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Simple Summary: The current evidence regarding Indigenous* women and breast cancer in Australia shows lower prevalence but higher mortality rates. There are a range of reasons for this, including co-morbidities, lack of access to health services and low health information fluency. Perhaps most importantly, breast cancer health policy and service delivery practice do not meet the needs of Indigenous women in Australia, according to Indigenous women. Talking and listening to Indigenous women about breast cancer highlight that the solutions to improve breast cancer outcomes are available and that they are not complex. Indigenous women must be involved in the improvement of policy and practice in order for these outcomes to improve. *Terminology: We respectfully refer to Aboriginal and Torres Strait Islander people as "Indigenous". In Australia, the incidence rate of breast cancer is lower in Indigenous* women than non-Indigenous women; however, the mortality rate is higher, with Indigenous women 1.2 times more likely to die from the disease. This paper provides practical and achievable solutions to improve health outcomes for Indigenous women with breast cancer in Australia. This research employed the Context–Mechanism–Outcome (CMO) framework to reveal potential mechanisms and contextual factors that influence breast cancer outcomes for Indigenous women, stratified into multiple levels, namely, micro (interpersonal), meso (systemic) and macro (policy) levels. The CMO framework allowed us to interpret evidence regarding Indigenous women and breast cancer and provides nine practical ways to improve health outcomes and survival rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer treatment during pregnancy can raise many difficult questions. Currently available clinical practice guidelines offer very limited ethical guidance for healthcare professionals. This article offers a theoretical framework and a practical ethics checklist for ethical and patient-centred care. It takes a holistic view to patient treatment, care and counselling that emphasises the need to recognise the relational context of individual patient's autonomy; balance maternal and foetal beneficence obligations; balance maternalistic and relational approaches to evidence-based personalised patient care; consider protection of the vulnerable in light of responsibilities towards the unborn; and ensure reasonable and just resource allocation. At the moment, very few studies have explored clinicians' attitudes and patients' experiences when cancer treatment is delivered during pregnancy. Therefore, future work will require patient engagement to develop ethical guidance in this setting. (1) Background: Caring for pregnant cancer patients is clinically and ethically complex. There is no structured ethical guidance for healthcare professionals caring for these patients. (2) Objective: This concept paper proposes a theoretically grounded framework to support ethical and patient-centred care of pregnant cancer patients. (3) Methodological approach: The framework development was based on ethical models applicable to cancer care during pregnancy—namely principle-based approaches (biomedical ethics principles developed by Beauchamp and Childress and the European principles in bioethics and biolaw) and relational, patient-focused approaches (relational ethics, ethics of care and medical maternalism)—and informed by a systematic review of clinical practice guidelines. (4) Results: Five foundational discussion themes, summarising the key ethical considerations that should be taken into account by healthcare professionals while discussing treatment and care options with these patients, were identified. This was further developed into a comprehensive ethics checklist that can be used during clinical appointments and highlights the need for a holistic view to patient treatment, care and counselling while providing ethical, patient-centric care. (5) Conclusion: The proposed framework was further operationalised into an ethics checklist for healthcare professionals that aims to help them anticipate and address ethical concerns that may arise when attending to pregnant cancer patients. Further studies exploring clinicians' attitudes towards cancer treatment in the course of pregnancy and patient experiences when diagnosed with cancer while pregnant and wider stakeholder engagement are needed to inform the development of further ethical, patient-centred guidance. [ABSTRACT FROM AUTHOR]

Simple Summary: Sentinel lymph node (SLN) mapping for the surgical staging of endometrial and cervical cancer is commonly performed by laparoscopy, but recently, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery approach has been described and developed by Jan Baekelandt. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLN assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is in Stage 2a, with only small case series as evidence of its feasibility. Provided that the standardized description of this surgical technique appears necessary to provide the homogeneity required to move further in its investigation, here, we describe a 10-step approach for performing it successfully. This could help other surgeons approach this new technique, and it proposes a common methodology necessary for evolving through future studies. (1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach has been described and developed by Jan Baekelandt. