Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Syndrome (GWS), and Fibromyalgia (FM) are complex, chronic illnesses with overlapping clinical features. Symptoms that are reported across these conditions include post-exertional malaise (PEM), fatigue, and pain, yet the etiology of these illnesses remains largely unknown. Diagnosis is challenging in patients with these conditions as definitive biomarkers are lacking; patients are required to meet clinical criteria and often undergo lengthy testing to exclude other conditions, a process that is often prolonged, costly, and burdensome for patients. The identification of reliable validated biomarkers could facilitate earlier and more accurate diagnosis and drive the development of targeted pharmacological therapies that might address the underlying pathophysiology of these diseases. Major driving forces for biomarker identification are the advancing fields of metabolomics and proteomics that allow for comprehensive characterization of metabolites and proteins in biological specimens. Recent technological developments in these areas enable high-throughput analysis of thousands of metabolites and proteins from a variety of biological samples and model systems, that provides a powerful approach to unraveling the metabolic phenotypes associated with these complex diseases. Emerging evidence suggests that ME/CFS, GWS, and FM are all characterized by disturbances in metabolic pathways, particularly those related to energy production, lipid metabolism, and oxidative stress. Altered levels of key metabolites in these pathways have been reported in studies highlighting potential common biochemical abnormalities. The precise mechanisms driving altered metabolic pathways in ME/CFS, GWS, and FM remain to be elucidated; however, the elevated oxidative stress observed across these illnesses may contribute to symptoms and offer a potential target for therapeutic intervention. Investigating the mechanisms, and their role in the disease process, could provide insights into disease pathogenesis and reveal novel treatment targets. As such, comprehensive metabolomic and proteomic analyses are crucial for advancing the understanding of these conditions in-order to identify both common, and unique, metabolic alterations that could serve as diagnostic markers or therapeutic targets.

The advent of immunotherapy has revolutionized the treatment paradigm for gastric cancer (GC), offering unprecedented clinical benefits. However, a detailed molecular characterization of the tumor immune microenvironment in GC is essential to further optimize these therapies and enhance their efficacy.

Consensus clustering was utilized to classify GC patients into distinct immune states, followed by an in-depth analysis of differences in mutation profiles, copy number variations, and DNA methylation patterns. Weighted gene co-expression network analysis (WGCNA) and correlation analysis were applied to identify gene modules underlying the classification of immune "hot" and "cold" tumors. Subsequently, 101 machine learning algorithm combinations were employed to construct a prognostic model based on the identified gene modules. Single-cell analysis was conducted to investigate cellular interactions associated with the immune-determinant gene module. Finally, immunofluorescence staining for CD8, CD45, and CXCR4 was performed on human GC tissue samples.

A total of 1,298 GC patients were included in this comprehensive analysis. For the first time, we identified and characterized immune "hot" and "cold" tumors in GC patients, revealing distinct molecular features associated with these tumor types. Immune "hot" tumor-related genes were identified, and their functional roles were validated through biological behavior analysis. A prognostic signature, termed the hot tumor top regulators (HTTR), was developed using 101 machine learning algorithm combinations. The HTTR signature emerged as an independent prognostic factor, effectively stratifying patients into low- and high-risk groups with significant differences in overall survival. High-risk groups demonstrated strong associations with immune checkpoint regulation, antigen presentation, and inhibitory pathways. Notably, single-cell analysis revealed that HTTR genes were highly active in CD8 + T cells, with the CXCL12-CXCR4 axis playing a critical role in mediating interactions between CD8 + T cells and endothelial cells.

In conclusion, the HTTR signature served as a robust prognostic biomarker for GC patients and effectively identified those with immune "hot" tumors. This finding provided valuable insights into the molecular mechanisms of tumor immunity in GC, offering potential avenues for targeted therapeutic interventions.

Following a gluten-free diet (GFD) is known as the main effective therapy available for celiac disease (CD) patients, which in some cases is not enough to heal all patients presentations completely. Accordingly, emerging researchers have focused on finding novel therapeutic/preventive strategies for this disorder. Moreover, previous studies have shown that celiac patients, especially untreated subjects, are at increased risk of developing viral and bacterial infections, which can become a challenge for the clinician. Viruses, such as Rotavirus, Reovirus, Adenovirus, Enterovirus, Rhinovirus, Astrovirus, Hepatitis virus, COVID-19, Norovirus, and Herpesvirus, have been related to CD pathogenesis. Therefore, clinicians need to pay more attention to evaluate CD patients' viral infection history (especially nonresponders to the GFD), to look for effective preventive strategies and educate patients about important risk factors. In addition, there are still viruses whose role in CD pathogenesis has not been fully studied. In this review, current information on the association between CD and various viral infections was gathered to improve knowledge in this subject area and draw researchers'/clinicians' attention to unstudied/less studied viruses in CD pathogenesis, which might guide future prevention approaches.

Long COVID should be limited to patients with multiple, persistent symptoms not related to well-defined organ damage. Once redefined, a focused review of long COVID demonstrates striking similarity to chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), fibromyalgia (FM) and irritable bowel syndrome (IBS). Research in long COVID has revealed similar findings to those noted in CFS/ME and FM, characterized by central nervous system organ dysfunction. Long COVID, like CFS/ME, FM and IBS, is best understood as a bidirectional mind-body, neuroimmune illness.

Background The variation in infection risk among individuals is thought to be partially influenced by occupational factors. This study aims to investigate the seropositivity rates of 17 common infectious agents in male airline pilots (APs), a professional group known to experience a high prevalence of cardiovascular and gastrointestinal diseases. Methodology In our study, we employed a case-control design with 100 male APs as cases, matched by age, sex, and tenure (i.e., at least five years of service) to 100 male office workers (OWs) who served as controls. We measured the IgG antibody levels to 17 pathogens using specific enzyme-linked immunosorbent assays, including herpes simplex virus 1, herpes simplex virus 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, human herpesvirus 7, Kaposi's sarcoma-associated herpesvirus, Toxoplasma gondii, human T-lymphotropic virus 1, BK virus, John Cunningham virus, Merkel cell polyomavirus, human papillomavirus 16, human papillomavirus 18, Chlamydia trachomatis, and Helicobacter pylori. The determination of seropositivity cutoffs for each pathogen was made in accordance with the guidelines provided by the respective kit manufacturers. Results The seropositivity rates for the 17 pathogens ranged from 1% for human T-lymphotropic virus 1 to 94% for varicella-zoster virus and were similar in both professions, except for herpes simplex virus 1 and Helicobacter pylori, which were more prevalent in APs. Conclusions Our findings suggest a higher prevalence of previous infections with herpes simplex virus 1 and Helicobacter pylori in APs compared to OWs. These infections may be associated with the prevalence of specific non-communicable diseases in this professional group. However, additional longitudinal studies are needed to substantiate this hypothesis.