Paradigm Shift Research Articles

Elucidating the potential of isorhapontigenin in targeting the MgrA regulatory network: a paradigm shift for attenuating MRSA virulence.

As methicillin-resistant Staphylococcus aureus (MRSA) exhibits formidable resistance to many drugs, the imperative for alternative therapeutic strategies becomes increasingly evident. At the heart of our study is the identification of a novel inhibitor through fluorescence anisotropy assays, specifically targeting the crucial multiple gene regulator A (MgrA) regulatory network in S. aureus. Isorhapontigenin (Iso), a natural compound, exhibits outstanding inhibitory efficacy, modulating bacterial virulence pathways without exerting direct bactericidal activity. This suggests a paradigm shift toward attenuating virulence instead of purely focusing on bacterial elimination. Through comprehensive in vitro and in vivo evaluations, we elucidated the complex interplay between Iso and MgrA, leading to reduced S. aureus adhesion, and overall virulence. At the cellular level, Iso offers significant protection to A549 cells infected with S. aureus, reducing cellular damage. Importantly, Iso augments the chemotaxis of neutrophils, curtailing the immune evasion capabilities of S. aureus. Furthermore, in vivo investigations highlight the notable effectiveness of Iso against MRSA-induced pneumonia and within the Galleria mellonella infection model, underscoring its pivotal role in the evolving realm of antibacterial drug discovery. Significantly, when Iso is used in combination with vancomycin, it outperforms its solo application, indicating a more pronounced therapeutic impact. This seminal research emphasizes Iso's potential as a primary defense against the surge of multidrug-resistant pathogens, heralding new prospects in antimicrobial therapy.

Industry 4.0 technologies: an examination of benefits, challenges and critical success factors for implementation in the Saudi construction industry

Purpose The construction industry is witnessing a paradigm shift as a consequence of the fourth industrial revolution (IR 4.0). The implementation of IR4.0 technologies is, however, elementary in emerging economies such as Saudi Arabia. Therefore, the purpose of this paper is to carry out an examination of benefits, challenges and critical success factors for IR4.0 implementation in the construction industry in Saudi Arabia. Design/methodology/approach The methodology entailed a thorough review of the extant literature and consultation with experienced construction professionals in Saudi Arabia through questionnaire surveys. The data collected was further analyzed using the relative importance index approach and the confirmatory factor analysis. Findings The most important benefits, challenges and critical success factors established by this study include “Improved Communication and Coordination,” “Cost of implementation (initial investment and maintenance)” and “Clear goals and objectives,” respectively. Confirmatory factor analysis established a theoretical model to serve as a foundation for IR4.0 adoption in the Saudi construction industry. Research limitations/implications The limitations may be perceived in terms of the local context of the research, as well as the sample size. This prevents the potential for generalization of the study’s results. Practical implications It is of practical value to the Saudi construction industry in facilitating the successful implementation of technology through policies, frameworks and best practice guidance. Originality/value The study advances the theoretical knowledge of technology implementation in the construction industry. Emerging economies such as Saudi Arabia seeking to leverage the capabilities of digital technologies will find the results of this to be of crucial value.

Area Deprivation and Disease Severity in Adult Patients With Discoid Lupus Erythematosus.

The association of area deprivation with outcomes in discoid lupus erythematosus (DLE) remains poorly understood. To determine the association between US Census block measures of deprivation and disease severity in adult patients with DLE. This cross-sectional study included 154 patients with DLE seen between January 1, 2007, and January 1, 2024, at a single-center referral-based specialty rheumatologic-dermatology clinic in Philadelphia, Pennsylvania. Patients were aged 18 to 73 years and were enrolled in the University of Pennsylvania's Cutaneous Lupus Erythematosus Database study. Data were analyzed between January 1, 2024, and May 8, 2024. Residence in a highly disadvantaged area as geocoded by a state area deprivation index (ADI). The main outcome was DLE disease severity as codified by the validated Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) damage and activity scores. A total of 154 adult patients with DLE (128 women [83%] and 26 men [17%]; mean [SD] age, 43 [13] years; 6 [4%] Asian individuals, 98 [64%] Black individuals, 2 [1%] Hispanic individuals, 46 [30%] White individuals, and 2 individuals [1%] with other race or ethnicity; 78 [51%] with an ADI >5; 43 who currently smoked [28%];and 56 [36%] with concurrent systemic lupus erythematosus) were included in the analysis. By multivariable logistic regression, residence within communities with an ADI greater than 5 was associated with nearly 4-fold greater odds of moderate to severe damage (odds ratio [OR], 3.90; 95% CI, 1.27-12.69] and activity (OR, 3.31; 95% CI, 1.27-9.44). Concurrent cigarette smoking was similarly associated with greater odds of moderate to severe damage (OR, 3.15; 95% CI, 1.09-10.29). After controlling for ADI and other confounders, race was not significantly associated with DLE disease severity. The results of this cross-sectional study suggest that geospatial disadvantage is associated with DLE disease severity independent of race. This invites a paradigm shift that considers the social context within which racial disparities are observed, highlighting the potential for geographically targeted interventions and policy changes to improve patient outcomes in DLE.

