Building on the threshold model developed by Pauker and Kassirer for a single test, the authors describe a decision analytic model for two tests with dichotomous outcomes. The model includes ten decision strategies that differ depending on which tests are performed, whether the tests are performed together or in sequence, and the definition of a positivity criterion used to make the treatment decision when the test results disagree. Formulas derived from the model are used to compute the preferred option as a function of disease probability and to calculate test and test-treatment thresholds. General guidelines developed from the model can be used without calculation to identify relative preferences for alternative options and to predict threshold effects.
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http://dx.doi.org/10.1177/0272989X8600600203 | DOI Listing |
J Neuroinflammation
January 2025
Department of Medical and Translational Biology, Umeå university, Umeå, 901 87, Sweden.
Background: Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability.
View Article and Find Full Text PDFBMC Chem
January 2025
Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Vidya Vihar, Pilani, Rajasthan, 333 031, India.
A large set of antimalarial molecules (N ~ 15k) was employed from ChEMBL to build a robust random forest (RF) model for the prediction of antiplasmodial activity. Rather than depending on high throughput screening (HTS) data, molecules tested at multiple doses against blood stages of Plasmodium falciparum were used for model development. The open-access and code-free KNIME platform was used to develop a workflow to train the model on 80% of data (N ~ 12k).
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Background: HER2-targeted therapies have revolutionized the treatment of HER2-positive breast cancer patients, leading to significant improvements in tumor response rates and survival. However, resistance and incomplete response remain considerable challenges. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel therapeutic strategy for the management of dyslipidemia by enhancing the clearance of low-density lipoprotein cholesterol receptors, however recent evidence also shows links between PCSK9 and cancer cells.
View Article and Find Full Text PDFCell Commun Signal
January 2025
Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning Province, China.
Background: Intracellular membraneless organelles formed by liquid-liquid phase separation (LLPS) function in diverse physiological processes and have been linked to tumor-promoting properties. The nucleolus is one of the largest membraneless organelle formed through LLPS. Deubiquitylating enzymes (DUBs) emerge as novel therapeutic targets against human cancers.
View Article and Find Full Text PDFMicrob Cell Fact
January 2025
Department of Laboratory Medicine, The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong, 528244, China.
Previous studies showed that the female genital tract microbiome plays a crucial role in regulating the host's immune defense mechanisms. Our previous research has shown that Lactobacillus gasseri LGV03 (L. gasseri LGV03) isolated from cervico-vagina of HPV-cleared women contributes to clearance of HPV infection and beneficially regulate immune response.
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