Browse Articles
Discover research articles across all indexed journals
Sequential platinum and PARP Inhibition enhances PD1 immunotherapy efficacy in murine Brca2 mutated pancreatic cancer
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy to treat, but emerging evidence suggests that specific subtypes may respond more favorably to certain therapies. BRCA -mutated PDAC represents a distinct subtype that is particularly sensitive to DNA-damaging therapies. The current standard of care for advanced BRCA -mutated PDAC involves induction platinum-based chemotherapy followed by maintenance therapy with a poly (ADP-ribose) polymerase inhibitor (PARPi). However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches. Additionally, there is a lack of robust models that recapitulate the tumor microenvironment of BRCA mutated PDAC, limiting the development of next-generation maintenance treatment options. In this study, we developed a syngeneic and immunocompetent mouse model of Brca2 -mutated PDAC. The model demonstrated high sensitivity to cisplatin plus gemcitabine, but limited efficacy of PARPi monotherapy. Induction with platinum-based chemotherapy sensitized tumors to PARPi maintenance therapy and promoted an exhausted, T cell-inflamed tumor microenvironment. However, resistance emerged which was associated with CDX2 expression and tumor differentiation. The addition of anti-PD1 treatment to PARPi maintenance enhanced tumor regression and prolonged overall survival. These findings provide preclinical support for ongoing clinical trials investigating immunotherapy with PARPi as a maintenance strategy in homologous recombination-deficient PDAC.
Morphological evolution of silicon surfaces nanopatterned by focused ion beam irradiation
Abstract Nanopatterning on solid surface has emerged as an important tool in the field of nanotechnology, nano/micro-electromechanical systems (NEMS/MEMS), photonics, and biotechnology. Among the available techniques, focused ion beam (FIB) enables controlled and precise nanopatterning on solid surfaces. The formation and evolution of nanoripple patterns on silicon (Si) surfaces by 30 keV Ga⁺ focused ion beam (FIB) irradiation has been investigated in this study. We perform a systematic study to investigate the well-defined ripple pattern formation by conducting experiments at different ion incidence angles (0°-45°), ion energies (10–30 keV), and ion fluences. Well-defined ripple patterns are observed near 30° ion incidence angle, with ripple periodicity and amplitude strongly dependent on ion fluence. A distinct morphological transition at higher ion fluences from ripple patterns to terrace-like structures is observed. The force measurements are also carried out in terms of pull-off force test on ripple patterned Si surfaces to investigate the effect of nanopattern on adhesion force as employed by atomic force microscopy (AFM) in force mode with normal sharp probe and silica colloidal probe. The observed results reveal that one can fabricate well-defined nano ripple pattern along with terrace pattern at high fluence and adhesion force can also be tuned with nanoscale pattern. The mechanism of ripple pattern formation and its transition to terrace-like structure are discussed in the framework of well-established continuum models. Potential applications of such nanopatterned surfaces for nanoelectromechanical systems (NEMS) and other functional properties are also highlighted.
Uncertainty and reward histories have distinct effects on decisions after wins and losses
Abstract Intelligent behavior necessitates an adaptive integration of feedback. It is well-known that animals asymmetrically learn from positive and negative feedback. While asymmetrical learning is a robust behavioral effect, the latent computations behind how animals represent their environments and use this to differentially weight wins and losses is poorly understood. Here we tested whether and how uncertainty and reward history modulate the weights placed on wins and losses using a behavioral data set collected in rats. We propose a reinforcement learning model that integrates uncertainty history via an unsigned average reward prediction error and a separate subjective reward history component. We showed that in a dynamic probabilistic reversal learning task with blocks of variable reward predictability, ongoing estimation of uncertainty history and reward history both distinctly influenced rats’ sensitivity to wins and losses. In more predictable environments, and under low uncertainty levels, i.e., when rats were certain in making ‘correct’ choices, rats weighted wins more than losses, as indicated by a higher win-stay, and lower lose-shift probability. This asymmetrical learning strategy enabled rats to remain with the correct action, while discounting the influence of rare losses. Further, male rats were more impacted by their uncertainty history when making win-stay decisions compared to females. Hence, we found sex-specific contributions of these latent computations in modulating behavior. We overall demonstrate that asymmetrically weighting wins and losses could form an important behavioral strategy when adapting to ongoing changes in reward and uncertainty history.
Human chorionic gonadotropin decreases cerebral cystic encephalomalacia and parvalbumin interneuron degeneration in a pro-inflammatory model of mouse neonatal hypoxia-ischemia
Computational design of foldable origami-based compressive ultrasound sensing
Abstract Ultrasound imaging is an essential part of the modern clinical routine. However, its dependence on costly multichannel electronics limits its use in chronic monitoring of disease. Single-detector compressed-sensing approaches have been proposed to simplify the signal acquisition pipeline, but they suffer from reduced acoustic sensitivity due to reliance on multiple scattering topologies. We propose foldable origami structures with built-in ultrasound sensing capabilities for single-pixel imaging that increase the acoustic sensitivity by leveraging a foldable transducer geometry. By detecting ultrasound fields at various origami folding states, target images in two- and three-dimensions are recovered using model-based reconstruction techniques. We simulated the Foldable Origami-based Compressive Ultrasound Sensing (FOCUS) concept and inverse designed the origami geometry for maximum imaging performance. We quantified the performance of the FOCUS concept with the reconstruction accuracy of synthetic target images including point-scatterers and vessel-like structures, reaching an average structure similarity index measure of 0.63 and $$\:{L}_{2}$$ error of 11.89. We showed that the optimized FOCUS pattern remains effective even when exposed to geometric distortions and electrical noise. Our approach can tailor the FOCUS design to various targets, scales, and applications, potentially transforming ultrasound imaging devices through miniaturized single-channel electronics.