Approach to the patient: New era emerges for craniopharyngioma management.

Papillary craniopharyngioma (PCP) and adamantinomatous craniopharyngioma (ACP) are distinct, slow growing tumors of the suprasellar region. Their location, composition and biology have historically evaded successful surgical, radiation, and medical therapy. Meanwhile compromise of critical structures either by tumor or treatments increase morbidity, impacting patient and carer quality of life. There has been a paradigm shift in the management of PCP, stemming from the discovery of BRAFV600E mutation in its tumorigenesis. Such a treatment breakthrough may soon be the case for ACP, changing the landscape of craniopharyngioma management. We use a case of ACP, partially responding to ERK inhibitor therapy to demonstrate chronicity of disease progression and discuss modern management strategies highlighting the importance of access to tumour agnostic clinical trials, and future directions.

Evolution and Paradigm Shift in Forest Health Research: A Review on of Global Trends and Knowledge Gaps

Evolution and Paradigm Shift in Forest Health Research: A Review on of Global Trends and Knowledge Gaps

Chronic kidney disease in type 2 diabetes: The size of the problem, addressing residual renal risk and what we have learned from the CREDENCE trial.

Chronic kidney disease (CKD) associated with type 2 diabetes (T2DM) is a global challenge; progression to end-stage kidney disease (ESKD) and increased risk of cardiovascular disease (CVD) associated with advancing nephropathy are a significant source of morbidity, mortality, and healthcare expenditure. Until recently, renin-angiotensin system (RAS) blockade was the mainstay of pharmacotherapy in diabetic kidney disease (DKD), representing a therapeutic paradigm shift towards interventions that delay disease progression independently of antihypertensive effects. However, a significant residual risk of DKD progression persisted in patients established on RAS blockade, highlighting the need for additional treatment options. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally licensed as glucose-lowering agents in people with T2DM, serendipitously demonstrated beneficial renal and cardiovascular outcomes in clinical trials designed primarily to evaluate their cardiovascular safety. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial was the first to study the effect of SGLT2 inhibition on a primary composite renal endpoint of ESKD, doubling of serum creatinine, or renal or cardiovascular death in 4401 people with T2DM and CKD established on RAS blockade. The trial was stopped early due to efficacy, demonstrating a 30% relative risk reduction in the primary endpoint in the canagliflozin group (hazard ratio 0.70, 95% confidence interval 0.59-0.82; p = 0.00001). Through discussion of the primary analysis from CREDENCE, and selected post hoc analyses, we review the significant benefits highlighted by this landmark study, its role in shaping clinical guidelines, and in re-establishing interest in interventions that reduce the residual risk of progression of DKD, alongside its interrelation with cardiovascular morbidity and heart failure. We also provide a brief narrative summary of key renal outcome trials since CREDENCE, which indicate emerging avenues for pharmacotherapy beyond SGLT2 inhibition.

Evolving Perspectives: the resurgence of wood in Quebec architecture

Over the past two decades, Quebec has undergone a radical transformation in its approach to using wood in architecture, spurred by trade constraints on wood exports to the United States. This evolution is the outcome of synergistic efforts that have facilitated a transition resulting in significant technological and architectural advancements. Historically, Quebec’s vast forest resources have played a pivotal role in the development of local timber construction, particularly through traditional timber frame techniques. However, the 19th century witnessed a shift towards light-frame construction methods like the Balloon Frame, driven by industrialisation and urbanisation. By the mid-20th century, concrete gained dominance, the fruit of prioritising aesthetics over ideology in architectural design, especially in Montreal, where concrete structures flourished. The 1980s trade dispute with the United States marked a turning point, fostering innovation and a paradigm shift in wood use. Collaboration between industry and academia, exemplified by the Krüger Pavilion and the founding of FP Innovations, has propelled large-scale wood construction forward. Cecobois further supports this trend by facilitating access to technological innovations. This era of change highlights both the potential and limitations of wood in architecture, showcasing its role as a versatile and eco-friendly material that can enhance architectural design while facing technical challenges that sometimes limit its visibility and application.

