Search Results (1,926)

Background/Objectives: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is a critical mediator of immune regulation, inflammation, and cancer progression. Although implicated in colorectal cancer (CRC) pathogenesis, its molecular heterogeneity and clinical significance remain insufficiently characterized—particularly within early-onset CRC (EOCRC) and across diverse treatment and demographic contexts. We present AI-HOPE-JAK-STAT, a novel conversational artificial intelligence platform built to enable the real-time, natural language-driven exploration of JAK/STAT pathway alterations in CRC. The platform integrates clinical, genomic, and treatment data to support dynamic, hypothesis-generating analyses for precision oncology. Methods: AI-HOPE-JAK-STAT combines large language models (LLMs), a natural language-to-code engine, and harmonized public CRC datasets from cBioPortal. Users define analytical queries in plain English, which are translated into executable code for cohort selection, survival analysis, odds ratio testing, and mutation profiling. To validate the platform, we replicated known associations involving JAK1, JAK3, and STAT3 mutations. Additional exploratory analyses examined age, treatment exposure, tumor stage, and anatomical site. Results: The platform recapitulated established trends, including improved survival among EOCRC patients with JAK/STAT pathway alterations. In FOLFOX-treated CRC cohorts, JAK/STAT-altered tumors were associated with significantly enhanced overall survival (p < 0.0001). Stratification by age revealed survival advantages in younger (age < 50) patients with JAK/STAT mutations (p = 0.0379). STAT5B mutations were enriched in colon adenocarcinoma and correlated with significantly more favorable trends (p = 0.0000). Conversely, JAK1 mutations in microsatellite-stable tumors did not affect survival, emphasizing the value of molecular context. Finally, JAK3-mutated tumors diagnosed at Stage I–III showed superior survival compared to Stage IV cases (p = 0.00001), reinforcing stage as a dominant clinical determinant. Conclusions: AI-HOPE-JAK-STAT establishes a new standard for pathway-level interrogation in CRC by empowering users to generate and test clinically meaningful hypotheses without coding expertise. This system enhances access to precision oncology analyses and supports the scalable, real-time discovery of survival trends, mutational associations, and treatment-response patterns across stratified patient cohorts. Full article

The ability to model the earliest stages of human embryonic development in vitro using pluripotent stem cells offers researchers new ways to understand and interrogate the intricacies of implantation. It also raises important ethical and regulatory considerations, both those common to research involving human embryos, as well as those unique to stem cell-based embryo and endometrial models. This review examines the underpinning scientific discoveries that have led to the development of this rapidly expanding area of research, and how three-dimensional embryo models could be employed in advancing assisted reproductive technologies and understanding implantation failure. Importantly, we also discuss the ethical and legal implications and explore various governance models that have been proposed to foster responsibility and innovation in this area of research. Given the heightened interest in the scientific community on this topic, we finish on the question of how and when to involve the public in the development of this technology and its regulation. Full article

Background and Clinical Significance: Evaluating wide complex rhythms in patients with permanent pacemakers can be a diagnostic challenge, particularly when the rhythm is irregular. While pacemaker-mediated rhythms are typically regular and predictable, the appearance of wide complex irregular rhythms raises concerns ranging from lead malfunction to life-threatening arrhythmias, such as ventricular tachycardia. Understanding the interplay between intrinsic cardiac activity and device function is crucial for timely and accurate diagnosis in this increasingly common clinical scenario. Case presentation: We report on a 74-year-old female with a VVI pacemaker implanted for binodal disease, who presented with intermittent palpitations and an irregular rhythm. The patient has a recent history of falling on her right shoulder, which is also the site of the device implantation. We used a clinical step-by-step approach to rule out pacemaker malfunction and to establish the need for an unscheduled device interrogation. Conclusions: This case presentation highlights the important role of clinical reasoning and the approach to such a patient, especially when a key method of pacemaker evaluation, such as device interrogation, is not readily available. Full article

