Special Interest Research Articles

Abstract PO5-18-12: Can we cure de novo oligometastatic stage IV HER2+ breast cancer with multimodality therapy? (CHLOE)

Abstract Background: The current standard of care is to treat all patients with metastatic breast cancer with palliative intent, regardless of extent of disease. However, in real world practice patients with oligometastatic disease are sometimes treated with surgery and/or radiation/ablation in combination with systemic therapy to render them as having no evidence of disease. Previous randomized clinical trials have not shown a benefit to adding surgery or radiation in metastatic breast cancer, however, these trials had a small number of HER2+ patients. HER2+ patients are uniquely responsive to combination of chemotherapy and targeted HER2 therapy and therefore may have different outcomes with a multimodality approach. The goal of this project is to use a novel, user friendly, on-line clinical study platform that registers patients and enables follow-up data collection to test the hypothesis that de novo stage IV oligometastatic HER2+ patients treated with multimodality therapy may result in improved long-term distant metastasis free survival and overall survival. Trial design: This is a prospective, nationwide registry study that will enroll newly diagnosed (de novo) oligometastatic (operationally defined by local tumor boards as disease where all metastatic lesions can be ablated) HER2+ breast cancer. A secure online portal has been created by the Yale IT team in accordance with HIPPA and cybersecurity guidelines. Data will be directly entered into the online portal by participating investigators and information regarding what treatment the patient received, if they completed treatment, and survival data will be collected. All treatment decisions will be at the discretion of the treating provider. Eligibility criteria: Patients with de novo oligometastatic HER2+ breast cancer in whom local treatment of all metastatic sites by either surgery, radiation, or ablative techniques is feasible as determined by multidisciplinary discussion or local tumor board. Specific aims: Primary: To estimate the 3 year distant metastasis free survival in patients with de novo oligometastatic HER2+ breast cancer treated with a multi-modality treatment plan. Secondary: To estimate 3 year overall survival and to monitor QOL. Statistical methods: The major analysis will occur after at least 3 years following the last subject’s enrollment in a cohort, to ensure that the objective of distant metastasis free survival at 3 years will be analyzed. It will include: tabulation of all cases entered, number and location of metastases, if treatment plan was implemented, compliance rate of treatment delivery, observed results with respect to the primary endpoint. Kaplan-Meier estimates will be presented for the analysis of survival endpoints together with a summary of associated statistics (median survival time if reached, landmark survival rate estimates and estimates for every 6 months thereafter if applicable), including the corresponding two-sided 95% confidence intervals. The 95% exact Clopper Pearson confidence intervals will be presented for binary endpoints. Paired t-test or Wilcoxon signed rank test will be used to assess the difference of continuous variables measured at different time points. The secondary clinical outcome is overall survival at 3 years, defined as the percentage of patients without an event at the 3-year follow-up time point measured from the study registration date. An event is considered death from any cause. OS time will be measured from the date of randomization to the date of first OS failure or last follow-up. OS will be estimated by the Kaplan-Meier method with OS failure defined as: death from any cause. Present accrual and target accrual: 4/42 patients Contact information for people with a specific interest in the trial: Mariya.Rozenblit@yale.edu https://chloe.yalepathaws.org Citation Format: Mariya Rozenblit, Nathalie Wiesendanger, Kelly Shanahan, Christine Hodgdon, Peter Gershkovich, Mehra Golshan, Meena Moran, Maryam Lustberg, Lajos Pusztai. Can we cure de novo oligometastatic stage IV HER2+ breast cancer with multimodality therapy? (CHLOE) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-12.

Abstract PO5-18-11: Use of DiviTum®TKa as a biomarker assay for CDK4/6 inhibitor medication compliance and drug-drug interaction assessment in ER/PR positive metastatic breast cancer