A Critical Phenomenology of Vulnerability: Toward a Paradigm Shift? A Contribution to an Interdisciplinary Trialogue on Vulnerability

A Critical Phenomenology of Vulnerability: Toward a Paradigm Shift? A Contribution to an Interdisciplinary Trialogue on Vulnerability

Toward a paradigm shift in prognostication and treatment of early-stage Hodgkin lymphoma.

Twenty years after the conceptual revolution that occurred in the millennium turnaround upon the introduction of PET/CT in lymphoma staging, restaging, and prognostication, a number of new parameters for PET reading have been proposed: (1) the shift from a qualitative to a semi-quantitative reading for PET reporting, (2) an international consensus on these novel interpretation keys, (3) a standardized and agreed procedure to measure the total metabolic tumour volume (TMTV), and (4) the proposition of new indexes to portray the tumour spread: (D-Max and Total Lesion Surface -TLS). These proved to be very powerful prognosticators, able to revolutionize the traditional Ann Arbor four-stage lymphoma staging. During the 17° Lugano meeting on lymphoma, one main question was asked to experts attending a closed workshop dedicated to new metrics for lymphoma diagnosis, staging, restaging, and prognostication: "Should the traditional 4-stage anatomic staging system be simplified to a more clinically relevant 2-stage system (e.g., limited vs. extensive disease)?" Early-stage HL is an example of how these new metrics could fit with this proposal.

Innovative Professional Learning Communities and Sustainable Education Practices through Digital Transformation

Education is the most important part of sustainable society development. Traditional approaches to permanent lifelong educator training often fail to produce lasting changes in teaching practices (UN, Goal 4). This paper examines how educator involvement in a professional learning community (PLC) ensures equitable quality education and promotes lifelong learning opportunities for all and a sustainable digital transformation of the teaching and learning process. Participation in PLC and the use of contemporary learning environments positively impact the quality of educators’ work, thereby enhancing the overall educational process. This study utilised a quantitative methodology, employing both descriptive and inferential statistics to analyse the data. Results indicate that a balanced integration of formal PLC structures and guidance, combined with elements of a non-formal, broader PLC and external incentives and support (such as projects), can surpass mere exchanges of best practices, foster innovation, and support the sustainable digital transformation of educators. This approach leads to a sustainable shift in pedagogical paradigms. The PLC_IP model (focused on including digital technologies and effective teaching strategies) enhances collective educator efficacy, contributing to improved teaching quality. For PLCs to achieve sustainability, they must be dynamic entities that adapt to the evolving educational landscape, ensuring their continued relevance and impact with rising completion rates over time. Our findings underscore the importance of innovative PLCs in driving sustainable educational development and improvement and provide a framework for future research and practical applications in educational settings. In addition, PLCs can strengthen the means of implementation and revitalise the global partnership for sustainable development (UN, Goal 17).

Advancing sustainable manufacturing: a systematic exploration of Industry 5.0 supply chains for sustainability, human-centricity, and resilience

The emergence of Industry 5.0 provides new perspectives for the manufacturing sector, aiming to create sustainable, human-centric, and resilient approaches. Supply chains perform a vital role in realising these objectives by connecting suppliers to customers and providing value-added products and services. However, despite growing interest, the consideration for this paradigm shift in the manufacturing industry remains amorphous. In order to address this gap, this paper presents a systematic literature review of 103 research articles from an initial corpus of 8,079 and proposes a conceptual framework for Supply Chain 5.0 within the manufacturing sector. The framework is scaffolded on a thematic analysis of the literature, including drivers to transition, impacts on manufacturing supply chains, challenges, and outcomes. This study provides valuable insights for researchers, practitioners, and policymakers seeking to examine the implications of Industry 5.0 supply chains, highlighting its potential to enhance sustainability, social well-being, and economic growth. Furthermore, the proposed conceptual framework and research opportunities serve to guide future research and practical applications around this emerging topic.

