Terms Of Specificity Research Articles

Women's Representation as Principal Investigators Among Pediatric Orthopaedic Clinical Trials: An Analysis of ClinicalTrials.Gov.

Despite recent efforts to increase the participation of women in orthopaedic surgery, there remains a gender gap, particularly when compared with other medical specialties. Acting as a principal investigator (PI) in a clinical trial can give physicians notable exposure and national recognition, which can improve their chances of promotion and tenure. This study aims to assess the proportion of women serving as PIs in pediatric orthopaedic clinical trials, examine associated trial characteristics, and explore geographic distribution. A cross-sectional analysis of clinical trials was conducted using data from the ClinicalTrials.gov registry. Specific search terms were used to identify pediatric orthopaedic trials. Data on trial characteristics, including phase, status, funding source, and intervention type, were collected. PI sex was determined using Genderize.io, an application program interface that predicts the sex of individuals based on their name, and the geographic distribution of women PIs was examined. From 2007 to 2022, women PIs increased from zero to 26.86%. The United States saw no significant increase (β = 1.553; P = 0.125), but international trials did (β = 2.845; P = 0.008). Women PIs led more active/completed trials and trials with behavioral/other interventions. Geographic analysis showed higher representation in North America (38.47%), especially the Northeast (28.17%) and West (25.35%). The United States had 28.74% women PIs, with California (15.49%) leading. Progress toward gender parity in pediatric orthopaedic research is evident; however, disparities still exist. Efforts to provide additional research opportunities for women in orthopaedics may be crucial in attracting and retaining diverse talent in the field. Targeted initiatives may have potential in achieving equal representation in orthopaedics.

Quantifying the essential tasks of offshore wind technicians.

Offshore wind technicians (WTs) have been identified as having an occupation with varying physical demands. Therefore, in order to assess WTs capability to undertake the job, there was a need to identify and quantify the physical requirements of the essential tasks. To establish the essential tasks and quantify the associated minimum physical demands of being an offshore WT. Wind Farm organisations (n = 10) across five countries, undertook a multi-modal observational approach comprising of semi-structured interviews (n = 45), focus groups (n = 14), survey (n = 167). In addition, observations, objective measurements, video footage and standard operating procedures were reviewed. A service campaign was broken down into component tasks, and analysed in terms of technical specifications, e.g. equipment, frequency, duration, rest breaks, clothing ensembles, and the methods of best practice for undertaking each of the tasks. Task descriptions were produced and minimum performance standards recommended. The job tasks associated with WTs can be broken down into two categories and five areas of work (Essential infrequent = casualty evacuation and prolonged ladder climbing; Essential frequent = short ladder climbs, manual handling and working in restricted spaces). The results presented constitute work carried out in Phases 1 and 2 of a three phased work programme to establish a physical employment standard required by WTs working in offshore wind. These findings will underpin the development of a minimum performance standard for the global offshore wind industry.

Anticaries and Antigingivitis Properties of Cannabinoid-Containing Oral Health Products: A Review.

To evaluate the anticaries and antigingivitis properties of cannabinoid-containing oral health products. A systematic research strategy was employed. Specific search terms were used, including "Cannabinoids AND dental caries," "Cannabinoids AND oral health," "Cannabinoids AND dental plaque," "Cannabinoids AND gingivitis AND periodontitis," "Cannabinoids AND S. mutans," "Cannabidiol AND oral health," and "Cannabidiol AND oral biofilm." The search was conducted in PubMed, Cochrane, and EBSCO Host databases. The search yielded a total of 73 articles, out of which 15 articles (20.5%) were relevant to the scope of this systematic review. Among the relevant articles, only eight (10.9%) directly addressed the research question. The findings from these articles suggest that cannabinoids have the potential to reduce the metabolism of cariogenic bacteria, specifically Streptococcus mutans, and decrease the number of bacterial colonies in dental plaque. In vitro studies also demonstrated a significant inhibitory effect of cannabinoids on oral biofilms and create a considerable inhibitory zone of growth when investigated on oral biofilms in vitro. Furthermore, CBD exhibited antibacterial properties against Porphyromonas gingivalis, a primary pathogen associated with periodontal disease. The current review shows insufficient data to conclude on the anticaries and antigingivitis effects of cannabinoids. Despite extensive research on their systemic therapeutic benefits, their oral health impact remains underexplored, lacking clinical trials and primary research.

