#Cancer Therapy

[mindblowingscience]

A phase II clinical trial for a skin cancer vaccine has delivered very promising results. Developed by Moderna, the vaccine is designed to work alongside another immunotherapy treatment called KEYTRUDA, which also helps the body fight cancer. KEYTRUDA is owned by Merck (also known as MSD), and the ongoing clinical trial is a collaboration between both pharmaceutical companies to treat patients who have had high-risk melanoma cut out of their skin.

Continue Reading.

#Science #Health #Biology #Immunology #Cancer #Cancer Therapy #Vaccines

[intelligentchristianlady]

Amazing indeed! Read the whole thread.

#cancer #cancer therapy #tumors #solid tumors #phase 1 clinical trials #there is hope

[eatclean-bewhole]

Another therapy my wellness center will be offering soon!

#redlighttherapy #photobiomodulation #lighttherapy #painrelief #health #cellhealth #inflammation #antiinflammatory #wellness #selfcare #painmanagement #ledlighttherapy #healing #recovery #nearinfrared #health #skin #redlight #facial #collagen #biohacking #healthylifestyle #healthyliving #musclesoreness #thermalimaging #skincare #healthtips #holistic #holistichealth #holistichealing

#red light therapy #cell health #cancer #cancer therapy #cancer fighting #Health #Healing #holistichealth #holisticliving #holistic healing #holistic health

[docresa]

How is it always

„modern cancer therapy is extremely complex, decisions should always be made by an interdisciplinary tumor board comprised by experienced experts in their respective fields, taking into consideration clinical factors, pathology as well as patient wishes“

but also

„how dare you not know the 3rd line therapy for BCLC stage C metastasized HCC by hard, you bad bad med student!“?

#i kind of don’t see how these two concepts go hand in hand #sigh #cancer therapy #i mean i even really like to get into the nitty gritty of cancer therapy #but I really don’t like studying huge tables by hard #resas final med school days #medblr

[jcmarchi]

Accelerating CAR T cell therapy: Lipid nanoparticles speed up manufacturing - Technology Org

New Post has been published on https://thedigitalinsider.com/accelerating-car-t-cell-therapy-lipid-nanoparticles-speed-up-manufacturing-technology-org/

Accelerating CAR T cell therapy: Lipid nanoparticles speed up manufacturing - Technology Org

For patients with certain types of cancer, CAR T cell therapy has been nothing short of life-changing. Developed in part by Carl June, Richard W. Vague Professor at Penn Medicine, and approved by the Food and Drug Administration (FDA) in 2017, CAR T cell therapy mobilizes patients’ own immune systems to fight lymphoma and leukemia, among other cancers.

Using activating lipid nanoparticles (aLNPs) to create CAR T cells requires fewer steps and less time.

However, the process for manufacturing CAR T cells itself is time-consuming and costly, requiring multiple steps over days. The state-of-the-art involves extracting patients’ T cells, then activating them with tiny magnetic beads, before giving the T cells genetic instructions to make chimeric antigen receptors (CARs), the specialized receptors that help T cells eliminate cancer cells.

Now, Penn Engineers have developed a novel method for manufacturing CAR T cells, one that takes just 24 hours and requires only one step. This method uses lipid nanoparticles (LNPs), the potent delivery vehicles that played a critical role in the Moderna and Pfizer-BioNTech COVID-19 vaccines.

In a new paper in Advanced Materials, Michael J. Mitchell, Associate Professor in Bioengineering, describes the creation of “activating lipid nanoparticles” (aLNPs), which can activate T cells and deliver the genetic instructions for CARs in a single step, greatly simplifying  the CAR T cell manufacturing process. “We wanted to combine these two extremely promising areas of research,” says Ann Metzloff, a doctoral student and NSF Graduate Research Fellow in the Mitchell lab and the paper’s lead author. “How could we apply lipid nanoparticles to CAR T cell therapy?”

In some ways, T cells function like a military reserve unit: in times of health, they remain inactive, but when they detect pathogens, they mobilize, rapidly expanding their numbers before turning to face the threat. Cancer poses a unique challenge to this defense strategy. Since cancer cells are the body’s own, T cells don’t automatically treat cancer as dangerous, hence the need to first “activate” T cells and deliver cancer-detecting CARs in CAR T cell therapy.

