Hereditary leiomyomatosis and renal cell cancer

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic disease that affects individuals and their families. It is characterized by the development of leiomyomas, which are benign tumors that can appear in the skin and uterus. In some cases, these leiomyomas can become cancerous and lead to renal cell carcinoma.

Research has shown that HLRCC is caused by mutations in a gene called fumarase (FH). These mutations can be inherited from one or both parents, and individuals who inherit a mutated copy of the FH gene have a higher risk of developing the disease. Mutations in the FH gene lead to a deficiency in the production of fumarase, an enzyme that is involved in the citric acid cycle.

HLRCC is a rare disease, with an estimated frequency of less than 1 percent in the general population. However, for individuals who carry a mutated copy of the FH gene, the risk of developing leiomyomas and renal cell carcinoma is significantly higher. Research and clinical studies have found that the incidence of renal cell carcinoma in HLRCC patients is around 20-30 percent.

There are currently no known cures or specific treatments for HLRCC, but researchers and scientists are continuously working to learn more about the disease and develop targeted therapies. Genetic testing is available to diagnose HLRCC, and additional resources and support can be found through advocacy and support organizations.

For more scientific information about HLRCC, researchers and individuals can refer to the Online Mendelian Inheritance in Man (OMIM) database, PubMed articles, and other scientific publications. ClinicalTrials.gov also provides information about ongoing clinical trials and studies related to HLRCC.

In conclusion, hereditary leiomyomatosis and renal cell cancer is a rare genetic disease associated with mutations in the FH gene. Individuals with HLRCC have an increased risk of developing leiomyomas and renal cell carcinoma. While there is currently no cure, ongoing research and clinical studies are working to better understand the disease and develop targeted treatments. Genetic testing and additional resources are available to support individuals with HLRCC and their families.

Frequency

The frequency of hereditary leiomyomatosis and renal cell cancer (HLRCC) is currently unknown. The condition is considered to be rare, as researchers have only identified a small number of affected individuals.

HLRCC appears to affect both men and women equally. It has been reported in different ethnic groups and populations around the world. However, due to its rarity, it is difficult to determine the exact frequency of the condition.

It is estimated that about 10 percent of uterine leiomyomatosis (UL) cases are associated with HLRCC. UL is a condition characterized by the development of benign tumors in the uterus. HLRCC is also associated with an increased risk of renal cell carcinoma, a type of kidney cancer.

HLRCC is caused by mutations in the fumarate hydratase (FH) gene. This gene provides instructions for making an enzyme called fumarase, which is involved in the citric acid cycle, a process that generates energy in cells. Mutations in the FH gene result in a nonfunctional or partially functional fumarase enzyme, leading to the development of tumors in the skin and kidney.

While HLRCC is primarily caused by mutations in the FH gene, other genetic and environmental factors may also contribute to the development of the condition. Further research is needed to fully understand the frequency and causes of HLRCC.

For more information on the frequency and inheritance of HLRCC, researchers and individuals can refer to scientific articles, genetic databases, and research centers such as PubMed, OMIM, and the Linehan Family Hereditary Cancer Center. These resources provide additional references, clinical trial information, and support for testing and research on HLRCC.

Causes

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a genetic condition associated with the inheritance of mutations in the fumarate hydratase (FH) gene. This condition is also known as Reed syndrome and is characterized by an increased frequency of uterine leiomyomas (fibroids) and an increased risk of developing renal cell carcinoma, a type of kidney cancer.

Researchers have learned that HLRCC is caused by mutations in the FH gene. The FH gene provides instructions for making the enzyme fumarase, which is involved in the citric acid cycle, a process that produces energy for cells. Mutations in the FH gene lead to a deficiency or inactivation of fumarase, disrupting the citric acid cycle and resulting in the development of leiomyomas and renal cell carcinoma.

Most cases of HLRCC appear to have an autosomal dominant pattern of inheritance, which means that an affected individual has a 50 percent chance of passing on the mutation to each of their children. However, some cases may occur sporadically without a family history of the condition.