Exploring variability in cognitive functioning in patients with spinal muscular atrophy: a scoping review.

The cognitive functioning of individuals with spinal muscular atrophy (SMA) is not well understood, prompting a call for more research to better grasp cognitive involvement in SMA. This study aims to explore recent findings regarding cognitive outcomes in SMA patients, including correlations between clinical features and cognitive abilities. The investigation seeks to identify commonly used measures for assessing cognitive function in this patient population. A scoping review following the Joanna Briggs Institute methodology examined literature until December 2023. Two databases were searched along with relevant article references using specific terms such as "spinal muscular atrophy," "SMA," "cognitive," "abilities," "functions," "intellective," or "intellectual." Screening focused on titles and abstracts from English language peer-reviewed journals. After the initial research, 1452 articles were identified. Subsequent screening and selection led to the inclusion of 13 articles in the review. Among these studies, four indicated a cognitive trend within the normal range for SMA patients. In four other studies, the majority of patients fell within the normal range. However, smaller proportions were observed to be either above or below the norm compared to the controls. Three studies reported noted cognitive performance below the average, while two showed above-average scores. The scoping review suggests that most SMA patients have cognitive abilities similar to the general population, with types II and III showing even lesser impact. However, certain cognitive domains may be affected in type I patients, highlighting the need for further research to fully understand cognitive involvement in SMA.

CORRELATION ANALYSIS OF THE INTERDEPENDENCE OF ECONOMY'S INNOVATION AND CREATIVITY INDICES

Creativity and the generation of innovative solutions are means of solving the problems of slow economic development and resistance to instability that have been observed in recent years. The key role of creativity of individuals and groups of workers as a defining feature of modern economic life is increasingly recognised. There is a consensus that people, as a source of creativity, are now a critical resource of the new era. In the new model of economic development, creativity, knowledge and free access to information are seen as powerful drivers of development and catalysts of globalisation. The subject of the research is to study the relationship between innovation and creativity in the economic sphere. In particular, the article examines how the creativity of various economic subjects affects the level of innovative indicators, which synthetically reflect the possibilities of achieving the goals of innovative development. The research methodology includes the use of global reports on innovation and creativity indices, as well as scientific sources on this topic. The study uses the methods of critical analysis of scientific papers and international rankings, comparison and correlation of interdependent indicators. The purpose of the research is to assess the relationship between creativity and the level of innovative indicators, which synthetically show the possibilities of achieving the goals of innovative development. Creativity of business entities and mechanisms for generating innovative solutions are determining factors of success of modern post-industrial societies. In most developed countries, long-term economic growth is supported by innovation and creativity of various economic entities. To create the research algorithm, the authors defined the chain of concepts "sustainable development – innovation – creativity". To assess and analyse creativity, the study uses methodological tools that can be applied in global and local contexts. The most well-known indices are the Global Innovation Index (GII), the Global Creativity Index (GCI), the City Creativity Index (CCI), and the Hong Kong Creativity Index (HKCI). The general correlation coefficients between the global innovation index and the creativity indices of some countries have been calculated. According to the results of the calculations, the correlation coefficients of creativity and innovation are very positive. They are closely related and belong to the group of significantly correlated indicators. This means that there is a very high correlation between innovation and creativity in the economies studied. Conclusions. The positive correlation between innovation and creativity indices confirms, in general and in specific terms, a close relationship between innovation and creativity in the economies of different countries. This may indicate that countries or regions with a higher level of economic development have higher rates of creativity and vice versa. The research demonstrates the importance of innovation for the development of creativity in the economy. Understanding this interaction can serve as a basis for designing strategies and policies aimed at promoting innovative development and the growth of creative potential. The economies of Poland, Bulgaria and Ukraine, which were studied in detail, are not innovative enough. The countries studied represent different levels of economic development and are in the phase of post-industrial development, which requires effective innovation policies and measures to support creativity. In order to increase the level of innovation and creativity, it is necessary to involve national governments and organisations (especially the European Union) that can contribute to this. The conclusions point to the need to develop comprehensive approaches to support innovation and creativity in the economies of the countries studied. This may include not only effective strategies to stimulate research and development, but also policies aimed at the cultural environment, education and other areas.