Until now, the most efficient means of activating T cells has been to extract them from a patient’s bloodstream and then mix those cells with magnetic beads attached to specific antibodies — molecules that provoke an immune response. “The beads are expensive,” says Metzloff. “They also need to be removed with a magnet before you can clinically administer the T cells. However, in doing so, you actually lose a lot of the T cells, too.”

Made primarily of lipids, the same water-repellent molecules that constitute household cooking fats like butter and olive oil, lipid nanoparticles have proven tremendously effective at delivering delicate molecular payloads. Their capsule-like shape can enclose and protect mRNA, which provides instructions for cells to manufacture proteins. Due to the widespread use of the COVID-19 vaccines, says Metzloff, “The safety and efficacy of lipid nanoparticles has been shown in billions of people around the world.”

To incorporate LNPs into the production of CAR T cells, Metzloff and Mitchell wondered if it might be possible to attach the activating antibodies used on the magnetic beads directly to the surface of the LNPs. Employing LNPs this way, they thought, might make it possible to eliminate the need for activating beads in the production process altogether. “This is novel,” says Metzloff, “because we’re using lipid nanoparticles not just to deliver mRNA encoding CARs, but also to initiate an advantageous activation state.”

Over the course of two years, Metzloff carefully optimized the design of the aLNPs. One of the primary challenges was to find the right ratio of one antibody to another. “There were a lot of choices to make,” Metzloff recalls, “since this hadn’t been done before.”

By attaching the antibodies directly to LNPs, the researchers were able to reduce the number of steps involved in the process of manufacturing CAR T cells from three to one, and to halve the time required, from 48 hours to just 24 hours. “This will hopefully have a transformative effect on the process for manufacturing CAR T cells,” says Mitchell. “It currently takes so much time to make them, and thus they are not accessible to many patients around the world who need them.”

CAR T cells manufactured using aLNPs have yet to be tested in humans, but in mouse models, CAR T cells created using the process described in the paper had a significant effect on leukemia, reducing the size of tumors, thereby demonstrating the feasibility of the technology.

Metzloff also sees additional potential for aLNPs. “I think aLNPs could be explored more broadly as a platform to deliver other cargoes to T cells,” she says. “We demonstrated in this paper one specific clinical application, but lipid nanoparticles can be used to encapsulate lots of different things: proteins, different types of mRNA. The aLNPs have broad potential utility for T cell cancer therapy as a whole, beyond this one mRNA CAR T cell application that we’ve shown here.”

Source: University of Pennsylvania

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#Administration #advanced materials #antibodies #antigen #Art #bioengineering #Biotechnology news #bloodstream #Cancer #cancer cells #Cancer Therapy #CAR T-cell therapy #Cars #cell #cell therapy #Cells #challenge #Chemistry & materials science news #cooking #course #covid #defense #Design #drug #engineers #FDA #Fight #Food #genetic #Giving

[cbccindia]

Understanding Immunotherapy for Autoimmune Diseases

Introduction

Immunotherapy, a groundbreaking approach primarily recognized for cancer therapy immunotherapy, is now making significant strides in treating autoimmune diseases. This article delves into how immunotherapy is applied beyond cancer immunology immunotherapy to manage and treat autoimmune conditions.

The Mechanism of Immunotherapy in Autoimmune Diseases

Immunotherapy works by modulating the immune system, enhancing its ability to fight diseases. Unlike in immunotherapy cancer treatment, where the goal is to target and destroy cancer cells, in autoimmune diseases, the therapy aims to recalibrate the immune system to stop attacking the body's tissues.

Types of Immunotherapy for Autoimmune Diseases

There are various types of immunotherapy used to treat autoimmune diseases. These include monoclonal antibodies, cytokine inhibitors, and immune checkpoint inhibitors, each designed to alter specific immune system pathways. While some of these therapies overlap with those used in cancer treatment, their application in autoimmune diseases focuses on immune regulation and suppression of overactive immune responses.

Immunotherapy Medications and Treatments

Immunotherapy medications for autoimmune diseases are tailored to reduce inflammation and curb the immune system's erroneous attacks on healthy cells. The precise medication or combination of therapies depends on the specific autoimmune condition being treated, highlighting the personalized nature of immunotherapy.

