Universal Trigger Research Articles

Membrane Tension Regulation is Required for Wound Repair.

Disruptions of the eukaryotic plasma membrane due to chemical and mechanical challenges are frequent and detrimental and thus need to be repaired to maintain proper cell function and avoid cell death. However, the cellular mechanisms involved in wound resealing and restoration of homeostasis are diverse and contended. Here, it is shown that clathrin-mediated endocytosis is induced at later stages of plasma membrane wound repair following the actual resealing of the wound. This compensatory endocytosis occurs near the wound, predominantly at sites of previous early endosome exocytosis which is required in the initial stage of membrane resealing, suggesting a spatio-temporal co-ordination of exo- and endocytosis during wound repair. Using cytoskeletal alterations and modulations of membrane tension and membrane area, membrane tension is identified as a major regulator of the wounding-associated exo- and endocytic events that mediate efficient wound repair. Thus, membrane tension changes are a universal trigger for plasma membrane wound repair modulating the exocytosis of early endosomes required for resealing and subsequent clathrin-mediated endocytosis acting at later stages to restore cell homeostasis and function.

Enhancing RNA detection and breast cancer subtyping with a universal 3D-hybridization chain reaction system

Breast cancer, a globally prevalent malignancy, is characterized by pronounced heterogeneity. Accurate subtyping requires the simultaneous detection of different biomarkers, which is crucial for personalized treatment strategies. However, existing methodologies are hindered by limited versatility and sensing performance. To overcome these hurdles, this study presents a universal 3D-Hybridization Chain Reaction (3D-HCR) system for RNA detection and subtype-specific diagnosis of breast cancer. The system integrated a universal trigger for HCR, thereby circumventing the need for complex sequence design and enabling the analysis of various RNA targets. Leveraging the spatial-confinement effect offered by DNA nanocarriers, this system exhibited superior amplification efficiency, achieving detection limits of 3.83 pM and 4.96 pM for PD-L1 mRNA and miR-21, respectively. Importantly, the system could differentiate between triple-negative breast cancer and estrogen receptor-positive breast cancer in both living cells and clinical tissues. These findings underscore the potential of the universal 3D-HCR system as a promising tool in clinical diagnostics. With its proven proficiency in breast cancer diagnostics and versatility in RNA analysis, this system holds the promise of broadening the horizons of precision medicine.

A universal nanoreactor triggering butterfly effect for encouraging Fenton/Fenton-like reactions and chemodynamic therapy

Fenton/Fenton-like reaction induced chemical dynamic therapy (CDT) has been widely recognized in tumor therapy. Due to the low efficiency of conversion from high-valent metal ions (M(n+1)+) to low-valent ions (Mn+) in the Fenton/Fenton-like catalytic process, enhancing the conversion efficiency safely and effectively would create a great opportunity for the clinical application of CDT. In the study, a universal nanoreactor (NR) consisting of liposome (Lip), tumor cell membrane (CM), and bis(2,4,5-trichloro-6-carboxyphenyl) oxalate (CPPO) is developed to tackle this challenge. The CPPO was first discovered to decompose under weak acidity and H2O2 conditions to generate carboxylic acids (R′COOH) and alcohols (R′OH) with reducibility, which will reduce M(n+1)+ to Mn+ and magnify the effect of CDT. Furthermore, glucose oxidase (GOx) was introduced to decompose glucose in tumor and generate H2O2 and glucose acid, which promote the degradation of CPPO, further strengthening the efficiency of CDT, leading to a butterfly effect. This demonstrated that the butterfly effect triggered by NR and GOx encourages Fenton/Fenton-like reactions of Fe3O4 and MoS2, thereby enhancing the tumor inhibition effect. The strategy of combining GOx and CPPO to strengthen the Fenton/Fenton-like reaction is a universal strategy, which provides a new and interesting perspective for CPPO in the application of CDT, reflecting the exquisite integration of Fenton chemistry and catalytic medicine.