Global impact of urbanization on ecosystems: A comprehensive bibliometric analysis

This paper demonstrates a comprehensive assessment of bibliometric analysis of published research on the global impact of urbanization on environmental consequences. Scopus database was used to collect data on the global impact of urbanization on ecosystem research from 2000 to 2023 and scrutinizes the progression of publications, keyword analysis, co-citation of authors, citation of documents, co-authorship of authors, and most efficient and influential authors, countries, and institutions. A total of 4322 research papers (journals) were published during the period (2000–2023). This bibliometric study was carried out with the Vos Viewer software. The study's findings demonstrate that the number of publications has continuously increased between 2000 and 2023. In 2020 and 2022, there were 396 and 635 publications, respectively. The top three influential journals in terms of citations are Remote Sensing of Environment (2415 citations), Ecological Economics (1456 citations), and PLoS (1410). From 2000 to 2023, the most often appearing terms were urbanization (3028), urban area (1111), people (853), land use (769), environmental monitoring (594), environmental effect (570), sustainable development (567), and climate change (534). We created a time series with four periods (2000–2005, 2006–2011, 2012–2017, and 2018–2023) based on the periodic changes, which also shows the trend. In more specific terms, this study demonstrates not just a logical structure but also the development of keywords throughout time. The empirical evidence also shows that while this field initially focused on a few themes, it has since broadened to include the many aspects of urban sustainability. This analysis also identifies the most efficient and influential authors, institutions, and nations in terms of total publishing (TP), proportion of cited publications (PCP), total citation (TC), h-index, and g-index. Yang K is the most prominent author, China and the United States are the most efficient nations, and the Chinese Academy of Science is the most powerful organization. The top two nations by co-authorship are China (40 ​695 citations and 1527 publications) and the United States (41 ​119 citations and 833 publications). Additionally, it is noted that while environmental concerns continue to dominate, basic socioeconomic problems like equality, justice, and public participation are underrepresented. Sustainable development indicators, energy, ecologically friendly infrastructure, water, the use of land, and urban planning are prominent subject topics, with the first three exerting a larger influence in shaping the field's growth. This research may be utilized as a resource for people intrigued in learning more about the evaluation of urban sustainability and its advancement.

A deep learning framework for accurate diagnosis of colorectal cancer using histological images

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, with high mortality and incidence rates. Early detection of the disease may increase the probability of survival, making it critical to develop effective procedures for precise treatment. In the past few years, there has been an increased use of deep learning techniques in image classification that aid in the detection of various types of cancer. In this study, convolutional neural network (CNN) models were used to classify colorectal cancer into benign and malignant. After applying various data preprocessing techniques to the image dataset, we evaluated our prototypes using three distinct subsets of testing data, representing 20%, 30%, and 40% of the total dataset. Additionally, four pre-trained CNN models (ResNet-18, ResNet-50, GoogLeNet, and MobileNetV2) were trained, and the network architectural techniques were compared by applying the Adam optimizer. Finally, we assessed the performance of algorithms in terms of accuracy, sensitivity, specificity, precision, F1-score, and area under the receiver operating characteristic (ROC) curve (AUC). In this research, deep learning approaches demonstrated high efficacy in accurately diagnosing colorectal cancer. This indicates that these techniques have an important and significant value for advancing medical research.

The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy.

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring. A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case-control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded. Increased levels of p-syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α-Syn RT-QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta-analyses and multicenter investigations have confirmed the diagnostic value of p-syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p-syn with other biomarkers has further improved the diagnostic accuracy of MSA. The p-syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p-syn as a reliable biomarker for MSA. If proven, p-syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.

Direct Oral Anticoagulation in Lung Transplant Recipients.

