New developments in immunotherapy for SCLC.

Small cell lung cancer (SCLC) is an aggressive form of neuroendocrine neoplasm known for its striking initial response to treatment, followed by fast relapse and refractoriness in response to additional lines of therapy. New advances in immunotherapy are paving the way for more effective treatment strategies and have promising results with early clinical trial data. While SCLC rarely harbors actionable mutations, the receptor DLL3 is extensively present in SCLC, making it a potential target for immunotherapy.

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial.

Background: Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.

Altered circadian gene expression in primary human airway epithelial cells in asthma.

https://bit.ly/3v9lOC6.

Extreme Ultraviolet Reflection Spectroscopy of Lanthanides and Actinides Using a High Harmonic Generation Light Source.

Absorption spectroscopy probing transitions from shallow-core d and f orbitals in lanthanides and actinides reveals information about bonding and the electronic structure in compounds containing these elements. However, spectroscopy in this photon energy range is challenging because of the limited availability of light sources and extremely short penetration depths. In this work, we address these challenges using a tabletop extreme ultraviolet (XUV), ultrafast, laser-driven, high harmonic generation light source, which generates femtosecond pulses in the 40-140 eV range.

Venous thromboembolism associated with medically assisted reproduction (MAR): British fertility society policy and practice guidance for assessment and prevention.

The association between Medically Assisted Reproduction (MAR) and thromboembolic complications has been reported widely in multiple published studies. Although venous thromboembolism (VTE) is not thought to be a common complication of MAR, it is associated with high morbidity and is often preventable. Since VTE usually occurs after completion of MAR treatment and is often managed outside of the treating fertility unit, these complications are likely to be underreported and there may be limited awareness of the risks among clinicians.

Exogenous Metabolic Modulators Improve Response to Carboplatin in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks targeted therapies, leaving cytotoxic chemotherapy as the current standard treatment. However, chemotherapy resistance remains a major clinical challenge. Increased insulin-like growth factor 1 signaling can potently blunt chemotherapy response, and lysosomal processes including the nutrient scavenging pathway autophagy can enable cancer cells to evade chemotherapy-mediated cell death.

Superoxide Radicals in Uranyl Peroxide Solids: Lasting Signatures Identified by Electron Paramagnetic Resonance Spectroscopy.

U(VI) peroxide phases (studtite and meta-studtite) are found throughout the nuclear fuel cycle and exist as corrosion products in high radiation fields. Peroxides are part of a family of reactive oxygen species (ROS) that include hydroperoxyl and superoxide species and are produced during alpha radiolysis of water. While U(VI) peroxides have been thoroughly investigated, the incorporation and stability of ROS species within studtite have not been validated.

Exceptional Quantum Efficiency Powers Biomass Production in Halotolerant Algae Picochlorum sp.

The green algal genus Picochlorum is of biotechnological interest because of its robust response to multiple environmental stresses. We compared the metabolic performance of P. SE3 and P.

Tirzepatide attenuates mammary tumor progression in diet-induced obese mice.

We report for the first time an anticancer benefit of tirzepatide-a dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist-in a model of obesity and breast cancer in female mice. Long-term tirzepatide treatment induced weight loss, mitigated obesity-driven changes in circulating metabolic hormone levels, and suppressed orthotopic E0771 mammary tumor growth. Relative to tirzepatide, chronic calorie restriction, an established anticancer intervention in preclinical models, promoted even greater weight loss, systemic hormonal regulation, and tumor suppression.

Attitudes and Experiential Factors Associated with Completion of mt-sDNA Test Kit for Colorectal Cancer Screening.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Despite the availability of multiple screening options, CRC screening is underutilized. We conducted a survey of patients (n = 2973) who were prescribed the multi-target stool DNA (mt-sDNA) screening test (commercialized as Cologuard and manufactured by Exact Sciences Corporation) to understand attitudes and experiences that influence test completion and likelihood of future test completion.

Extracellular vesicles from retinal pigment epithelial cells expressing R345W-Fibulin-3 induce epithelial-mesenchymal transition in recipient cells.

We have shown previously that expression of R345W-Fibulin-3 induces epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells. The purpose of the current study was to determine if extracellular vesicles (EVs) derived from RPE cells expressing R345W-Fibulin-3 mutation are sufficient to induce EMT in recipient cells. ARPE-19 cells were infected with luciferase-tagged wild-type (WT)- Fibulin-3 or luciferase-tagged R345W-Fibulin-3 (R345W) using lentiviruses.

