Journal of Translational Medicine

BackgroundMyalgic encephalomyelitis (also known as ME/CFS or simply ME) has severely impacted the lives of tens of millions of people globally, but the disease currently has no accurate diagnostic tools or effective treatments. Identifying the biological causes of ME has proven challenging due to its wide range of symptoms and affected organs, and the lack of reproducible genetic associations across ME populations. This has prolonged misunderstanding, lack of awareness, and denial of the disease...

The etiology of Long COVID is poorly understood despite its estimated global burden of 65 million cases. There exists a paucity of genetic studies that can shed light on potential mechanisms leading to Long COVID. Using consented and genotyped data from 23andMe adult research participants, we conducted the largest multi-ancestry meta-analysis of genome-wide association studies of Long COVID across European (42,899 cases, 94,721 controls), Latinx (8,631 cases, 20,351 controls), and African-Americ...

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogeneous, and systemic disease defined by a suite of symptoms, including unexplained persistent fatigue, post-exertional malaise (PEM), cognitive impairment, myalgia, orthostatic intolerance, and unrefreshing sleep. The disease mechanism of ME/CFS is unknown, with no effective curative treatments. In this study, we present a multi-site ME/CFS whole-genome analysis, which is powered by a novel deep learning framework, ...

There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies of IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective is to assess the...

One in 25 deaths worldwide is related to liver disease, and often with multiple hepatosplenic conditions. Yet, little is understood of the risk factors for hepatosplenic multimorbidity, especially in the context of chronic infections. We present a novel Bayesian multitask learning framework to jointly model 45 hepatosplenic conditions assessed using point-of-care B-mode ultrasound for 3155 individuals aged 5-91 years within the SchistoTrack cohort across rural Uganda where chronic intestinal sch...

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 30% of the global population but is often underdiagnosed. To fill this diagnostic gap, we developed a digital score reflecting presence and severity of MASLD. We fitted a machine learning model to electronic health records from 37,212 UK Biobank participants with proton density fat fraction measurements and/or a MASLD diagnosis to generate a "MASLD score". In holdout testing, our model achieved areas under the receiver-oper...

IntroductionThis pilot study evaluates the impact of short-term androgen deprivation therapy (ADT) on the findings on 18F-flotufolastat PSMA PET/CT scan when used for staging prostate cancer prior to a robot-assisted radical prostatectomy (RARP) and bilateral pelvic lymphadenectomy (PLND). MethodsTen patients with unfavorable intermediate, high, or very-high risk prostate cancer were assigned to one of two cohorts, A and B (n=5 each). Baseline serum prostate-specific antigen (PSA) and testoster...

Benign prostatic hyperplasia (BPH) is the most common condition in aging men, associated with lower urinary tract symptoms. BPH has been suggested to be a risk factor for certain urologic cancers, but the current evidence is inconsistent. The gold-standard method for the diagnosis of BPH is histopathology. Histopathology displays the cellular morphologies of tissues wherein characteristic changes pertaining specifically to BPH can be identified. However, the onset of BPH might be associated with...

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, poorly understood disease that has no effective treatments, and has long been underserved by scientific research and national health systems. It is a sex-biased disease towards females that is often triggered by an infection, and its hallmark symptom is post-exertional malaise. People with ME/CFS often report their symptoms being disbelieved. The biological mechanisms causing ME/CFS remain unclear. We recruited 21,620 ME/...

IntroThe molecular mechanisms of chronic fatigue syndrome (CFS, or Myalgic encephalomyelitis), a disease defined by extreme, long-term fatigue, remain largely uncharacterized, and presently no molecular diagnostic test and no specific treatments exist to diagnose and treat CFS patients. While CFS has historically had an estimated prevalence of 0.1-0.5% [1], concerns of a "long hauler" version of Coronavirus disease 2019 (COVID-19) that symptomatically overlaps CFS to a significant degree (Supple...