Abstract Background: CDK4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) is standard first line (1L) treatment for metastatic hormone positive (ER/PR+) HER2- negative breast cancer (mBC). Some patients have progression free survival (PFS) of 2 years or more whereas some patients have very short PFS on these medications. Thymidine kinase is a biomarker that reflects cell proliferation. DiviTum®TKa is an assay that was cleared by the FDA in July 2022 based on data that showed that thymidine kinase activity (TKa) value of < 250 DiviTum units (DuA) is associated with the decreased likelihood of disease progression within 30 days or 60 days post testing. The purpose of this study is to assess the use of TKa as a biomarker for identifying potential medical compliance issues and drug-drug interactions (DDI) in patients on CDK4/6i and to evaluate whether counseling and optimization of concurrent medications will lead to lower TKa levels in subsequent treatment cycles and possibly longer PFS. Trial design: This is a pilot study to assess whether TKa can serve as a biomarker to identify patients with a suboptimal reduction in tumor cell proliferation caused by a potential CDK4/6i compliance or DDI issue. We will also assess whether correction of the issue can improve suppression of TKa levels in ER/PR+ mBC patients on 1L CDK4/6i and ET. For screening, we are utilizing a novel automated real-time data driven cohort identification system designed by Dr. Guannan Gong at Yale. Patients will be treated and monitored as per standard of care. An aliquot of serum obtained during routine blood draws will be sent to a CLIA-certified Biovica lab for TKa testing. TKa results will be returned in real time. Patients with a detectable TKa baseline level (above 145 DuA), followed by a sustained TKa level (>145 DuA) at cycle 1 D15 and D28 will be assessed for medication compliance and DDI. TKa levels will be repeated at subsequent standard of care blood draws to assess if the intervention affected TKa levels. Patients will be followed for 2 years. Eligibility criteria: Participants must have ER+ mBC and starting 1L CDK4/6i + ET and be previously CDK4/6i -naïve. Specific aims: Primary objective: to estimate the rate of improvement in CDK4/6i response (change in TKa levels) after counseling for medication compliance and adjustment of potential deleterious DDIs. Secondary objectives: 1) estimate the rate of sub-optimal CDK 4/6i response in cycle 1 of treatment. 2) Compare clinical benefit rate (CBR) in patients with sub-optimal and optimal CDK4/6i response after both cycles 1 and cycle 3. 3) Compare PFS in patients with sub-optimal and optimal CDK 4/6i response after both cycles 1 and cycle 3. 4) Assess CDK4/6i response via TKa levels upon CDK4/6i dose reductions or changes in CDK4/6i regimens. 5) Compare CDK4/6i response profiles across the three CDK 4/6i among different patients and within the same patients if CDK4/6i is changed throughout treatment course. 6) Correlate TKa levels with tumor marker levels. 7) Assess plasma concentrations of CDK4/6i in patients with suboptimal TKa levels. Statistical methods: For binary endpoints measured at a given time point, we will estimate the two-sided 95% exact CI using Clopper-Pearson method. With a sample size of 120 patients, assuming 20% drop out rate, we predict that about 15% of patients will have suboptimal CDK4/6i response, estimating a 95% CI of 0.086-0.235 in the first cycle. Comparisons between paired outcomes will be completed using the paired t-test or Wilcoxon signed-rank test for continuous parameters of interest, or McNemar’s Chi-square test for categorical parameters of interest. Time to event endpoints will be estimated using Kaplan-Meier method. Present accrual and target accrual: This trial has just been activated. Target accrual is 120 patients. Contact information for people with a specific interest in the trial: Mariya.Rozenblit@yale.edu Citation Format: Mariya Rozenblit, Adriana Kahn, Guannan Gong, Amy Williams, Lajos Pusztai. Use of DiviTum®TKa as a biomarker assay for CDK4/6 inhibitor medication compliance and drug-drug interaction assessment in ER/PR positive metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-11.

Social App for Connecting Similar Interests People

In today's era, characterized by a profound desire for personal human connection, individuals seek to engage with like-minded people who share their interests, hobbies, passions, and ideological perspectives. Addressing this need, our social media app provides a platform for users to connect with others who resonate with their unique identities and aspirations. Built upon Flutter for frontend design and powered by Python algorithms for profile matching and recommendation systems, the app facilitates meaningful connections in both digital and physical realms. Alongside profile matching and recommendation features, the app offers a recommended system for real-world meetups, suggesting ideal venues such as restaurants, cafes, and hotels. Moreover, the app fosters the formation of communities around specific interests, ranging from classical singing to machine learning enthusiasts. Looking ahead, our vision extends into Web 3.0, where users can forge immersive virtual connections, enhancing the depth and authenticity of their interactions. Through these innovative features and future-oriented perspectives, our app endeavors to redefine social networking by enabling individuals to forge deeper, more meaningful connections aligned with their passions and aspirations.

