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Illnesses of Unknown Etiology

Section Edited by Monica C. Panelli

This section aims to provide a translational medicine forum for the publication of research on illnesses, multi-system diseases and syndromes of unknown etiology. Examples of these include Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) and Fibromyalgia Syndrome (FMS).

There has been a continuous albeit undervalued progress in this arena. However, among the many medical specialties that try to diagnose and treat the multiple symptoms presented by patients affected by these diseases, an avenue of rapid and simultaneous communication is missing.

Studies on all aspects of ME/CFS and multi-system diseases of unknown cause with applications in medicine and biotechnology will be considered for publication. The section welcomes contributions that employ traditional clinical, metabolic, epidemiologic, genomics and proteomics methods as diagnostic and prognostic tools.

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  1. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in it...

    Authors: Chou-Yi Hsu, Irfan Ahmad, Rana Warid Maya, Mayada Ahmed Abass, Jitendra Gupta, Abhayveer Singh, Kamal Kant Joshi, J. Premkumar, Samir Sahoo and Mohsen Khosravi
    Citation: Journal of Translational Medicine 2025 23:530
    Content type: Review Published on:

  3. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post COVID-19 Condition (PCC) are debilitating, chronic multi-systemic illnesses that require multidisciplinary care. However, people with ME/CFS...

    Authors: Breanna Weigel, Maira Inderyas, Natalie Eaton-Fitch, Kiran Thapaliya and Sonya Marshall-Gradisnik
    Citation: Journal of Translational Medicine 2025 23:318
    Content type: Review Published on:

  5. The relationship between the brain and fatigue is gaining increasing attention, with numerous studies indicating that certain specific brain regions may be closely linked to fatigue. Our study aimed to identif...

    Authors: Yifei Zhang, Zehan Zhang, Qingqian Yu, Yutong Jiang, Chenyu Fei, Fengzhi Wu and Feng Li
    Citation: Journal of Translational Medicine 2025 23:293
    Content type: Research Published on:

  6. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown aetiology characterised by symptoms of post-exertional malaise (PEM) and fatigue leading to substantial impairment in functio...

    Authors: Krista S. P. Clarke, Caroline C. Kingdon, Michael Pycraft Hughes, Eliana Mattos Lacerda, Rebecca Lewis, Emily J. Kruchek, Robert A. Dorey and Fatima H. Labeed
    Citation: Journal of Translational Medicine 2025 23:149
    Content type: Review Published on:

  7. We have noted that some adolescents and young adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) report difficulty with arms-overhead activities, suggestive of brachial plexus dysfunction ...

    Authors: Charles C. Edwards III, Julia M. Byrnes, Camille A. Broussard, Alba M. Azola, Meghan E. Swope, Colleen L. Marden, Renee L. Swope, Ying Wei Lum, Richard L. Violand and Peter C. Rowe
    Citation: Journal of Translational Medicine 2025 23:106
    Content type: Research Published on:

  8. The pathogenesis of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains unclear, though increasing evidence suggests inflammatory processes play key roles. In this study, single-cell RNA sequen...

    Authors: Yujing Sun, Zhenhua Zhang, Qincheng Qiao, Ying Zou, Lina Wang, Tixiao Wang, Bo Lou, Guosheng Li, Miao Xu, Yanxiang Wang, Zhenhong Zhang, Xinguo Hou, Li Chen and Ruxing Zhao
    Citation: Journal of Translational Medicine 2024 22:925
    Content type: Research Published on:

  9. Numerous observational studies have indicated that patients with Guillain-Barré syndrome (GBS) frequently had infections with various pathogens before the onset of the disease, particularly several viral infec...

    Authors: Qing-Xiang Kong, Zhao-Kun Gao, Yan Liu, Lu-Lu Jiang, Yuan-Jie Liu and Zhi-Yun Lian
    Citation: Journal of Translational Medicine 2024 22:890
    Content type: Research Published on:

  10. Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be place...

