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PURPOSE: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC). METHODS: Participants with PROC who received 1-2 previous lines of therapy were treated with niraparib (200 or 300 mg once daily), dostarlimab (500 mg once every 3 weeks for four 21-day cycles, followed by 1,000 mg once every 6 weeks), and bevacizumab (15 mg/kg once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1. Safety was also assessed. Exploratory biomarker end points included evaluation of changes in the tumor molecular profile and microenvironment using baseline and on-treatment tumor samples. RESULTS: Of 41 enrolled participants (median age, 66.0 years [range, 37-83 years]), 9.8% had tumors that were BRCA-mutated, 19.5% were homologous recombination (HR)-deficient, and 17.1% were HR repair (HRR)-mutated. As of the cutoff date, all participants discontinued treatment. The ORR was 17.1% (80% CI, 9.8 to 27.0), including one complete response (2.4%); the disease control rate was 73.2% (80% CI, 62.3 to 82.2). Two participants withdrew before first postbaseline scan because of adverse events (AEs). Grade ≥3 treatment-emergent AEs were reported in 92.7% of participants, with the most common being hypertension (26.8%). Response was not correlated with BRCA, HRR, HR deficiency (HRD), or PD-L1 status. Changes suggesting immune activation were observed in on-treatment samples after triplet therapy. CONCLUSION: Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for poor treatment response. Most participants with response were bevacizumab-naïve. No association was found with HRD, BRCA, or PD-L1 status. AEs were consistent with previous monotherapy reports, except that hypertension was reported more frequently.

Radio Frequency (RF) sputtered germanium (Ge) thin films were deposited on glass substrate at in situ annealing temperatures of 400, 450, 500, 550, and 600 °C. X‐ray diffraction (XRD) and Raman spectroscopy revealed that the Ge films were initially amorphous but transformed to polycrystalline after annealing at 450 °C. Further annealing up to 600 °C resulted in improved crystallinity. Strain studies of the films using XRD and Raman showed compressive (out‐of‐plane) and tensile (in‐plane) strains, respectively, throughout all the annealing temperatures. The surface morphology of the films was recorded using atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM), which showed grain growth with annealing temperatures. The optical energy gap evaluated from absorption spectra for crystalline films decreased with annealing temperature, indicating improvement in crystallinity of films. The resistivity of the films deduced using current‐voltage measurements was found to decrease with annealing temperature, which can be attributed to enhancement in grain size. This study establishes a correlation between strain, grain size, optical energy gap, and electrical resistivity with temperature for Ge films deposited on glass substrates. Thus, the present study provides insights into variation in physical and electrical properties of films with in situ annealing temperature for their applicability in optoelectronic devices. [ABSTRACT FROM AUTHOR]

Mouth cancer is the most frequent cancer of the head and neck in both older and younger people. Achyranthes aspera L. has been used in ethnotraditional and pharmacological applications since ancient times for a variety of disorders. This study was formulated to examine bioactive phenolic and flavonoid compounds from the ethanolic extract of Achyranthes aspera and their binding efficacy targeting growth factor receptors (GFRs) against mouth cancer through in silico molecular docking and simulation studies. Phytochemicals were investigated through the UHPLC technique. A molecular docking study was accomplished using docking software AutoDock 4.2, and MD simulation was executed through GROMACS software. Drug‐likeness, pharmacokinetics, and toxicity profiles of phytocompounds were evaluated using Molinspiration, Swiss ADME, OSIRIS Data Warrior tools, respectively. UHPLC analysis detected phenolics and flavonoids, viz., fisetin, rutin, and fumaric acid, which satisfied Lipinski's rule of five and pharmacokinetic properties. In molecular docking assessment, fisetin exhibited promising interactions with core targeted proteins VEGFR‐2 (B.E. = −8.30 kcal mol−1) and FGFR‐2 (B.E. = −7.64 kcal mol−1) of mouth cancer. Moreover, molecular dynamics simulation data demonstrated stable interactions with both VEGFR‐2 and FGFR‐2 proteins. This binding interaction and stability of A. aspera phytocompounds with therapeutic proteins might contribute to their therapeutic potential in mouth cancer management. [ABSTRACT FROM AUTHOR]

Agriculture and changing environmental conditions are closely related, as weather changes could adversely affect living organisms or regions of crop cultivation. Changing environmental conditions trigger different abiotic stresses, which ultimately cause the accumulation of reactive oxygen species (ROS) in plants. Common ROS production sites are the chloroplast, endoplasmic reticulum, plasma membrane, mitochondria, peroxisomes, etc. The imbalance in ROS production and ROS detoxification in plant cells leads to oxidative damage to biomolecules such as lipids, nucleic acids, and proteins. At low concentrations, ROS initiates signaling events related to development and adaptations to abiotic stress in plants by inducing signal transduction pathways. In plants, a stress signal is perceived by various receptors that induce a signal transduction pathway that activates numerous signaling networks, which disrupt gene expression, impair the diversity of kinase/phosphatase signaling cascades that manage the stress response in the plant, and result in changes in physiological responses under various stresses. ROS production also regulates ABA-dependent and ABA-independent pathways to mitigate drought stress. This review focuses on the common subcellular location of manufacturing, complex signaling mechanisms, and networks of ROS, with an emphasis on cellular effects and enzymatic and non-enzymatic antioxidant scavenging mechanisms of ROS in Poaceae crops against drought stress and how the manipulation of ROS regulates stress tolerance in plants. Understanding ROS systems in plants could help to create innovative strategies to evolve paths of cell protection against the negative effects of excessive ROS in attempts to improve crop productivity in adverse environments. [ABSTRACT FROM AUTHOR]

Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high‐temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA‐induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane‐bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties. [ABSTRACT FROM AUTHOR]

Vigna radiata (L.) R. Wilczek, generally known as mung bean, is a crucial pulse crop in Southeast Asia that is renowned for its high nutritional value. However, its cultivation faces substantial challenges due to numerous abiotic stresses. Here, we investigate the influence of salt and drought stress on mung bean genotypes by evaluating its morpho-physiological traits and biochemical characteristics. This phenotypic analysis revealed that both salt and drought stress adversely affected mung bean, which led to reduced plant height, leaf senescence, loss of plant biomass, and premature plant death. Reactive oxygen species (ROS) production increased under these abiotic stresses. In response, to prevent damage by ROS, the plant activates defense mechanisms to scavenge ROS by producing antioxidants. This response was validated through morpho-physiological, histological, and biochemical assays that characterized KVK Puri-3 and KVK Jharsuguda-1 as salt and drought sensitive genotypes, respectively, and Pusa ratna was identified as a drought and salt tolerant genotype. [ABSTRACT FROM AUTHOR]