Fruit yield and quality improvement are challenges for researchers and farmers. This study reveals that the main fruit traits of blueberry (Vaccinium ashei ‘Bluegem’) were significantly improved after hydrogen (H₂)-based irrigation, assessed by the increased single fruit weight (14.59 ± 6.66%) and fruit equatorial diameter (4.19 ± 2.39%), decreased titratable acidity, increased solid–acid and sugar–acid ratios. The enhancement of fruit quality was confirmed by the increased total volatiles, vitamin C contents, and antioxidant capacity. Using weighted protein co-expression network analysis (WPCNA), proteomic interrogation revealed that serine carboxypeptidase-like proteins I/II (SCPLI/II), ADP ribosylation factor 1/2 (ARF1/2), and UDP-glucosyltransferase 85A (UGT85A) might be functionally associated with the increased fruit weight and size driven by H₂. Reduced organic acid accumulation was caused by the regulation of the specific enzymes involved in sucrose metabolism (e.g., α-amylase, endoglucanase, β-glucosidase, etc.). H₂ regulation of fatty acid degradation (e.g., acyl CoA oxidase 1 (ACX1), acetyl CoA acyltransferase 1 (ACAA1), etc.) and phenylpropanoid metabolism were used to explain the improved fruit aroma and anthocyanin accumulation. Meanwhile, the upregulated heat shock protein 20/70 matched with the enhanced antioxidant activity. Together, this study provides a novel approach for yield and quality improvement in horticultural crops. Full article

The signal-processing architecture of passive surface acoustic wave (SAW) sensors presents significant implementation challenges due to its radar-like operational principle and the inherent complexity of discrete component-based hardware design. While System-in-Package (SiP) has demonstrated remarkable success in miniaturizing electronic systems for smartphones, automotive electronics, and IoT applications, its potential for revolutionizing SAW sensor interrogator design remains underexplored. This paper presents a novel architecture that synergistically combines time-domain ADC design with SiP-based miniaturization to achieve unprecedented simplification of SAW sensor readout systems. The proposed time-domain ADC incorporates an innovative delay chain calibration methodology that integrates physical unclonable function (PUF) principles during time-to-digital converter (TDC) characterization, enabling the simultaneous generation of unique system IDs. The experimental results demonstrate that the integrated security mechanism provides variable-length bit entropy for device authentication, and has a reliability of 97.56 and uniqueness of 49.43, with 53.28 uniformity, effectively addressing vulnerability concerns in distributed sensor networks. The proposed SiP is especially suitable for space-constrained IoT applications requiring robust physical-layer security. This work advances the state-of-the-art wireless sensor interfaces by demonstrating how time-domain signal processing and advanced packaging technologies can be co-optimized to address performance and security challenges in next-generation sensor systems. Full article

Measuring pH is a critical parameter in environmental monitoring, biomedical diagnostics, food safety, and industrial processes. Optical fiber sensors have proven highly effective for pH detection due to their exceptional sensitivity, rapid response, and resistance to electromagnetic interference, making them well suited for real-time monitoring. This review offers a comprehensive analysis of recent advances in optical fiber-based pH sensors, covering key techniques such as fluorescence-based, absorbance-based, evanescent wave, and interferometric methods. Innovations in Fiber Bragg Grating and Surface Plasmon Resonance technologies are also examined. The discussion extends to the impact of pH-sensitive coatings—ranging from nanomaterials and polymeric films to graphene-based compounds—on enhancing sensor performance. Recent advancements have also enabled automation in data analysis and improvements in remote sensing capabilities. The review further compares the economic viability of optical fiber sensors with traditional electrochemical methods, while acknowledging persistent issues such as temperature cross-sensitivity, long-term stability, and fabrication costs. Overall, recent developments have broadened the functionality and application scope of these sensors by improving efficiency, accuracy, and scalability. Future research directions are outlined, including advanced optical interrogation techniques, such as Addressed Fiber Bragg Structures (AFBSs), microwave photonic integration, and optimized material selection. These approaches aim to enhance performance, reduce costs, and enable the broader adoption of optical fiber pH sensors. Full article

Evolving technologies available to clinical laboratories and laboratory-related updates to clinical guidelines both drive the need for clinical laboratories to keep their test menu updated and in line with current technological and clinical developments. Our laboratory has developed a targeted Illumina-based amplicon next-generation sequencing (NGS) assay to interrogate the hsp65 and erm(41) genes of Mycobacterium spp. for the purposes of providing species-level ± subspecies-level identification of Mycobacterium spp. organisms in clinical samples and genotypic predictions for inducible macrolide resistance (in the case of M. abscessus complex members). The developed assay demonstrated 100% sensitivity and specificity for M. tuberculosis and M. abscessus complex cultured organisms, 98% ID overall concordance relative to the available reference identification, and a nearly 60% “rescue” rate for primary samples that could not be identified using our previous method. There was 94.6% concordance between genotypic and phenotypic results for inducible macrolide resistance. The developed assay was successfully implemented in our clinical laboratory and has been accredited for clinical use. Full article