    Authors: Tao Han, Chunqiu Dai, Ying Liang, Xiaodong Lin, Ming Gao, Xinyu Liu, Xiangbo Wu, Yuheng Lu, Xiao Xi, Fei Tian, Chenguang Zhao, Xiaolong Sun and Hua Yuan
    Citation: Journal of Translational Medicine 2024 22:720
    Content type: Research Published on:

  11. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with a broad overlap of symptomatology with Post-COVID Syndrome (PCS). Despite the severity of symptoms and various neurolo...

    Authors: Matthias Löhn and Klaus Josef Wirth
    Citation: Journal of Translational Medicine 2024 22:630
    Content type: Review Published on:

  12. Post-exertional malaise (PEM), the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), represents a constellation of abnormal responses to physical, cognitive, and/or emotional exe...

    Authors: Betsy Keller, Candace N. Receno, Carl J. Franconi, Sebastian Harenberg, Jared Stevens, Xiangling Mao, Staci R. Stevens, Geoff Moore, Susan Levine, John Chia, Dikoma Shungu and Maureen R. Hanson
    Citation: Journal of Translational Medicine 2024 22:627
    Content type: Research Published on:

  13. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness medically unexplained, affecting approximately 1% of the global population. Due to the subjective complaint, assessing the ...

    Authors: Jae-Woong Park, Byung-Jin Park, Jin-Seok Lee, Eun-Jung Lee, Yo-Chan Ahn and Chang-Gue Son
    Citation: Journal of Translational Medicine 2024 22:529
    Content type: Research Published on:

    The Correction to this article has been published in Journal of Translational Medicine 2024 22:603

  14. Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. Howeve...

    Authors: Joan Carles Domingo, Federica Battistini, Begoña Cordobilla, Maria Cleofé Zaragozá, Ramón Sanmartin-Sentañes, Jose Alegre-Martin, Trinitat Cambras and Jesus Castro-Marrero
    Citation: Journal of Translational Medicine 2024 22:343
    Content type: Research Published on:

  15. In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90–150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to ass...

    Authors: Merel E. B. Cornelissen, Lizan D. Bloemsma, Anouk W. Vaes, Nadia Baalbaki, Qichen Deng, Rosanne J. H. C. G. Beijers, Lieke C. E. Noij, Laura Houweling, Somayeh Bazdar, Martijn A. Spruit and Anke H. Maitland-van der Zee
    Citation: Journal of Translational Medicine 2024 22:191
    Content type: Research Published on:

  16. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a significant medical challenge, with no indisputable pathophysiological mechanism identified to date.

    Authors: Jin-Seok Lee, Ji-Yun Kang, Samuel-Young Park, Seung-Ju Hwang, Sung-Jin Bae and Chang-Gue Son
    Citation: Journal of Translational Medicine 2024 22:34
    Content type: Research Published on:

  17. Causative genetic variants cannot yet be found for many disorders with a clear heritable component, including chronic fatigue disorders like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These c...

    Authors: Julia Oakley, Martin Hill, Adam Giess, Mélanie Tanguy and Greg Elgar
    Citation: Journal of Translational Medicine 2023 21:825
    Content type: Research Published on:

  18. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms.

    Authors: N. Azcue, R. Del Pino, M. Acera, T. Fernández-Valle, N. Ayo-Mentxakatorre, T. Pérez-Concha, A. Murueta-Goyena, J. V. Lafuente, A. Prada, A. López de Munain, G. Ruiz Irastorza, D. Martín-Iglesias, L. Ribacoba, I. Gabilondo, J. C. Gómez-Esteban and B. Tijero-Merino
    Citation: Journal of Translational Medicine 2023 21:814
    Content type: Research Published on:

  19. Previous serological studies have indicated an association between viruses and atypical pathogens and Chronic Fatigue Syndrome (CFS). This study aims to investigate the correlation between infections from comm...