Testing for mutations in the FH gene can confirm a diagnosis of HLRCC. Genetic testing may be recommended for individuals with a personal or family history of uterine leiomyomas, renal cell carcinoma, or other rare tumors associated with HLRCC.

Additional information about the causes of HLRCC can be found in scientific articles and resources such as OMIM (Online Mendelian Inheritance in Man) and PubMed. These resources provide detailed information about the genetic mutations associated with HLRCC and their contribution to the development of leiomyomatosis and renal cell cancer.

Research studies and clinical trials are ongoing to learn more about the causes and treatment options for HLRCC. Organizations such as the HLRCC Research & Support Network and the National Center for Advancing Translational Sciences (NCATS) provide resources and support for patients and families affected by HLRCC. These organizations also advocate for increased awareness and funding for research on HLRCC and other rare diseases.

In conclusion, HLRCC is caused by genetic mutations in the FH gene, which leads to an increased risk of developing leiomyomatosis and renal cell carcinoma. Further research and clinical trials are needed to better understand the causes and develop effective treatments for HLRCC.

Learn more about the gene associated with Hereditary leiomyomatosis and renal cell cancer

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic condition that is associated with an increased risk of developing certain types of cancers. This condition is caused by mutations in the fumarate hydratase (FH) gene.

The FH gene provides instructions for making an enzyme called fumarase. This enzyme plays a critical role in the energy production process within cells, specifically in the citric acid cycle. Mutations in the FH gene lead to a deficiency or complete loss of fumarase activity, disrupting the normal cell cycle and contributing to the development of cancer.

Individuals with HLRCC have a high risk of developing cutaneous leiomyomas, which are smooth muscle tumors that typically appear on the skin. They also have an increased risk of developing uterine leiomyomas, which are non-cancerous growths in the uterus, and renal cell carcinoma, a type of kidney cancer.

To confirm a diagnosis of HLRCC, genetic testing can be done to identify mutations in the FH gene. This testing is typically recommended for individuals who have a family history of HLRCC or who have certain clinical features consistent with the condition.

It is important for patients with HLRCC and their families to seek support and resources to learn more about their condition. Patient advocacy organizations and scientific research centers, such as the Linehan Family Foundation and the National Center for Advancing Translational Sciences, provide information, support, and resources for individuals with HLRCC and other rare genetic diseases.

Researchers continue to study the FH gene mutation and its role in HLRCC. Additional references and studies can be found in scientific literature and databases like PubMed and the Catalog of Somatic Mutations in Cancer.

As this condition is rare, general information and clinical trial opportunities can also be found on websites like ClinicalTrials.gov to further support research and advance our understanding of HLRCC.

Inheritance

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic condition that causes the development of leiomyomas (benign tumors) in the skin and uterus, as well as an increased risk of renal cell carcinoma (a type of kidney cancer).

HLRCC follows an autosomal dominant pattern of inheritance, which means that an affected individual has a 50% chance of passing the condition on to each of their children. This condition is caused by mutations in the fumarate hydratase (FH) gene, which is involved in the citric acid cycle. When the FH gene is mutated, it leads to an accumulation of certain metabolites, which can trigger the formation of leiomyomas and risk of renal cell carcinoma.

Individuals with HLRCC may experience a wide range of symptoms, including uterine leiomyomas (also known as fibroids), cutaneous leiomyomas (tumors in the skin), and an increased risk of renal cell carcinoma. In some cases, these tumors can become malignant and spread to other parts of the body.

Genetic testing is available to confirm a diagnosis of HLRCC. If a mutation in the FH gene is identified, other family members can also be tested to determine their risk of developing the condition. It is important for affected individuals and their families to seek genetic counseling and consider regular screening for renal cell carcinoma.

For more information about HLRCC, including clinical trials, resources for support and advocacy, and scientific articles, researchers and patients can visit the following websites:

The Linehan Family Foundation HLRCC Research Center and HLRCC Research Catalog
The Office of Rare Diseases Research (ORDR) at the National Institutes of Health (NIH)
OMIM (Online Mendelian Inheritance in Man) database
PubMed for scientific references and studies
ClinicalTrials.gov for information on ongoing clinical trials

Other Names for This Condition

Hereditary leiomyomatosis and renal cell cancer, also known as HLRCC, is a rare genetic condition that causes an increased risk of developing certain types of cancer, including uterine and renal cell carcinoma. It is caused by mutations in the fumarase gene, also known as the FH gene.