Universal adversarial backdoor attacks to fool vertical federated learning

Vertical federated learning (VFL) is a privacy-preserving distribution learning paradigm that enables participants, owning different features of the same sample space to train a machine learning model collaboratively while retaining their data locally. This paradigm facilitates improved efficiency and security for participants such as financial or medical fields, making VFL an essential component of data-driven Artificial Intelligence systems. Nevertheless, the partitioned structure of VFL can be exploited by adversaries to inject a backdoor, enabling them to manipulate the VFL predictions. In this paper, we aim to investigate the vulnerability of VFL in the context of binary classification tasks. To this end, we define a threat model for backdoor attacks in VFL and introduce a universal adversarial backdoor (UAB) attack to poison the predictions of VFL. The UAB attack, consisting of universal trigger generation and clean-label backdoor injection, is incorporated during the VFL training at specific iterations. This is achieved by alternately optimizing VFL sub-problems' universal trigger and model parameters. Our work distinguishes itself from existing studies on designing backdoor attacks for VFL, as those require the knowledge of auxiliary information that is not accessible within the split VFL architecture. In contrast, our approach does not require additional data to execute the attack. On the real-world datasets, our approach surpasses existing state-of-the-art methods, achieving up to 100% backdoor task performance while maintaining the main task performance. Our results in this paper make a major advance in revealing the hidden backdoor risks of VFL, hence paving the way for the future development of secure VFL. Our results in this paper make a major advance in revealing the hidden backdoor risks of VFL, hence paving the way for the future development of secure VFL applications such as finance.

Cognitive disturbances during perimenopause: are they linked to dementia?

Women have a greater risk of developing Alzheimer's disease (AD) compared to men. This biological sex difference is primarily due to the greater longevity of women compared to men, but other factors also contribute to this difference, including a greater risk of AD among those with the apolipoprotein epsilon 4 (APOE4) genetic risk factor. Sex steroid hormones have myriad effects on the central nervous system, and other bodily systems that play an important role in brain health, including immune, metabolic and cardiovascular systems. Knowledge of the brain changes that occur in menopause is limited by the lack of large-scale longitudinal neuroimaging studies of women transitioning through the menopause, though such studies are currently underway. Initial evidence from cross-sectional studies and small longitudinal studies suggest that both brain structure and function may undergo changes, and that AD biomarkers may accumulate more rapidly during the menopause. Clearly the menopause is not a universal trigger for the development of AD, as all women who live into late life transition through the menopause and only a minority of women with develop AD. One of the factors that may make certain women more vulnerable to AD is vasomotor symptoms (VMS). Although a causal role of VMS is not established, correlational studies link objectively measured VMS with memory deficits, disruptions in brain function and the accumulation of white matter hyperintensities, small ischemic lesions that increase the risk of both vascular dementia and AD. Mood symptoms and sleep disruption also contribute to cognitive changes and alterations in brain health. Some evidence indicates that hormone therapy (HT) may be associated with lower levels of AD biomarkers, but more clinical trial data is needed, particularly in women with VMS. Medical societies reliably conclude based on the evidence to date that HT should not be used for the treatment of cognitive issues or the prevention of dementia. The use of HT for the treatment of VMS, however, is indicated and may help women to maintain more optimal brain health as they age.

Role of mitophagy in the hallmarks of aging.

Aging, subjected to scientific scrutiny, is extensively defined as a time-dependent decline in functions that involves the majority of organisms. The time-dependent accretion of cellular lesions is generally a universal trigger of aging, while mitochondrial dysfunction is a sign of aging. Dysfunctional mitochondria are identified and removed by mitophagy, a selective form of macroautophagy. Increased mitochondrial damage resulting from reduced biogenesis and clearance may promote the aging process. The primary purpose of this paper is to illustrate in detail the effects of mitophagy on aging and emphasize the associations between mitophagy and other signs of aging, including dietary restriction, telomere shortening, epigenetic alterations, and protein imbalance. The evidence regarding the effects of these elements on aging is still limited. And although the understanding of relationship between mitophagy and aging has been long-awaited, to analyze details of such a relationship remains the main challenge in aging studies.