The Role of Immunotherapy and Vaccines

Exploring the intersection of immunotherapy and vaccines reveals potential for preventative strategies in autoimmune diseases. Vaccines designed to induce tolerance in the immune system are under research, potentially preventing autoimmune diseases from developing or worsening.

Managing Side Effects and Costs

While immunotherapy offers new hope, it's crucial to consider immunotherapy side effects and immunotherapy cost. Side effects vary widely, from mild to severe, and must be carefully managed under medical supervision. The cost can also be significant, necessitating a discussion about healthcare resources and insurance coverage.

Conclusion

Immunotherapy for autoimmune diseases represents a promising frontier in medical treatment, offering hope for millions suffering from these conditions. As research progresses, it could redefine the therapeutic landscape for autoimmune diseases, much like it has for cancer.

Discovering Excellence in Cancer and Autoimmune Disease Treatment at CBCC India

At the forefront of medical innovation and care, CBCC India stands as one of the leading Cancer Hospital in India, dedicated to eliminating cancer and advancing treatment for autoimmune diseases. Our commitment to innovative research and exceptional care ensures that every patient receives personalized, state-of-the-art treatment. Discover the pinnacle of healthcare excellence at CBCC India, where we strive to conquer cancer and improve the lives of those with autoimmune diseases through cutting-edge immunotherapy and comprehensive care.

#Immunotherapy #Autoimmune diseases #Cancer therapy #Immune system modulation #Monoclonal antibodies #Immune checkpoint inhibitors #Inflammation reduction #Personalized treatment #Vaccines

[indiancancercare]

True Healthcare For Your Family

Selecting the right hospital for cancer treatment is a critical decision, especially when faced with life-changing news. Dr. Sanjog Singh provides comprehensive cancer care in India, offering several compelling reasons why his services stand out:

Specialized Training

Research & Innovation Leadership in Investigative Studies

Primary Investigator in Original Research on HPV Incidence in Oral and Oropharyngeal Cancers in Central India

Contributing to Advancements in Cancer Understanding

A Decade of Excellence

More than 10 Years of Dedicated Service

Over 8 Years of Practice in Mumbai Worked in Prestigious Institutions like Nair Hospital, Hinduja Hospital, and KLS Memorial Hospital Affiliated to EHNS (European Head & Neck Society and ASCO)

Leading Cancer Care Department

Comprehensive Multidisciplinary Approach

Heads the Oncology Department at Shri Krishna Hrudayalaya

A Collaborative Team of Medical Oncologists, Radiation Oncologists, General Oncosurgeon, Prosthodontist, Dietician, Physiotherapist, Speech & Swallow Specialist

Patient Support and Education

Understanding that cancer care extends beyond medical treatments, Dr. Sanjog Singh provides robust support and educational programs. Integrative and complementary therapies, counseling, support groups, and educational resources help patients navigate the emotional and physical challenges of their cancer journey.

Comprehensive lifestyle change support, including nutrition counseling, exercise consultations, and tobacco cessation programs, ensures a holistic approach to treatment, making it more effective and reducing the risk of recurrence.

Discover hope, healing, and a supportive community at Cancer Care India. Dr. Sanjog Singh and our dedicated team are committed to guiding you through your cancer journey with expertise, empathy, and personalized care.

#cancer treatment #cancer therapy #cancer hospital

[drsameekshacancercare]

Understanding the Role of Immune Checkpoints in Cancer: A Key to Unleashing the Body’s Defense

In the field of oncology, years of research and practice are devoted to understanding the complexities of cancer and its relationship with the immune system. In recent times, the concept of immune checkpoints has emerged as a groundbreaking avenue in cancer therapy, rerevolutionizinghe way we approach treatment strategies.

What are Immune Checkpoints?

To comprehend the significance of immune checkpoints in cancer, let’s first grasp the basics. Immune checkpoints are pathways in the immune system that regulate the duration and strength of an immune response. They act as crucial gatekeepers, preventing the immune system from attacking healthy cells while also modulating the immune response against threats like cancer cells.

The Role of Immune Checkpoints in Cancer

Cancer cells can exploit these checkpoints, tricking the immune system into believing they are harmless, thus evading detection and destruction. Tumours often express molecules that interact with checkpoint proteins, effectively putting the brakes on the immune response, allowing cancer to thrive unchecked.

