Search Results (1,418)

The biopharmaceutical industry is undergoing a fundamental transformation from traditional batch manufacturing to continuous manufacturing (CM) for recombinant drugs and biosimilars, driven by regulatory support through the International Council for Harmonization (ICH) Q13 guidance and compelling economic advantages. This comprehensive review examines the technical, economic, and regulatory aspects of implementing continuous manufacturing specifically for recombinant protein production and biosimilar development, synthesizing validated data from peer-reviewed research, regulatory sources, and global implementation case studies. The analysis demonstrates that continuous manufacturing offers substantial benefits, including a reduced equipment footprint of up to 70%, a 3- to 5-fold increase in volumetric productivity, enhanced product quality consistency, and facility cost reductions of 30–50% compared to traditional batch processes. Leading biomanufacturers across North America, Europe, and the Asia–Pacific region are successfully integrating perfusion upstream processes with connected downstream bioprocesses, enabling the fully end-to-end continuous manufacture of biopharmaceuticals with demonstrated commercial viability. The regulatory framework has been comprehensively established through ICH Q13 guidance and region-specific implementations across the FDA, EMA, PMDA, and emerging market authorities. This review provides a critical analysis of advanced technologies, including single-use perfusion bioreactors, continuous chromatography systems, real-time process analytical technology, and Industry 4.0 integration strategies. The economic modeling presents favorable return-on-investment profiles, accompanied by a detailed analysis of global market dynamics, regional implementation patterns, and supply chain integration opportunities. Full article

The integration of artificial intelligence (AI) and advanced digital workflows is revolutionising full-arch implant dentistry, particularly for geriatric patients with edentulous and atrophic arches, for whom achieving both prosthetic passivity and optimal aesthetic outcomes is critical. This narrative review evaluates current challenges in intraoral scanning accuracy—such as scan distortion, angular deviation, and cross-arch misalignment—and presents how innovations like the Medit SmartX AI-guided workflow and the Scan Ladder system can significantly enhance precision in implant position registration. These technologies mitigate stitching errors by using real-time scan body recognition and auxiliary geometric references, yielding mean RMS trueness values as low as 11–13 µm, comparable to dedicated photogrammetry systems. AI-driven prosthetic design further aligns implant-supported restorations with facial symmetry and smile aesthetics, prioritising predictable midline and occlusal plane control. Early clinical data indicate that such tools can reduce prosthetic misfits to under 20 µm and lower complication rates related to passive fit, while shortening scan times by up to 30% compared to conventional workflows. This is especially valuable for elderly individuals who may not tolerate multiple lengthy adjustments. Additionally, emerging AI applications in design automation, scan validation, and patient-specific workflow adaptation continue to evolve, supporting more efficient and personalised digital prosthodontics. In summary, AI-enhanced scanning and prosthetic workflows do not merely meet functional demands but also elevate aesthetic standards in complex full-arch rehabilitations. The synergy of AI and digital dentistry presents a transformative opportunity to consistently deliver superior precision, passivity, and facial harmony for edentulous implant patients. Full article

Mitochondria, pivotal organelles in cellular metabolism and energy production, have emerged as critical players in the pathogenesis of cancer. This review outlines the progress in mitochondrial profiling through mass spectrometry-based metabolomics and its applications in cancer research. We provide unprecedented insights into the mitochondrial metabolic rewiring that fuels tumorigenesis, metastasis, and therapeutic resistance. The purpose of this review is to provide a comprehensive guide for the implementation of mitochondrial metabolomics, integrating advanced methodologies—including isolation, detection, and data integration—with insights into cancer-specific metabolic rewiring. We first summarize current methodologies for mitochondrial sample collection and pretreatment. Furthermore, we then discuss the recent advancements in mass spectrometry-based methodologies that facilitate the detailed profiling of mitochondrial metabolites, unveiling significant metabolic reprogramming associated with tumorigenesis. We emphasize how recent technological advancements have addressed longstanding challenges in the field and explore the role of mitochondrial metabolism-driven cancer development and progression for novel drug discovery and translational research applications in cancer. Collectively, this review delineates emerging opportunities for therapeutic discovery and aims to establish a foundation for future investigations into the therapeutic modulation of mitochondrial pathways in cancer, thereby paving the way for innovative diagnostic and therapeutic approaches targeting mitochondrial pathways. Full article