Abstract PO2-19-05: Randomized Phase II trial evaluating three anti-diarrhoeal prophylaxis strategies in patients with HER2+/HR+ early breast cancer treated with extended adjuvant neratinib (DIANER GEICAM/2018-06)

Abstract Background: Neratinib (NER), and irreversible pan-HER tyrosine kinase inhibitor, is approved for the extended adjuvant treatment of HER2+/HR+ early breast cancer (EBC) patients within 1 year of trastuzumab (T)-based therapy completion. The ExteNET trial showed that the extended adjuvant NER compared with placebo modifies the risk of recurrence by an absolute rate of 2.5% at 5 years in HR+/HER2+ patients (Martin et al., 2017). However, without prespecified prophylaxis, diarrhoea was the most common reason for NER discontinuation in the first three cycles in said study. The CONTROL trial evaluated effectiveness of different anti-diarrhoeal strategies showing a reduction of severe diarrhoea and early discontinuation when indirectly compared to ExteNET (Chan et al., 2022). DIANER (NCT05252988) evaluates the 3 best reported anti-diarrhoeal strategies from CONTROL in patients receiving NER as per European approved label. Trial design and patients: DIANER is an international, multicenter, controlled, randomized, phase II study. Patients with HER2+/HR+ EBC (stage IB-IIIC) who completed prior neo/adjuvant T-based therapy within 2 weeks and 1 year will be included and randomized 1:1:1 to 3 treatment arms. Arm A: NER (240 mg/day[d] x 1 year) + loperamide (12 mg/d x 14 d → 8 mg/d till end of cycle 2 → as needed [PRN]), Arm B: NER dose escalation (120 mg/d x 7 d → 160 mg/d till d 14 → 240 mg/d x 13 cycles) + loperamide PRN, and Arm C: NER (like Arm A) + loperamide (12 mg/d x 14 d → 8 mg/d till end of cycle 1 → PRN) + colesevelam (3,750 mg/d x 28 d). Patients are stratified by menopausal status and prior anti-HER2 therapy (T versus T + pertuzumab). Specific aims: Primary objective is incidence of NER discontinuations due to diarrhoea in the first 3 cycles. Secondary objectives are: incidence of NER discontinuations; AEs and hospitalizations; duration, severity, and treatments for diarrhoea; NER exposure; and health-related quality of life (HRQoL) using FACT B and EQ5D-5L. Exploratory objectives include HRQoL using STIDAT; minimal residual disease and molecular alterations. Statistical methods: A maximum of 315 pts (105 per arm) will be needed using a Simon’s optimal two-stage design with the hypotheses of a desirable early discontinuation rate of 5% (H1) versus an undesirable early discontinuation rate of 13% (H0). In the first stage, arms with ≥ 4 pts discontinuing due to diarrhoea in the first 3 cycles, will be closed for enrolment. The 2-sided 90% confidence intervals using the method described by Koyama et al. (Koyama and Chen 2008) will be provided for the primary endpoint at the end of the 2nd stage of the Simon 2-stage design. Present accrual and target accrual: DIANER will take place in 81 sites in 5 European countries. As of Jul 10/2023 the study is open in 52 sites in Spain with 80 randomized patients. Contact information for people with a specific interest in the trial: Evelia Cortazar (Geicam PM): ecortazar@geicam.org Citation Format: Miguel Gil-Gil, Miguel Martín, Eva Carrasco, Elena Galve, Noelia Martínez-Jáñez, Santiago González-Santiago, Barbara Adamo, María Valero, Clara Martínez, Angel Guerrero, Silvia Antolin Novoa, Manuel Ruíz - Borrego, Isabel Blancas, Raquel Andrés, José L Alonso-Romero, ANDREA Vethencourt, J. Ignacio Chacón, Natalia Chavarría, Enrique Espinosa, Blanca Hernando, Encarnación Adrover, Federico Rojo, Maribel Casas, Leanne McCulloch, Jean-Claude Vedovato. Randomized Phase II trial evaluating three anti-diarrhoeal prophylaxis strategies in patients with HER2+/HR+ early breast cancer treated with extended adjuvant neratinib (DIANER GEICAM/2018-06) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-05.

The reaction of London newspapers to the proclamation of the Monroe doctrine

The presented article analyzes the reaction of the British press to the proclamation of the Monroe Doctrine by the American president in 1823. The reaction of leading London periodicals such as The Examiner, The Monthly Magazine, The London Magazine and The Morning Post is considered. The author describes in detail the diversity of opinions: from support for Republican ideals and their contrast with the monarchical aspects of the policy of the Holy Alliance to expressing concerns about the negative impact of the doctrine on Britain's trade and economic interests in Latin America. The author concludes that the London newspapers have a balanced, albeit emotional assessment of the influence of the Monroe Doctrine on international relations and the specific interests of Great Britain. The article focuses on the period of the 1820s and the British reaction to American foreign policy activity, neglecting to consider the British position in the context of the War of Independence of the Spanish colonies of 1808-1819. In the study of newspaper materials by domestic and foreign scientists, general philosophical (deduction and induction, systematic approach, synergetic approach, etc.), general scientific (observation, comparative method, etc.) and private scientific methods specific to a particular field of knowledge. The Monroe Doctrine provides a rare example of a 200-year-old speech that remains the subject of regular references when discussing the current international political agenda to this day. The article examines the reaction to the Monroe Doctrine, which is one of the fundamental documents of American public policy, which became one of the first steps for the formation of American strategic culture in its current state. The relevance of the article is based on the need for a comprehensive study of the reports of the leading London press to identify their impact on international relations and the specific interests of the United Kingdom. Despite the fact that the Monroe Doctrine has been around for two hundred years, it does not lose its relevance in relation to Latin American states with the United States, and, more importantly, in relation to the United States, with other actors in world politics.