The discovery of immune checkpoint proteins such as CTLA-4 and PD-1/PD-L1 has led to a paradigm shift in cancer treatment. These checkpoints act as ‘immune brakes’ that, when inhibited, can unleash the body’s immune system to recognize and attack cancer cells.

Revolutionising Cancer Therapy: Immune Checkpoint Inhibitors

Enter immune checkpoint inhibitors (ICIs), a class of drugs designed to block these checkpoints, reinvigorating the immune response against cancer. Drugs targeting CTLA-4, PD-1, or PD-L1 have shown remarkable success in various cancers, significantly improving patient outcomes and survival rates.

Take, for instance, the success of anti-PD-1/PD-L1 therapies in melanoma, lung cancer, and bladder cancer. By blocking the PD-1/PD-L1 interaction, these therapies enable T cells to recognize and destroy cancer cells effectively.

Challenges and Future Directions

Despite the promising results, challenges persist. Not all patients respond to immune checkpoint inhibitors, responses may take a long duration to become apparent on radiology and some may experience adverse effects due to the unleashed immune response attacking healthy tissues, known as immune-related adverse events (irAEs). Understanding the factors influencing response rates and managing these side effects remain crucial areas of research. 

Moreover, combination therapies involving ICIs, chemotherapy, targeted therapy, or other immunotherapies are being explored to enhance efficacy and overcome resistance mechanisms developed by tumours.

The Need for Personalized Medicine

Every patient’s cancer is unique, necessitating a personalised approach to treatment. Biomarkers play a pivotal role in predicting a patient’s response to immune checkpoint inhibitors. Identifying reliable biomarkers can aid in selecting patients who are most likely to benefit from these therapies, optimising treatment strategies for better outcomes.

Conclusion

The discovery and utilisation of immune checkpoints in cancer therapy represent a monumental leap forward in oncology. By unleashing the body’s natural defence mechanisms, immune checkpoint inhibitors have transformed the landscape of cancer treatment, offering hope to patients and paving the way for more targeted, effective therapies.

As we continue to delve deeper into the complexities of the immune system and cancer interactions, the future holds immense promise for further advancements in immunotherapy. It’s a privilege to witness and contribute to this groundbreaking era in cancer research, bringing us closer to more personalised and effective treatments for patients worldwide.

#Immune Checkpoints in Cancer #Cancer Therapy

[aamrc]

Ayurvedic Diet for Cancer Recovery

Explore the transformative power of food in Ayurvedic cancer care. From antioxidant-rich fruits and vegetables to detoxifying spices, discover how dietary choices can support your body's healing journey.

#ayurvedic treatment for cancer #ayurvedha #cancer therapy

[ecomehdi]

Unveiling the Battle Against Pancreatic Cancer: HDAC Inhibitors in Focus 2023

Welcome to the fascinating realm of battling Pancreatic cancer, where scientific warriors are deploying innovative strategies against a formidable foe. In this journey, we delve into the promising domain of HDAC Inhibitors and their extraordinary potential in piercing through the fibrotic shield that often obstructs conventional treatments. Understanding Pancreatic Cancer Let’s begin our…

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#Cancer therapy #Cancer Treatment #clinical trials #Fibrotic barrier #Future of cancer care #HDAC Inhibitors #Healthcare insights #Innovative treatments #Medical advancements #Medical Breakthroughs #Molecular medicine #Oncology #Pancreatic cancer #Pancreatic cancer research #Patient stories

[advancedhealthindia]

#pancreatitis treatment #pancreas cancer treatment #chronic kidney disease treatments #kidney disease treatment #Cancer treatment #Cancer therapy

[headlinehorizon]

Unlocking the 'Kill Switch': A New Breakthrough in Cancer Therapy

Researchers at the UC Davis Comprehensive Cancer Center have discovered a protein on the CD95 receptor that can trigger the death of cancer cells, leading to a potential therapeutic path forward. This groundbreaking discovery, named in honor of cancer patient Anna Healey, could revolutionize cancer treatment.