Presently, the management of direct oral anticoagulants lacks specific guidelines for patients before and after transplant, particularly for lung transplant recipients. We aimed to consolidate the existing literature on direct oral anticoagulants and explore their implications in lung transplant recipients. We conducted a comprehensive search in PubMed and Google Scholar databases for studies published between January 2000 and December 2022, using specific search terms. We only included studies involving lung transplant recipients and focusing on direct oral anticoagulants. Five relevant publications were identified, providing varied insights. None of the studies specifically addressed bleeding complications associated with direct oral anticoagulants in lung transplant recipients. Limited details were available on the type of solid-organ transplant or the specific direct oral anticoagulant used in these studies. Varied bleeding complications associated with direct oral anticoagulants in lung transplant recipients were reported, but studies lacked specificity on transplant type and direct oral anticoagulant variations. Notably, the incidence of venous thrombotic embolism in lung transplant recipients was comparatively higher than in other solid-organ transplant recipients, potentially linked to factors such as corticosteroid therapy, calcineurin inhibitors, and cytomegalovirus infections. Our synthesis on findings of use of direct oral anticoagulant in lung transplant recipients emphasized challenges of managing these medications in urgent transplant situations. Recommendations from experts suggested caution in initiation of direct oral anticoagulants posttransplant until stability in renal and hepatic function is achieved. The limited evidence on safety of direct oral anticoagulants in lung transplant recipients underscores the need for further research and guidance in this specific patient population.

Quality and Readability Assessment of Web-based Arabic Health Information on Early Childhood Caries.

Patients are increasingly using the internet for searching health-related information. However, the quality and readability of the information available on the internet need to be assessed. To date, no study has assessed the quality and readability of web-based Arabic health information on early childhood caries. To evaluate the quality and readability of patient-oriented online Arabic health information regarding early childhood caries. For this infodemiological study, the Google and Yahoo search engines were searched using specific Arabic terms for early childhood caries, and the top 100 searches from both search engines were considered. Eligible websites were categorized in terms of affiliation as commercial, health portal, dental practice, professional, and journalism. The quality of the websites was assessed using the QUality Evaluation Scoring Tool (QUEST), and readability using the Gunning Fog index (GFI). A total of 140 websites were included after applying the exclusion criteria, of which 50.7% websites were of journalism. The majority of the websites (70%) had an overall low-quality level, with a QUEST score <10. The quality of websites retrieved from Google searches was of significantly higher quality than those from Yahoo (P < 0.0001). More than half (51.4%) of the websites had good readability, with a GFI score ≤8. Journalism websites had a significantly higher proportion of websites with poor readability level (62%) compared with other affiliations (P = 0.0072). The web-based Arabic information regarding early childhood caries is currently of low quality and moderate readability level, thereby indicating a need for improving such patient-facing content.

Navigating Higher Education Insurance: An Experimental Study on Demand and Adverse Selection

We conduct a survey-based experiment with 2,776 students at a non-profit university to analyze income insurance demand in education financing. We offered students a hypothetical choice: either a federal loan with income-driven repayment or an income-share agreement (ISA), with randomized framingof downside protections. Emphasizing income insurance increased ISA uptake by 43%. We observe that students are responsive to changes in contract terms and possible student loan cancellation, which is evidence of preference adjustment or adverse selection. Our results indicate that framing specific terms can increase demand for higher education insurance to potentially address risk for students with varying outcomes.

NBCAL violation of products that compete with breastfeeding on the social network Instagram.

The article aims to identify NBCAL violations and analyze the content of messages posted on the Instagram social network. This qualitative-quantitative study consisted of a convenience sample of profiles identified through specific terms preceded by the hashtag symbol (#). Data were collected for two months by trained researchers using a structured questionnaire. We calculated the product promotion frequency that characterized violation of the NBCAL per category and manufacturer. The messages were analyzed using the content analysis technique. We identified 64 personal accounts of mothers with violations in 89 products, mainly food (n = 72), dairy compounds (54.2%), and infant formulas (45.8%) were the most publicized. Two thematic categories emerged from the posted texts, one related to the quality of the products and the other about breastfeeding difficulty, especially low milk production. The study identified NBCAL violations on the Instagram social network, alerting the need to recognize digital marketing to include it in the rules imposed by the Norm in the virtual context, considering the capillarity of social networks in disseminating information to the public in question.