A Dual Model Watermarking Framework for Copyright Protection in Image Processing Networks

Image processing networks have gained great success in many fields, and thus the issue of copyright protection for image processing networks has become a focus of attention. Model watermarking techniques are widely used in model copyright protection, but there are two challenges: (1) designing universal trigger sample watermarking for different network models is still a challenge; (2) existing methods of copyright protection based on trigger s watermarking are difficult to resist forgery attacks. In this work, we propose a dual model watermarking framework for copyright protection in image processing networks. The trigger sample watermark is embedded in the training process of the model, which can effectively verify the model copyright. And we design a common method for generating trigger sample watermarks based on generative adversarial networks, adaptively generating trigger sample watermarks according to different models. The spatial watermark is embedded into the model output. When an attacker steals model copyright using a forged trigger sample watermark, which can be correctly extracted to distinguish between the piratical and the protected model. The experiments show that the proposed framework has good performance in different image segmentation networks of UNET, UNET++, and FCN (fully convolutional network), and effectively resists forgery attacks.

NEPHROPROTECTIVE THERAPY IN ACUTE PERITONITIS

Increasing the effectiveness of peritonitis treatment remains an urgent issue for abdominal urgent surgery. So far, several effective surgical technologies have been developed. However, conservative therapy in the early postoperative period is an object for development, including the target organ protection influence.
 The aim of the study is to determine the nephroprotective efficacy of complex treatment with remaxol in acute peritonitis.
 Materials and Methods. The authors examined 46 patients with acute peritonitis. The patients were divided into two groups: Groups 1 (comparison, n=26) received standardized treatment, Group 2 (main, n=20) was treated with remaxol. Research methods, in addition to routine ones, included the assessment of kidney functional state, endotoxicosis, and oxidative stress.
 Results. It is revealed that in acute peritonitis, the authors recorded substantial deviations in the functional state of the kidneys, such as endogenous intoxication, and oxidative stress. Maximum imbalance is diagnosed on the 1st day of the early postoperative period. The use of remaxol in the complex therapy of patients with acute peritonitis significantly improves the functional state of the kidneys, thus, optimizing the course of the early postoperative period and reducing the severity of endogenous intoxication. The positive effect of the drug is caused by its ability to manage the oxidative stress, a universal pathogenetic trigger for system and organ damage, including kidneys.
 Conclusions. Remaxol has a nephroprotective effect and improves the course of the early postoperative period.

On a New Paradigm of the Development of Neurodegenerative Diseases by the Example of Alzheimer’s Disease and Parkinson’s Disease