Understanding the role of boron in plant adaptation to soil salinity.

Soil salinity is a major environmental constraint affecting the sustainability and profitability of agricultural production systems. Salinity stress tolerance has been present in wild crop relatives but then lost, or significantly weakened, during their domestication. Given the genetic and physiological complexity of salinity tolerance traits, agronomical solutions may be a suitable alternative to crop breeding for improved salinity stress tolerance. One of them is optimizing fertilization practices to assist plants in dealing with elevated salt levels in the soil. In this review, we analyse the causal relationship between the availability of boron (an essential metalloid micronutrient) and plant's adaptive responses to salinity stress at the whole-plant, cellular, and molecular levels, and a possibility of using boron for salt stress mitigation. The topics covered include the impact of salinity and the role of boron in cell wall remodelling, plasma membrane integrity, hormonal signalling, and operation of various membrane transporters mediating plant ionic and water homeostasis. Of specific interest is the role of boron in the regulation of H+-ATPase activity whose operation is essential for the control of a broad range of voltage-gated ion channels. The complex relationship between boron availability and expression patterns and the operation of aquaporins is also discussed.

IPAttributor: Cyber Attacker Attribution with Threat Intelligence-Enriched Intrusion Data

In the dynamic landscape of cyberspace, organizations face a myriad of coordinated advanced threats that challenge the traditional defense paradigm. Cyber Threat Intelligence (CTI) plays a crucial role, providing in-depth insights into adversary groups and enhancing the detection and neutralization of complex cyber attacks. However, attributing attacks poses significant challenges due to over-reliance on malware samples or network detection data alone, which falls short of comprehensively profiling attackers. This paper proposes an IPv4-based threat attribution model, IPAttributor, that improves attack characterization by merging a real-world network behavior dataset comprising 39,707 intrusion entries with commercial threat intelligence from three distinct sources, offering a more nuanced context. A total of 30 features were utilized from the enriched dataset for each IP to create a feature matrix to assess the similarities and linkage of associated IPs, and a dynamic weighted threat segmentation algorithm was employed to discern attacker communities. The experiments affirm the efficacy of our method in pinpointing attackers sharing a common origin, achieving the highest accuracy of 88.89%. Our study advances the relatively underexplored line of work of cyber attacker attribution, with a specific interest in IP-based attribution strategies, thereby enhancing the overall understanding of the attacker’s group regarding their capabilities and intentions.

Revivals, or the Talbot effect, for the Airy equation

AbstractWe study Dirichlet‐type problems for the simplest third‐order linear dispersive partial differential equations (PDE), often referred to as the Airy equation. Such problems have not been extensively studied, perhaps due to the complexity of the spectral structure of the spatial operator. Our specific interest is to determine whether the peculiar phenomenon of revivals, also known as Talbot effect, is supported by these boundary conditions, which for third‐order problems are not reducible to periodic ones. We prove that this is the case only for a very special choice of the boundary conditions, for which a new type of weak cusp revival phenomenon has been recently discovered. We also give some new results on the functional class of the solution for other cases.

Beauty Therapy to Support Psychosocial Recovery from Oncological Care: A Qualitative Research on the Lived Experience of Women with Breast Cancer Treated with Chemotherapy.

During the oncological care path, breast cancer patients treated with chemotherapy suffer from a number of psycho-physical changes, and appearance-related side effects are among the primary determinants of psychosocial impairment. Appropriate interventions are needed due to the fact that treatment-induced transformations have been associated with a decline in overall quality of life, interpersonal and sexual difficulties, and adverse effects on therapeutic adherence. In the framework of integrative oncology, beauty therapy is an affordable and straightforward intervention that could be used in the clinical management of breast cancer side effects. This study aims to comprehend the emotional and lived experiences of women undergoing chemotherapy after a brief beauty therapy intervention with licensed beauticians. The Interpretative Phenomenological Analysis was used as a methodological guideline. Sixteen women were purposefully recruited in a day hospital of a cancer unit, where the beauty therapy was implemented. At the end of the intervention, data were gathered using a semi-structured interview with open-ended questions. A thematic analysis was performed on verbatim transcriptions. Findings support the proposal of beauty therapy for patients undergoing chemotherapy. Assuming a relational viewpoint, beauty therapy could improve patients' feelings about themselves and the way they feel about others, even if they do not declare a specific interest in their outward appearance.

