Search Results (525)

Background: Chemotherapy, targeted therapy and radiotherapy are the cornerstones of cancer treatment. However, therapeutic resistance—not only to these classic modalities but also to novel therapeutics like immune checkpoint inhibitors (ICIs) and antibody-drug conjugates—remains a major hurdle. Resistance significantly limits efficacy and increases recurrence rates. A deep understanding of the molecular mechanisms driving this resistance is critical for developing personalized therapeutic strategies and improving patient outcomes. Recent Advances: Patient-derived cancer organoids have emerged as a powerful preclinical platform that faithfully recapitulates the genetic, phenotypic, and histological characteristics of original tumors. Consequently, PDOs are being widely utilized to evaluate drug responses, investigate resistance mechanisms, and discover novel therapeutic targets for a range of therapies. Limitations: While organoid models have been instrumental in studying resistance, significant limitations persist. First, standard organoid-only models lack key tumor microenvironment components, such as immune cells, limiting immunotherapy research. Second, there is a significant lack of research on acquired resistance, particularly in lung cancer. This gap is largely driven by the clinical infeasibility of rebiopsy in patients with progressive diseases. Third, the absence of standardized protocols for generating and validating resistance models hinders reproducibility and complicates clinical translation. Conclusions: This review summarizes recent advances in using organoid models to study resistance to chemotherapy, radiotherapy, and novel therapeutics (ICIs and ADCs). We emphasize the critical need for standardization in resistance organoid research. We also propose future directions to overcome existing challenges, including the integration of co-culture systems (to include the TME) and advanced technologies (e.g., scRNA-seq, Spatial Transcriptomics). Our specific focus is on advancing lung cancer resistance modeling to enable functional precision medicine. Full article

Methamphetamine (MA) abuse has emerged as a multisystem insult driving cardiovascular and neurovascular consequences. Methamphetamine-associated cardiomyopathy (MACM) remains an underrecognized cause of cardioembolic stroke through left ventricular thrombus (LVT) formation. MA-induced gut dysbiosis and enteric neural disruption exacerbate systemic inflammation and autonomic imbalance, resulting in broader dysregulation of the brain–heart–gut axis. This study aimed to synthesize contemporary evidence on chronic MA exposure and its role in LVT formation, stroke pathogenesis, diagnostic approaches, and anticoagulation management. We conducted a focused narrative review of PubMed- and Scopus-indexed literature (1990–2025) addressing cardiovascular, neurovascular, and gut-mediated consequences of chronic MA exposure. Observational cohorts and case reports were integrated to characterize pathophysiology, imaging approaches, and therapeutic considerations, supplemented by a representative clinical case. Chronic MA exposure mediates persistent catecholamine excess, myocardial fibrosis, ventricular dysfunction, and a prothrombotic milieu. Gut dysbiosis-related inflammation and autonomic dysregulation further promote intracardiac stasis. Affected individuals are typically young men with severe systolic dysfunction (left ventricular ejection fraction 20–30%), with a substantial proportion demonstrating apical or mural LVT on systematic imaging. Case-level evidence highlights a broader systemic embolic burden, involving the limbs, kidneys, and aorta. Echocardiography remains the first-line screening method, while cardiac CT and MRI offer greater sensitivity for thrombus detection. Anticoagulation is challenged by bleeding risk, inconsistent adherence, and the absence of standardized protocols. MACM represents a critical and underrecognized etiology of cardioembolic stroke in young adults. Early recognition of brain–heart–gut axis disruption, systematic cardiac imaging, and individualized anticoagulation are crucial for preventing emboli. Prospective registries and standardized imaging-guided treatment strategies are needed to improve outcomes in this high-risk population. Full article

The deparser stage in the Protocol-Independent Switch Architecture (PISA) is often overshadowed by parser and match-action optimizations. Yet, it remains a critical performance bottleneck in P4-programmable FPGA data planes. Challenges associated with the deparser stem from dynamic header layouts, variable emission orders, and alignment constraints, which often necessitate resource-intensive designs, such as wide, dynamic crossbar routing. While compile-time specialization techniques can reduce logic usage, they sacrifice runtime adaptability: any change to the protocol graph, including adding, removing, or reordering headers, requires full hardware resynthesis and re-implementation, limiting their practicality for evolving or multi-tenant workloads. This work presents a unified FPGA-targeted deparser architecture that merges templated and overlay concepts within a hardware–software co-design framework. At design time, template parameters define upper bounds on protocol complexity, enabling resource-efficient synthesis tailored to specific workloads. Within these bounds, runtime reconfiguration is supported through overlay control tables derived from static deparser DAG analysis, which capture the per-path emission order, header alignments, and offsets. These tables drive protocol-agnostic, chunk-based emission blocks that eliminate the overhead of crossbar interconnects, thereby significantly reducing complexity and resource usage. The proposed design sustains high throughput while preserving the flexibility needed for in-field updates and long-term protocol evolution. Full article