The role of neuronal inflammation developing during the formation of amyloid plaques and Lewy bodies has been investigated. The influence of various exogenous and endogenous factors on the development of neuroinflammation has been established, but the role of various infectious agents in the development of this process has been much less studied. Today, the existence of a universal trigger mechanism of the neurodegenerative process is obvious: a specific pathogen of a bacterial or viral nature (including a long-term persistent in the nervous tissue in a latent state), reactivating, penetrates into certain cerebral structures, where it is influenced by either Aβ or resident macrophages of the central nervous system, which, in turn, are activated and induce the release of pro-inflammatory cytokines, leading to the development of neuronal inflammation, autophagy and neurodegeneration. Reactivation of latent, such as herpes, infection in individuals who are carriers of APOE4 significantly increases the risk of developing Alzheimer's disease. Class II genes of the HLA locus (HLA II) may be related to the progression of neurodegenerative diseases. The increase in iron levels in the glia is induced by inflammation, which leads to neurodegeneration. Disruption of the homeostasis of redox-active metals, iron and copper, is an integral part of the pathogenesis of Alzheimer's disease and Parkinson's disease. The developing neuroinflammation leads to the intensification of the processes of peroxidation, oxidation of metals and the development of ferroptosis.Изучена роль развивающегося при образовании амилоидных бляшек и телец Леви нейронального воспаления. Установлено влияние различных экзогенных и эндогенных факторов на развитие нейровоспаления, однако значительно меньше изучена роль различных инфекционных агентов в этом процессе. На сегодняшний день очевидно существование универсального триггерного механизма нейродегенеративного процесса: специфичный возбудитель бактериальной или вирусной природы (в том числе длительно персистирующий в нервной ткани в латентном состоянии), реактивируясь, проникает в определенные церебральные структуры, где оказывается под влиянием либо Аβ, либо резидентных макрофагов ЦНС, которые, в свою очередь, активируются и индуцируют высвобождение провоспалительных цитокинов, приводящих к развитию нейронального воспаления, аутофагии и нейродегенерации. Реактивация латентной, например герпетической, инфекции у лиц, являющихся носителями АПОЕ4, существенно повышает риск развития болезни Альцгеймера. К прогрессированию нейродегенеративных заболеваний может иметь отношение II класс генов локуса HLA (HLA II). Повышение уровня железа в глии индуцировано воспалением, что приводит к нейродегенерации. Нарушение гомеостаза редокс-активных металлов, железа и меди является составляющей частью патогенеза болезни Альцгеймера и болезни Паркинсона. Развивающееся нейровоспаление приводит к интенсификации процессов перекисного окисления, окисления металлов и развитию ферроптоза.

The Event Timing Finder for the Central Drift Chamber Level-1 Trigger at the Belle II experiment

The level-1 trigger system of the Belle II experiment is designed to select physics events of interest with almost 100% efficiency for hadronic events. In terms of event timing decision, the level-1 trigger is required to have an accuracy of less than 10 ns. The Central Drift Chamber (CDC) level-1 trigger provides the event timing information as one of the level-1 timing sources. We developed the new algorithm to measure the event timing with an accuracy of about 10 ns based on the CDC hit timing. Two-dimensional charged track reconstruction by Hough transformation was utilized to reduce high background hits. We used a new-developed general-purpose FPGA board (Universal Trigger board 4) for this module for the first time. We report the performance of the new algorithm using e + e − collision data collected in 2020.

A novel label-free universal biosensing platform based on CRISPR/Cas12a for biomarker detection

The development of a biosensing platform with high sensitivity, high specificity, and low cost for the detection of biomarkers, especially one that is programmable and universal, is critical for disease surveillance and diagnosis, yet it remains a difficulty. Herein, we combined the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system with a fluorescent label-free biosensor platform for sensitive and specific detection of disease-related protein, small molecule and nucleic acid. In this strategy, we designed an exonuclease III-mediated target cycle and released a universal trigger chain to stimulate the enzyme activity of CRISPR/Cas12a for additional signal amplification. The hydrolysis of ssDNA-templated silver nanoclusters (ssDNA-Ag NCs) as the reporter probe resulted in a significant decrease of fluorescence intensity. This biosensing platform can be flexibly used to the sensitive and specific determination of protein, small molecule, or microRNA in biological samples by simply transforming the target recognized sequences in the DNA hairpin. In this work, a new label-free sensing system used the fluorescent ssDNA-Ag NCs as the signal output does not need to be marked in advance and has no background signal. In addition, the method has the advantages of low cost, simple operation and high speed, and provides an innovative idea for the development of a powerful clinical diagnosis tool.