#kill switch #cancer therapy #CD95 receptor #headline horizon #news #latest news

[eatclean-bewhole]

Hear this and watch it in its entirety. Chris is a cancer survivor who, like my mom, educated himself and has healed naturally. The corruption he speaks of is why I left nursing school to become a nutritionist. I mean no offense to nurses. I can appreciate the sacrifice and service. I especially appreciate the nurses trying to bridge the gap between medicine and nutrition. For me, nursing wasn’t a good fit. As I was shadowing in hospitals, it became clear that I would not be on the proactive side of health, like I intended. Once I started studying nutrition and its powerful healing effects on the human body, I became enamored. I haven’t looked back since and I will continue to do my part in getting this information out. You are only being told one side, but it’s a human right to know ALL of your healthcare, preventative, and treatment options.

#cancer #chemotherapy #radiation #health #cancertherapy #inegrativenutrition #integrativemedicine #cancerfighting #cancersupport #cancercare #cancertreatment #holistichealth #holistichealing #hyperbaricoxygentherapy #vitaminctherapy #holistictherapies #healthy #health #healthychoices #healthyliving #healthylife #healthybody #healthcare #nutrition #HealthyDiet #infrared #integrativenutrition #nutritionist #integrativenutritionist #healthtips

#cancer #anticancer #chemo #chemotherapy #radiation #healthcare #Health care #health #cancer therapy #integrative medicine #Nutrition #diet #exercise #cancerfighting #cancer support #cancer care #integrative health #integrative nutrition #integrativenutrition #holistic #holistic approach #holistic healing #healthy lifestyle #healthy choices #Healthy living #healthy diet #Disease #disease fighting #disease management

[harmeet-saggi]

Can Immunotherapy Revolutionize Cancer Treatment?

Cancer is a relentless foe, affecting millions of lives worldwide. Conventional cancer treatments like chemotherapy and radiation therapy have been the primary choices for years, but they often come with severe side effects and limitations. Is there a more effective and less invasive way to combat this deadly disease? That's where cancer immunotherapy comes into play. In this comprehensive guide, we will explore the groundbreaking advances in cancer immunotherapy and the challenges it faces, as well as how online resources can enhance the cancer therapy process.

#cancer treatment #immunotherapy #cancer therapy #cancer immunotherapy #CAR T-Cell Therapy #online doctor consultation #online lab test

[jcmarchi]

NSF, NIH Partner on New Research to Develop RNA-based Methods for Biotech Innovations - Technology Org

New Post has been published on https://thedigitalinsider.com/nsf-nih-partner-on-new-research-to-develop-rna-based-methods-for-biotech-innovations-technology-org/

NSF, NIH Partner on New Research to Develop RNA-based Methods for Biotech Innovations - Technology Org

The U.S. National Science Foundation has awarded over $12.7 million across nine research teams to understand better the untapped capabilities of ribonucleic acid (RNA) for potentially far-reaching biotechnology applications, from disease prevention in crops to cancer-fighting therapies.

The nine teams will each receive $1 million to $1.65 million from NSF through the Molecular Foundations for Biotechnology (MFB) program, a joint effort of NSF in partnership with the National Institutes of Health’s National Human Genome Research Institute (NHGRI). NHGRI plans to invest in additional projects to be announced later in 2024, focusing on developing novel technologies to investigate RNA biology. 

Supported by the Molecular Foundations for Biotechnology program, researchers will explore RNA’s roles and actions to use them to create new RNA-based methods for treating cancerous cells, making crops more resistant to blight and disease, fighting viral infections like the common cold, and more. The program is a joint effort of the U.S. National Science Foundation in partnership with the National Institutes of Health’s National Human Genome Research Institute. Image Credit: U.S. National Science Foundation

“Innovative new modes of inquiry into the molecular-level structure, dynamics and function of RNA is expected to lead to significant biotech breakthroughs at the intersection of chemistry and biology,” says NSF’s Chemistry Division Director David Berkowitz. “By advancing this fundamental science, we open the door to new avenues of use-inspired research and applications that can benefit society and improve our quality of life.” 

“We are excited to partner with NSF to support research into the structures, interactions, functions and applications of RNA,” says Carolyn Hutter, Director of the Division of Genome Sciences at NHGRI. “New tools and technologies that harness RNA research have the potential to transform the biomedical field and improve human health.” 

RNA is a complex organic molecule that performs essential tasks within the biological and chemical machinery of all living cells. Although RNA was first identified nearly a century ago, many of its functional aspects are not fully understood or predictable.