    Authors: Hsun Chang, Chien-Feng Kuo, Teng-Shun Yu, Liang-Yin Ke, Chung-Lieh Hung and Shin-Yi Tsai
    Citation: Journal of Translational Medicine 2023 21:804
    Content type: Research Published on:

  20. Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It is characterized by a diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory p...

    Authors: Krystyna Taylor, Matthew Pearson, Sayoni Das, Jason Sardell, Karolina Chocian and Steve Gardner
    Citation: Journal of Translational Medicine 2023 21:775
    Content type: Research Published on:

  21. Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar ...

    Authors: Jae-Hyun Hwang, Jin-Seok Lee, Hyeon-Muk Oh, Eun-Jung Lee, Eun-Jin Lim and Chang-Gue Son
    Citation: Journal of Translational Medicine 2023 21:763
    Content type: Review Published on:

  22. Controversy over treatment for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a barrier to appropriate treatment. Energy management or pacing is a prominent coping strategy for people ...

    Authors: Nilihan E. M. Sanal-Hayes, Marie Mclaughlin, Lawrence D. Hayes, Jacqueline L. Mair, Jane Ormerod, David Carless, Natalie Hilliard, Rachel Meach, Joanne Ingram and Nicholas F. Sculthorpe
    Citation: Journal of Translational Medicine 2023 21:720
    Content type: Review Published on:

  23. Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study...

    Authors: Menghui Yao, Shuolin Wang, Yingdong Han, He Zhao, Yue Yin, Yun Zhang and Xuejun Zeng
    Citation: Journal of Translational Medicine 2023 21:594
    Content type: Research Published on:

  24. Limited published data suggests that absence of uplifts (minor pleasant events) is associated with clinical worsening in patients with chronic fatigue syndrome (CFS). The current study aimed to assess the rela...

    Authors: Fred Friedberg, Jenna L. Adamowicz, Patricia Bruckenthal, Maria Milazzo, Sameera Ramjan, Xiaoyue Zhang and Jie Yang
    Citation: Journal of Translational Medicine 2023 21:557
    Content type: Research Published on:

  25. Chronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transp...

    Authors: Tapani Salonen, Elina Jokinen, Reetta Satokari and Perttu Lahtinen
    Citation: Journal of Translational Medicine 2023 21:513
    Content type: Research Published on:

  26. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness that affects many body systems including the immune, nervous, endocrine, cardiovascular, and urinary systems. There is cu...

    Authors: Asher Taccori, Rebekah Maksoud, Natalie Eaton-Fitch, Maharshi Patel and Sonya Marshall-Gradisnik
    Citation: Journal of Translational Medicine 2023 21:440
    Content type: Review Published on:

  27. The dose–effect relationship of Long-snake-like moxibustion for chronic fatigue syndrome (CFS) remains poorly understood. In order to address this gap, we designed this trial to assess the association between ...

    Authors: Hong Luo, Rui Gong, Rui Zheng, Jing Tan, Ruixue Chen, Jie Wu and Tingting Ma
    Citation: Journal of Translational Medicine 2023 21:430
    Content type: Research Published on:

  28. Myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease (ME/CFS/SEID) is a condition diagnosed primarily based on clinical symptoms, including prolonged fatigue and post-exerti...

    Authors: Ryuhei Jinushi, Sakue Masuda, Yuki Tanisaka, Sho Nishiguchi, Kento Shionoya, Ryo Sato, Kei Sugimoto, Takahiro Shin, Rie Shiomi, Akashi Fujita, Masafumi Mizuide and Shomei Ryozawa
    Citation: Journal of Translational Medicine 2023 21:398
    Content type: Review Published on:

  29. Post-COVID-19 syndrome (PCS) shares many features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PCS represents a major health issue worldwide because it severely impacts patients’ work acti...

    Authors: Alaa Ghali, Valentin Lacombe, Camille Ravaiau, Estelle Delattre, Maria Ghali, Geoffrey Urbanski and Christian Lavigne
    Citation: Journal of Translational Medicine 2023 21:375
    Content type: Research Published on:

  30. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogenous disease characterized by unexplained persistent fatigue and other features including cognitive impairment, myalgias, post-...