MINIMAL: Mining Models for Universal Adversarial Triggers

It is well known that natural language models are vulnerable to adversarial attacks, which are mostly input-specific in nature. Recently, it has been shown that there also exist input-agnostic attacks in NLP models, called universal adversarial triggers. However, existing methods to craft universal triggers are data intensive. They require large amounts of data samples to generate adversarial triggers, which are typically inaccessible by attackers. For instance, previous works take 3000 data samples per class for the SNLI dataset to generate adversarial triggers. In this paper, we present a novel data-free approach, MINIMAL, to mine input-agnostic adversarial triggers from models. Using the triggers produced with our data-free algorithm, we reduce the accuracy of Stanford Sentiment Treebank’s positive class from 93.6% to 9.6%. Similarly, for the Stanford Natural LanguageInference (SNLI), our single-word trigger reduces the accuracy of the entailment class from 90.95% to less than 0.6%. Despite being completely data-free, we get equivalent accuracy drops as data-dependent methods

Adenosine Associated Pre- and Postconditioning in Real Medical Practice

It has been established that adenosine is a universal trigger of the processes of preparation (conditioning) of the myocardium for ischemic injury, which is confirmed by randomized clinical trials AMISTAD II, TIMI-4, TIMI-9B. Adenosine is included in the guidelines of the ESC Task Force (European Society of Cardiology) as a means of basic therapy, as a representative of the class of potassium channel stimulants (2019) [1]. However, the use of adenosine as an injectable form for intracoronary or intravenous administration is associated with a number of side effects - rapid degradation of the drug in the bloodstream, the need for careful monitoring of systemic hemodynamics (hypotension, tachy- or bradyarrhythmia, ventricular tachycardia, atrioventricular block), frequent development of undesirable gastrointestinal manifestations. All this prompted the search for an alternative form of adenosine use, which would allow wider use of the potentially beneficial effect of adenosine on ischemic pre- and post-conditioning in real medical practice.
 More recently, on the pharmaceutical market of Ukraine for the first time appeared a pharmacological agent - Advocard, as a drug with the ability to start the processes of pre- and post-conditioning, with sublingual (oral) form of application. Advocard is an original combined polypill drug with three components: adenosine-5-triphosphate-gluconate-magnesium (II) trisodium salt (magladen) – 18,6-29,25 mg, molsidomine – 0,3 mg and folic acid - 0,45 mg. Recommendations for the use of the Advocard in medical practice are based on the results of clinical studies, which proved that the oral (sublingual) form of adenosine is not only effective and appropriate, but also safe with long-term use.
 The therapeutic efficacy of Advocard in chronic coronary syndromes [stable, vasospastic, microvascular angina (pain of small coronary vessels), painless myocardial ischemia] and acute coronary syndromes (STEMI / NSTEMI, instability to stenocardia) before or immediately after coronary stenting is in counteracting the mechanisms of reperfusion injury.
 Clinical practice has shown that Advocard is appropriate for the prevention of NO-REFLOW after opening the epicardial coronary artery, even with the result of TIMI-3. Thus, the Advocard opens the prospect of improving the effectiveness of coronary interventions and is an adjunct to complete myocardial revascularization.

Implementing a New Rubber Plant Functional Type in the Community Land Model (CLM5) Improves Accuracy of Carbon and Water Flux Estimation

Rubber plantations are an economically viable land-use type that occupies large swathes of land in Southeast Asia that have undergone conversion from native forest to intensive plantation forestry. Such land-use change has a strong impact on carbon, energy, and water fluxes in ecosystems, and uncertainties exist in the modeling of future land-use change impacts on these fluxes due to the scarcity of measured data and poor representation of key biogeochemical processes. In this current modeling effort, we utilized the Community Land Model Version 5 (CLM5) to simulate a rubber plant functional type (PFT) by comparing the baseline parameter values of tropical evergreen PFT and tropical deciduous PFT with a newly developed rubber PFT (focused on the parameterization and modification of phenology and allocation processes) based on site-level observations of a rubber clone in Indonesia. We found that the baseline tropical evergreen and baseline tropical deciduous functions and parameterizations in CLM5 poorly simulate the leaf area index, carbon dynamics, and water fluxes of rubber plantations. The newly developed rubber PFT and parametrizations (CLM-rubber) showed that daylength could be used as a universal trigger for defoliation and refoliation of rubber plantations. CLM-rubber was able to predict seasonal patterns of latex yield reasonably well, despite highly variable tapping periods across Southeast Asia. Further, model comparisons indicated that CLM-rubber can simulate carbon and energy fluxes similar to the existing rubber model simulations available in the literature. Our modeling results indicate that CLM-rubber can be applied in Southeast Asia to examine variations in carbon and water fluxes for rubber plantations and assess how rubber-related land-use changes in the tropics feedback to climate through carbon and water cycling.

