Squamous cell carcinoma arising in chronically damaged skin (Marjolin's Ulcer): still an unmet need in the era of immunotherapy.

Background: Cutaneous squamous cell carcinoma (cSCC) is characterized by a high tumor mutational burden due to solar damage and a favorable response to anti-PD-1 immunotherapy. Yet, we encounter tumors arising in areas with minimal sun exposure, such as cSCC that develops in chronically inflamed skin, also known as Marjolin's Ulcer (MU). The response of MU-SCC to immunotherapy remains unknown.

Eccentricity pacing and rapid termination of the early Antarctic ice ages.

Earth's obliquity and eccentricity cycles are strongly imprinted on Earth's climate and widely used to measure geological time. However, the record of these imprints on the oxygen isotope record in deep-sea benthic foraminifera (δO) shows contradictory signals that violate isotopic principles and cause controversy over climate-ice sheet interactions. Here, we present a δO record of high fidelity from International Ocean Drilling Program (IODP) Site U1406 in the northwest Atlantic Ocean.

Development and validation of an electronic frailty index in a national health maintenance organization.

Background: Frailty constitutes a major factor that puts the elderly at risk of health and functional deterioration.

Objectives: To develop and validate an Electronic Frailty Index based on electronic data routinely collected in the HMO.

Study Design And Setting: A retrospective cohort of the HMO members.

The long-read assembly of Apareiodon sp., a neotropical fish with a ZZ/ZW sex chromosome system.

Neotropical fishes emerge as an extremely diverse group of vertebrates where genomic strategies to evaluate structural and functional features are still beginning. Here, we present a second draft genome of Apareiodon sp. (2n=54, ZZ/ZW), adding PacBio technology whole genome sequencing, and assembling by combining two technologies (long and short reads).

Characterisation of the complete chloroplast genome of Solanum tuberosum cv. White Lady.

Potato (Solanum tuberosum) is considered worldwide as one of the most important non-cereal food crops. As a result of its adaptability and worldwide production area, potato displays a vast phenotypical variability as well as genomic diversity. Chloroplast genomes have long been a core issue in plant molecular evolution and phylogenetic studies, and have an important role in revealing photosynthetic mechanisms, metabolic regulations and the adaptive evolution of plants.

A new silicon phthalocyanine dye induces pyroptosis in prostate cancer cells during photoimmunotherapy.

Photoimmunotherapy (PIT) combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers (PS) and is a promising new cancer therapy. We designed and synthesized, in a highly convergent manner, the silicon phthalocyanine dye WB692-CB2, which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines. In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen (PSMA).

Efflux pumps and membrane permeability contribute to intrinsic antibiotic resistance in .

is a pulmonary pathogen that exhibits intrinsic resistance to antibiotics, but the factors driving this resistance are incompletely understood. Insufficient intracellular drug accumulation could explain broad-spectrum resistance, but whether antibiotics fail to accumulate in and the mechanisms required for drug exclusion remain poorly understood. We measured antibiotic accumulation in using mass spectrometry and found a wide range of drug accumulation across clinically relevant antibiotics.

The effect of long-standing lymphopenia after radiation therapy on survival in rectal cancer.

Background: Lymphopenia and high neutrophil-to-lymphocyte ratio are known negative prognostic factors in rectal cancer. Until recently, however, lymphopenia was regarded as a minor sequela following radiation therapy (RT). The immune system's influence on rectal cancer treatment outcomes led us to evaluate the impact of lymphopenia at various time points, before, during, and following radiotherapy.

The impact of extensive intraductal component (EIC) on the genomic risk of recurrence in early hormone receptor positive breast cancer.

Background: Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal component (EIC). The impact of EIC on the genomic risk of recurrence is unclear.

Methods: Patients with early hormone receptor-positive HER2neu-negative (HR + HER2-) IDC breast cancer and a known OncotypeDX Breast Recurrence Score® (RS) who underwent breast surgery at our institute were included.

Modeling lung endothelial dysfunction in sepsis-associated ARDS using a microphysiological system.

Endothelial dysfunction is a critical feature of acute respiratory distress syndrome (ARDS) associated with higher disease severity and worse outcomes. Preclinical in vivo models of sepsis and ARDS have failed to yield useful therapies in humans, perhaps due to interspecies differences in inflammatory responses and heterogeneity of human host responses. Use of microphysiological systems (MPS) to investigate lung endothelial function may shed light on underlying mechanisms and targeted treatments for ARDS.