Locally advanced rectal cancer (LARC) remains a major clinical challenge due to its high risk of local recurrence and distant metastasis. Although total mesorectal excision (TME) has been established as the gold standard surgical approach, high recurrence rates associated with surgery alone have driven the development of multimodal preoperative strategies, such as radiotherapy and chemoradiotherapy. More recently, total neoadjuvant therapy (TNT)—which integrates systemic chemotherapy and radiotherapy prior to surgery—and non-operative management (NOM) for patients who achieve a clinical complete response (cCR) have further expanded treatment options. These advances aim not only to improve oncologic outcomes but also to enhance quality of life (QOL) by reducing long-term morbidity and preserving organ function. However, several unresolved issues persist, including the optimal sequencing of therapies, precise risk stratification, accurate evaluation of treatment response, and effective surveillance protocols for NOM. The advent of molecular biomarkers, next-generation sequencing, and artificial intelligence (AI) presents new opportunities for individualized treatment and more accurate prognostication. This narrative review provides a comprehensive overview of the current status of preoperative treatment for LARC, critically examines emerging strategies and their supporting evidence, and discusses future directions to optimize both oncological and patient-centered outcomes. By integrating clinical, molecular, and technological advances, the management of rectal cancer is moving toward truly personalized medicine. Full article

In this paper, we argue that what is sometimes at fault for the poor attendance and lack of engagement in schools observed from historically marginalized families is a missed opportunity to increase understanding or cultural relevance on the part of schools. In this paper, we use the construct of “counter stories” which has the potential to change the script on the instrumentalist demands of quantity versus quality in parent engagement. By providing examples of what we consider “quality” engagement techniques via the staff’s interpretation of their roles within one demographically rich early learning center, the strategies used to engage parents are documented. Counter-stories of practice show family-centrism as interpreted by school leaders. By describing one community context and its practices of building relationships with newcomer families, relationally driven parent engagement techniques are revealed. The authors highlight how inquiry-based methods surpass the generic approaches described in policy. When parent engagement “arises” from within parents’ motivations and informs authentic knowing (by teachers and school leaders), community systems are elevated. Professionals’ decisions about children and community groups that are informed by families’ knowledge are consequently meaningful and authentic. Full article

Multi-source fusion techniques have emerged as cutting-edge approaches for spatial precipitation estimation, yet they face persistent accuracy limitations, particularly under extreme conditions. Machine learning offers new opportunities to improve the precision of these estimates. To bridge this gap, we propose a hybrid artificial neural network–geographically weighted regression (ANN–GWR) model that synergizes event recognition and quantitative estimation. The ANN module dynamically identifies precipitation events through nonlinear pattern learning, while the GWR module captures location-specific relationships between multi-source data for calibrated rainfall quantification. Validated against 60-year historical data (1960–2020) from China’s Yongding River Basin, the model demonstrates superior performance through multi-criteria evaluation. Key results reveal the following: (1) the ANN-driven event detection achieves 10% higher accuracy than GWR, with a 15% enhancement for heavy precipitation events (>50 mm/day) during summer monsoons; (2) the integrated framework improves overall fusion accuracy by more than 10% compared to conventional GWR. This study advances precipitation estimation by introducing an artificial neural network into the event recognition period. Full article

The seasonal patterns of viral diseases in farm animals present significant challenges to global livestock productivity, with cold stress emerging as a potential modulator of host–pathogen interactions. This review synthesizes current knowledge on the expression dynamics of heat shock protein 70 (HSP70) in farm animals under cold-stress conditions and its potential roles as (1) a viral replication facilitator and (2) an immune response regulator. This review highlights cold-induced HSP70 overexpression in essential organs, as well as its effects on significant virus life cycles, such as porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and bovine viral diarrhea virus (BVDV), through processes like viral protein chaperoning, replication complex stabilization, and host defense modulation. By integrating insights from thermophysiology, virology, and immunology, we suggest that HSP70 serves as a crucial link between environmental stress and viral disease seasonality. We also discuss translational opportunities targeting HSP70 pathways to break the cycle of seasonal outbreaks, while addressing key knowledge gaps requiring further investigation. This article provides a framework for understanding climate-driven disease patterns and developing seasonally adjusted intervention strategies. Full article

Bamboo gene science has witnessed significant advancements over the past two decades, driven by breakthroughs in gene cloning, marker-assisted breeding, sequencing, gene transformation, and gene editing technologies. These developments have not only enhanced our understanding of bamboo’s genetic diversity and adaptability but also provided critical tools for its genetic improvement. Compared to other crops, bamboo faces unique challenges, including its long vegetative growth cycle, environmental dependency, and limited genetic transformation efficiency. Then, the launch of China’s “Bamboo as a Substitute for Plastic” initiative in 2022, supported by the International Bamboo and Rattan Organization, has opened new opportunities for bamboo gene science as well as for bamboo production systems. This policy framework has spurred research into bamboo genetic regulation, fiber-oriented recombination, and green separation technologies, aiming to develop sustainable alternatives to plastic. Future research directions include overcoming bamboo’s environmental limitations, improving genetic transformation efficiency, and deciphering the mechanisms behind its flowering. By addressing these challenges, bamboo genetic science can enhance its economic and ecological value, contributing to global sustainability goals and the “dual-carbon” strategy. Full article

