Photon Absorption Remote Sensing Imaging of Breast Needle Core Biopsies Is Diagnostically Equivalent to Gold Standard H&E Histologic Assessment.

Photon absorption remote sensing (PARS) is a new laser-based microscope technique that permits cellular-level resolution of unstained fresh, frozen, and fixed tissues. Our objective was to determine whether PARS could provide an image quality sufficient for the diagnostic assessment of breast cancer needle core biopsies (NCB). We PARS imaged and virtually H&E stained seven independent unstained formalin-fixed paraffin-embedded breast NCB sections. These identical tissue sections were subsequently stained with standard H&E and digitally scanned. Both the 40× PARS and H&E whole-slide images were assessed by seven breast cancer pathologists, masked to the origin of the images. A concordance analysis was performed to quantify the diagnostic performances of standard H&E and PARS virtual H&E. The PARS images were deemed to be of diagnostic quality, and pathologists were unable to distinguish the image origin, above that expected by chance. The diagnostic concordance on cancer vs. benign was high between PARS and conventional H&E (98% agreement) and there was complete agreement for within-PARS images. Similarly, agreement was substantial (kappa > 0.6) for specific cancer subtypes. PARS virtual H&E inter-rater reliability was broadly consistent with the published literature on diagnostic performance of conventional histology NCBs across all tested histologic features. PARS was able to image unstained tissues slides that were diagnostically equivalent to conventional H&E. Due to its ability to non-destructively image fixed and fresh tissues, and the suitability of the PARS output for artificial intelligence assistance in diagnosis, this technology has the potential to improve the speed and accuracy of breast cancer diagnosis.

A Conductive Hydrogel-Based Microneedle Platform for Real-Time pH Measurement in Live Animals.

Conventional microneedles (MNs) have been extensively reported and applied toward a variety of biosensing and drug delivery applications. Hydrogel forming MNs with the added ability to electrically track health conditions in real-time is an area yet to be explored. The first conductive hydrogel microneedle (HMN) electrode that is capable of on-needle pH detection with no postprocessing required is presented here. The HMN array is fabricated using a swellable dopamine (DA) conjugated hyaluronic acid (HA) hydrogel, and is embedded with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) to increase conductivity. The catechol-quinone chemistry intrinsic to DA is used to measure pH in interstitial fluid (ISF). The effect of PEDOT:PSS on the characteristics of the HMN array such as swelling capability and mechanical strength is fully studied. The HMN's capability for pH measurement is first demonstrated using porcine skin equilibrated with different pH solutions ranging from 3.5 to 9. Furthermore, the HMN-pH meter is capable of in vivo measurements with a 93% accuracy compared to a conventional pH probe meter. This HMN technology bridges the gap between traditional metallic electrochemical biosensors and the direct extraction of ISF, and introduces a platform for the development of polymeric wearable sensors capable of on-needle detection.

Exploring the Limits and Causes of Plastid Genome Expansion in Volvocine Green Algae.

Plastid genomes are not normally celebrated for being large. But researchers are steadily uncovering algal lineages with big and, in rare cases, enormous plastid DNAs (ptDNAs), such as volvocine green algae. Plastome sequencing of five different volvocine species has revealed some of the largest, most repeat-dense plastomes on record, including that of Volvox carteri (∼525 kb). Volvocine algae have also been used as models for testing leading hypotheses on organelle genome evolution (e.g., the mutational hazard hypothesis), and it has been suggested that ptDNA inflation within this group might be a consequence of low mutation rates and/or the transition from a unicellular to multicellular existence. Here, we further our understanding of plastome size variation in the volvocine line by examining the ptDNA sequences of the colonial species Yamagishiella unicocca and Eudorina sp. NIES-3984 and the multicellular Volvox africanus, which are phylogenetically situated between species with known ptDNA sizes. Although V. africanus is closely related and similar in multicellular organization to V. carteri, its ptDNA was much less inflated than that of V. carteri. Synonymous- and noncoding-site nucleotide substitution rate analyses of these two Volvox ptDNAs suggest that there are drastically different plastid mutation rates operating in the coding versus intergenic regions, supporting the idea that error-prone DNA repair in repeat-rich intergenic spacers is contributing to genome expansion. Our results reinforce the idea that the volvocine line harbors extremes in plastome size but ultimately shed doubt on some of the previously proposed hypotheses for ptDNA inflation within the lineage.