    Authors: Ludovic Giloteaux, Jiayin Li, Mady Hornig, W. Ian Lipkin, David Ruppert and Maureen R. Hanson
    Citation: Journal of Translational Medicine 2023 21:322
    Content type: Research Published on:

  31. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by...

    Authors: Troy D. Querec, Jin-Mann S. Lin, Yang Chen, Britany Helton, Andreas M. Kogelnik, Nancy G. Klimas, Daniel L. Peterson, Lucinda Bateman, Charles Lapp, Richard N. Podell, Benjamin H. Natelson and Elizabeth R. Unger
    Citation: Journal of Translational Medicine 2023 21:242
    Content type: Research Published on:

  32. N6-methyladenosine (m6A) modification has been recognized to play fundamental roles in the development of autoimmune diseases. However, the implication of m6A modification in myasthenia gravis (MG) remains lar...

    Authors: Shuang Li, Hui Liu, Zhe Ruan, Rongjing Guo, Chao Sun, Yonglan Tang, Xiaoxi Huang, Ting Gao, Sijia Hao, Huanhuan Li, Na Song, Yue Su, Fan Ning, Zhuyi Li and Ting Chang
    Citation: Journal of Translational Medicine 2023 21:166
    Content type: Research Published on:

  33. Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a complex, heterogenous disease. It has been suggested that subgroups of people with ME/CFS exist, displaying a specific cluster of symptoms. In...

    Authors: Anouk W. Vaes, Maarten Van Herck, Qichen Deng, Jeannet M. Delbressine, Leonard A. Jason and Martijn A. Spruit
    Citation: Journal of Translational Medicine 2023 21:112
    Content type: Research Published on:

  34. An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the pre...

    Authors: Chi Chen, Hei-Tung Yip, Kam-Hang Leong, Wei-Cheng Yao, Chung-Lieh Hung, Ching-Huang Su, Chien-Feng Kuo and Shin-Yi Tsai
    Citation: Journal of Translational Medicine 2023 21:98
    Content type: Research Published on:

  35. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with an unexplained aetiology in which viral infections are possible trigger factors.

    Authors: Santa Rasa-Dzelzkaleja, Angelika Krumina, Svetlana Capenko, Zaiga Nora-Krukle, Sabine Gravelsina, Anda Vilmane, Lauma Ievina, Yehuda Shoenfeld and Modra Murovska
    Citation: Journal of Translational Medicine 2023 21:33
    Content type: Research Published on:

  36. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the ...

    Authors: Sayoni Das, Krystyna Taylor, James Kozubek, Jason Sardell and Steve Gardner
    Citation: Journal of Translational Medicine 2022 20:598
    Content type: Research Published on:

  37. Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion whic...

    Authors: Elisabeth Petter, Carmen Scheibenbogen, Peter Linz, Christian Stehning, Klaus Wirth, Titus Kuehne and Marcus Kelm
    Citation: Journal of Translational Medicine 2022 20:580
    Content type: Research Published on:

    The Correction to this article has been published in Journal of Translational Medicine 2023 21:243

  38. In chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), the capacity for activity and participation is strongly limited. The disease definition is very broad, and considering the lack of evidence for b...

    Authors: Gabriella Bernhoff, Eva Rasmussen-Barr and Lina Bunketorp Käll
    Citation: Journal of Translational Medicine 2022 20:577
    Content type: Research Published on:

  39. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequ...

    Authors: N. Azcue, J. C. Gómez-Esteban, M. Acera, B. Tijero, T. Fernandez, N. Ayo-Mentxakatorre, T. Pérez-Concha, A. Murueta-Goyena, J. V. Lafuente, Á. Prada, A. López de Munain, G. Ruiz-Irastorza, L. Ribacoba, I. Gabilondo and R. Del Pino
    Citation: Journal of Translational Medicine 2022 20:569
    Content type: Research Published on:

  40. Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathoph...