High‐Speed Short Infrared Detector Based on Vertical Gr/Se0.2Te0.8/GaAs Heterojunction

AbstractIn the domain of high‐performance short‐wave infrared (SWIR) photodetection and imaging, existing technologies predominantly utilize single‐crystal germanium and III‐V semiconductors. Despite their efficacy, these materials are encumbered by laborious synthesis and complex fabrication demands. In this study, the synthesis of large‐area, high‐crystallinity Se0.2Te0.8 thin films through a CMOS‐compatible vacuum thermal evaporation process is reported. A high‐speed, broad‐spectrum photodetector engineered with an innovative Gr/Se0.2Te0.8/GaAs vertical heterostructure is presented, which capitalizes on the augmented carrier mobility and employs graphene innovatively as both a carrier collection interface and an electrode. This configuration facilitates a remarkably swift response time of 800 ns/1 µs at the crucial 1310 nm wavelength for optical communications. Moreover, the fabrication of a 5 × 5 array device demonstrates substantial SWIR imaging capabilities at ambient conditions, marking a paradigm shift in uncooled infrared imaging and communication technologies. This work not only extends the boundaries of SWIR photodetector performance but also underscores the potential of novel material systems in high‐speed optical applications.

An implementation manual for an interprofessional enhanced recovery after surgery protocol in cardiac surgery following international established frameworks

IntroductionEnhanced Recovery After Surgery (ERAS) protocols represent a paradigm shift in perioperative care, aim to optimize patient outcomes and accelerate recovery. This manual presents findings from implementing the INCREASE study, a bicentric prospective randomized controlled trial focusing on ERAS in minimally invasive heart valve surgery.MethodsUtilizing the Consolidated Framework for Implementation Research (CFIR) and the Template for Intervention Description and Replication (TIDieR), the study examined contextual factors, intervention components, and implementation strategies.ResultsKey findings from the CFIR analysis revealed critical domains influencing implementation success. These included innovation characteristics, external and internal settings, and individual dynamics. The study showcased ERAS's adaptability to diverse healthcare systems, emphasizing its potential for successful integration across varying contexts. Furthermore, the importance of interprofessional collaboration emerged as a foundation of practical implementation, fostering teamwork, communication, and patient-centered care. Utilizing the TIDieR framework, this manual comprehensively describes ERAS intervention components, detailing preoperative counseling, intraoperative management, and postoperative care strategies. The manual underscored the importance of tailored, patient-centered approaches, highlighting the role of an academic ERAS nurse, early mobilization, and psychosomatic interventions in promoting optimal recovery outcomes.DiscussionIn conclusion, the INCREASE study provided valuable insights for creating an implementation manual for ERAS in cardiac surgery, emphasizing adaptability, collaboration, and ongoing evaluation as key drivers of successful implementation. These findings have broad implications for improving patient care outcomes and advancing perioperative practices in cardiac surgery settings.

New epilepsy therapies in development.

Epilepsy is a common brain disorder, characterized by spontaneous recurrent seizures, with associated neuropsychiatric and cognitive comorbidities and increased mortality. Although people at risk can often be identified, interventions to prevent the development of the disorder are not available. Moreover, in at least 30% of patients, epilepsy cannot be controlled by current antiseizure medications (ASMs). As a result of considerable progress in epilepsy genetics and the development of novel disease models, drug screening technologies and innovative therapeutic modalities over the past 10 years, more than 200 novel epilepsy therapies are currently in the preclinical or clinical pipeline, including many treatments that act by new mechanisms. Assisted by diagnostic and predictive biomarkers, the treatment of epilepsy is undergoing paradigm shifts from symptom-only ASMs to disease prevention, and from broad trial-and-error treatments for seizures in general to mechanism-based treatments for specific epilepsy syndromes. In this Review, we assess recent progress in ASM development and outline future directions for the development of new therapies for the treatment and prevention of epilepsy.

Restrictions of internet access in Turkey: legislation, methods and practice

The opportunities presented by the internet expand certain rights while also leading to the violation of others. States are obligated to establish cybersecurity for their citizens and protect personal rights against various infringements. However, this rationale can sometimes be used to obscure digital authoritarianism. Therefore, the age-old dilemma of balancing freedom and security is at the heart of internet law. It is inevitable that methods such as internet access restrictions, which every state resorts to, must be evaluated comprehensively in their legal, technical, and practical dimensions to enable more accurate analysis of national practices. This study analyzes the justifications for internet restrictions in Turkey compared with their implementation. Contrary to what is envisaged by legal regulations, it has been found that precautionary measures are mostly issued by administrative authorities. There is inconsistency between lower and upper judicial authorities, and judicial decisions are rendered ineffective by the legislative branch. The methods of restriction are applied ambiguously. Some regulations deviate from the legislative intent, while others are rendered ineffective by the administration. To solve structural problems, action is needed from the legislative body, and addressing implementation issues requires a more fundamental paradigm shift.