This article reports on the interrogation of fiber Bragg grating (FBG)-based sensors that have been multiplexed in a ladder topology. In each line of this topology, FBGs with different wavelengths are connected. In addition, delay fibers have been inserted between each line to enable reflections from different lines to be distinguished. Seven FBGs are interrogated simultaneously by applying time- and wavelength-division multiplexing techniques. To improve the signal-to-noise ratio of the weak reflected signals, the heterodyne detection technique is applied. Through the simulation of three different failure cases, we evaluate the fault detection capability of our method. Full article

Extensive attention has been given to children’s play spaces in public environments. Still, there exists a research need to devise a more comprehensive and structured design framework for space design addressing more comprehensive and structured activity modeling capabilities. The Context-Based Activity Modeling (CBAM) has been proposed as a framework for service design where activities are represented by elements like action verb, actors, object, tool, and contexts, where context is further represented by goal, relevant structure, physical, and psychological contexts. In this paper, children’s play activities such as throw, run, chase, hide, seek, and seize as observed in a community courtyard setting have been represented and interrogated using the CBAM method. Then, six specific design strategies have been derived for enhancing children’s play space design. As demonstrated in this way, CBAM is proposed as a framework for activity-centered space design for child playground. Experiential sustainability of children’s play activities are supported by play space design fully addressing detailed context elements of CBAM. Full article

Background/Objectives: SCCOHT is an aggressive and often fatal cancer that belongs to the ~20% of cancers defined by mutations to subunits of the SWI/SNF chromatin remodeling complex. In SCCOHT, mutations to the SMARCA4 gene, which encodes the SWI/SNF ATPase BRG1, are sufficient to impair SWI/SNF function. This single genetic lesion leads to a cascade of events that promote tumorigenesis, some of which may involve the intersection of SWI/SNF with oncogenic pathways such as those regulated by the MYC oncogene. In SCCOHT tumors and other cancers marked by SWI/SNF subunit mutation, MYC target genes are recurrently activated, pointing to a relationship between SWI/SNF and MYC that has yet to be fully explored. Methods: In this study, we investigate the contribution of MYC to SCCOHT biology by performing a combination of chromatin binding and transcriptome assays in genetically engineered SCCOHT cell lines, with subsequent validation using patient tumor expression data. Results: We find that MYC binds to thousands of active promoters in the BIN-67 SCCOHT cell line and that the depletion of MYC results in a broad range of gene expression changes with a notable effect on the expression of genes related to DNA repair. We uncover an MYC-regulated DNA repair gene expression program in BIN-67 cells that is antagonized by BRG1 reintroduction. Finally, we identify a DNA repair gene signature that is upregulated in SCCOHT tumors and in tumors defined by loss of the SWI/SNF subunit SNF5. Conclusions: Collectively, these data implicate MYC as a robust regulator of DNA repair gene expression in SCCOHT and lay a foundation for future studies focused on interrogating the relationship between BRG1 and MYC. Full article

This article reports on the interrogation of fiber Bragg grating (FBG)-based sensors that are multiplexed in an asymmetric tree topology. At each stage in the topology, FBGs are connected at one output port of a 50:50 coupler with fibers of different lengths. This asymmetric structure allows the simultaneous interrogation of long-distance and parallel sensor networks to be realized. Time- and wavelength-division multiplexing techniques are used to multiplex the FBGs. Using the heterodyne detection technique, high-sensitivity detection of reflection signals that have been weakened by losses induced by a round-trip transmission through the couplers and long-distance propagation is performed. Quasi-distributed FBGs are interrogated simultaneously, over distances ranging from 15 m to 80 km. Full article