The role of infectious agents in the development of neurodegenerative diseases

Actually, there is no consensus about the causes of the development in most neurodegenerative diseases. Recent international publications describe various hypotheses of the genesis of such diseases. Infectious is considered as one of them, assuming an infectious agent can trigger a cascade of pathological processes that eventually lead to the manifestation of various neurodegenerative diseases. The direct relationship between infectious invasion and the development of neurodegenerative diseases is not fully proved yet, but these publications confirm the hypothesis that a variety of pathogens (viruses, bacteria, intracellular parasites etc.) can induce the process of neuronal inflammation with subsequent neurodegeneration. As a result of the scientific research, various ways of penetration of infectious agents into the central nervous system have been studied and proven. In the case of neuroinfections already studied, inflammatory and alterative changes in nervous tissue occur with the direct participation of neuroglia and cells of the immune system, which may be part of the universal trigger mechanism of the neurodegenerative process. At the same time, in the case of a number of diseases, the primary role of specific infectious agents is possible. It has been shown that neurological complications of a novel coronavirus infection can also occur as a result of both direct cytopathic action of the pathogen or activation of neuroinflammation processes. Of course, this hypothesis of neurodegenerative pathology requires a comprehensive analysis and subsequent confirmation, however, the investigation of molecular and cellular mechanisms of neuroinflammation and neurodegeneration already opens up broad prospects for finding possible pathogenetic therapy of these diseases (bibliography: 42 refs)

Young, Empowered and Strong: A Web-Based Education and Supportive Care Intervention for Young Women With Breast Cancer Across the Care Continuum.

Patient-centered digital interventions may help empower young women to self-manage symptoms and psychosocial concerns and support informational needs often unaddressed in clinic. Young, Empowered and Strong (YES) is an interactive web-based intervention designed to engage young women with personalized education and symptom self-management resources on the basis of responses to patient-reported outcome-based questionnaires. We piloted YES among young women (< 45 years) with newly diagnosed early breast cancer (EBC) or metastatic breast cancer (MBC) and breast cancer survivors (BCSs). Assessments were deployed weekly (EBC and MBC) or every 4 weeks (BCSs) over 12 weeks. At study completion, use, feasibility, and acceptability of YES were evaluated via a survey and semistructured interview. Thirty women were enrolled between April and June 2019: 10 EBC, 10 BCSs, and 10 MBC. The mean age at diagnosis and enrollment was 36 (range 25-44) and 39 (range 31-44) years, respectively. Most participants were actively treated (96%, 27 of 28) with endocrine therapy (54%, 15 of 28) or chemotherapy (43%, 12 of 28). Overall, 61% (180 of 296) of assessments were completed (EBC: 70%, BCSs: 63%, and MBC: 52%). Of 37 patient-reported outcome and need domains, the most frequently triggered were sexual health (EBC: 90%, BCSs: 90%, and MBC: 90%), anxiety (EBC: 80%, BCSs: 90%, and MBC: 90%), stress and mindfulness (EBC: 80%, BCSs: 90%, and MBC: 90%), and fatigue (EBC: 90%, BCSs: 80%, and MBC: 90%). On postpilot survey, participants reported that YES helped them to learn (50%, 7 of 14), monitor (43%, 6 of 14), and manage (57%, 8 of 14) their symptoms. YES is a feasible and acceptable digital intervention to support young women across the breast cancer care continuum. The nearly universal triggering of sexual and mental health needs suggests suboptimal management in the clinical setting and the potential for self-management through a digital platform.