According to Sigmund Freud, the unconscious is full of contradictions (wild emotional impulses, baseless fears, and repressive forces) but it is also a control mechanism. It is no wonder that digital platforms—requiring uniformity, reliable protocols, secure transmissions and proprietary algorithms as well as an enormous database about human desire and impulses—would gravitate toward a model of control, or more specifically, the ideal of automating impulsive actions and reactions. Similar to the Freudian unconscious, digital platforms and networks are infamously black-boxed, meaning their operations (inner workings) are made invisible to the average user, including information about them. Yet, the digital unconscious also seems to perfect and promote this as an automatic destructive force (a death drive fed by extraction, consumption and a will to endless profit) that is incommensurate with life on the planet. Using the recent pleas by the Tuvaluan Minister of Justice, Communication, and Foreign Affairs (Simon Kofe) to the United Nations Convention on Climate Change, this article will argue that denial has replaced repression as the key mechanism of the digital unconscious, allowing twenty-first century media to offer itself as pharmakon (both poison and a remedy or at least a distraction) to those twenty-first century crises that nineteenth-, twentieth-, and twenty-first-century media continue to advance. Full article

Background: Lung cancer (LC) is a leading cause of cancer mortality worldwide. While radiotherapy (RT) has been a lasting cornerstone of LC management, there are concerns due to tumor radioresistance and unintended damage to surrounding healthy tissue. Ferroptosis is a recently described mechanism of programmed cell death which has potential to serve as a complementary adjunct to facilitate RT-based LC treatment. Objectives: This review is a comprehensive overview of ferroptosis in the broader context of synergism with RT for LC. Summary: Ferroptosis is essentially driven by intracellular iron overload, which drives the formation of reactive oxygen species, ultimately resulting in membrane instability and cell death. LC lines have been shown to exhibit a heterogeneous mix of pro- and anti-ferroptotic changes. RT shows promise as a potential ferroptosis inducer, especially when complemented with pharmacologic agents such as erastin. Conclusions: Ferroptosis represents a promising modern adjunct to a traditional therapeutic strategy. Future work should focus on rigorous dosage standards to avoid unintended toxicity, repurposing of currently available drugs into ferroptosis inducers, and establishment of safety protocols to begin the pathway towards clinical studies. Full article

Carbapenem-resistant Gram-negative (CR-GN) pathogens pose a critical threat to patient outcomes in high-dependency and intensive care environments. This study aimed to delineate species prevalence, antimicrobial resistance phenotypes, carbapenemase genotypes, and clinical–environmental transmission dynamics across critical-care units. Cross-sectional surveillance was conducted in six ICUs and HDUs of a tertiary-care hospital in Karachi, Pakistan. We identified predominant species, quantified resistance patterns, and detected carbapenemase genes using PCR, exclusively on meropenem-resistant isolates. Network analysis highlighted high-centrality contamination hubs across ICUs and HDUs. Acinetobacter baumannii (36.7%) and Klebsiella pneumoniae (33.9%) were predominant, with 58% originating from environmental reservoirs. Meropenem non-susceptibility was 55% (60/109), and colistin non-susceptibility was 68.6% (35/51), based on standardized CLSI testing. ICU isolates exhibited significantly higher meropenem resistance than HDU isolates. Among carbapenem-resistant isolates, blaOXA-48-like (52.8%) and blaNDM (25%) were most prevalent. Network topology revealed ICU1 and HDU2 as high-centrality transmission nodes. These findings highlight pervasive environmental colonization and heightened antimicrobial pressure in ICUs, necessitating reinforced decontamination protocols, antimicrobial stewardship, and continuous molecular surveillance. This study provides the first integrated clinical–environmental surveillance of MDR Gram-negative bacteria in Pakistan, revealing that over half of isolates originated from surfaces and that network-based mapping can pinpoint contamination hubs driving hospital transmission. Full article