The worldwide agriculture industry is facing increasing problems due to rapid population increase and increasingly unfavorable weather patterns. In order to reach the projected food production targets, which are essential for guaranteeing global food security, innovative and sustainable agricultural methods must be adopted. Conventional approaches, including traditional breeding procedures, often cannot handle the complex and simultaneous effects of biotic pressures such as pest infestations, disease attacks, and nutritional imbalances, as well as abiotic stresses including heat, salt, drought, and heavy metal toxicity. Applying phytohormonal approaches, particularly those involving hormonal crosstalk, presents a viable way to increase crop resilience in this context. Abscisic acid (ABA), gibberellins (GAs), auxin, cytokinins, salicylic acid (SA), jasmonic acid (JA), ethylene, and GA are among the plant hormones that control plant stress responses. In order to precisely respond to a range of environmental stimuli, these hormones allow plants to control gene expression, signal transduction, and physiological adaptation through intricate networks of antagonistic and constructive interactions. This review focuses on how the principal hormonal signaling pathways (in particular, ABA-ET, ABA-JA, JA-SA, and ABA-auxin) intricately interact and how they affect the plant stress response. For example, ABA-driven drought tolerance controls immunological responses and stomatal behavior through antagonistic interactions with ET and SA, while using SnRK2 kinases to activate genes that react to stress. Similarly, the transcription factor MYC2 is an essential node in ABA–JA crosstalk and mediates the integration of defense and drought signals. Plants’ complex hormonal crosstalk networks are an example of a precisely calibrated regulatory system that strikes a balance between growth and abiotic stress adaptation. ABA, JA, SA, ethylene, auxin, cytokinin, GA, and BR are examples of central nodes that interact dynamically and context-specifically to modify signal transduction, rewire gene expression, and change physiological outcomes. To engineer stress-resilient crops in the face of shifting environmental challenges, a systems-level view of these pathways is provided by a combination of enrichment analyses and STRING-based interaction mapping. These hormonal interactions are directly related to the United Nations Sustainable Development Goals (SDGs), particularly SDGs 2 (Zero Hunger), 12 (Responsible Consumption and Production), and 13 (Climate Action). This review emphasizes the potential of biotechnologies to use hormone signaling to improve agricultural performance and sustainability by uncovering the molecular foundations of hormonal crosstalk. Increasing our understanding of these pathways presents a strategic opportunity to increase crop resilience, reduce environmental degradation, and secure food systems in the face of increasing climate unpredictability. Full article

Cross-border energy trading activity via interconnection has received much attention in Southern Asia to help the South Asian Association for Regional Cooperation (SAARC) region’s energy deficit states. This research article proposed a smart metering system to reduce energy losses and increase distribution sector efficiency. The implementation of smart metering systems in utility management plays a pivotal role in advancing several Sustainable Development Goals (SDGs), i.e.; SDG (Affordable and Clean Energy), and SDG Climate Action. By enabling real-time monitoring, accurate measurement, and data-driven management of energy resources, smart meters promote efficient consumption, reduce losses, and encourage sustainable behaviors among consumers. The adoption of a smart metering system along with Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis, socio-economic analysis, current challenges, and future prospects was also investigated. Besides the economics of the electrical distribution system, one feeder with non-technical losses of about 16% was selected, and the cost–benefit analysis and cost–benefit ratio was estimated for the SAARC region. The import/export ratio is disturbing in various SAARC grids, and a solution in terms of community microgrids is presented from Pakistan’s perspective as a case study. The proposed work gives a guidelines for SAARC countries to reduce their losses and improve their system functionality. It gives a composite solution across multi-faceted evaluation for the betterment of a large region. Full article

Japan’s 8.5 million vacant homes (Akiyas) represent a paradox of scarcity amid surplus: while rural depopulation leaves properties abandoned, housing shortages and bureaucratic inefficiencies hinder their reuse. This study proposes AKI2ALL, an AI-blockchain framework designed to automate the circular repurposing of Akiyas into ten high-value community assets—guesthouses, co-working spaces, pop-up retail and logistics hubs, urban farming hubs, disaster relief housing, parking lots, elderly daycare centers, exhibition spaces, places for food and beverages, and company offices—through smart contracts and data-driven workflows. By integrating circular economy principles with decentralized technology, AKI2ALL streamlines property transitions, tax validation, and administrative processes, reducing operational costs while preserving embodied carbon in existing structures. Municipalities list properties, owners select uses, and AI optimizes assignments based on real-time demand. This work bridges gaps in digital construction governance, proving that automating trust and accountability can transform systemic inefficiencies into opportunities for community-led, low-carbon regeneration, highlighting its potential as a scalable model for global vacant property reuse. Full article