STRATEGY FOR INCREASING THE INCOME OF THE SUMBER AGUNG PEKON, WEST PESIR DISTRICT THAT IMPACT THE COMMUNITY ECONOMY FROM THE SIYASAH MALIYAH PERSPECTIVE

The enactment of Law Number 6 of 2014 concerning Villages and Law Number 23 of 2014 concerning Regional Government gives villages the right to regulate their regional affairs. In increasing the village's original income, the village government has the right and authority to widely utilize village wealth. Regarding village income sources, efforts to mobilize resources to develop the people's economic potential will increase people's productivity, so that the productivity of both human resources and natural resources around the people can be increased. In this research study, the formulation of the problem is how the strategy for increasing village original income has an impact on the community's economy and how siyāsah māliyah reviews this strategy. The aim of this research are to find out how the strategy of increasing village original income has an impact on the community's economy and how siyāsah māliyah views this strategy. The type of research used in this research is field research, where this research was carried out by interviewing staff at Sumber Agung Pekon, Ngambur District, Pesisir Barat Regency. Data analysis was carried out qualitatively, processing data analysis using descriptive analysis methods, namely discussions based on general thought patterns and then concluded in specific terms. The research results show that the strategy to increase village original income which has an impact on the community economy in the Sumber Agung area, Ngambur District, Pesisir Barat Regency is by establishing village-owned business entities, developing beach tourism, and also having village markets. The conclusion from the results of this research is that the strategy to increase village original income which has an impact on the economy of the community in the Ngambur area has made a contribution, although not much. Siyāsah māliyah's review of the increase in original village income which has an impact on the economy of the community in the Sumber Agung District of Ngambur is in accordance with the principle of benefit, namely prioritizing the interests of the people rather than the interests of the individual.

Features of teaching social humanitarian disciplines at the university for students studying in English

The article is devoted to the description of the research conducted within the framework of teaching the course “Political Science” at the Karaganda Medical University using CLIL (Content and Language Integrated Learning) technology. In the last decade, CLIL technology has become widely used. This is a dual educational approach in which an additional language is used to study and teach a general education subject, both its content and language. Authentic materials have a special role in this approach. They help to enrich students' learning experience, broaden their horizons and acquire knowledge not only about the subject, about the contextual interdisciplinary environment, but also about specific terms in the study of the subject and their use within authentic texts. According to the results of the work the positive dynamics of the understanding of authentic texts was observed in all students to varying degrees. It should be noted that in the oral survey students repeatedly expressed interest in the prepared tasks with Indian content, which undoubtedly confirms the high motivation of students to the developed lessons with authentic material, and, consequently, to the subject and language being studied, which can serve as an incentive for further development and use of this experience.

Future-fit and Innovative School Leadership in the African Context: Lesson for Sustainability in Underdeveloped and Developing Countries

ABSTRACT This study explored a future-fit scoping review from the perspective of leadership in schools within the context of Africa. A qualitative method was adopted for the study following a search of four databases, using specific key terms. Sequel to the search, articles were retrieved, coded and thematically analyzed. The findings of the study showed that while past colonial practices influence the current practices in the education system and societies of countries in Africa, the Fourth Industrial Revolution, together with its challenges, influences the envisaged future. Thus, curricula revision for alignment, and investment in human capital development and technology is needed.