Universal and Programmable Rolling Circle Amplification-CRISPR/Cas12a-Mediated Immobilization-Free Electrochemical Biosensor.

The development of a sensing platform with high sensitivity and specificity, especially programmability and universal applicability, for the detection of clinically relevant molecules is highly valuable for disease monitoring and confirmation but remains a challenge. Here, for the first time, we introduce the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system into an immobilization-free electrochemical biosensing platform for sensitively and specifically detecting the disease-related nucleic acids and small molecules. In this strategy, a modular rolling circle amplification (RCA) is designed to transform and amplify the target recognition event into the universal trigger DNA strand that is used as the trigger to activate the deoxyribonuclease activity of CRISPR/Cas12a for further signal amplification. The cleavage of the target-activated blocker probe allows the methylene blue-labeled reporter probes to be captured by the reduced graphene oxide-modified electrode, leading to an obviously increased electrochemical signal. We only need to simply tune the sequence for target recognition in RCA components, and this strategy can be flexibly applied to the highly sensitive and specific detection of microRNAs, Parvovirus B19 DNA, and adenosine-5'-triphosphate and the calculated limit of detection is 0.83 aM, 0.52 aM, and 0.46 pM, respectively. In addition, we construct DNA logic circuits (YES, NOT, OR, AND) of DNA inputs to experimentally demonstrate the modularity and programmability of the stimuli-responsive RCA-CRISPR/Cas12a system. This work broadens the application of the CRISPR/Cas12a system to the immobilization-free electrochemical biosensing platform and provides a new thinking for developing a robust tool for clinical diagnosis.

Abstract PD12-08: Young, empowered &amp; strong (YES): A web-based education and supportive care intervention for young women with breast cancer across the care continuum

Abstract Background: Young women diagnosed with breast cancer have unique physical and psycho-social needs that are often unaddressed. Patient-centered models of care, including eHealth strategies, can help empower young women to self-manage symptoms and psychosocial concerns, as well as support informational needs throughout the cancer care trajectory. Methods: YES (Young, Empowered and Strong) is an interactive web-based portal designed with patient-reported outcome questionnaires (PROs) that trigger delivery of young breast cancer patient-specific education and symptom management materials. Personal journal and messaging components are also available. We piloted the YES portal among young women (&amp;lt;45 years) with newly diagnosed early breast cancer (EBC), breast cancer survivors (BC-S) and women living with metastatic breast cancer (MBC), for whom PROs were deployed weekly (EBC, MBC) or every 4 weeks (BC-S) over 12-weeks. At study completion, the use, feasibility and acceptability of the YES portal was assessed via a survey and a structured interview. Results: Thirty women were enrolled between April and June 2019: 10 EBC, 10 BC-S and 10 MBC. Mean age at diagnosis and enrollment was 36 (range 25-44) and 39 (range 31-44) years respectively and 13% (4/30) were non-white. Nearly all participants were receiving treatment (96%, 27/28) including 54% (15/28), endocrine therapy and 43% (12/28), chemotherapy. Overall, 61% (180/296) of PROs deployed were completed, with completion rates highest for EBC patients (EBC: 70%, BC-S: 63%, MBC: 52%). Of 37 PROs domains, the most frequently triggered were sexual health (EBC: 90%, BC-S: 90%, MBC: 90%), anxiety (EBC: 80%, BC-S: 90%, MBC: 90%) and fatigue (EBC: 90%, BC-S: 80%, MBC: 90%). Physical domains and young breast cancer specific domains commonly addressed in clinic (i.e., fertility, genetic testing) were less frequently triggered. The post-pilot survey was answered by 15 participants: 8/15 reported the information shared through YES was helpful, 6/14 felt the portal helped monitor side effects and 8/14 felt the portal helped manage side-effects. Nineteen women completed post-pilot interviews: most women with EBC and MBC said the portal increased symptom awareness and complemented information communicated by providers; the BC-S group more frequently commented that features of the YES portal focusing on symptom monitoring/management would have been more useful when they were earlier in their care (newly diagnosed or undergoing more active treatment). Conclusions: YES, a novel eHealth intervention designed to support young women with breast cancer, is feasible and acceptable to young women across the breast cancer care continuum. The nearly universal triggering of information and support for sexual and mental health suggests sub-optimal management of these issues in the clinical setting and the potential role for self-management through an eHealth platform for this population. Future efforts will aim to evaluate whether provision of information through the YES portal reduces symptom burden and unaddressed needs and concerns in young women with breast cancer. Citation Format: Tal Sella, Craig Snow, Hannah Freeman, Phillip D Poorvu, Shoshana M Rosenberg, Ann H Partridge. Young, empowered &amp; strong (YES): A web-based education and supportive care intervention for young women with breast cancer across the care continuum [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-08.