Accurate Doppler frequency estimation for Low Earth Orbit (LEO)-based Signals of Opportunity (SoOP) positioning faces significant challenges from extreme dynamics (±40 kHz Doppler shift, 0.4 Hz/ms fluctuation) and severe SNR fluctuations induced by multi-beam switching. Empirical analysis reveals that phased-array beamforming generates three-tiered SNR fluctuation patterns during unpredictable beam handovers, rendering conventional single-algorithm solutions fundamentally inadequate. To address this limitation, we propose KDFE (KNN-Driven Fusion Estimator)—an adaptive framework integrating the Rife–Vincent algorithm and MLE via intelligent switching. Global FFT processing extracts real-time Doppler-SNR parameter pairs, while a KNN-based arbiter dynamically selects the optimal estimator by: (1) Projecting parameter pairs into historical performance space, (2) Identifying the accuracy-optimal algorithm for current beam conditions, and (3) Executing real-time switching to balance accuracy and robustness. This decision model overcomes the accuracy-robustness trade-off by matching algorithmic strengths to beam-specific dynamics, ensuring optimal performance during abrupt SNR transitions and high Doppler rates. Both simulations and field tests demonstrate KDFE’s dual superiority: Doppler estimation errors were reduced by 26.3% (vs. Rife–Vincent) and 67.9% (vs. MLE), and 3D positioning accuracy improved by 13.6% (vs. Rife–Vincent) and 49.7% (vs. MLE). The study establishes a pioneering framework for adaptive LEO-SoOP positioning, delivering a methodological breakthrough for LEO navigation. Full article

As digital transformation progresses, schools are increasingly confronted with psychosocial challenges such as technostress, digital overload, and unequal participation in digital (learning) environments. This article investigates the conceptual relevance of digital well-being for school development, particularly in relation to social inequality. Despite growing attention, the term remains theoretically underdefined in educational research—a gap addressed through a theory-driven review. Drawing on a systematic search, 25 key studies were analyzed for their conceptual understanding and refinement of digital well-being, with a focus on educational relevance. Findings suggest that digital well-being constitutes a multidimensional state shaped by individual, media-related, and socio-structural factors. It emerges when individuals are able to successfully manage the demands of digital environments and is closely linked to digital inequality—particularly in terms of access, usage practices, and the resulting opportunities for participation and health promotion. Since the institutional role of schools has thus far received limited attention, this article shifts the focus toward schools as key arenas for negotiating digital norms and practices and calls for an equity-sensitive and health-conscious perspective on school development in the context of digitalization. In doing so, digital well-being is repositioned as a pedagogical cross-cutting issue that requires coordinated efforts across all levels of the education system, highlighting that equitable digital transformation in schools depends on a critical reflection of power asymmetries within society and educational institutions. The article concludes by advocating for the systematic integration of digital well-being into school development processes as a way to support inclusive digital participation and to foster a health-oriented digital school culture. Full article

The commercialization of Km 0 agricultural and livestock products represents a strategic opportunity to enhance rural economic resilience and reduce greenhouse gas emissions in the food sector. This paper presents an original, policy-oriented framework that connects Km 0 distribution models with measurable CO₂ reductions, proposing a structured system of economic incentives to support their adoption. Grounded in a mixed-methods approach, including normative analysis, empirical modeling, and a regional case study in Galicia, Spain, we demonstrate the alignment of Km 0 policies with the EU’s Common Agricultural Policy (CAP) 2023–2027 and the Sustainable Development Goals (SDGs). Findings reveal substantial potential for environmental mitigation, improved farm profitability, and revitalization of rural economies. This work provides a comprehensive roadmap for integrating Km 0 into national agricultural strategies, supported by data-driven justification and scalable implementation models. Full article

This study investigates public perceptions of sustainable mobility within university environments, which are important trip generation hubs with the potential to influence and disseminate sustainable mobility behaviors. Using sentiment analysis on 120,236 tweets from São Paulo, Rio de Janeiro, Lisbon, and Porto, tweets were classified into positive, neutral, and negative sentiments to assess perceptions across transport modes. It was hypothesized that universities would exhibit more positive sentiment toward active and public transport modes compared to perceptions of these modes within the broader city environment. Results show that active modes and public transport consistently receive higher positive sentiment rates than individual motorized modes, and, considering the analyzed contexts, universities demonstrate either similar (São Paulo) or more positive perceptions compared to the overall sentiment observed in the city (Rio de Janeiro, Lisbon, and Porto). Chi-square tests confirmed significant associations between transport mode and sentiment distribution. An exploratory analysis using topic modeling revealed that perceptions around bicycle use are linked to themes of safety, cycling infrastructure, and bike sharing. The findings highlight opportunities to promote sustainable mobility in universities by leveraging user sentiment while acknowledging limitations such as demographic bias in social media data and potential misclassification. This study advances data-driven methods to support targeted strategies for increasing active and public transport in university settings. Full article