Hasil untuk "Genetics"

Rachel S. Meyer, M. Purugganan

Y. Nikiforov, M. Nikiforova

J. Bluestone, K. Herold, G. Eisenbarth

T. Mackay, Eric A. Stone, J. Ayroles

A. Feder, E. Nestler, D. Charney

E. Calonje, P. Komminoth, T. Brenn

Jm Roberts, D. Cooper

L. Lepiniec, I. Debeaujon, J. Routaboul et al.

Jeffrey H. Miller

Fred E. Cohen, S. B. Prusiner, D. G. Hardie et al.

W. Becker

E. Maher, F. Furnari, R. Bachoo et al.

Malignant brain tumors strike deep into the psyche of those receiving and those delivering the diagnosis. Malignant gliomas, the most common subtype of primary brain tumors, are aggressive, highly invasive, and neurologically destructive tumors considered to be among the deadliest of human cancers. In its most aggressive manifestation, glioblastoma (GBM), median survival ranges from 9 to 12 months, despite maximum treatment efforts—a statistical fact that has changed little over several decades of technological advances in neurosurgery, radiation therapy, and clinical trials of conventional and novel therapeutics. Over the same time period, there has been an explosion of knowledge in cancer biology and basic science discovery that has fueled meaningful progress in the treatment of many common human cancers, including those of the breast, lung, and prostate. It is perplexing that therapies used effectively in the treatment of these solid tumors are overwhelmingly ineffective in the treatment of GBM, perhaps reflecting the eccentric biology and cellular origin of this neoplasm. To date, only one new agent has been documented to have modest activity against intermediate-grade gliomas, whereas no effective agents have emerged for the treatment of GBM, despite 20 years of enrolling patients in clinical trials. It is ironic that although a comprehensive view of the genetic lesions encountered in malignant gliomas has been compiled, substantive conceptual and practical barriers remain in assigning functional significance to these genetic changes and in harnessing this basic information into the development of drugs that make a difference in patient care. The history of treating malignant gliomas dates back to the middle of the 19th century and parallels landmark advances in modern surgical technique and the clinical discipline of neurology. The first brain tumor surgery of the modern era was performed in 1884 by Rickman

S. Palumbi

J. M. Greeff, B. V. van Vuuren

C. Wills, M. Nei

S. Leal

M. Rose, F. Winston, P. Hieter

David Núñez-Jurado, Alejandro Fernández-Vega, Carmen del Río et al.

Abstract Background Timely differentiation between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is critical for guiding appropriate acute management strategies. While neuroimaging is the diagnostic gold standard, its accessibility is often limited in urgent clinical settings. Blood biomarkers offer a promising, scalable diagnostic alternative; however, no validated panel is yet available for distinguishing stroke subtypes during the hyperacute phase. Methods In a multicenter study, plasma samples were collected within 6 h of symptom onset. A total of 3,072 proteins were measured using Olink® proximity extension assays. We applied differential expression analysis, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and receiver operating characteristic (ROC) curve evaluation. To interpret the biological relevance of the findings, we conducted functional enrichment and protein–protein interaction (PPI) analyses. Results Among the 388 patients (344 IS, 44 ICH), 2,531 proteins were retained; 878 reached nominal significance (p < 0.05), and 67 remained significant after multiple-testing correction (FDR-adjusted p < 0.05). Of these, 844 were overexpressed in ICH and 34 in IS. GFAP, a glial marker, emerged as the most discriminative biomarker for ICH versus IS (AUC = 0.887; sensitivity: 80%, specificity: 90%), followed by BCAN (AUC = 0.820), SNAP25 (AUC = 0.797), and SPOCK1 (AUC = 0.786). For IS, S100A12 (AUC = 0.677) and MNDA (AUC = 0.657) showed the best performance. Multivariate analyses confirmed the presence of distinct proteomic patterns, with enrichment revealing a significant overrepresentation of neurodevelopmental and synaptic pathways. In PPI networks, GFAP and LYN emerged as central hubs. Conclusion This study reveals a robust plasma proteomic signature distinguishing IS from ICH within hours of onset. These results lay the groundwork for scalable, blood-based diagnostics to guide early stroke management when imaging is delayed or unavailable.

Maha Arkan Khudhair, Rikke Christensen, Anne Skakkebæk et al.

Caroli’s syndrome is a rare autosomal recessive disorder characterized by segmental cystic dilation of the intrahepatic bile ducts and congenital hepatic fibrosis. It is associated with autosomal recessive polycystic kidney disease. Here, we report a 63-year-old male known with polycystic kidney disease, who was admitted to our hospital with intermittent fever, accompanied by weight loss. Magnetic resonance cholangiopancreatography suggested the presence of Caroli’s syndrome, characterized by cystic dilation of the intrahepatic proximal bile ducts on both the right and left lobes of the liver. Shear wave elastography revealed the presence of mild liver fibrosis. The patient recovered with broad-spectrum antibiotics. Genetic testing found no evidence of variation in the PKHD1 gene. However, a heterozygous deletion of the PKD1 gene was identified, a deletion that has not previously been linked to disease, and therefore the patient’s family was offered genetic analysis. The patient has since remained free of cholangitis and icterus and continues to be followed in the nephrology department.

Yuan Yao, Dan Guo, Fang-Lin Liu et al.

Sleep disruption is common in older adults and has been linked to many negative health outcomes, including impaired cognitive, emotional, and interpersonal functioning and maladaptive metabolic changes. Sleep disturbance is the most common symptom in depressive patients, and it was formerly thought to be a major secondary manifestation of depression. Many longitudinal studies have identified insomnia as an independent risk factor for the development of emerging or recurrent depression in older adults, with bidirectional relationships between sleep quality and depression. This narrative review summarizes recent research or evidence on the sleep–depression association in older adults, as well as the potential common mechanisms underlying the comorbidity of sleep and depression disorders, focusing on the clock system, neurochemical substrates, and neurocircuits. A better understanding of the pathophysiological mechanisms underlying sleep disturbance and depression can assist psychiatrists in better managing this comorbidity.