Lubowa Hill, Uganda

Multi-omics Study in Citrin Deficiency

Citrin deficiency (CD) is an inherited autosomal recessive metabolic condition that is also a secondary urea cycle disorder caused by mutations in the SLC25A13 gene, which encodes for the mitochondrial transporter, citrin. Citrin is a key component of the mitochondrial malate-aspartate shuttle (MAS) and is responsible for moving Nicotinamide Adenine Dinucleotide (NADH) from the cytosol into the mitochondria via reducing equivalents such as malate, which drives mitochondrial respiration to produce energy in the form of adenosine triphosphate (ATP). The MAS is also critical in regulating Nicotinamide Adenine Dinucleotide (NAD+/NADH) redox balance to maintain cytosolic redox-dependent metabolic pathways such as glycolysis, gluconeogenesis, amino acid metabolism, and lipid metabolism. Citrin is also required to supply cytosolic aspartate, which is the substrate of one of the urea cycle enzymes, namely argininosuccinate synthetase 1, and thus important for the proper functioning of the urea cycle. The clinical presentations of citrin deficiency often vary widely between patients but can generally be distinguished by distinct clinical phenotypes, which are neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) that affects infants, the "failure to thrive and dyslipidemia" form of CD (FTTDCD) in childhood, the adaptation or silent period, and citrullinemia type II (CTLN2), which represents the most severe form of the condition. While only a small percentage of CD patients develop CTLN2, the prognosis for these patients is typically poor. It is notable that all CD patients above 1 year old (post-NICCD) naturally develop a characteristic food preference that favors a diet rich in protein and fat while being low in carbohydrates. Other clinical findings observed in some CD patients include fatty liver, fatigue, hypoglycemia, and failure to thrive. There is currently no effective cure for CD. Before the onset of CTLN2, patients are primarily managed by diet control with a low carbohydrate, high protein and high-fat diet, as well as medium chain triglyceride (MCT) supplementation. CTLN2 patients have been treated with sodium pyruvate, arginine, and MCT with limited success, with severe cases requiring liver transplantation as the only solution. There are currently no specific biomarkers that effectively track the disease progression, making it challenging to monitor how well patients are actually doing or to measure the effectiveness of therapies. Without proper management or timely medical interventions, patients may develop CTLN2. Given the urgent and unmet need for biomarkers specific to CD, the main goal of this study is to uncover disease-specific biomarkers by analyzing blood samples collected from CD patients using both targeted and untargeted metabolomics, proteomics, lipidomics, and transcriptomics. Targeted omics will involve the analysis of cellular pathways associated with the condition, such as the MAS pathway, glycolysis, protein metabolism, de novo lipogenesis, lipolysis, gluconeogenesis, NAD+ metabolism, ureagenesis, and the glutamine synthetase pathway. Identification of such biomarkers will allow a deeper understanding of the disease pathogenesis. Importantly, these biomarkers may enable better tracking of disease progression and may help to prevent the onset of CTLN2. Finally, these biomarkers will also greatly benefit the development of effective therapeutic options for CD in clinical trials by serving as measurable endpoints. Obtaining the necessary material from patients consists of a minimally invasive venous blood sampling taken during a regular outpatient visit and after the informed consent of the patients or caretakers.

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

A Study of TAK-279 in Participants With Moderate-to-Severe Plaque Psoriasis

This study consists of 2 parts: Part A and Part B. Part A: Participants who did not participate in either parent study (TAK-279-3001 [NCT06088043] or TAK-279-3002 [NCT06108544]) may be enrolled and will be treated for up to 52 weeks. Participants who successfully complete Part A of the study are eligible to continue in Part B, but investigators must confirm their eligibility to continue in Part B. Part B: Participants who complete the treatment period of TAK-279-3001 (NCT06088043) or TAK-279-3002 (NCT06108544) parent studies or who complete Part A are eligible to enroll directly into open label extension treatment in Part B and will be treated for up to 156 weeks.

Software as a Medical Device for the Treatment of Patients With PTSD

ARTEMIS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With a Heart Attack

Japanese Coronary Intervention Using Drug Eluting and Perfusion Therapy for Left Main Disease (JDEPTH-LM Registry)

JDEPTH-LM Registry is a prospective observational multi-center study. The investigators will enroll and treat patients in the registry who meet the selection criteria under usual care and for whom PCI with W-KBT following on crossover stenting for LMT-LAD direction, proximal optimization technique (POT), and conventional kissing balloon technique (C-KBT) is the optimal treatment. The operators shall obtain oral or written consent from patients who meet the criteria before performing PCI, indicating the intention to perform PCI with W-KBT, and shall keep records. The investigators will continuously register cases attempting PCI with W-KBT according to the protocol and evaluate its efficacy and safety using data from this multi-center registry.

An Exosome-Based Liquid Biopsy for the Differential Diagnosis of Primary Liver Cancer

Primary liver cancers (PLCs) encompass a diverse group of malignancies originating from the liver, collectively ranking as the third leading cause of cancer-related mortality worldwide in 2020. Among PLCs, intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) represent the most predominant subtypes. Despite their collective grouping as PLCs, ICC and HCC patients exhibit distinct etiologies, pathologies, and clinical characteristics, necessitating different treatment approaches. Accurate differentiation between ICC and HCC is paramount to optimize patient outcomes and guide personalized treatment decisions. However, a definitive diagnosis is often obtained only after the pathological review of the resected neoplastic tissue, which requires invasive tumor sampling and poses risks of complications such as hemorrhage and tumor cell seeding. Consequently, there is a pressing clinical need to develop noninvasive diagnostic approaches to achieve an accurate differential diagnosis for patients with these distinct forms of PLCs. This study involves the development and validation of a liquid biopsy, assessing circulating exosomal microRNAs (exo-miRNA) for indirect sampling of tumor tissue in the bloodstream. The researchers intend to harness machine learning and bioinformatics to create a cost-efficient, non-invasive, clinic-friendly assay with high sensitivity and specificity, aiding the differential diagnosis between ICC and HCC. The researchers intend to do so in three phases: 1. To perform comprehensive small RNA-Seq from exo-miRNA from patients with ICC and HCC. 2. To develop and train a differential diagnosis panel based on advanced machine-learning models to obtain a final differential diagnosis biomarker. 3. To validate the findings in an independent cohort of ICC and HCC. In summary, this proposal promises to improve patient care and help clinicians perform a more reliable differential diagnosis between ICC and HCC in patients with primary liver cancer.

A Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults With Elevated Lipoprotein(a) - ACCLAIM-Lp(a)

A Multicenter Multinational Observational Study of Children With Hypochondroplasia

An Observational Study to Assess Change in Disease Activity and Adverse Events of Rinvoq in Adult Participants With Moderate to Severe Ulcerative Colitis (UC) in Japan