The Lateral Metalation of Isoxazolo[3,4-]pyridazinones towards Hit-to-Lead Development of Selective Positive Modulators of Metabotropic Glutamate Receptors.

Isoxazolo[3,4-] pyridazinones ([3,4-]s) were previously shown to have selective positive modulation at the metabotropic glutamate receptor (mGluR) Subtypes 2 and 4, with no functional cross-reactivity at mGluR, mGluR, or mGluR. Additional analogs were prepared to access more of the allosteric pocket and achieve higher binding affinity, as suggested by homology modeling. Two different sets of analogs were generated.

The Quest for Excellence: A Quality Improvement Project on the Effects of a Standardized PACU/Phase II Bedside Report in a High Turnover Pediatric Ambulatory Surgery Center.

Purpose: To evaluate the impact of an evidence-based standardized bedside report within a pediatric ambulatory surgery center on length of handoff time, registered nurse (RN) workflow, and patient and family satisfaction.

Design: Quality improvement project using an evidence-based standardized bedside report intervention with pre- and postimplementation evaluation of process and outcome measures.

Methods: In January 2019, a unit-based task force evaluated ways to improve current report process and consistency of communication between staff and families.

How chloride functions to enable proton conduction in photosynthetic water oxidation: Time-resolved kinetics of intermediates (S-states) in vivo and bromide substitution.

Chloride (Cl) is essential for O evolution during photosynthetic water oxidation. Two chlorides near the water-oxidizing complex (WOC) in Photosystem II (PSII) structures from Thermosynechococcus elongatus (and T. vulcanus) have been postulated to transfer protons generated from water oxidation.

Comparing Virtual and In-Person Implementation of a School-Based Sexual Health Promotion Program in High Schools with Large Latino Populations.

Many sexual health programs transitioned to virtual implementation during the COVID-19 pandemic. Despite its devastation, the pandemic provided an opportunity to learn about virtual compared to in-person implementation of a sexual health promotion program-El Camino. This study assessed differences in program attendance, engagement, quality, and student ratings for virtual versus in-person implementation of El Camino as part of a rigorous evaluation in high schools with high Latino populations in Maryland.

Mass Spectrometry-Based Vitreous Proteomics: Validated Methods and Analysis Pipeline.

Retinal diseases like diabetic retinopathy and age-related macular degeneration affect millions of individuals worldwide and often lead to vision loss. Vitreous fluid abuts the retina, is accessible for sampling, and contains many proteins related to retinal disease. Therefore, analysis of vitreous is an important tool for studying retinal disease.

Functional Annotation Routines Used by ABRF Bioinformatics Core Facilities - Observations, Comparisons, and Considerations.

The functional annotation of gene lists is a common analysis routine required for most genomics experiments, and bioinformatics core facilities must support these analyses. In contrast to methods such as the quantitation of RNA-Seq reads or differential expression analysis, our research group noted a lack of consensus in our preferred approaches to functional annotation. To investigate this observation, we selected 4 experiments that represent a range of experimental designs encountered by our cores and analyzed those data with 6 tools used by members of the Association of Biomolecular Resource Facilities (ABRF) Genomic Bioinformatics Research Group (GBIRG).

Regulation of light energy conversion between linear and cyclic electron flow within photosystem II controlled by the plastoquinone/quinol redox poise.

Ultrapurified Photosystem II complexes crystalize as uniform microcrystals (PSIIX) of unprecedented homogeneity that allow observation of details previously unachievable, including the longest sustained oscillations of flash-induced O yield over > 200 flashes and a novel period-4.7 water oxidation cycle. We provide new evidence for a molecular-based mechanism for PSII-cyclic electron flow that accounts for switching from linear to cyclic electron flow within PSII as the downstream PQ/PQH pool reduces in response to metabolic needs and environmental input.

Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia.

Background: Previous population health studies examining adults with acute myeloid leukemia (AML); however many of these, such as the Cancer Genome Atlas, are derived from databases collected by large urban centers. Due to its unique industry and environmental exposures, we hypothesized the West Virginia Appalachian population may have different mutational trends and clinical outcomes.

Aims: To address the concern of under-representation of rural minorities in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML in rural Appalachia.

A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies.

Streptococcus pneumoniae (Spn) remains a major cause of global mortality, with extensive antigenic diversity between capsular serotypes that poses an ongoing challenge for vaccine development. Widespread use of pneumococcal conjugate vaccines (PCVs) targeting Spn capsules has greatly reduced infections by vaccine-included serotypes but has led to increased infections by nonincluded serotypes. To date, high cost of PCVs has also limited their usefulness in low-income regions where disease burdens are highest.