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLN assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is in Stage 2a, with only small case series as evidence of its feasibility. Its standardized description appears necessary to provide the surgical homogeneity required to move further. (2) Methods: Description of a standardized approach for retroperitoneal pelvic SLN mapping by vNOTES. (3) Results: We describe a 10-step approach to successfully perform retroperitoneal vNOTES SLN mapping, including pre-, intra-, and postoperative management. (4) Conclusions: This IDEAL Stage 2a study could help other surgeons approach this new technique, and it proposes a common methodology necessary for evolving through future IDEAL Stage 2b (multi-center studies) and Stage 3 (randomized controlled trials) studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer genome analysis often reveals structural variants (SVs) involving fusion genes that are difficult to classify as drivers or passengers. Obtaining accurate AI predictions and explanations, which are crucial for a reliable diagnosis, is challenging. We developed an explainable AI (XAI) system that predicts the pathogenicity of SVs with gene fusions, providing reasons for its predictions. Our XAI achieved high accuracy, comparable to existing tools, and generated plausible explanations based on pathogenic mechanisms. This research represents a promising step towards AI-supported decision making in genomic medicine, enabling efficient and accurate diagnosis. When analyzing cancer sample genomes in clinical practice, many structural variants (SVs), other than single nucleotide variants (SNVs), have been identified. To identify driver variants, the leading candidates must be narrowed down. When fusion genes are involved, selection is particularly difficult, and highly accurate predictions from AI is important. Furthermore, we also wanted to determine how the prediction can make more reliable diagnoses. Here, we developed an explainable AI (XAI) suitable for SVs with gene fusions, based on the XAI technology we previously developed for the prediction of SNV pathogenicity. To cope with gene fusion variants, we added new data to the previous knowledge graph for SVs and we improved the algorithm. Its prediction accuracy was as high as that of existing tools. Moreover, our XAI could explain the reasons for these predictions. We used some variant examples to demonstrate that the reasons are plausible in terms of pathogenic basic mechanisms. These results can be seen as a hopeful step toward the future of genomic medicine, where efficient and correct decisions can be made with the support of AI. [ABSTRACT FROM AUTHOR]

Simple Summary: The immune system can fight foreign invaders by different means, expressed by different classes of immunity. There are two main classes: antibodies and cell-mediated immunity. Studies directed at how distinct classes of immunity are differentially generated and regulated have been ongoing for the better part of a century. Various quantitative variables of immunization, such as antigen doses, are critical, and were first identified more than fifty years ago. It was shown that lower and higher doses, respectively, lead to cell-mediated and antibody responses. The importance of these variables has stood the test of time. We argue here for a framework, the Threshold Hypothesis, that is consistent with these variables and accounts for their central role in determining the class of immunity generated. This framework leads to an understanding of many observations in the fields of tumor immunology and immunity against pathogens uniquely contained by cell-mediated attack. This understanding relies on the generalization that cancers are uniquely susceptible to cell-mediated attack. This confidence in the threshold mechanism led me to propose non-invasive and efficacious strategies to prevent and treat cancer and infectious diseases caused by pathogens uniquely susceptible to cell-mediated immunity. Different frameworks, which are currently employed to understand how immune responses are regulated, can account for different observations reported in the classical literature. I have argued that the predominant frameworks, employed over the last two/three decades to analyze the circumstances that determine whether an immune response is generated or this potential is ablated, and that determine the class of immunity an antigen induces, are inconsistent with diverse classical observations. These observations are "paradoxical" within the context of these frameworks and, consequently, tend to be ignored by most contemporary researchers. One such observation is that low and high doses of diverse types of antigen result, respectively, in cell-mediated and IgG antibody responses. I suggest these paradoxes render these frameworks implausible. An alternative framework, The Threshold Hypothesis, accounts for the paradoxical observations. Some frameworks are judged more plausible when found to be valuable in understanding findings in fields beyond their original compass. I explore here how the Threshold Hypothesis, initially based on studies with chemically well-defined and "simple antigens", most often a purified protein, can nevertheless shed light on diverse classical and more recent observations in the fields of immunity against cancer and against infectious agents, thus revealing common, immune mechanisms. Most cancers and some pathogens are best contained by cell-mediated immunity. The success of the Threshold Hypothesis has encouraged me to employ it as a basis for proposing strategies to prevent and to treat cancer and those infectious diseases caused by pathogens best contained by a cell-mediated attack. [ABSTRACT FROM AUTHOR]