Enhancing sand production assessment through accurate determination of Young’s modulus and Poisson’s ratio
Staphylococcus capitis strain producing dual bacteriocins, capidermicin and micrococcin P1, shows broad-spectrum antimicrobial activity
Cryovial versus straw for sheep semen cryopreservation: a comparative study of surface area-to-volume ratio on post-thaw viability and in vitro embryo production
Increasing trust in science through a “Do Your Own Research” intervention
Prevalence of diabetes/prediabetes and their associated risk factors among adults with hypertension from iran: a nationwide study
Acute beetroot juice supplementation enhances short duration high-intensity exercise performance and influences muscle oxygenation in football players
Abstract Beetroot juice (BJ), a nitrate-rich supplement, may enhance exercise performance, but its acute effects on anaerobic power and muscle oxygenation in football players are unclear. This study investigated these effects during a Wingate test in trained male footballers. In a randomized, crossover, double-blind, placebo-controlled design, 16 male football players (age: 18.2 ± 0.4 years, weight: 69.6 ± 6.5 kg, height: 177.5 ± 5.5 cm) consumed 140 mL of BJ (12.8 mmol nitrate) or a placebo (blackcurrant juice (< 0.1 mmol nitrate)). After 2.5 h, a 30-s Wingate test was performed. Muscle oxygenation, heart rate, blood pressure, and blood lactate were assessed. BJ supplementation increased peak power (placebo: 720.33 ± 107.78 W; BJ: 803.50 ± 127.23 W, p = 0.002) and mean power (placebo: 541.23 ± 62.05 W; BJ: 581.42 ± 80.09 W, p = 0.001), and reduced the time to peak power (placebo: 7.32 ± 0.84 s; BJ: 8.10 ± 0.94 s, p = 0.032) compared to placebo. Muscle oxygenation did not differ during exercise ( p > 0.05); however, post-exercise muscle oxygen saturation was higher (∼10%, p = 0.017) and deoxygenated haemoglobin was lower (∼13%, p = 0.019) with BJ. Post-exercise blood lactate levels were higher in BJ compared to placebo ( p < 0.05). Blood pressure at all time points and heart rate during exercise did not differ between conditions ( p > 0.05). Acute BJ supplementation increases anaerobic power output and post-exercise muscle oxygenation in football players, without affecting heart rate or blood pressure. Trial registration The randomized controlled trial was registered on 03/07/2025 at ClinicalTrials.gov, under the registration number NCT07048912.
Risk factor identification for large scale amusement facilities using mixture of experts and fusion of multiple models
Changes in EGFR activity following CRISPR/Cas9-editing of the EGF binding domain
Evaluation of heavy metal contamination in coastal aquifer groundwater of Alappuzha district (Kerala, India) using OSPRC framework
Oxidative stress-associated genes TPPP3 and VEGFA in COPD revealed by bulk and single-cell sequencing analysis
Impact of neuroendocrine neoplasm-specific systemic treatments on expression and function of CXCR4 in neuroendocrine tumor cells
Abstract As neuroendocrine neoplasms (NEN) undergo increasing dedifferentiation, CXC chemokine receptor type 4 (CXCR4) becomes upregulated. Higher levels of CXCR4 are associated with invasive growth, metastasis formation, and poor prognosis. CXCR4 is considered a potential diagnostic biomarker and a promising target for precision therapies — e.g., endoradiotherapeutic approaches, monoclonal antibodies, or small-molecule inhibitors. A variety of systemic therapies are used to treat metastatic NEN, which may modulate CXCR4 expression and potentially influence the efficacy of future CXCR4-targeted strategies. In the NEN cell lines BON-1, QGP-1, and MS-18, we applied cisplatin, etoposide, streptozotocin, 5-fluorouracil, temozolomide, and everolimus- all systemic agents used in highly proliferative NEN. Following incubation, CXCR4 expression was quantified by qRT-PCR, Western blot, and immunohistochemistry. The functional receptor activity was determined by measuring uptake of the radioligand [68Ga]Pentixafor. Cisplatin induced a significant reduction in CXCR4 mRNA levels in BON-1 and QGP-1 cells ( p < 0.05) and decreased radioligand uptake in QGP-1 and MS-18. Etoposide, 5-FU, and streptozotocin had no significant impact on CXCR4 expression or uptake activity. Temozolomide and Everolimus markedly diminished both CXCR4 mRNA and protein levels with no significant impact on radioligand uptake. In high-grade NEN cell lines, Cisplatin, Everolimus, and Temozolomide substantially diminish CXCR4 expression, with Cisplatin significantly decreasing CXCR4-targeted radioligand uptake. These findings might have an impact on the optimal therapy sequence and patient selection for future CXCR4-targeted approaches. Further, the decreased CXCR4 expression could represent a new mechanism of action of the established drugs Cisplatin, Temozolomide, and Everolimus.