Lie Symmetries and the Invariant Solutions of the Fractional Black–Scholes Equation under Time-Dependent Parameters

In this paper, we consider the time-fractional Black–Scholes model with deterministic, time-varying coefficients. These time parametric constituents produce a model with greater flexibility that may capture empirical results from financial markets and their time-series datasets. We make use of transformations to reduce the underlying model to the classical heat transfer equation. We show that this transformation procedure is possible for a specific risk-free interest rate and volatility of stock function. Furthermore, we reverse these transformations and apply one-dimensional optimal subalgebras of the infinitesimal symmetry generators to establish invariant solutions.

Wave Basin Tests of a Multi-Body Floating PV System Sheltered by a Floating Breakwater

The development of floating photovoltaic systems (FPV) for coastal and offshore locations requires a solid understanding of a design’s hydrodynamic performance through reliable methods. This study aims to extend insights into the hydrodynamic behavior of a superficial multi-body FPV system in mild and harsh wave conditions through basin tests at scale 1:10, with specific interest in the performance of hinges that interconnect the PV panels. Particular effort is put into correctly scaling the elasticity of the flexible hinges that interconnect the PV modules. Tests of a 5 × 3 FPV matrix are performed, with and without shelter, by external floating breakwater (FBW). The results show that the PV modules move horizontally in the same phase when the wave length exceeds the length of the FPV system, but shorter waves result in relative motions between modules and, for harsh seas, in hinge buckling. Relative motions suggest that axial loads are highest for the hinges that connect the center modules in the system and for normal wave incidence, while shear loads are highest on the outward hinges and for oblique incidence. The FBW reduces hinge loads as it attenuates the high-frequency wave energy that largely drives relative motions between PV modules.

Artificial Intelligence in the Future of Iraqi Healthcare System

The development of artificial intelligence in medicine in Iraq indicates the increasing need for this new idea to be taught to medical students. The objective of such research study having this specific interest is to examine the attitudes of Iraqi medical students toward AI, with the focus made on the level of their understanding of AI and the types of career prospects that they envisage. In a study conducted on Iraqi medical students, a doctrine was outlaid; Iraqi med students were requested to complete anonymously in an online survey respectively. Analysis of the collected data was done by using SPSS21 software. Such an approach gave you the opportunity to investigate the behavioral patterns, trends and relations of the data, which allowed you to gain important outcomes about how the respondents see AI in medical education. The results showed that a total of 23 medical universities participated in the study and their response was collected to the extent of 318. The most of respondents (s=91,5%) is confident in the fact that AI is going to affect health care in the not so far future. Specially, the responses were summarized into those who are going to show strong agreement (33.6%, s = 107) and those who are going to show agreement (57.9%, s = 184). In this regard, the research found that Iraqi medical students find AI indeed adjacently affecting and are open to interacting with such new technology. Additionally, it leaves open a question - we should provide accompanying training programs against Artificial Intelligence during medical education for doctors.

P182 Exercise and activity in polymyalgia rheumatica: co-creating an education resource acceptable to patients and health professionals

