Real-World and Clinical Trial Validation of a Deep Learning Radiomic Biomarker for PD-(L)1 Immune Checkpoint Inhibitor Response in Advanced Non-Small Cell Lung Cancer.

Purpose: This study developed and validated a novel deep learning radiomic biomarker to estimate response to immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC) using real-world data (RWD) and clinical trial data.

Materials And Methods: Retrospective RWD of 1,829 patients with advanced NSCLC treated with PD-(L)1 ICIs were collected from 10 academic and community institutions in the United States and Europe. The RWD included data sets for discovery (Data Set A-Discovery, n = 1,173) and independent test (Data Set B, n = 458).

Systemic Therapy Options for Peritoneal Mesothelioma.

Peritoneal mesothelioma is an uncommon malignancy affecting approximately 300 new patients annually in the United States. Due to its low incidence, prospective clinical trials specific to this disease are scant. Recommendations regarding systemic therapy are mostly extrapolated from clinical trials conducted among patients with pleural mesothelioma.

Costs and cost-effectiveness of the Kerala pilot screening programme for diabetic retinopathy in the public health system.

Background/objectives: The Government of Kerala initiated a pilot screening programme for diabetic retinopathy in 16 Family Health Centres in Thiruvananthapuram district in 2019 in collaboration with the ORNATE India project. The evaluation of this pilot included a study of its costs and cost-effectiveness to inform decisions about extending the programme throughout Kerala.

Subjects/methods: The participants comprise all 5307 people who were screened for diabetic retinopathy under the pilot programme for whom data could be collected.

OxyR is required for oxidative stress resistance of the entomopathogenic bacterium and has a minor role during the bacterial interaction with its hosts.

is a Gram-negative bacterium, mutualistically associated with the soil nematode , and this nemato-bacterial complex is parasitic for a broad spectrum of insects. The transcriptional regulator OxyR is widely conserved in bacteria and activates the transcription of a set of genes that influence cellular defence against oxidative stress. It is also involved in the virulence of several bacterial pathogens.

Temperature-dependent iron motion in extremophile rubredoxins - no need for 'corresponding states'.

Extremophile organisms are known that can metabolize at temperatures down to - 25 °C (psychrophiles) and up to 122 °C (hyperthermophiles). Understanding viability under extreme conditions is relevant for human health, biotechnological applications, and our search for life elsewhere in the universe. Information about the stability and dynamics of proteins under environmental extremes is an important factor in this regard.

Real-World Impact of Comprehensive Genomic Profiling on Biomarker Detection, Receipt of Therapy, and Clinical Outcomes in Advanced Non-Small Cell Lung Cancer.

Purpose: Therapeutic decision making for patients with advanced non-small cell lung cancer (aNSCLC) includes a growing number of options for genomic, biomarker-guided, targeted therapies. We compared actionable biomarker detection, targeted therapy receipt, and real-world overall survival (rwOS) in patients with aNSCLC tested with comprehensive genomic profiling (CGP) versus small panel testing (SP) in real-world community health systems.

Methods: Patients older than 18 years diagnosed with aNSCLC between January 1, 2015, and December 31, 2020, who received biomarker testing were followed until death or study end (September 30, 2021), and categorized by most comprehensive testing during follow-up: SP (≤52 genes) or CGP (>52 genes).

A Homochiral Porous Organic Cage-Polymer Membrane for Enantioselective Resolution.

Membrane-based enantioselective separation is a promising method for chiral resolution due to its low cost and high efficiency. However, scalable fabrication of chiral separation membranes displaying both high enantioselectivity and high flux of enantiomers is still a challenge. Here, the authors report the preparation of homochiral porous organic cage (Covalent cage 3 (CC3)-R)-based enantioselective thin-film-composite membranes using polyamide (PA) as the matrix, where fully organic and solvent-processable cage crystals have good compatibility with the polymer scaffold.

Accurate prediction of solvent flux in sub-1-nm slit-pore nanosheet membranes.

Nanosheet-based membranes have shown enormous potential for energy-efficient molecular transport and separation applications, but designing these membranes for specific separations remains a great challenge due to the lack of good understanding of fluid transport mechanisms in complex nanochannels. We synthesized reduced MXene/graphene hetero-channel membranes with sub-1-nm pores for experimental measurements and theoretical modeling of their structures and fluid transport rates. Our experiments showed that upon complete rejection of salt and organic dyes, these membranes with subnanometer channels exhibit remarkably high solvent fluxes, and their solvent transport behavior is very different from their homo-structured counterparts.

Krumholzibacteriota and Deltaproteobacteria contain rare genetic potential to liberate carbon from monoaromatic compounds in subsurface coal seams.

Biogenic methane in subsurface coal seam environments is produced by diverse consortia of microbes. Although this methane is useful for global energy security, it remains unclear which microbes can liberate carbon from the coal. Most of this carbon is relatively resistant to biodegradation, as it is contained within aromatic rings.

Facile electrocatalytic proton reduction by a [Fe-Fe]-hydrogenase bio-inspired synthetic model bearing a terminal CN ligand.

An azadithiolate bridged CN bound pentacarbonyl bis-iron complex, mimicking the active site of [Fe-Fe] Hase is synthesized. The geometric and electronic structure of this complex is elucidated using a combination of EXAFS analysis, infrared and Mössbauer spectroscopy and DFT calculations. The electrochemical investigations show that complex 1 effectively reduces H to H between pH 0-3 at diffusion-controlled rates (10 M s) 10 s at pH 3 with an overpotential of 140 mV.