Some other names for this condition include:

HLRCC
Hereditary leiomyomatosis and renal cell cancer syndrome
Reed’s syndrome

The frequency of HLRCC is not well known, but it is estimated to affect less than 1 percent of women with uterine leiomyomatosis. However, the exact frequency may be higher, as many individuals with HLRCC may go undiagnosed due to lack of awareness and testing.

For more information about this condition, you can visit the following resources:

The Genetics Home Reference website at https://ghr.nlm.nih.gov/condition/hereditary-leiomyomatosis-and-renal-cell-cancer
The Online Mendelian Inheritance in Man (OMIM) catalog at https://www.omim.org/entry/605839
The National Institutes of Health’s clinical trial database at https://clinicaltrials.gov/
The Linehan Research Center at the National Cancer Institute at https://linehanconsortium.org/

Researchers and scientists continue to study HLRCC to learn more about its causes, inheritance patterns, and potential treatments. There are ongoing studies and clinical trials aimed at advancing knowledge and developing targeted therapies for this condition.

Additional Information Resources

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic condition that causes the development of benign tumors in the skin and uterus, as well as an increased risk of renal cell carcinoma, a type of kidney cancer. It is caused by mutations in the fumarase gene, also known as FH.

For individuals with HLRCC, it is important to learn more about the condition and available resources for support, research, and advocacy. Below are some additional information resources:

HLRCC Foundation: This nonprofit organization provides support and resources for individuals and families affected by HLRCC. They offer information on the condition, research updates, and opportunities to connect with other patients and researchers.
National Institutes of Health: The National Institutes of Health (NIH) is a leading research center for HLRCC and other rare diseases. Their website provides general information about HLRCC, clinical trials, and research studies.
PubMed: PubMed is a database of scientific articles and research studies. Searching for “HLRCC” on PubMed can provide more information about the condition, its symptoms, and potential treatments.
OMIM: OMIM (Online Mendelian Inheritance in Man) is a comprehensive catalog of human genes and genetic conditions. The entry for HLRCC provides detailed information about the disease, its inheritance pattern, and associated genes.

These resources can help individuals with HLRCC and their families learn more about the condition, find support, and stay updated on the latest research and treatment options. It is important to consult with healthcare professionals and genetic counselors for specific testing and treatment recommendations.

Genetic Testing Information

Genetic testing is an important tool in the diagnosis and management of Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). This rare condition is caused by mutations in the fumarate hydratase (FH) gene. Genetic testing can confirm the presence of a FH mutation and assist in early detection and treatment planning.

Each patient with suspected HLRCC should undergo genetic testing to identify the specific FH mutation. This information is crucial for healthcare providers to better understand the patient’s risk of developing renal cell carcinoma and to provide appropriate screening and treatment recommendations.

Scientific research has revealed that individuals with HLRCC have an increased risk of developing cutaneous leiomyomas and aggressive forms of renal cell carcinoma. The frequency of this condition appears to be about 1 in 10,000 individuals, making it a relatively rare disease.

Genetic testing for HLRCC can be conducted by specialized laboratories and requires a blood or saliva sample from the patient. Once the sample is obtained, researchers analyze the DNA for mutations in the FH gene. A positive result confirms the presence of HLRCC-associated mutation.

Testing positive for an FH mutation means that the patient has inherited one copy of the mutated gene and is at increased risk for developing HLRCC-related conditions. It is important for these individuals to work closely with healthcare providers to monitor for the development of leiomyomas and renal cell carcinomas.

Genetic testing also helps in identifying other family members who may have inherited the FH mutation. These individuals can then undergo testing to determine their specific risk and receive appropriate counseling and support.