Abstract Background/Aims People with PMR report experiencing pain, stiffness and weakness, often impacting everyday tasks. Many fear exercise will exacerbate symptoms and need reassurance that exercise is helpful and not harmful. However, no PMR-specific, exercise educational resource currently exists. The aim of this funded study was to co-create an exercise educational resource for, and with, people with PMR that would be acceptable to both patients and health professionals. Methods A steering group of people with PMR and UK clinicians/academics from Keele and Leeds universities was identified. People with PMR and clinical/academic health professionals with specific interest in PMR were invited to participate in a one-hour online focus group (FG), recruited via social media, the PMRGCAuk charity and professional networks. Ethical approval was obtained. Separate FGs (four with patient participants and two with multi-disciplinary health professionals), held during the summer of 2023, were facilitated by steering group members over two rounds. Exemplars of non-PMR health education literature were shared with participants in round 1 to prompt discussion and invite participant opinions about what might be essential exercise content and the optimal format of the new PMR educational resource. Summaries of proposed content and resource format suggestions were collated after each FG and informed the next iteration of the exercise and physical activity educational resource. In the final round 3 a prototype version of the educational booklet was shared with all FG participants via email. All participants were invited to provide final feedback and comments, after which the booklet was finalised. Results Participants desired a visually appealing pocket-size (A5), multiple-page, patient education booklet suitable for either printing or reading online. Colour-themed text and images with logos of PMRGCAuk and contributing universities were requested. Positive messaging promoting movement and physical activity, as well as exercise, were considered important. Feedback following draft booklet iterations concluded “a self-help guide” title was valuable, as were starter and progression instructions to accompany exercise illustrations. Participants desired explanation of prioritised “top tips”, including keeping moving, listening to your body, balancing rest and activity, and the physical and mental health benefits of exercising. Patient quotations were included with permissions together with signposting to other resources. Conclusion An exercise-focused education booklet, acceptable to both people with PMR and UK expert health professionals, has been co-created and professionally designed. Future research plans include piloting the feasibility of using this resource to support people living with PMR to engage and continue with exercise, and to evaluate the impact of people with PMR exercising. Disclosure A.V. O’Brien: Grants/research support; This project was funded by Polymyalgia Rheumatica, Giant Cell Arteritis UK charity - PMRGCAuk. S. Eng: None. S.L. Mackie: Consultancies; Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer. Grants/research support; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. NIHR Leeds Biomedical Research Centre. Investigator on clinical trials for Sanofi, GSK, Sparrow. N. Scrafton: None. S. Hider: None. A. Tan: None. C. McClean: None. J. Barber: None. J. Gundle: None. M. Lonsdale: None. M. Baxter: None.

The Territorial Planning Process of the Fez-Meknes Region from a Gender Perspective: An Exploratory Study

Since 2015, Morocco has become aware of the imperative to integrate the gender dimension into the territorial planning process. In this context, the region, as a key actor in territorial management, is called upon to take into account the gender approach during the elaboration of its Regional Development Programme (RDP) as a planning tool in accordance with Law 111-14 concerning regions in Morocco. This article aims to understand how the gender approach is integrated by stakeholders in the process of drawing up the RDP by analysing the specific interests and needs of women and men. Analysis of the various phases of the RDP elaboration process from a gender perspective, including preparation, diagnosis, strategic vision, action planning, budgeting, and finally, the implementation and monitoring-evaluation phase, led us to adopt a qualitative methodology. This approach was implemented through the mobilization of a single case study focusing on the RDP of the Fes-Meknes region for the period 2016-2021. Consequently, we conducted semi-structured interviews with a sample of 15 key informants directly involved in the elaboration of the RDP at its different stages. The results indicate that little account is taken of the specific needs of women at all stages of the process, from preparation to implementation and monitoring-evaluation. This is due to several factors, including the scarcity of sex-disaggregated data at the regional level, the ambiguity of the new legal text on the concept of gender and its integration into the RDP, the ineffectiveness of organizational mechanisms related to gender issues, the lack of knowledge and tools for gender-sensitive planning, as well as the weakness of the 'gender culture' among members of the regional council (RC).

Making Data Work Count

In this paper, we examine the work of data annotation. Specifically, we focus on the role of counting or quantification in organising annotation work. Based on an ethnographic study of data annotation in two outsourcing centres in India, we observe that counting practices and its associated logics are an integral part of day-to-day annotation activities. In particular, we call attention to the presumption of total countability observed in annotation - the notion that everything, from tasks, datasets and deliverables, to workers, work time, quality and performance, can be managed by applying the logics of counting. To examine this, we draw on sociological and socio-technical scholarship on quantification and develop the lens of a 'regime of counting' that makes explicit the specific counts, practices, actors and structures that underpin the pervasive counting in annotation. We find that within the AI supply chain and data work, counting regimes aid the assertion of authority by the AI clients (also called requesters) over annotation processes, constituting them as reductive, standardised, and homogenous. We illustrate how this has implications for i) how annotation work and workers get valued, ii) the role human discretion plays in annotation, and iii) broader efforts to introduce accountable and more just practices in AI. Through these implications, we illustrate the limits of operating within the logic of total countability. Instead, we argue for a view of counting as partial - located in distinct geographies, shaped by specific interests and accountable in only limited ways. This, we propose, sets the stage for a fundamentally different orientation to counting and what counts in data annotation.