Comparing national device-based physical activity surveillance systems: a systematic review.

Background: Physical activity surveillance systems are important for public health monitoring but rely mostly on self-report measurement of physical activity. Integration of device-based measurements in such systems can improve population estimates, however this is still relatively uncommon in existing surveillance systems. This systematic review aims to create an overview of the methodology used in existing device-based national PA surveillance systems.

Photoimmunotherapy of HER2-expressing Breast Cancer Cells.

Background/aim: Breast cancer (BC) is the most common malignant disease worldwide. Localized stages of BC can be successfully treated by surgery. However, local recurrence occurs in about 4-10% of patients, requiring systemic treatments that impair the patients' quality of life and shortens life expectancy.

Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

Background/aim: The standard treatment for localized prostate cancer involves surgical removal of the prostate with curative intent. However, when tumor cells persist in the operation site, there is high risk of local recurrence and tumor spread, leading to stressful follow-up treatments, impaired quality of life, and reduced overall survival. This study examined photoimmunotherapy (PIT) as a new treatment option for prostate cancer cells.

Targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy.

Proteolysis-targeting chimeras (PROTACs) represent a new therapeutic modality involving selectively directing disease-causing proteins for degradation through proteolytic systems. Our ability to exploit targeted protein degradation (TPD) for antibiotic development remains nascent due to our limited understanding of which bacterial proteins are amenable to a TPD strategy. Here, we use a genetic system to model chemically-induced proximity and degradation to screen essential proteins in Mycobacterium smegmatis (Msm), a model for the human pathogen M.

Visions for our future regional electricity system: Citizen preferences in four EU countries.

As climate targets tighten, all countries must transition toward a renewable electricity system, but conflicts about generation and infrastructure deployment impede transition progress. Although the triggers of opposition are well studied, remains understudied. We survey citizen preferences for a renewable electricity future through a conjoint analysis among 4,103 individuals in Denmark, Portugal, Poland, and Germany.

Glucagon-like peptide-1 analogs activate AMP kinase leading to reversal of the Warburg metabolic switch in breast cancer cells.

Breast cancer (BC) is associated with type 2 diabetes mellitus (T2DM) and obesity. Glucagon-like peptide (GLP)-1 regulates post-prandial insulin secretion, satiety, and gastric emptying. Several GLP-1 analogs have been FDA-approved for the treatment of T2DM and obesity.

Potential global cis and trans regulation of lncRNAs in Saccharomyces cerevisiae subjected to ethanol stress.

Long noncoding RNAs (lncRNAs) are regulatory RNAs. Saccharomyces cerevisiae strains transcribe hundreds of lncRNAs. LncRNAs can regulate the expression of adjacent genes (cis-regulation) or distant genes from lncRNAs (trans-regulation).

Antibody-dye Conjugates Targeting EGFR and HER2 for the Photoimmunotherapy of Bladder Cancer.

Background/aim: Although there are curative treatment options for non-muscle-invasive bladder cancer, the recurrence of this tumor is high. Therefore, novel targeted therapies are needed for the complete removal of bladder cancer cells in stages of localized disease, in order to avoid local recurrence, to spare bladder cancer patients from stressful and expensive treatment procedures and to increase their quality of life and life expectancy. This study tested a new approach for the photoimmunotherapy (PIT) of bladder cancer.

Experiences of Providers and Immigrants/Refugees with Health Care: A Meta-Synthesis of the Latin American Context.

Introduction: The experiences of providers and immigrants/refugees related to healthcare in the Latin American context have not yet been aggregated. This study aimed to synthesize the qualitative evidence on this theme.

Method: A systematic review of qualitative evidence with meta-synthesis.

Plasma Proteome-Based Test for First-Line Treatment Selection in Metastatic Non-Small Cell Lung Cancer.

Purpose: Current guidelines for the management of metastatic non-small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1 inhibitors, either alone or in combination with chemotherapy. This approach fails to account for individual patient variability and host immune factors and often results in less-than-ideal outcomes. To address the limitations of the current guidelines, we developed and subsequently blindly validated a machine learning algorithm using pretreatment plasma proteomic profiles for personalized treatment decisions.

Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy.

Introduction: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.