On the feasibility and the impact resistance of a 3D cross-based fractal produced by powder bed fusion additive manufacturing

Designers have been fascinated by exploring new geometries made by high-performance structures. In more specific terms, biological systems have always been proven to be characterised by sophisticated structures with adapting properties to nature challenges. Insightful analyses have shown how these natural structures are dominated by characteristics such as high energy absorption and elevated strength-weight proportion. Fractal geometries are examples of bio-inspired mathematical objects whose complex 3D structures can be obtained only by advanced manufacturing systems, such as additive manufacturing (AM). This study investigates the feasibility and energy absorption properties of a novel fractal structure based on a 3D Greek cross (3D-CFS). The structure was designed with different volume fractions and produced by powder bed fusion (PBF) AM processes in polyamide (PA12) and thermoplastic polyurethane (TPU). The 3D-CFS properties are investigated under quasi-static and dynamic compression tests. The analysis revealed that for certain geometrical parameters, the manufacturing of the structures is constrained by the sintered powder entrapped in the structure. However, in the case of powder-free structures, the results showed a high impact resistance and cushioning capability. Overall, in terms of specific energy absorption (SEA), the TPU structures showed values between 2.5 and 3.5 kJ/kg, while PA12 ones are between 7.5 and 17.4 kJ/kg, making the 3D-CFS structure compatible with personal protective equipment (PPE) applications. Compared to the literature data on cellular structures made by AM, 3D-CFS performs considerably better. Also, PA12 3D-CFS is better, with a SEA value up to 170% higher than that of a typical material employed for head PPE (e.g. EPS-60 SEA equal to 2.76 kJ/kg). In contrast, TPU 3D-CFS looks more promising in the case of multiple impact conditions.

Use of Community Health Workers Among U.S. Male Latino Population: A Scoping Review.

Community Health Workers (CHWs) are an effective strategy to address the health needs of specified communities. The purpose of this scoping review was to explore the use of CHWs to address the health needs of the Latino male population. This project used specific search terms to identify relevant articles from PubMed, PsycINFO, and Google Scholar. Eligible articles included studies, conducted in the U.S. and in English from 2010 to 2022, that assessed the use of CHWs among a predominantly male (≥ 50%) Latino population. Twenty articles consisting of 13 interventions were identified for review and were further categorized into male-only participant samples (n = 10) and mixed-gender but predominantly-male participant samples (n = 10) for synthesis. Male-only participant samples focused on occupational health and participant's social support and networks. Predominantly-male, mixed-gender participant sample interventions were disease-centered and emphasized the longitudinal support of CHWs as well as social networks. Of the 13 interventions reviewed, almost all (n = 10) utilized existing social networks for engagement and nearly half (n = 6) employed community-based participatory research (CBPR) principles. Findings suggest that recruiting CHWs from within existing social networks and using CBPR are important factors for successful health promotion among male Latinos.

Breaking It Down: A Systematic Review Unravelling the Impact of Attention Deficit Hyperactivity Disorder and Methylphenidate on Childhood Fractures.

Limb fractures are a common cause of pediatric hospital admissions and surgeries, with a significant prevalence in the United Kingdom across all injury categories. Among psychiatric conditions in children, attention deficit hyperactivity disorder (ADHD) stands out as frequently associated with fractures, particularly those involving extremities. ADHD, with diagnoses prevalent among a significant proportion of school-age children and adolescents, has witnessed a growing global incidence. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist for our systematic literature search, using various databases and specific search terms related to ADHD and fractures. We considered articles from 2018 to 2023, focusing on English language papers with free full-text access. Our selection process used the PRISMA flowchart. We began with 1,890 articles and, after deduplication, title screening, abstract assessment, and quality evaluation included nine research papers in our review. Our primary focus was on examining fracture-related outcomes in individuals with ADHD compared to those without, considering medication status. These studies encompassed various designs, with a focus on the ADHD-fracture relationship and methylphenidate's (MPH) impact. Our study confirms that ADHD increases fracture risk and suggests that MPH may help mitigate this risk. Early ADHD detection is vital for nonpharmacological interventions. Orthopedic surgeons should proactively identify ADHD, while healthcare professionals should offer injury prevention guidance, particularly for at-risk groups.

Prevalence of non-neurogenic male lower urinary tract symptoms after kidney transplantation.