From collections to connections in libraries, archives and museums: Do theories meet practice?

Libraries, archives and museums are primarily seen as institutions that preserve and promote collections. However, ongoing social changes are causing them to increasingly focus on their social partners and the relationships that can be established with them. The evolving nature of these institutions’ priorities raises questions about how they are adapting to this shift and its impact on their operations. The objective of this research is to contribute to the conceptualization of the paradigm shift through verification of how selected social and cultural theories of social relations are reflected in the activities of libraries, archives and museums, as well as their connections with various partners. A content analysis of articles from three journals indicates that the relation-centric theories studied, and the concepts presented therein, are taken into account by their authors, albeit to varying degrees. The relationships of libraries, archives and museums primarily concern local communities and special user groups, but also involve other legal or individual entities, as well as the professional community.

Common femoral artery: a paradigm shift to the vascular surgeon's comfort zone?

Common femoral artery: a paradigm shift to the vascular surgeon's comfort zone?

Assessing lethal and sublethal effects of pesticides on honey bees in a multifactorial context

The registration of novel pesticides that are subsequently banned because of their unexpected negative effects on non-target species can have a huge environmental impact. Therefore, the pre-emptive evaluation of the potential effects of new compounds is essential. To this aim both lethal and sublethal effects should be assessed in a realistic scenario including the other stressors that can interact with pesticides. However, laboratory studies addressing such interactive effects are rare, while standardized laboratory-based protocols focus on lethal effects and not on sub-lethal effects.We propose to assess both lethal and sublethal effects in a multifactorial context including the other stressors affecting the non-target species. We tested this approach by studying the impact on honey bees of the insecticide sulfoxaflor in combination with a common parasite, a sub-optimal temperature and food deprivation. We studied the survival and the transcriptome of honey bees, to assess both the lethal and the potential sublethal effects of the insecticide, respectively. With this method we show that a field realistic concentration of sulfoxaflor in food does not affect the survival of honey bees; however, the significant impact on some key genes indicates that sublethal effects are possible in a realistically complex scenario.Moreover, our results demonstrate the feasibility and reliability of a novel approach to hazard assessment considering the interactive effects of pesticides. We anticipate our approach to be a starting point for a paradigm shift in toxicology: from an unifactorial, mortality-centered assessment to a multifactorial, comprehensive approach. This is something of the utmost importance to preserve pollination, thus contributing to the sustainability of our food production system.

Ethical concerns in aging research: perspectives of global frontline researchers.

This study investigated the ethical landscape of aging research amid the increasing global focus on extending the human lifespan and health span. Our global survey of 180 researchers across 38 jurisdictions revealed divergent perceptions of aging, a consensus regarding the feasibility of delaying aging, and multiple perspectives regarding lifespan extension. The present findings underscore a paradigm shift toward inclusive and ethically sound research, emphasizing the need for an approach that strikes a balance between basic and clinical research. In addition, this study highlighted key ethical concerns in aging research, including the effects of misleading advertising, potential inequality in access to aging interventions, and risks pertaining to the extrapolation of research findings from lower-model organisms to humans. The insights presented in this paper call for an integrated approach for overcoming the complex ethical and societal challenges in aging research to ensure responsible and equitable advancements in this burgeoning field.

Preventing diabetes complications.

The key aim of diabetes management is to prevent complications, which are a major cause of morbidity and mortality. At an individual level, people with diabetes are less likely than they were several decades ago to experience classical macrovascular and microvascular complications as a result of improvements in modifiable cardiovascular risk factors and preventive healthcare. However, a significant burden of diabetes complications persists at a population level because of the increasing incidence of diabetes, as well as longer lifetime exposure to diabetes because of younger diagnosis and increased life expectancy. Trials have shown that the most effective strategy for preventing complications of diabetes is a multifactorial approach focussing simultaneously on the management of diet, exercise, glucose levels, blood pressure and lipids. In addition to the cornerstone strategies of addressing diet, exercise and lifestyle measures, the introduction of newer glucose-lowering agents, including sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists, have brought about a paradigm shift in preventing the onset and progression of complications of type 2 diabetes, particularly cardiovascular and renal disease. The improvement in rates of classical complications of diabetes over time has been accompanied by a growing awareness of non-traditional complications, including non-alcoholic fatty liver disease. These emerging complications may not respond to a glycaemic-centred approach alone and highlight the importance of foundational strategies centred on lifestyle measures and supported by pharmaceutical therapy to achieve weight loss and reduce metabolic risk in patients living with diabetes.