Perspective: rethinking therapeutic strategies in oncology.

Immuno-oncology has revolutionized cancer care, drug development, the design of clinical trials, standard treatment paradigms, and the evaluation of response to therapy. These are all areas, however, that have not fully incorporated principles of tumor immunology. Insufficient emphasis is put on the effect drugs have on the immune system, and specifically, the impact that multiple lines of therapy can have on the functioning of the immune system, hindering a robust anti-tumor immune response.

Osimertinib afatinib as first-line treatment for patients with metastatic non-small cell lung cancer with an exon 19 deletion or exon 21 L858R mutation.

Background: The optimal treatment sequencing for patients with metastatic epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC) remains a subject of debate. In the United States, osimertinib is the preferred tyrosine kinase inhibitor (TKI) in the first-line setting. However, small retrospective studies suggest that alternative TKI sequencing strategies may produce similar outcomes.

Dual-Channel-Ion Conductor Membrane for Low-Energy Lithium Extraction.

The development of energy-efficient and environmentally friendly lithium extraction techniques is essential to meet the growing global demand for lithium-ion batteries. In this work, a dual-channel ion conductor membrane was designed for a concentration-driven lithium-selective ion diffusion process. The membrane was based on a porous lithium-ion conductor, and its pores were modified with an anion-exchange polymer.

Deciphering Brain Metastasis Stem Cell Properties From Colorectal Cancer Highlights Specific Stemness Signature and Shared Molecular Features.

Background & Aims: Brain metastases (BMs) from colorectal cancer (CRC) are associated with significant morbidity and mortality, with chemoresistance and short overall survival. Migrating cancer stem cells with the ability to initiate BM have been described in breast and lung cancers. In this study, we describe the identification and characterization of cancer stem cells in BM from CRC.

Anthropogenic petroleum signatures and biodegradation in subantarctic Macquarie Island soils.

Special Antarctic Blend (SAB) diesel is the main fuel used on Macquarie Island and has been identified as the primary contaminant in several past spill events. This study evaluates the environmental impact of petroleum spills at high latitudes, in the soils of subantarctic Macquarie Island. Soil samples were collected from seven locations, including the "fuel farm" and main powerhouse that have been contaminated by petroleum in the past, and five reference locations, away from station infrastructure and from any obvious signs of contamination.

Sulfur X-ray Absorption and Emission Spectroscopy of Organic Sulfones.

The sulfones are a widespread group of organo-sulfur compounds, which contain the sulfonyl SO group attached to two carbons and have a formal sulfur oxidation state of +2. We have examined the sulfur K near-edge X-ray absorption spectroscopy (XAS) of a range of different sulfones and find substantial spectroscopic variability depending upon the nature of the coordination to the sulfonyl group. We have also examined the sulfur Kβ X-ray emission spectroscopy (XES) of selected representative sulfones.

The mucormycosis and stroke: The learning curve during the second COVID-19 pandemic.

Background: The Angio-invasive Rhino-orbito-cerebral mucormycosis (ROCM) producing strokes is a less explored entity. Our hospital, a stroke-ready one, had an opportunity to manage mucormycosis when it was identified as the nodal center for mucormycosis management. We are sharing our experiences and mistakes in managing the cerebrovascular manifestations of ROCM.

Biogeochemistry of Recently Fossilized Siliceous Hot Spring Sinters from Yellowstone, USA.

Active hot springs are dynamic geobiologically active environments. Heat- and element-enriched fluids form hot spring sinter deposits that are inhabited by microbial and macroscopic eukaryotic communities, but it is unclear how variable heat, fluid circulation, and mineralization within hot spring systems affect the preservation of organic matter in sinters. We present geological, petrographic, and organic geochemical data from fossilized hot spring sinters (<13 Ka) from three distinct hot spring fields of Yellowstone National Park.

A Phase 1, Open-Label, Dose-Escalation Study of L-DOS47 in Combination With Pemetrexed Plus Carboplatin in Patients With Stage IV Recurrent or Metastatic Nonsquamous NSCLC.

Introduction: L-DOS47, a targeted urease-anti-CEACAM6 immunoconjugate, alters the acidity of the tumor microenvironment by increasing local ammonia production. In vitro, the cytotoxic effects of L-DOS47 were additive when combined with pemetrexed and carboplatin.

Methods: This phase I, open-label, dose-escalation study evaluated the safety and tolerability of up to four cycles of L-DOS47 (administered on days 1, 8, and 15 of each cycle at doses ranging from 0.

Tailoring the humidity response of cellulose nanocrystal-based films by specific ion effects.

Hypothesis: The optical properties and humidity response of iridescent films made of cellulose nanocrystal (CNC) and polyethylene glycol (PEG) can be tailored by the incorporation of electrolytes chosen based on specific ion effects (SIE).

Experiments: A series of inorganic salts comprising five different cations and five anions based on the Hofmeister series were mixed with CNC/PEG suspensions, followed by an air-dried process into iridescent solid films. These films were tested in changing relative humidity (RH) environments from 30% to 90% and their photonic properties and mass change monitored.

Extrusion and 3D printing of novel lipid-polymer blends for oral drug applications.

Lipids are interesting biological materials that can offer a number of pharmaceutical benefits when used as carriers for drug delivery. However, 3D printing of lipids alone by fused deposition processing techniques is very difficult as they have very poor mechanical properties that cause their filaments to fail when they are loaded into a fused deposition 3D printer. If this problem could be overcome, then lipids could be 3D printed into bespoke tablets and assist progress towards such personalised medicines.