Lack of Immune Resilience Negatively Affects Physical Resilience: Results From the InCHIANTI Follow-Up Study.

There is consistent evidence that immune response declines with aging, with wide interindividual variability and a still unclear relationship with the development of frailty. To address this question, we assessed the role of immune resilience (capacity to restore immune functions), operationalized as the neutrophil-to-lymphocytes ratio (NL-ratio) and monocytes-to-lymphocytes ratio (ML-ratio), in the pathway that from robust status shifts to pre-frailty and frailty, and finally to death. The InCHIANTI study enrolled representative samples from the registry lists of 2 towns in Tuscany, Italy.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

Prognostic Associations of Concomitant Antibiotic Use in Patients with Advanced NSCLC Treated with Atezolizumab: Sensitivity Analysis of a Pooled Investigation of Five Randomised Control Trials.

Background: Immune checkpoint inhibitors (ICIs) have been a significant milestone for the treatment of advanced non-small cell lung cancer (NSCLC). However, the efficacy of ICIs can vary substantially between patients, with disparities in treatment outcomes being potentially driving by changes in the microbiome. Antibiotics can cause dysbiosis and are hypothesised to impact the efficacy of ICIs Methods: Data were pooled from five randomised clinical control trials, IMpower130, IMpower131, IMpower150, OAK, and POPLAR, assessing atezolizumab in advanced NSCLC.