There are advantages and limitations to using genetically heterogeneous stocks and selective breeding procedures in gerontological and health span research. Animal models that address complex systems of aging involve constraint or manipulation of genetic diversity. They derive from levels of genetic analysis ranging from molecular to quantitative and are relevant to levels of causal hierarchy from base sequences to complex multivariate phenotypes. For some research purposes control of the genotypic source of phenotypic variability by fixation is desirable; others involve establishing genetic diversity or deliberately manipulating identified genes or anonymous gene complexes to specification. Genetic heterogeneity is essential or advantageous for multivariate description of complex phenomena, the examination of associations among variables, or manipulation of polygenic systems. This review concentrates on these latter quantitative requirements. Space limitations preclude a comprehensive review, but relevant sample references and some hints of historical perspectives are provided, with apologies to the many relevant authors not cited.
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http://dx.doi.org/10.1093/ilar.52.1.16 | DOI Listing |
JCO Oncol Adv
December 2024
Department of Surgery, Oregon Health & Science University, Portland, OR.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a 5-year survival rate of 13%. Surgical resection remains the only curative option as systemic therapies offer limited benefit. Poor response to chemotherapy and immunotherapy is due, in part, to the dense stroma and heterogeneous tumor microenvironment (TME).
View Article and Find Full Text PDFJ Stroke Cerebrovasc Dis
December 2024
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States. Electronic address:
Background: Anterior cerebral artery (ACA) occlusions account for up to 4 % of all acute ischemic strokes and may lead to debilitating outcomes. While endovascular thrombectomy (EVT) is a well-established treatment for large vessel occlusions, its efficacy and safety for primary ACA occlusions remains unclear. This systematic review and meta-analysis aims to address this gap by evaluating the clinical outcomes, safety, and efficacy of EVT in the treatment for primary ACA occlusions.
View Article and Find Full Text PDFHum Reprod
December 2024
Unit for Human Reproduction, 1st Dept of Obstetrics and Gynaecology, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Study Question: Is the probability of pregnancy different between women using biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART?
Summary Answer: Meta-analysis of eight randomized clinical trials (RCTs) suggests that live birth, clinical, and ongoing pregnancy rates are significantly lower with biosimilars of follitropin alfa compared to the originator.
What Is Known Already: All biosimilars of follitropin alfa have received regulatory approval by demonstrating non-inferiority in the number of retrieved oocytes compared to the originator. Nevertheless, the most clinically relevant outcome in ART for both clinicians and patients is live birth.
Sleep Breath
December 2024
Faculty of Medicine, Assiut University, Assiut, Egypt.
Purpose: Noradrenergics and antimuscarinics have been proposed as future pharmacotherapy for obstructive sleep apnea (OSA). However, the available randomized controlled trials (RCTs) showed heterogeneous results regarding the safety and efficacy of the combined regimen in OSA. Therefore, we performed this meta-analysis from the published RCTs to clarify this conflicting evidence.
View Article and Find Full Text PDFNat Biomed Eng
December 2024
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors.
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