Background/Objectives: Temperature control after cardiac arrest remains a recommended component of post-cardiac arrest care, yet substantial practice variability persists. Conflicting evidence regarding optimal temperature targets and mixed interpretations of recent trials, such as TTM2, may contribute to inconsistent bedside implementation. Understanding physician knowledge, attitudes, and practice patterns is essential for aligning post-cardiac arrest management with evolving evidence. This study aimed to characterize international physician perceptions of temperature control, patterns of use, understanding of neurologic injury, and the influence of emerging literature. Methods: A 39-item web-based survey was developed through iterative expert review and pilot testing and disseminated to members of critical care, neurology, and emergency medicine societies between September 2021 and January 2022. The instrument assessed demographics, temperature control practices, interpretation of new literature, and post-cardiac arrest management. Responses were analyzed using descriptive statistics in R Studio, with proportions reported for categorical variables and mode responses for ranked questions. Results: Among 501 respondents, 471 (94%) completed the survey. Most were attending-level physicians (73%), primarily practicing intensive care medicine (75%), and based in academic centers (60%). Targeted temperature management (TTM) was commonly initiated by the admitting intensivist (66%), most often because guidelines recommended it (67%). The most influential factors driving initiation were institutional protocols (21%), perceived neurologic prognosis (17%), and arrest etiology (14%). The most frequently selected temperature target was 36 °C (44%). Awareness of the TTM2 trial was high (70%), though only 31% reported altering their practice in response. Neurologists were more likely to individualize temperature targets and select lower temperatures, while physicians caring for higher cardiac arrest volumes also favored lower targets. Community clinicians more commonly selected lower temperature targets compared with those in academic settings. Conclusions: Substantial heterogeneity exists in the practice and rationale for temperature control after cardiac arrest. Physician specialty, cardiac arrest volume, and local practice environment influence the temperature target selection and attitudes toward emerging evidence. Despite awareness of new data, institutional protocols remain the dominant factor guiding implementation. Standardized, evidence-based institutional pathways may help reduce practice variability and promote consistent post-cardiac arrest care. Full article

Background: Self-medication with leftover antibiotics (SMLA) drives antimicrobial resistance (AMR), particularly in developing countries. This study examined knowledge–practice gaps regarding antibiotic use and handling among individuals with prior SMLA across seven developing countries. Methods: A cross-sectional study (February 2023–February 2024) included 3191 adults from Bangladesh, Brazil, Egypt, India, Jordan, Lebanon, and Serbia who reported previous leftover antibiotic use. The questionnaires assessed knowledge of antibiotic use (15 items), resistance (12 items), and SMLA risks (15 items). Storage and disposal practices were evaluated using dichotomized correct/incorrect measures. Results: Participants demonstrated above-average knowledge scores as follows: antibiotic use (54.4 ± 8.4), resistance (43.3 ± 6.1), and SMLA risks (58.4 ± 10.3). However, substantial practice gaps emerged. Only 21.9% properly disposed of leftover antibiotics, while 47.0% used household garbage. For storage, 55.1% used appropriate methods, but 32.6% stored antibiotics inappropriately, and 12.8% lacked protocols. Serbian participants showed the highest SMLA risk knowledge (64.3 ± 10.6), Bangladeshi participants the lowest (52.0 ± 8.5, p < 0.001). Women had superior knowledge (59.6 ± 10.4 versus 56.5 ± 9.8, p < 0.001) and storage practices (56.6% versus 52.7%, p = 0.031). Paradoxically, higher AMR knowledge was associated with poorer disposal practices (OR = 0.97, p < 0.001). Conclusions: Despite extensive theoretical knowledge, unsafe medication practices persist, revealing a critical knowledge–practice gap. Our findings challenge education-focused AMR approaches, suggesting cognitive awareness alone cannot drive behavioral change. Effective interventions must address structural barriers, cultural factors, and individual health beliefs beyond traditional knowledge-deficit models. Full article

Background: Adolescence is marked by heightened reward sensitivity and incomplete maturation of cognitive control, creating conditions that favor engagement in risky behaviors. Traditional self-report methods often overlook the fast, automatic processes—such as attentional biases, approach–avoidance tendencies, and associative schemas—that shape adolescent decision-making in real time. Aims: This Perspective aims to synthesize recent (2018–2025) advances in the study of implicit measures relevant to adolescent risk behaviors, evaluate their predictive value beyond explicit measures, and identify translational pathways for prevention and early intervention. Methods: A narrative synthesis was conducted, integrating evidence from eye-tracking, drift-diffusion modeling, approach–avoidance tasks, single-category implicit association tests, ecological momentary assessment (EMA), and passive digital phenotyping. Emphasis was placed on multi-method phenotyping pipelines and on studies validating these tools in adolescent populations. Results: Implicit indices demonstrated incremental predictive validity for risky behaviors such as substance use, hazardous driving, and problematic digital engagement, outperforming self-reports in detecting context-dependent and state-specific risk patterns. Integrative protocols combining laboratory-based measures with EMA and passive sensing captured the influence of peer presence, affective state, and opportunity structures on decision-making. Mobile-based interventions, including approach bias modification and attention bias training, proved feasible, scalable, and sensitive to change in implicit outcomes. Acoustic biomarkers further enhanced low-burden state monitoring. Conclusions: Implicit measures provide a mechanistic, intervention-sensitive complement to explicit screening, enabling targeted, context-aware prevention strategies in adolescents. Future priorities include multi-site validations, school-based implementation trials, and the use of implicit parameter change as a primary endpoint in prevention research. Full article