UaiGuia: Enhancing tourist experiences in São João del-Rei, Brazil, through personalized route creation and cultural immersion

<p>Digital transformation is becoming increasingly essential for developing the global economy. Within this advancement framework lies the tourism industry, where the growing demand from travelers for new experiences drives the search for increasingly technological solutions. Among the many tourism segments are religious, natural, gastronomic, and cultural tourism. These, in turn, seek to offer travelers personalized options based on individual preferences and specific interests. Given the significant growth of Brazilian tourism in recent years, it seems coherent to enhance new technologies that can invigorate the sector. In this regard, this research proposes the development of a mobile application designed to assist users in creating personalized routes in the city of São João del-Rei (Brazil). The study employed design science research with software engineering methods to achieve the desired outcome. The result is the creation of the mobile application called UaiGuia, which provides a distinct approach to exploring the rich culture and tourist attractions in the city of São João del-Rei. The app’s main characteristic is allowing tourists to create routes based on their interests according to the local features. Moreover, access to cultural events, festivals, and other attractions via the application enhances the stay in the city even further, supporting a better immersion in the richness of the region’s heritage.<strong></strong></p>

Trusting by Numbers: An Analysis of a Chinese Social Credit System Governance Infrastructure

To govern, states collect and evaluate information about citizens. This paper examines a social credit system (SCS) in China, a state initiative aimed at governing trust through the quantification of social behavior. Our analysis opens the ‘black box’ of an SCS metric, investigating how trust is translated into numbers and the implications of this translation. We reveal that the SCS is deeply relational and embedded in specific interests, biases, and logics of governance. The system has the potential to reinforce structural injustices and inequalities as it particularly disadvantages rural residents. Meanwhile, it subjects government employees to stricter surveillance, indicating its multifaceted objectives. Our finding uncovers the nuanced ways the system interacts with social stratification in Chinese society and the administrative structure inside the state. We problematize the individualistic, decontextualized, and behavioral assumptions undergirding the metric, and advocate for a critical reassessment of the sociopolitical dimensions of such quantitative governance infrastructures.

The effects of virtual reality interventions on occupational participation and distress from symptoms in palliative care patients: A pilot study.

Virtual reality (VR) offers the prospect of a safe and effective adjunct therapeutic modality to promote mental health and reduce distress from symptoms in palliative care patients. Common physiological and psychological symptoms experienced at the end of life may impact the person's participation in day-to-day activities that bring them meaning. The purpose of this study was to examine the effect of VR interventions on occupational participation and distress from symptoms. To describe the stimulus, results, and learnings from a single-site pilot study of virtual reality therapy in a specialist palliative care setting. Participants engaged in a VR session lasting from 9 to 30 minutes related to coping with pain, inner peace and mindfulness, adventure, and bucket list. The pilot prospective quantitative observational cohort study was conducted from November 2021 through March 2022 using a pre-post VR intervention research design. Quantitative data was collected using patient-rated assessments and a wireless pulse oximeter. Occupational performance, satisfaction, and distress symptoms were measured using the Canadian Occupational Performance Measure and the Palliative Care Outcomes Collaboration Symptom Assessment Scale (PCOC SAS). The intervention and study design adhered to international guidelines. Ten participants engaged in the VR interventions. Data showed significantly improved occupational performance and satisfaction scores (p < .001), decreases in PCOC SAS distress from pain (p = .01), fatigue (p < .001), and heart rate (p = .018). No adverse side effects were observed. Outcomes included an analysis of virtual reality's effectiveness to alleviate symptom burden and increase occupational participation for palliative care patients. Of specific interest to the research team was the application of virtual reality in a community-based and inpatient palliative care context to supplement allied health services and its feasibility of integration into standard palliative care. VR therapy showed positive improvements in the participants' occupational performance, satisfaction, and distress from pain and fatigue.

Intra-arterial chemotherapy for locally advanced nasal cavity and sinonasal tract cancers

Introduction. Malignant tumors of the nasal cavity and sinonasal tract are rare, less than 3 % of all of the head and neck malignant neoplasm. The leading treatment is combined methods with surgery as a first step. However, operation is limited in a locally advanced process due to requires the use of complex reconstructive techniques and removal of aesthetic and functionally important structures. In this regard, the interest of specialists is understandable in use of organ-preserving techniques with comparable oncological results. Intra-arterial chemotherapy has shown high effectiveness in various localizations of malignant neoplasms, so its use in locally advanced tumors of the nasal cavity and sinonasal tract seems promising.Aim. To evaluate the results of complex treatment of patients with locally advanced cancer of the nasal cavity and sinonasal tract using induction intra-arterial chemotherapy.Materials and methods. The study included 28 from 2017 to 2023 with locally advanced cancer of the nasal cavity and sinonasal tract underwent TPF induction intra-arterial chemotherapy, followed by radiation or chemoradiotherapy. The primary endpoint of the study was survival, secondary – objective response rate, treatment toxicity and the possibility of organ preservation.Results. The median follow-up was 19.1 months. We obtained results for all patients of 1-year overall survival – 85.7 % (T3 – 100 %, T4a – 92.7 %, T4b – 55.6 %), and 1-year progression-free survival – 66.7 % (T3 – 75 %, T4a – 71.4 %, T4b – 50 %), respectively. The response rate after intra-arterial chemotherapy was 85.2 %. Overall survival and progression-free survival did not differ significantly between patients with complete response, partial response, and stable disease. However, in patients with a complete response after chemoradiotherapy, 1-year overall survival was 100 % (p = 0.009) and progression-free survival – 90 % (p &lt;0.001). The main side effect in patients in the study was the development of neutropenia (35.7 %), and occurrence of neurological complications was noted in 10.7 %. Of the 35.7 % of patients with tumor orbital invasion, survival with preserved visual function in the first year of life was 80 %; all patients retained vision; as a result of treatment, not a single patient underwent surgery with exenteration.Conclusion. Induction intra-arterial chemotherapy in treatment of patients with locally advanced cancer of the nasal cavity and sinonasal tract demonstrates high efficiency and a high level of complete responses with a fairly low level of toxicity, and also allows preserve the eye function for the majority of patients.