    Authors: Andrea Polli, Jolien Hendrix, Kelly Ickmans, Jelena Bakusic, Manosij Ghosh, Dora Monteyne, Brigitte Velkeniers, Bram Bekaert, Jo Nijs and Lode Godderis
    Citation: Journal of Translational Medicine 2022 20:487
    Content type: Research Published on:

  41. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause o...

    Authors: Zheng Wang, Michelle F. Waldman, Tara J. Basavanhally, Aviva R. Jacobs, Gonzalo Lopez, Regis Y. Perichon, Johnny J. Ma, Elyse M. Mackenzie, James B. Healy, Yixin Wang and Sarah A. Hersey
    Citation: Journal of Translational Medicine 2022 20:486
    Content type: Research Published on:

  42. Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-wav...

    Authors: Frédérique Retornaz, Stanislas Rebaudet, Chloé Stavris and Yves Jammes
    Citation: Journal of Translational Medicine 2022 20:429
    Content type: Research Published on:

  43. There is no approved pharmaceutical intervention for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Fatigue in these patients can last for decades. Long COVID may continue to ME/CFS, and current...

    Authors: Alan Cash and David Lyons Kaufman
    Citation: Journal of Translational Medicine 2022 20:295
    Content type: Research Published on:

  44. The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective ...

    Authors: Sławomir Kujawski, Joanna Słomko, Beata R. Godlewska, Agnieszka Cudnoch-Jędrzejewska, Modra Murovska, Julia L. Newton, Łukasz Sokołowski and Paweł Zalewski
    Citation: Journal of Translational Medicine 2022 20:273
    Content type: Research Published on:

  45. This study aims to provide 12-year nationwide epidemiology data to investigate the epidemiology and comorbidities of and therapeutic options for chronic fatigue syndrome (CFS) by analyzing the National Health ...

    Authors: Kam-Hang Leong, Hei-Tung Yip, Chien-Feng Kuo and Shin-Yi Tsai
    Citation: Journal of Translational Medicine 2022 20:268
    Content type: Research Published on:

  46. Molecular chaperones assist protein folding, facilitate degradation of misfolded polypeptides, and thereby maintain protein homeostasis. Impaired chaperone activity leads to defective protein quality control t...

    Authors: Manar Elkenani, Amal Z. Barakat, Torsten Held, Daniel Marques Rodrigues, Sherok Mobarak, Surabhi Swarnka, Ibrahim M. Adham and Belal A. Mohamed
    Citation: Journal of Translational Medicine 2022 20:229
    Content type: Research Published on:

  48. Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic ...

    Authors: Milan Haffke, Helma Freitag, Gordon Rudolf, Martina Seifert, Wolfram Doehner, Nadja Scherbakov, Leif Hanitsch, Kirsten Wittke, Sandra Bauer, Frank Konietschke, Friedemann Paul, Judith Bellmann-Strobl, Claudia Kedor, Carmen Scheibenbogen and Franziska Sotzny
    Citation: Journal of Translational Medicine 2022 20:138
    Content type: Research Published on:

  49. Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experien...

    Authors: Tse-Yen Yang, Cheng-Li Lin, Wei-Cheng Yao, Chon-Fu Lio, Wen-Po Chiang, Kuan Lin, Chien-Feng Kuo and Shin-Yi Tsai
    Citation: Journal of Translational Medicine 2022 20:99
    Content type: Research Published on:

  50. Orthostatic intolerance-OI is common in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-ME/CFS. We used a 10-min passive vertical lean test as orthostatic challenge-OC and measured changes in vitals and end...

    Authors: Benjamin H. Natelson, Jin-Mann S. Lin, Michelle Blate, Sarah Khan, Yang Chen and Elizabeth R. Unger
    Citation: Journal of Translational Medicine 2022 20:95
    Content type: Research Published on:

Previously published in Journal of Translational Medicine

Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) articles

Journal of Translational Medicine

ISSN: 1479-5876

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