The nine research teams will explore RNA’s roles and actions with the goal of creating new RNA-based methods for treating cancerous cells, making crops more resistant to blight and disease, fighting viral infections like the common cold and more. The teams include experts in a range of fields from chemistry, biology and physics to mathematical modeling and machine learning. Their projects are expected to provide opportunities to partner with industry to translate knowledge gained in the lab into marketable new biotechnologies. 

In addition to supporting the research, NSF’s investment will provide hands-on training for students and early-career researchers through mentorship, workshops and internships for high school and undergraduate students and other activities to expand and broaden participation in the U.S. STEM workforce.  

The nine projects and teams are: 

Next-generation Proximity Labeling Technologies to Map Subcellular Transcriptomes and RNA Interactomes in Living Cells with Nanometer Resolution (Stanford University) aims to create new technologies to enable scientists to quickly visualize where RNAs localize within living cells and identify other genetic materials nearby that could interact with the RNAs; these technologies could be useful in studying in-cell interactions in diseases such as cancer. 

Stabilizing Hairpin Inserts in RNA Virus Induced Gene Silencing Vectors (University of Maryland, College Park and Silvec Biologics) will work to create stable RNA genomes that can be used as delivery devices to disable the bacteria that cause diseases in plants, such as citrus greening; a serious plant disease that impacts economically and agriculturally important citrus trees internationally and for which there is no cure.  

Cracking the Codes: Understanding the Rules of mRNA Localization and Translation (University of Colorado Denver) aims to use recent developments in RNA sequencing technology to create a model capable of predicting protein output from a messenger RNA, which could have a broad impact on what we understand about how genes encode and transmit information. 

Better Homologous Folding using Computational Linguistics and Deep Learning (Oregon State University and the University of Rochester) seeks to use artificial intelligence to develop faster and better algorithms and software tools to model RNA secondary structures, which has the potential for advancing therapeutic and diagnostic design. 

Characterization of the Biogenesis, Uptake, and Cellular Response to the Ribonucleoprotein Cargoes of Extracellular Vesicles using EV-CLASP (Vanderbilt University) will work to increase our understanding of extracellular vesicle-derived RNAs, which could enhance our ability to understand RNA dynamics during cellular communication, which would help identify novel gene regulatory elements and develop ways to deliver RNA treatments into cells. 

RNA Modifications of Frameshifting Stimulators: Cellular Platforms to Engineer Gene Expression by Computational Mutation Predictions and Functional Experiments (New York University and the University of North Carolina at Chapel Hill) aims to predict and model how two proteins can be generated from the same messenger RNA with the goal of applying that knowledge to limit how RNA viruses can use this mutation to infect humans or to develop new forms of drug delivery. 

Evaluating and Advancing Cryo-EM for RNA Conformational Ensembles (Stanford University) will test whether cryogenic electron microscopy and computational methods can accurately visualize functionally critical features of RNA machines to create a validated toolkit that could help researchers develop models of a variety of RNA-based machines of biological or biotechnological interest. 

Massively Parallel Identification of Translation Regulatory Sequences in Human and Viral mRNAs (Yale University) will take a systems-level approach to understand the various factors that impact the amount of protein synthesized from messenger RNAs, which could aid in designing new classes of therapeutic messenger RNAs. 

Continuous Evolution of RNAs with Novel Functions in Mammalian Cells (Weill Cornell Medicine and Massachusetts Institute of Technology) aims to overcome the challenges in deploying functional RNA into live cells, which could transform biotechnology, biomedicine and biology broadly by allowing scientists to develop and deliver RNAs that can bind to target proteins in living cells. 

The MFB program is a cross-disciplinary initiative led by NSF’s Directorates for Mathematical and Physical Sciences and Biological Sciences, with additional support from the Directorate for Computer and Information Science and Engineering and the Directorate for Engineering. 

Source: NSF

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#2024 #Algorithms #applications #approach #artificial #Artificial Intelligence #Bacteria #Biology #biomedicine #biotech #biotechnology #Biotechnology news #Cancer #cancer prevention #Cancer Therapy #career #cell #Cells #chemical #chemistry #classes #college #communication #computer #continuous #crops #Deep Learning #Design #Developments #devices

[scottguy]

Some good news!

Note: This research was done by doctors in a hospital, but you can bet some big pharma company will end up with the patent and right to charge whatever the market will bear.

Yet another reason to nationalize healthcare like every civilized country did long ago.

#cancer therapy #cancer research