Tumor growth inhibition-overall survival modeling in non-small cell lung cancer: A case study from GEMSTONE-302.

Overall survival is vital for approving new anticancer drugs but is often impractical for early-phase studies. The tumor growth inhibition-overall survival (TGI-OS) model could bridge the gap between early- and late-stage development. This study aimed to identify an appropriate TGI-OS model for patients with non-small cell lung cancer from the GEMSTONE-302 study of sugemalimab.

Can a propensity score matching method be applied to assessing efficacy from single-arm proof-of-concept trials in oncology?

As a result of the escalating number of new cancer treatments being developed and competition among pharmaceutical companies, decisions regarding how to proceed with phase III trials are frequently based on findings from either single-arm phase I expansion cohorts or phase II studies that compare the efficacy of the study drug to a standard-of-care benchmark derived from historical data. However, even when eligibility criteria are matched, differences in the distribution of baseline patient features may influence the outcome of single-arm trials in real-world scenarios. Therefore, novel methods are needed to enhance the accuracy of efficacy prediction from current cohorts relative to historical data.

Robust circadian oscillations in growing cyanobacteria require transcriptional feedback.

The remarkably stable circadian oscillations of single cyanobacteria enable a population of growing cells to maintain synchrony for weeks. The cyanobacterial pacemaker is a posttranslational regulation (PTR) circuit that generates circadian oscillations in the phosphorylation state of the clock protein KaiC. Layered on top of the PTR is transcriptional-translational feedback regulation (TTR), common to all circadian systems, consisting of a negative feedback loop in which KaiC regulates its own production.

Active regulation of receptor ratios controls integration of quorum-sensing signals in Vibrio harveyi.

Quorum sensing is a chemical signaling mechanism used by bacteria to communicate and orchestrate group behaviors. Multiple feedback loops exist in the quorum-sensing circuit of the model bacterium Vibrio harveyi. Using fluorescence microscopy of individual cells, we assayed the activity of the quorum-sensing circuit, with a focus on defining the functions of the feedback loops.

Measurement of the copy number of the master quorum-sensing regulator of a bacterial cell.

Quorum-sensing is the mechanism by which bacteria communicate and synchronize group behaviors. Quantitative information on parameters such as the copy number of particular quorum-sensing proteins should contribute strongly to understanding how the quorum-sensing network functions. Here, we show that the copy number of the master regulator protein LuxR in Vibrio harveyi can be determined in vivo by exploiting small-number fluctuations of the protein distribution when cells undergo division.

Imaging human bone marrow stem cell morphogenesis in polyglycolic acid scaffold by multiphoton microscopy.

The noninvasive imaging of tissue engineering constructs is vital for understanding the physiological changes in construct formation and the design of improved products for therapeutic purposes. In this work, we use the combination of multiphoton autofluorescence and second harmonic generation (SHG) microscopy to image the physiological changes to the engineered constructs of human mesenchymal stem cells seeded in a polyglycolic acid (PGA) scaffold under induction by chondrogenic transforming growth factor-beta3. Without histological procedures, we found that multiphoton autofluorescence is useful for imaging the PGA scaffold and stem cells while SHG is useful for following the progress of extracellular matrix (ECM) formation.

Multiphoton fluorescence and second harmonic generation microscopy for imaging infectious keratitis.

The purpose of this study is to demonstrate the application of multiphoton fluorescence and second harmonic generation (SHG) microscopy for the ex-vivo visualization of human corneal morphological alterations due to infectious processes. The structural alterations of both cellular and collagenous components can be respectively demonstrated using fluorescence and SHG imaging. In addition, pathogens with fluorescence may be identified within turbid specimens.

Intact corneal stroma visualization of GFP mouse revealed by multiphoton imaging.

The aim of this work is to demonstrate that multiphoton microscopy is a preferred technique to investigate intact cornea structure without slicing and staining. At the micron resolution, multiphoton imaging can provide both large morphological features and detailed structure of epithelium, corneal collagen fibril bundles and keratocytes. A large area multiphoton cross-section across an intact eye excised from a GFP mouse was obtained by a homebuilt multiphoton microscope.

Multiphoton autofluorescence and second-harmonic generation imaging of the ex vivo porcine eye.

Purpose: The purpose of this work was to demonstrate the use of the combined imaging modality of multiphoton autofluorescence and second-harmonic generation (SHG) microscopy in obtaining spectrally resolved morphologic features of the cornea, limbus, conjunctiva, and sclera in whole, ex vivo porcine eyes.

Methods: The 780-nm output of a femtosecond, titanium-sapphire laser was used to induce broadband autofluorescence (435-700 nm) and SHG (390 nm) from various regions of the surface of ex vivo porcine eyes. A water-immersion objective was used for convenient imaging of the curved surface of the eye.

Characterizing the thermally induced structural changes to intact porcine eye, part 1: second harmonic generation imaging of cornea stroma.

We characterize the structural changes of porcine corneal structures from 25 to 90 degrees C using second harmonic generation (SHG) microscopy. Our results show that porcine stroma undergoes several distinct stages of structural changes between 25 and 90 degrees C. A decrease in SHG intensity from 30 to 45 degrees C and the existence of SHG intensity peaks at 53, 65, and 77 degrees C correlate to distinct structural alterations of the corneal stroma.