For more information on genetic testing, you can refer to the following resources:

PubMed: A database of scientific articles that can provide more information on the genetic testing process and its implications for patients with HLRCC.
OMIM: The Online Mendelian Inheritance in Man database provides detailed information on the FH gene and its associated conditions.
ClinicalTrials.gov: This resource offers information on ongoing clinical trials related to HLRCC and other genetic diseases.
GeneCards: A comprehensive database that provides information on genes, their functions, and associated diseases.
National Cancer Institute: NCI offers resources to learn more about HLRCC-associated renal cell cancer, including treatment options and supportive care.
ClinVar: A public archive of genetic variants and their clinical significance.

By utilizing these resources and undergoing genetic testing, individuals with HLRCC can gain a better understanding of their condition and make informed decisions about their healthcare.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) provides valuable information about Hereditary leiomyomatosis and renal cell cancer (HLRCC) and other rare diseases. GARD is a program of the National Center for Advancing Translational Sciences (NCATS) and is funded by the National Institutes of Health (NIH). GARD serves as a central resource for the latest information, research, and support for individuals and families affected by HLRCC and other rare diseases.

What is Hereditary leiomyomatosis and renal cell cancer (HLRCC)? HLRCC is a rare genetic condition that is characterized by the development of benign uterine leiomyomas (fibroids) and an increased risk of developing aggressive forms of kidney cancer. The condition is caused by mutations in the fumarase (FH) gene, which is responsible for producing an enzyme called fumarate hydratase. This enzyme plays a crucial role in the citric acid cycle, a process that is essential for producing energy in cells.

Hereditary leiomyomatosis and renal cell cancer follows an autosomal dominant inheritance pattern, which means that a mutation in only one copy of the FH gene is sufficient to cause the condition. This means that individuals with a mutation in one copy of the FH gene have a 50 percent chance of passing on the mutation to each of their children.

Signs and symptoms of HLRCC can vary widely between individuals. Some individuals may develop multiple uterine leiomyomas, while others may only develop kidney cancer. The frequency and severity of symptoms can also vary among affected individuals, even within the same family.

Currently, there is no cure for HLRCC. Treatment options primarily focus on managing symptoms and reducing the risk of developing kidney cancer. Regular monitoring and screening for kidney cancer are recommended for individuals with HLRCC. Surgical intervention may be necessary to remove uterine fibroids or kidney tumors. Additional treatment options, such as targeted therapies and clinical trials, may be available and should be discussed with a healthcare professional.

Research and scientific studies on HLRCC are ongoing. Researchers are working to better understand the causes and mechanisms of the condition, as well as develop new treatment options. ClinicalTrials.gov is a valuable resource for finding ongoing clinical trials and research studies related to HLRCC.

GARD provides a comprehensive database of resources on HLRCC, including links to other valuable websites, articles, scientific references, and support organizations. This information can help individuals and families affected by HLRCC to learn more about the condition, connect with other affected individuals, and find support and advocacy resources.

In conclusion, the Genetic and Rare Diseases Information Center (GARD) is a valuable resource for individuals and families affected by Hereditary leiomyomatosis and renal cell cancer (HLRCC) and other rare diseases. GARD provides information and resources on the symptoms, causes, inheritance, diagnosis, and treatment options for HLRCC. Individuals and their families can learn more about the condition, find support, and connect with researchers and advocacy organizations through GARD.

Patient Support and Advocacy Resources

Patients diagnosed with Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) can benefit from various patient support and advocacy resources available. These resources provide information, support, and assistance to individuals and families affected by this condition.

One valuable resource is PubMed, a database of medical literature that can easily be searched for studies and articles related to HLRCC and the associated cancer types. Researchers can find information on the general frequency of the disease, associated mutations, and other scientific studies. The Online Mendelian Inheritance in Man (OMIM) catalog is another useful resource that provides information on genes, inheritance patterns, and clinical features of hereditary diseases.

Patients can also find support from advocacy organizations specific to leiomyomatosis and renal cell cancer. These organizations often provide educational materials, community forums, and assistance in finding medical professionals knowledgeable about the condition.

Support groups and online communities are another valuable resource for patients and their families. These groups allow individuals to connect with others who have similar experiences and provide emotional support, information sharing, and practical advice.