Abstract ND02: Discovery of BMS-986365, a ligand-directed androgen receptor degrader (AR LDD) with a dual mechanism-of-action and best-in-class potential, for the treatment of advanced prostate cancer

Abstract The androgen receptor (AR) is a key driver of the cellular processes that contribute to the pathology of prostate cancers at most stages, and drugs that inhibit the activity of this receptor or interfere with androgen biosynthesis have become the cornerstone of treatments for prostate cancer. While both types of therapy have had a significant positive impact on disease progression and overall survival, de novo and acquired resistance remains an impediment to a durable clinical response in patients with metastatic castration-resistant prostate cancer (mCRPC). The mechanisms underlying drug resistance are complex and multifactorial, being attributable to AR overexpression, point mutations in the receptor that alter drug pharmacology, and to the upregulation of receptor-associated coregulators, which render AR less dependent on an activating ligand. Regardless, absolute inhibition of AR signaling remains the objective of contemporary approaches to treat prostate cancer. Recently, there has been specific interest in the development of approaches to eliminate AR proteins using drugs that enable targeted degradation of AR in cancer cells.This puts in context the significance of our discovery of BMS-986365 (also known as CC-94676), a heterobifunctional ligand-directed degrader (LDD) that enables the CRL4CRBN E3 ligase-dependent ubiquitination and degradation of AR (DC50 10 to 40 nM, Ymin 7 to 19%). BMS-986365 is a highly potent and selective AR degrader that induces rapid and deep degradation of both wildtype and mutant forms of the receptor residing in either the cytoplasmic or nuclear compartments of the cell. The drug is ~100-fold more potent than enzalutamide (ENZ) at inhibiting androgen-stimulated transcription of AR target genes, and 10 to 120-fold more potent than ENZ at inhibiting AR-dependent proliferation of multiple prostate cancer cell lines in vitro. In animal models of advanced prostate cancer, BMS-986365 demonstrates on-target activity, degrading AR, suppressing AR signaling, and inhibiting tumor growth. Indeed, tumor volume reductions of 63-92% were achieved by BMS-986365 in validated models of advanced CRPC and therapy resistant patient-derived xenografts, including those with acquired resistance to ENZ. Collectively our preclinical data suggest that the AR degrader BMS-986365 is superior to standard-of-care AR antagonists, such as ENZ, in both preclinical and disease-relevant animal models, and support its clinical development for treatment of prostate cancer. BMS-986365 has advanced into clinical studies where it has demonstrated encouraging clinical activity in patients with mCRPC. Citation Format: Shuichan Xu, Surendra Nayak, John D. Norris, Massimo Ammirante, Emyly Rychak, Suzanne E. Wardell, Toshiya Tsuji, Ken Liu, Joseph Meiring, Joseph R. Piccotti, Deepak Dalvie, Debbie Liao, Raju Kandimalla, Nadia Guerrero, Lisa Sapinoso, Jennifer G. Baker, Yeeun Bae, Joshua Baughman, Brandon Toyama, Celia Fontanillo Fontanillo, Stephen Norris, Evan J. Horn, Veronique Plantevin-Krenitsky, Deborah Mortensen, Brian Cathers, Marie Hong Nguyen, Joshua D. Hensen, Lawrence G. Hamann, Donald P. McDonnell, Rama Krishna Narla, Mark Rolfe. Discovery of BMS-986365, a ligand-directed androgen receptor degrader (AR LDD) with a dual mechanism-of-action and best-in-class potential, for the treatment of advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr ND02.