The temperate coral maintains acid-base homeostasis through heat stress.

Heat stress can disrupt acid-base homeostasis in reef-building corals and other tropical cnidarians, often leading to cellular acidosis that can undermine organismal function. Temperate cnidarians experience a high degree of seasonal temperature variability, leading us to hypothesize that temperate taxa have more thermally robust pH homeostasis than their tropical relatives. To test this, we investigated how elevated temperature affects intracellular pH and calcification in the temperate coral .

Hypoxia disrupts metabolism in coral and sea anemone larvae.

Anthropogenic pollution is driving an increase in the frequency and severity of seawater hypoxic events in coastal marine ecosystems. Although hypoxia decreases physiological performance in coral and sea anemone (phylum Cnidaria) larvae, the underlying cellular mechanisms remain unexplored. Here, larvae of the reef-building corals Galaxea fascicularis and Porites astreoides and the estuarine sea anemone Nematostella vectensis were exposed to normoxia or a simulated hypoxic event (6 h at <2 mg dissolved O2 l-1), and their metabolomic response was quantified at the end of the exposure period using targeted liquid chromatography-mass spectrometry.

Hypoxia Disrupts Sex-Specific Physiology and Gene Expression Leading to Decreased Fitness in the Estuarine Sea Anemone Nematostella vectensis.

Coastal seawater hypoxia is increasing in temperate estuaries under global climate change, yet it is unknown how low oxygen conditions affect most estuarine species. We found that hypoxia has increased since the 1990s in an estuary hosting the sea anemone Nematostella vectensis (Jacques Cousteau National Estuarine Research Reserve, New Jersey, USA). Adult N.

Deployment of a Machine Learning Algorithm in a Real-World Cohort for Quality Control Monitoring of Human Epidermal Growth Factor-2-Stained Clinical Specimens in Breast Cancer.

Context.—: Precise determination of biomarker status is necessary for clinical trial enrollment and endpoint analyses, as well as for optimal treatment determination in real-world practice. However, variabilities may be introduced into this process due to the processing of clinical specimens by different laboratories and assessment by distinct pathologists.

Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer.

Unlabelled: Understanding the role of the tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs in treatment-naïve early-stage lung cancer using imaging mass cytometry in the TRACERx study (n = 81 patients/198 samples/2.3 million cells).

Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments.

Assessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated.

Divergent bleaching and recovery trajectories in reef-building corals following a decade of successive marine heatwaves.

Increasingly frequent marine heatwaves are devastating coral reefs. Corals that survive these extreme events must rapidly recover if they are to withstand subsequent events, and long-term survival in the face of rising ocean temperatures may hinge on recovery capacity and acclimatory gains in heat tolerance over an individual's lifespan. To better understand coral recovery trajectories in the face of successive marine heatwaves, we monitored the responses of bleaching-susceptible and bleaching-resistant individuals of two dominant coral species in Hawai'i, and , over a decade that included three marine heatwaves.

Acute heat priming promotes short-term climate resilience of early life stages in a model sea anemone.

Across diverse taxa, sublethal exposure to abiotic stressors early in life can lead to benefits such as increased stress tolerance upon repeat exposure. This phenomenon, known as hormetic priming, is largely unexplored in early life stages of marine invertebrates, which are increasingly threatened by anthropogenic climate change. To investigate this phenomenon, larvae of the sea anemone and model marine invertebrate were exposed to control (18 °C) or elevated (24 °C, 30 °C, 35 °C, or 39 °C) temperatures for 1 h at 3 days post-fertilization (DPF), followed by return to control temperatures (18 °C).

Characterization of a sperm motility signalling pathway in a gonochoric coral suggests conservation across cnidarian sexual systems.

Most stony corals liberate their gametes into the water column via broadcast spawning, where fertilization hinges upon the activation of directional sperm motility. Sperm from gonochoric and hermaphroditic corals display distinct morphological and molecular phenotypes, yet it is unknown whether the signalling pathways controlling sperm motility are also distinct between these sexual systems. Here, we addressed this knowledge gap using the gonochoric, broadcast spawning coral .