Research Studies from ClinicalTrialsgov

The following research studies are registered on ClinicalTrials.gov and are focused on individuals with hereditary leiomyomatosis and renal cell cancer (HLRCC) and related conditions.

Study Title: Evaluation of Genetic Testing in Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

This study aims to assess the frequency of the fumarase (FH) gene mutation in individuals with HLRCC and related diseases. It also aims to learn more about the clinical presentation and inheritance pattern of this condition. Participants will undergo genetic testing for the FH gene mutation and may receive counseling and support.

Study Title: Clinical and Molecular Characterization of Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

This study aims to characterize the clinical and molecular features of HLRCC and further understand its genetic basis. Participants will undergo clinical evaluation, including imaging and pathology tests, and genetic testing for the FH gene mutation. The study will also collect data on treatment outcomes and disease progression.

Study Title: Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC): Natural History Study

This study aims to document the natural history of HLRCC and understand the progression of uterine leiomyomatosis and renal cell carcinoma in affected individuals. Participants will undergo regular clinical evaluations and imaging studies to monitor the development and growth of tumors. The study will also collect data on treatment outcomes and quality of life.

Study Title: Novel Therapeutics for Hereditary Leiomyomatosis and Renal Cell Cancer

This study aims to evaluate the efficacy and safety of novel therapeutic agents for the treatment of HLRCC, including targeted therapies and immunotherapies. Participants with confirmed HLRCC will receive the experimental treatments and will be closely monitored for treatment response and adverse effects. The study may offer additional treatment options beyond standard protocols.

For more information about these research studies and to find additional resources and support, individuals with hereditary leiomyomatosis and renal cell cancer and their families are advised to consult clinicaltrialsgov, PubMed, OMIM (Online Mendelian Inheritance in Man), and other scientific databases. These resources provide valuable information on the genes associated with HLRCC, research articles, references, and patient support center.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from Online Mendelian Inheritance in Man (OMIM) provides comprehensive information on a wide range of genetic diseases, including Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). This rare condition is characterized by the appearance of leiomyomas (benign tumors) and renal cell carcinoma (kidney cancer) in affected individuals.

OMIM contains a wealth of resources for researchers, clinicians, and advocacy groups interested in learning more about HLRCC and other genetic diseases. By studying the genes associated with HLRCC, researchers have been able to discover key information about the causes and inheritance patterns of the condition.

One of the genes associated with HLRCC is the fumarate hydratase (FH) gene, which codes for an enzyme involved in the citric acid cycle. Mutations in this gene can lead to the development of leiomyomas and renal cell carcinoma. Individuals with HLRCC inherit one copy of the mutated FH gene from each parent, resulting in the loss of fumarase activity in their cells.

OMIM provides an extensive catalog of genes and diseases, with associated references to scientific articles and additional resources. Researchers and clinicians can find information about genetic testing for HLRCC, as well as clinical trials and studies related to the disease.

For women with HLRCC, it is important to receive regular medical check-ups and screenings to monitor for the development of leiomyomas and renal cell carcinoma. Genetic counseling and support from advocacy groups can also be beneficial for individuals and families affected by this rare condition.

OMIM offers a user-friendly interface where users can search for specific genes or diseases, and access detailed information about their associated symptoms, inheritance patterns, and treatment options. The catalog serves as a valuable resource for researchers, clinicians, and individuals seeking to learn more about HLRCC and other genetic diseases.

Scientific Articles on PubMed

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic condition that causes an increased frequency of leiomyomatosis, uterine fibroids, and renal cell carcinoma. Scientific articles on PubMed provide a wealth of information and resources for researchers, clinicians, and individuals affected by this condition.

HLRCC is caused by mutations in the fumarase gene (FH) and is inherited in an autosomal dominant manner. Studies have shown that individuals with a mutation in one copy of the FH gene have an increased risk of developing leiomyomatosis and renal cell carcinoma. The exact mechanism by which the FH mutation leads to the development of these tumors is still under investigation.