Exposure to chronic stress creates vulnerability to drug misuse and presents a barrier to sustained recovery for many individuals experiencing substance use disorders (SUDs). Preclinical literature demonstrates that stress modulates psychostimulant intake and seeking, yet there are wide gaps in our understanding of the specific mechanisms by which stress promotes brain changes that may govern addiction-related behaviors. Recent data suggest that microglia, innate immune cells in the central nervous system, are highly responsive to chronic stressors, and several mechanistic links have been explored highlighting the critical role microglia play in stress-related brain adaptation. Importantly, psychostimulants may engage similar microglial machinery, which opens the door for investigation into how microglia may be involved in shaping motivation for psychostimulants, especially in the context of stress exposure. The aims of this review are threefold: 1. Offer a brief overview of microglial biology in the adult brain. 2. Review current methods of interrogating microglial function with a focus on morphometric analyses. 3. Highlight preclinical research describing how microglia contribute to brain changes following chronic stress and/or psychostimulant exposure. Ultimately, this review serves to prime investigators studying the intersection of stress and SUDs to consider the relevant impacts of microglial actions. Full article

Background/Objectives: T1-weighted magnetic resonance imaging (MRI) and the Montreal Cognitive Assessment are standard, efficient, and swift clinical and research tools used when interrogating cognitively impairing (CI) conditions, such as Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). However, the associations between gross cognitive impairment (CI) as compared to domain-specific functioning and underlying neuroanatomical correlates have not been investigated among individuals with early-onset Mild Cognitive Impairment (MCI) or Alzheimer’s disease (EOAD), who can benefit greatly from early diagnosis and intervention strategies. Methods: We analyzed T1-weighted MRIs and Montreal Cognitive Assessment (MoCA) scores from the ADNI database in individuals < 65 years old who were either cognitively normal (CN) or had MCI or EOAD. Gray matter volume (GMV) was estimated in voxel-based morphometry (VBM) and ROI-parcellation general linear models examining associations with individual MoCA scores after adjusting for demographic covariates. Results: Results from 120 subjects (44 CN, 62 MCI, and 14 EOAD), identified significant global but also individually distinct domain-specific topographical signatures spanning the temporal, parietal, limbic, occipital, frontal lobes, and cingulate gyri. Conclusions: The results highlight neural correlates of cognitive functioning in a sample of young patients representative of the AD continuum, in addition to studying the structural MRI and functional cognitive difference. Full article

Background: Administration of PARP inhibitors against breast and ovarian cancers with BRCA1 and BRCA2 mutations has shown clinical benefits in patients. However, these agents are also toxic and have a narrow therapeutic index. Objectives: In this work, we aimed to identify membrane proteins that are specifically upregulated in these cancers. Methods: We interrogated public datasets to analyze genes upregulated or downregulated when these mutations were present, compared with wild-type cancers. Surface protein expression and functional annotation analyses were also performed. Results: In breast cancer, we identified 11 upregulated and 44 downregulated transcripts in BRCA1-mut, while 10 upregulated and 57 downregulated transcripts were identified in BRCA2-mut cancers. In ovarian cancer, 79 transcripts were upregulated and 123 were downregulated in BRCA1-mut cancers, while five were upregulated and seven were downregulated in BRCA2-mut tumors. Regarding the biological function related to these genes, in BRCA1-mutated ovarian cancers, the main functions of upregulated genes included MHC assembly or regulation of the interferon gamma pathway; in BRCA2-mut ovarian cancers, regulation of phosphorylation and signaling; in BRCA1-mut breast cancers, cell damage repair and angiogenesis; and finally, in BRCA2-mut breast cancers, cytokine production and T-cell migration. Genes expressed in the surface membrane or extracellular matrix and related to patient outcomes included B3GNT7 and CTSV in BRCA2-mut breast cancers, exhibiting detrimental prognoses. CD6, CXCL9, and CXCL13 were associated with favorable outcomes in BRCA1-mutant ovarian cancers. The last three genes were also correlated with the infiltration of effector T cells and dendritic cells in ovarian tumors. Conclusions: In summary, we identified deregulated candidate genes that could be used as therapeutic targets. Full article

This article explores the potentialities of “translanguages” as a lens for interpreting transnational women authors whose writing navigates multiple languages. By “translanguages”, we refer to the generation of a collage that results either from the writer’s alternation of various languages within the same work or from their concoction of a language of their own that reappropriates the contents and expressions of various source languages. We will illustrate our tenets by exploring case studies from Assia Djebar and Maxime Garcia Diaz. By resorting to feminist close-reading methodology, we intend to interrogate the possibilities of interpretation (and their limits) from a socially situated position. This, in turn, involves our approach to how the authors’ multiple languages interact and operate upon one another to create meaning and, last but not least, our analysis of the extent to which the transnational and translingual position of these authors shapes our own situated interpretations of the texts as readers. Full article