Parental exposure to ocean acidification impacts gamete production and physiology but not offspring performance in Nematostella vectensis.

Ocean acidification (OA) resulting from anthropogenic CO2 emissions is impairing the reproduction of marine organisms. While parental exposure to OA can protect offspring via carryover effects, this phenomenon is poorly understood in many marine invertebrate taxa. Here, we examined how parental exposure to acidified (pH 7.

Association of artificial intelligence-powered and manual quantification of programmed death-ligand 1 (PD-L1) expression with outcomes in patients treated with nivolumab ± ipilimumab.

Assessment of programmed death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) has emerged as an important predictive biomarker across multiple tumor types. However, manual quantitation of PD-L1 positivity can be difficult and leads to substantial inter-observer variability. Although the development of artificial intelligence (AI) algorithms may mitigate some of the challenges associated with manual assessment and improve the accuracy of PD-L1 expression scoring, use of AI-based approaches to oncology biomarker scoring and drug development has been sparse, primarily due to the lack of large-scale clinical validation studies across multiple cohorts and tumor types.

Developing Expertise in H NMR Spectral Interpretation.

Advancements in organic chemistry depend upon chemists' ability to interpret NMR spectra, though research demonstrates that cultivating such proficiency requires years of graduate-level study. The organic chemistry community thus needs insight into how this expertise develops to expedite learning among its newest members. This study investigated undergraduate and doctoral chemistry students' understanding and information processing during the interpretation of H NMR spectra and complementary IR spectra.

Androgen Receptor Expression and Breast Cancer Survival: Results From the Nurses' Health Studies.

Background: Hormone receptor signaling is critical in the progression of breast cancers, although the role of the androgen receptor (AR) remains unclear, particularly for estrogen receptor (ER)-negative tumors. This study assessed AR protein expression as a prognostic marker for breast cancer mortality.

Methods: This study included 4147 pre- and postmenopausal women with invasive breast cancer from the Nurses' Health Study (diagnosed 1976-2008) and Nurses' Health Study II (1989-2008) cohorts.

Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy.

Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding a specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin, and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples.

EZH2 protein expression in normal breast epithelium and risk of breast cancer: results from the Nurses' Health Studies.

Background: Enhancer of zeste homolog 2 (EZH2) is a polycomb-group protein that is involved in stem cell renewal and carcinogenesis. In breast cancer, increased EZH2 expression is associated with aggressiveness and has been suggested to identify normal breast epithelium at increased risk of breast cancer development. However, the association between EZH2 expression in benign breast tissue and breast cancer risk has not previously been evaluated in a large prospective cohort.

The SIRT2 Deacetylase Stabilizes Slug to Control Malignancy of Basal-like Breast Cancer.

Overabundance of Slug protein is common in human cancer and represents an important determinant underlying the aggressiveness of basal-like breast cancer (BLBC). Despite its importance, this transcription factor is rarely mutated in BLBC, and the mechanism of its deregulation in cancer remains unknown. Here, we report that Slug undergoes acetylation-dependent protein degradation and identify the deacetylase SIRT2 as a key mediator of this post-translational mechanism.

LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer.

Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3.

Methodological Issues in Predicting Pediatric Epilepsy Surgery Candidates Through Natural Language Processing and Machine Learning.

We describe the development and evaluation of a system that uses machine learning and natural language processing techniques to identify potential candidates for surgical intervention for drug-resistant pediatric epilepsy. The data are comprised of free-text clinical notes extracted from the electronic health record (EHR). Both known clinical outcomes from the EHR and manual chart annotations provide gold standards for the patient's status.

Extensive rewiring of epithelial-stromal co-expression networks in breast cancer.

Background: Epithelial-stromal crosstalk plays a critical role in invasive breast cancer pathogenesis; however, little is known on a systems level about how epithelial-stromal interactions evolve during carcinogenesis.

Results: We develop a framework for building genome-wide epithelial-stromal co-expression networks composed of pairwise co-expression relationships between mRNA levels of genes expressed in the epithelium and stroma across a population of patients. We apply this method to laser capture micro-dissection expression profiling datasets in the setting of breast carcinogenesis.