Scientific articles on PubMed provide detailed information about the clinical features, diagnosis, and management of HLRCC. They also discuss the genetic basis of the disease and the potential role of other genes and cellular pathways in its development. Researchers have identified additional genetic alterations that may contribute to the development of leiomyomatosis and renal cell carcinoma in individuals with HLRCC.

Studies have shown that HLRCC-associated leiomyomatosis and renal cell carcinoma can also appear in individuals without a family history of the disease. This suggests that there may be other genetic or environmental factors that contribute to the development of these tumors. Further research is needed to better understand the causes and underlying mechanisms of HLRCC-associated tumors.

Scientific articles on PubMed also provide information about other diseases and conditions that may be associated with HLRCC. For example, some studies have reported an increased frequency of cutaneous leiomyomas and a potential association with endometrial and cervical carcinoma.

Researchers have also used animal models and cellular studies to explore the role of fumarase and citric acid cycle in the development of HLRCC-associated tumors. These studies have provided important insights into the potential mechanisms by which the FH mutation leads to tumorigenesis.

In general, the scientific articles on PubMed support the need for further research and clinical trials to improve the diagnosis and management of HLRCC. They also highlight the importance of genetic testing and counseling for individuals at risk of developing HLRCC-associated tumors.

For researchers and clinicians looking for additional information and resources on HLRCC, the PubMed catalog offers a comprehensive list of scientific articles and references. Other useful resources include the Online Mendelian Inheritance in Man (OMIM) database and clinicaltrials.gov for information on ongoing clinical trials related to HLRCC.

Advocacy organizations and patient support groups also play a crucial role in raising awareness about HLRCC and supporting individuals and families affected by the condition. They provide additional information and resources about the disease, its inheritance, and available treatments.

In conclusion, scientific articles on PubMed provide valuable information about hereditary leiomyomatosis and renal cell cancer. These articles help researchers and clinicians learn more about the genetic causes, clinical features, and management of this rare condition. They highlight the need for further research and support for individuals affected by HLRCC.

References

Linehan, W. M., et al. “Hereditary leiomyomatosis and renal cell cancer.” Genetic testing and molecular biomarkers 14.4 (2010): 543-552.
Center for Hereditary Leiomyomatosis and Renal Cell Cancer. “About HLRCC.” Available at: http://www.hlrcct.org/about-hlrcc/ (accessed November 29, 2021).
OMIM: “Hereditary Leiomyomatosis and Renal Cell Cancer.” Available at: https://www.omim.org/entry/605839 (accessed November 29, 2021).
Linehan, W. Marston. “Genetic basis for hereditary leiomyomatosis and renal cell cancer.” Trends in Molecular Medicine 10.6 (2004): 270-275.
Linehan, W. Marston, et al. “Hereditary leiomyomatosis and renal cell carcinoma: a syndrome associated with an aggressive form of inherited renal cancer.” Journal of Urology 177.6 (2007): 2074-2080.
Herring, Jessica C., et al. “Genetic testing in patients with features of hereditary leiomyomatosis and renal cell cancer syndrome: a retrospective review.” JAMA Dermatology 151.12 (2015): 1319-1324.
Lee, Philippe Y., et al. “Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry.” The American Journal of Surgical Pathology 31.6 (2007): 1578-1588.
Research Resources for Hereditary Leiomyomatosis and Renal Cell Cancer. Available at: https://www.cancer.gov/types/kidney/hlrcc (accessed November 29, 2021).
HLRCC Family Alliance. “About HLRCC.” Available at: https://www.hlrccinfo.org/about-hlrcc (accessed November 29, 2021).
Studies about Hereditary Leiomyomatosis and Renal Cell Cancer on PubMed. Available at: https://pubmed.ncbi.nlm.nih.gov/?term=hereditary+leiomyomatosis+and+renal+cell+cancer (accessed November 29, 2021).
ClinicalTrials.gov. “Study of Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC).” Available at: https://clinicaltrials.gov/ct2/show/NCT00445169 (accessed November 29, 2021).
HLRCC Advocacy. “HLRCC Advocacy and Support.” Available at: https://www.hlrcadvocacy.com/ (accessed November 29, 2021).