This review investigates the prevalence of male non-neurogenic lower urinary tract symptoms (LUTS) after renal transplant, as kidney transplantation is a transformative intervention for patients with end-stage renal disease significantly enhancing quality of life that might be diminished by LUTS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A systematic search in the PubMed and Scopus databases was performed using specific terms. Inclusion criteria considered male kidney transplant recipients, analysing outcomes in English-language studies. Discrepancies were resolved by consultation. Among 18 studies involving 29 086 recipients, the prevalence of non-neurogenic LUTS ranged from 5.8% to 33.0%. Studies predominantly used the International Prostate Symptom Score for evaluation. Surgical interventions, mostly for benign prostatic obstruction, ranged from 2.5% to 20.0%. Voiding and post-micturition symptoms were under-represented. This review found varied non-neurogenic LUTS prevalence and characteristics in male kidney transplant recipients, emphasising the need for standardised assessments, prospective studies, and improved understanding of LUTS mechanisms. Enhanced knowledge can guide interventions, additionally benefiting recipient quality of life.

Abstract 3998: Preclinical efficacy of a synthetic Notch-based combinatorial immunotherapy against colorectal cancer with HER2 amplification

Abstract HER2 amplification occurs in about 5% of colorectal cancers (CRC) and is only partially associated with clinical response to combined HER2/EGFR targeted treatment. An alternative approach, based on Adoptive Cell Therapy (ACT) using T cells engineered with anti-HER2 Chimeric Antigen Receptor (CAR), proved toxic due to "on-target off-tumor" activity. Therefore, we developed a combinatorial ACT strategy to safely target HER2 amplification in CRC using a synNotch-based artificial regulatory network. A synthetic Notch receptor was employed in which the extracellular domain is an anti-HER2 scFv and the intracellular domain contains the GAL4VP64 artificial transcription factor. Engagement of the HER2-synNotch by overexpressed HER2 on the surface of target cells induces GAL4VP64 cleavage and translocation to the nucleus, where it drives expression of a CAR under a GAL4-responsive promoter. In this way, only cells co-expressing both HER2 and the CAR target are killed. Carcinoembryonic antigen (CEA) was selected as a colon-specific CAR target: CEA expression is indeed restricted to the digestive tract and is increased in CRC. The natural killer cell line NK-92 was chosen as effector to be engineered. NK-92 cells transduced with HER2-synNotch and inducible CEA-CAR lentiviral vectors were subsequently sorted in the OFF and ON state to select those with the higher CAR induction after synNotch engagement. Subsequently, cloning of sorted cells led to identification of an optimally responsive clone (clone 5F), in terms of specificity and amplitude of CAR induction. The 5F clone demonstrated significant activity in vitro and in vivo specifically against HER2amp CRC models, with no effects on cells with physiological HER2 levels. In vitro, the 5F clone displayed selective cytotoxicity against HER2amp/CEA+ CRC cells, with minimal killing activity against HER2amp/CEA- cells, or HER2norm/CEA+ cells. Additional assays on 3D organoids highlighted better recruitment and infiltration by the 5F clone respect to NK-92 WT cells, only in HER2amp models. In vivo, NK-92.5F significantly impaired tumor growth in two different HER2amp CRC models, with no effect on HER2norm CRC cells. To further improve survival, tumor penetration and in vivo efficacy of the NK-92.5F clone, a more complex system was built, in which HER2 synNotch engagement drives expression of both the CEA-CAR and IL2. 5F-IL2 cells displayed further increased cytotoxicity in vitro. In vivo, 5F-IL2 cells drastically increased survival of mice carrying HER2amp CRC xenografts with respect to the parental 5F clone. The observed selective therapeutic efficacy both in vitro and in vivo of this innovative HER2 synNotch/CEA-CAR system, and its future evolutions, opens perspectives for possible clinical applications in cases of HER2amp CRC resistant or partially responsive to HER2/EGFR blockade. Citation Format: Marco Cortese, Erica Torchiaro, Alice D'Andrea, Consalvo Petti, Federica Invrea, Letizia Franco, Chiara Donini, Valeria Leuci, Simonetta M. Leto, Valentina Vurchio, Francesca Cottino, Claudio Isella, Sabrina Arena, Elisa Vigna, Andrea Bertotti, Livio Trusolino, Dario Sangiolo, Enzo Medico. Preclinical efficacy of a synthetic Notch-based combinatorial immunotherapy against colorectal cancer with HER2 amplification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3998.