Genesis, Evolution and Indicators of Leadership in the World Economy

The article reflects the results of scientific research on leadership in the world economy. The purpose of the article is to analyze the problems of determining the key factors of the genesis and evolution of this phenomenon, as well as to identify indicators of the leading position of countries in the global economy. The relevance of the topic is due to the current global processes of the structural shifts within the world economic system and trends concerning a new change in the geo-economic leadership. Based on the world-system methodology, the geo-economic approach, as well as the comparative and historical methods in economics, methods of global political economy, the author developed and demonstrated their synergic potential applied to the research of the world economy’s evolution. Heuristic possibilities of the methodological-theoretical concept of a geo-economic polarity (including multipolarity) are used. The author concludes that the leadership is characterized by the presence of immanent factors that determine the genesis of becoming a leader. It is substantiated the significance of each of these factors and proved that their effective combination leads to the formation of a leadership in the global economy. The article provides and describes the chronological periodization of leadership, and its universal triggers, which are unique for each specific stage of the world economy’s development. It is established the presence of key indicators that reflect this leadership, and emphasizes the change and expansion of the range of these indicators in the process of the evolutionary development of productive forces. It is justified that current leadership tends to geographic dispersion and is expressed in the gradual establishment of a geo-economic multipolarity of the world economy. The article predicts the current change in the nature of geo-economic leadership itself.

ALICE Central Trigger System for LHC Run 3

A major upgrade of the ALICE experiment is in progress and will result in high-rate data taking during LHC Run 3 (2022-2024). The LHC interaction rate at Point 2 where the ALICE experiment is located will be increased to 50 kHz in Pb–Pb collisions and 1 MHz in pp collisions. The ALICE experiment will be able to read out data at these interaction rates leading to an increase of the collected luminosity by a factor of up to about 100 with respect to LHC Runs 1 and 2. To satisfy these requirements, a new readout system has been developed for most of the ALICE detectors, allowing the full readout of the data at the required interaction rates without the need for a hardware trigger selection. A novel trigger and timing distribution system will be implemented, based on Passive Optical Network (PON) and GigaBit Transceiver (GBT) technology. To assure backward compatibility a triggered mode based on RD12 Trigger- Timing-Control (TTC) technology, as used in the previous LHC runs, will be maintained and re-implemented under the new Central Trigger System (CTS). A new universal ALICE Trigger Board (ATB) based on the Xilinx Kintex Ultrascale FPGA has been designed to function as a Central Trigger Processor (CTP), Local Trigger Unit (LTU), and monitoring interfaces. In this paper, this new hybrid multilevel system with continuous readout will be described, together with the triggering mechanism and algorithms. An overview of the CTS, the design of the ATB and the different communication protocols will be presented.