BackgroundLiterature suggests that prostate MRI exhibits better predictive capabilities compared to prostate-specific antigen (PSA) in detecting prostate cancer (PCa). Based on this, our present study investigates biparametric MRI (bpMRI) as a PSA-independent screening tool for PCa. ObjectiveThe primary endpoint was to assess the efforts and effectiveness of identifying 20 participants with clinically significant prostate cancer (csPCa) using bpMRI. Design, Setting, and ParticipantsBiopsy-naiv...

ObjectivesTo understand the relevance of symptomatic hypermobility and related connective tissue variants to the expression of symptoms in Fibromyalgia and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The study further tested if specific subfactors within the diagnostic classification of hypermobility predict clinical presentations. DesignWe report part of a larger case-control study exploring mechanisms of chronic pain and fatigue in Fibromyalgia and ME/CFS (https://doi.org/10....

Background and ObjectiveDiagnostic needle biopsies that miss clinically significant prostate cancers (PCa) likely sample benign tissue adjacent to cancer. Such samples may contain changes indicating the presence of cancer elsewhere in the organ. Our goal is to evaluate if artificial intelligence (AI) can identify morphological characteristics in benign biopsies of men with raised PSA that predict the future detection of clinically significant PCa during a 30-month follow-up. MethodsA retrospect...

BackgroundAggressive prostate cancer (PC) represents a significant health concern worldwide. Conventional initial screening methods, primarily based on prostate-specific antigen (PSA) levels, lack specificity, leading to a high rate of unnecessary biopsies and an urgent need for more accurate diagnostic tools. This study addresses the gap by exploring the potential of integrating clinical and routine blood laboratory parameters including a comprehensive hormone assessment to enhance the non-inva...

IntroductionTwo randomized trials demonstrated a survival benefit of triplet therapy (androgen deprivation therapy [ADT]) plus androgen receptor pathway inhibitor [ARPI] plus docetaxel) over doublet therapy (ADT plus docetaxel) changing treatment strategies in metastatic hormone-sensitive prostate cancer (mHSPC). Patients and methodsWe conducted the first real-world analysis including 97 mHSPC patients from sixteen Austrian medical centers. 79.4% of patients received abiraterone, 17.5% daroluta...

Our previous studies identified three microRNAs (miR-92a-1-5p, miR-375 and miR-148a-3p) potentially associated with prostate cancer (PCa), particularly in advanced stages such as bone-metastatic PCa. To evaluate their clinical diagnostic utility, we isolated extracellular vesicles (EVs) from the plasma of patients with benign prostatic hyperplasia (BPH) and PCa (including localized and bone-metastatic disease). The absolute quantification of these three miRNAs within plasma EVs was performed usi...

BackgroundMRI, bone scan, and CT staging is recommended in the staging of prostate cancer. However, prostate-specific membrane antigen positron emission tomography (PSMA PET) could be superior in detection of local and distant prostate cancer cells. Most PSMA PET scans for prostate cancer are performed with a Gallium-68 ligand, with the Fluorine-18 (18F) ligand being introduced more recently. Methods: We will conduct a retrospective review of electronic patient records for all consecutive patien...

PurposeThe use of MRI-targeted biopsies has led to lower detection of Gleason Grade Group 1 (GG1) prostate cancer and increased detection of GG2 disease. Although this finding is generally attributed to improved sensitivity and specificity of MRI for aggressive cancers, it might also be explained by grade inflation. Our objective was to determine the likelihood of definitive treatment and risk of post-treatment recurrence for patients with GG2 cancer diagnosed using targeted biopsies relative to...

Urologic chronic pelvic pain syndrome patients include men chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and patients, mainly women, with interstitial cystitis/bladder pain syndrome (IC/BPS or IC). CP/CPPS is marked by severe chronic pelvic pain of unknown etiology that is differentially associated with prostatic inflammation. Microbes are known to modulate sensory responses, and microbiota are increasingly understood to drive normal biological processes and pathogenesis, including ...

BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, debilitating disease of unknown cause for which there is no specific therapy. Patients suffering from ME/CFS commonly experience persistent fatigue, post-exertional malaise, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever and irritable bowel syndrome (IBS). Recent evidence implicates gut microbiome dysbiosis in ME/CFS. However, most prior studies are limited by small sample size, differe...