic CRC (mCRC) remains poor. Recent advancements in translational research have led to the identification of several new therapeutic targets and improved the treatment outcome of patients with tumours harbouring BRAF V600E mutation, (HER2) ErBB2 alterations, NTRK gene fusions and KRAS(G12C) mutation. Improved understanding towards the mechanism of resistance to targeted therapy such as anti-epidermal growth factor receptor antibodies and the evolving role of therapeutic monitoring with circulating tumour DNA (ctDNA) has enabled the longitudinal tracking of clonal evolution during treatment and the individualization of subsequent treatments. To broaden the community-based implementation of precision oncology in directing targeted therapies for patients with gastrointestinal cancers including mCRC, the feasibility of 'Master Protocols' that utilizes ctDNA-based genotyping platforms is currently being evaluated. Such protocols encompass both observational and interventional clinical trials of novel targeted therapies conducted within a large clinical trial network. In this review, we will discuss the latest developments in targeted therapies, and therapeutic strategies for overcoming acquired drug resistance in patients with mCRC.

A Decade of Clinical Advances in Chronic Rhinosinusitis: 2012–2022

The field of chronic rhinosinusitis (CRS) is constantly evolving. In the past 10 years, key advancements in basic and translational research as well as clinical studies have improved our understanding and management of CRS. Notably, treatment options have expanded to include novel therapeutic drugs, devices, and surgical techniques. Assessments of patient symptoms and their impact on quality of life have become more standardized. Progress has also been made in both determining the true prevalence of CRS and recognizing comorbidities that can impact CRS severity. Practice guidelines have also shifted from expert opinion to more data-driven analyses. This review highlights major clinical advancements made in the field of CRS over the past 10 years as well as identifies current gaps in knowledge that can form the basis for new areas of study over the next decade.

Sample Collection Methods in Upper Gastrointestinal Research.

In recent years, significant translational research advances have been made in the upper gastrointestinal (GI) research field. Endoscopic evaluation is a reasonable option for acquiring upper GI tissue for research purposes because it has minimal risk and can be applied to unresectable gastric cancer. The optimal number of biopsy samples and sample storage is crucial and might influence results. Furthermore, the methods for sample acquisition can be applied differently according to the research purpose; however, there have been few reports on methods for sample collection from endoscopic biopsies. In this review, we suggested a protocol for collecting study samples for upper GI research, including microbiome, DNA, RNA, protein, single-cell RNA sequencing, and organoid culture, through a comprehensive literature review. For microbiome analysis, one or two pieces of biopsied material obtained using standard endoscopic forceps may be sufficient. Additionally, 5 mL of gastric fluid and 3-4 mL of saliva is recommended for microbiome analyses. At least one gastric biopsy tissue is necessary for most DNA or RNA analyses, while proteomics analysis may require at least 2-3 biopsy tissues. Single cell-RNA sequencing requires at least 3-5 tissues and additional 1-2 tissues, if possible. For successful organoid culture, multiple sampling is necessary to improve the quality of specimens.

Advances in Basic and Translational Research as Part of the Center for the Study of Complex Malaria in India.

The Center for the Study of Complex Malaria in India (CSCMi) is one of 10 International Centers of Excellence in Malaria Research funded by the National Institutes of Health since 2010. The Center combines innovative research with capacity building and technology transfer to undertake studies with clinical and translational impact that will move malaria control in India toward the ultimate goal of malaria elimination/eradication. A key element of each research site in the four states of India (Tamil Nadu, Gujarat, Odisha, and Meghalaya) has been undertaking community- and clinic-based epidemiology projects to characterize the burden of malaria in the region. Demographic and clinical data and samples collected during these studies have been used in downstream projects on, for example, the widespread use of mosquito repellants, the population genomics of Plasmodium vivax, and the serological responses to P. vivax and Plasmodium falciparum antigens that reflect past or present exposure. A focus has been studying the pathogenesis of severe malaria caused by P. falciparum through magnetic resonance imaging of cerebral malaria patients. Here we provide a snapshot of some of the basic and applied research the CSCMi has undertaken over the past 12 years and indicate the further research and/or clinical and translational impact these studies have had.