The increasing inclusion of robots in social areas requires continuous improvement of behavioral strategies that robots must follow. Although behavioral strategies mainly focus on operational efficiency, other aspects should be considered to provide a reliable interaction in terms of sociability (e.g., methods for detection and interpretation of human behaviors, how and where human–robot interaction is performed, and participant evaluation of robot behavior). This scoping review aims to answer seven research questions related to robotic motion in socially aware navigation, considering some aspects such as: type of robots used, characteristics, and type of sensors used to detect human behavioral cues, type of environment, and situations. Articles were collected on the ACM Digital Library, Emerald Insight, IEEE Xplore, ScienceDirect, MDPI, and SpringerLink databases. The PRISMA-ScR protocol was used to conduct the searches. Selected articles met the following inclusion criteria. They: (1) were published between January 2018 and August 2025, (2) were written in English, (3) were published in journals or conference proceedings, (4) focused on social robots, (5) addressed Socially Aware Navigation (SAN), and (6) involved the participation of volunteers in experiments. As a result, 22 studies were included; 77.27% of them employed mobile wheeled robots. Platforms using differential and omnidirectional drive systems were each used in 36.36% of the articles. 50% of the studies used a functional robot appearance, in contrast to bio-inspired appearances used in 31.80% of the cases. Among the frequency of sensors used to collect data from participants, vision-based technologies were the most used (with monocular cameras and 3D-vision systems each reported in 7 articles). Processing was mainly performed on board (50%) of the robot. A total of 59.1% of the studies were performed in real-world environments rather than simulations (36.36%), and a few studies were performed in hybrid environments (4.54%). Robot interactive behaviors were identified in different experiments: physical behaviors were present in all experiments. A few studies employed visual behaviors (2 times). In just over half of the studies (13 studies), participants were asked to provide post-experiment feedback. Full article

Exosome-derived microRNAs (miRNAs) have been proposed as minimally invasive biomarkers for laryngeal squamous- cell carcinoma (LSCC). Because oral and maxillofacial surgeons are integral to head-and-neck oncologic and reconstructive pathways, such liquid-biopsy signals could support perioperative decision-making (selection for organ-preserving surgery), margin surveillance, and reconstructive planning. We conducted a preregistered, protocol-driven search of PubMed/MEDLINE, Web of Science, and Scopus from inception to 1 June 2025. Given the very small number of clinically comparable diagnostic studies, discordant index tests/thresholds, and high heterogeneity, we did not perform quantitative pooling or publication-bias testing. Instead, we undertook a narrative synthesis and constructed an evidence map; risk of bias tools (QUADAS-2; ROBINS-I) were applied descriptively to inform qualitative confidence. Nine studies were formally analysed based on eligibility to the study topic. Two serum-based case–control investigations (111 LSCC, 80 controls) reported areas under the ROC curve of 0.876 (miR-21 + HOTAIR) and 0.797 (miR-941), with corresponding sensitivities of 94% and 82%. Seven mechanistic papers showed that vesicular cargos—including miR-1246, circPVT1, and LINC02191—drive STAT3-dependent M2 polarisation, NOTCH1-mediated stemness, Rap1b-VEGFR2 angiogenesis, and glycolytic re-programming, producing 1.6–2.6-fold increases in invasion, tube formation, or xenograft growth. Only three studies fulfilled MISEV-2018 characterisation criteria, and none incorporated external validation. This narrative review and evidence map identifies promising but preliminary diagnostic signals and biologically plausible mechanisms for exosomal miRNAs in LSCC; however, the evidence is sparse, single-region, methodologically inconsistent, and at high risk of bias. Findings do not support clinical implementation at this stage. Priorities include harmonised EV workflows, prespecified thresholds, and prospective, multi-centre validation. Full article

