Early kinetics of C reactive protein for cancer-agnostic prediction of therapy response and mortality in patients treated with immune checkpoint inhibitors: a multicenter cohort study

Background C reactive protein (CRP) kinetics have recently been suggested as predictive biomarkers for the efficacy of immune checkpoint inhibitor (ICI) therapy in selected cancer types. The aim of this study was to characterize early CRP kinetics as a tumor-agnostic biomarker for ICI treatment outcomes.Methods In this multicenter retrospective cohort study, two independent cohorts of patients with various cancer types undergoing palliative ICI treatment at Austrian academic centers served as the discovery (n=562) and validation cohort (n=474). Four different patterns of CRP kinetics in the first 3 months of ICI therapy were defined (CRP-flare responders, CRP-responders, CRP non-responders, patients with all-normal CRP). Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were defined as coprimary endpoints. Univariable and multivariable logistic regression, landmark analysis and Cox regression including CRP kinetics as time-dependent variable were performed.Results The ORR in patients with all-normal CRP, CRP responders, CRP flare-responders and CRP non-responders was 41%, 38%, 31% and 12%, respectively. The median OS and PFS estimates were 24.5 months (95% CI 18.5 to not reached) and 8.2 months (95% CI 5.9 to 12.0) in patients with all-normal CRP, 16.1 months (95% CI 12.6 to 19-8) and 6.1 months (95% CI 4.9 to 7.2) in CRP-responders, 14.0 months (95% CI 8.5 to 19.4) and 5.7 months (95% CI 4.1 to 8.5) in CRP flare-responders and 8.1 months (95% CI 5.8 to 9.9) and 2.3 months (95% CI 2.2 to 2.8) in CRP non-responders (log-rank p for PFS and OS<0.001). These findings prevailed in multivariable analysis and could be fully confirmed in our validation cohort. Pooled subgroup analysis suggested a consistent predictive significance of early CRP kinetics for treatment efficacy and outcome independent of cancer type.Conclusion Early CRP kinetics represent a tumor-agnostic predictor for treatment response, progression risk and mortality in patients with cancer undergoing ICI therapy

Безопасность облака и управление им

Каждый ответственный ИТ-руководитель в первую очередь интересуется безопасностью приложений и данных в облаке. Безопасность обеспечивается, если применяются соответствующие технологии и средства управления. Обеспечение безопасности - это одна из областей, в которой применяются как технологии, так и управление. Действительно, перенос приложений в облако не сводит на нет множество традиционных функций ИТ, - безопасность, соответствующее управление данными, контроль за расходами и надлежащее управление изменениями остаются ключевыми обязанностями. Но при работе в облаке меняются способы управления на предприятии. В этой статье рассматривается безопасность облака и управление им, а также рекомендации ИТруководителям по планированию в этих областях

Precision and accuracy of single-molecule FRET measurements - a multi-laboratory benchmark study

Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between ±0.02 and ±0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and discuss potential uncertainties in the experiment and the modeling. Our quantitative assessment of the reproducibility of intensity-based smFRET measurements and a unified correction procedure represents an important step toward the validation of distance networks, with the ultimate aim of achieving reliable structural models of biomolecular systems by smFRET-based hybrid methods

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Broadband excitation pulses for high-field solid-state nuclear magnetic resonance spectroscopy

In nuclear magnetic resonance spectroscopy, experimental limits due to the radiofrequency transmitter and/or coil means that conventional radiofrequency pulses (“hard pulses”) are sometimes not sufficiently powerful to excite magnetization uniformly over a desired range of frequencies. Effects due to nonuniform excitation are most frequently encountered at high magnetic fields for nuclei with a large range of chemical shifts. Using optimal control theory, we have designed broadband excitation pulses that are suitable for solid-state samples under magic-angle-spinning conditions. These pulses are easy to implement, robust to spinning frequency variations, and radiofrequency inhomogeneities, and only four times as long as a corresponding hard pulse. The utility of these pulses for uniformly exciting 13C nuclei is demonstrated on a 900 MHz (21.1 T) spectrometer