This paper presents a detailed experimental evaluation of a newly developed diesel fuel additive, specifically formulated to enhance the energy efficiency and emission characteristics of internal combustion engine (ICE) vehicles, with particular emphasis on its applicability to aging vehicle fleets. Diesel engines are known for producing significant amounts of harmful emissions, necessitating the development of effective mitigation strategies. One such approach involves the use of fuel additives. The additive under investigation is a proprietary formulation containing 1-(N,N-bis(2-ethylhexyl)aminomethyl)-1,2,4-triazole and other compounds. To the best of our knowledge, this specific additive composition has not yet been tested or reported in the existing scientific literature. To evaluate the real-world contribution of such additives, a comprehensive set of controlled measurements was conducted in a certified chassis dynamometer laboratory, including an exhaust gas analyser and supplementary diagnostic equipment. The testing protocol comprised repeated measurement cycles under identical driving conditions, both without and with the additive. Exhaust gas concentrations of CO₂, CO, and NOx were continuously monitored. Simultaneously, fuel consumption and engine performance were tracked over a cumulative driving distance of 2000 km. The results indicate measurable improvements across all monitored domains. CO₂ emissions decreased by 4.57%, CO by 14.29%, and NOx by 3.12%. Fuel consumption was reduced by 4.79%, while engine responsiveness and power delivery showed moderate but consistent enhancements. These improvements are attributed to more complete combustion and an increased cetane number enabled by the additive’s chemical structure. The findings support the adoption of advanced additive technologies as part of transitional strategies towards low-emission transportation systems. Full article

The validation of sensor systems, particularly lidar, is crucial in advancing autonomous vehicle technology. Despite their robust perception capabilities, certain weather conditions and object characteristics can challenge detection performance, leading to potential safety concerns. This study investigates corner cases where object detection may fail due to physical constraints. Utilizing virtual testing environments like Carla and ROS2, simulations analyze how reflection characteristics affect detectability by implementing weather models into a real-time simulation. Results reveal challenges in detecting black objects compared to white ones, particularly in adverse weather conditions. A time-sensitive corner case was analyzed, revealing that while bad weather and wet roads restrict the safe driving speed range, complete deactivation of the driving assistant at certain speeds may be unnecessary despite current manufacturer practices. The study underscores the importance of considering such factors in future safety protocols to mitigate accidents and ensure reliable autonomous driving systems. Full article

The study presents a systematic review of the state of the art on Information Technology (IT) governance research. Following the PRISMA 2020 protocol and drawing on Scopus and Web of Science, covering publications from 1999 to May 2025, 380 relevant articles were identified, analysed and categorised. A bibliometric analysis supported by tools such as VOSviewer and SciMaT mapped the principal thematic strands, influential authors and institutions, and revealed research gaps. The results indicate a consolidated field in which resource allocation, industrial management, strategic alignment and board-level IT governance operate as driving themes, while information management, the configuration of the IT function and the regulatory nexus between laws and information security remain emerging areas. The conclusions emphasise the theoretical implications of clarifying how IT governance shapes IT investment and initiative prioritisation, sectoral configurations and strategic alignment, and the practical implications of using these mechanisms to design and refine governance structures, processes and metrics in regulated organisations so that value creation risk control and accountability are more explicitly aligned. Full article

The high failure rate of anticancer drugs in clinical trials highlights the need for preclinical models that accurately reproduce the structural, biochemical, and mechanical complexity of human tumors. Conventional two-dimensional cultures and animal models often lack the physiological complexity required to predict clinical outcomes, driving the development of three-dimensional systems that better emulate the tumor microenvironment. Among these, microfluidic-based spheroid models have emerged as powerful tools for cancer research and drug screening. By integrating 3D spheroids with microfluidics, these platforms allow precise control of nutrient flow, oxygen gradients, shear stress, and interstitial pressure, while supporting co-culture with stromal, immune, and endothelial cells. Such systems enable the investigation of drug response, angiogenesis, metastasis, and immune interactions under dynamic and physiologically relevant conditions. This review summarizes recent advances in microfluidic spheroid models for cancer, covering both carcinomas and sarcomas, with an emphasis on device design, biomaterial integration, and translational validation. Key challenges remain, including technical complexity, scalability constraints, and the absence of standardized protocols. Overall, the merger of microfluidic technology with 3D spheroid culture provides a promising pathway toward predictive, ethical, and personalized preclinical testing, bridging the gap between in vitro modeling and clinical oncology. Full article