Breast cancer survival is shaped by a complex interaction of tumor-specific, biological, and patient-related factors. Stage at diagnosis remains the strongest predictor of outcome. Tumor size, nodal involvement, and histologic grade further aid in prognostic prediction by reflecting the biological aggressiveness of the disease. Since the early 2000s, molecular characteristics gained importance in risk stratification. Hormone receptor-positive cancers generally respond well to endocrine therapy, while HER2-positive tumors, once associated with poor outcomes, now benefit from targeted therapy. Newer agents and combinations such as CDK4/6 and PI3K/AKT/mTOR inhibitors are being investigated recently. Patient factors, including age, comorbidities, and overall health, also influence outcome and treatment tolerance. Cardiovascular toxicity from chemotherapy and radiotherapy has become an important consideration, particularly in the elderly. Although modern radiotherapy techniques have reduced cardiac risks, long-term cardiovascular mortality remains a competing cause of death in many survivors. Studies comparing breast-conserving therapy with mastectomy suggest improved overall survival with the former, partly due to reduced treatment morbidity. Early detection through mammography, ultrasound, and awareness campaigns greatly improves survival, yet access remains unequal in low-resource settings. Strengthening healthcare systems, tailoring treatments, expanding multidisciplinary care and improving public education are essential. Affordable personalized therapies, better infrastructure, and international collaboration can reduce disparities and enhance global breast cancer outcomes. Our international team researched literature information as well as summarizing up-to-date opinions from global experts, including those with limited resources and war-torn regions.

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The human gut microbiota plays a critical role in regulating host health and disease, making it a key target for the development of targeted microbial therapies. This review focuses on designer probiotics and synbiotics, which are genetically engineered microorganisms used in combination with prebiotics to modulate the gut microbiota and support personalised health outcomes. Unlike conventional probiotics, these engineered strains are designed to perform specific metabolic or signalling functions, thereby enhancing colonisation efficiency and functional efficacy. The article summarises recent advancements in systems biology, synthetic biology, and omics technologies (including genomics, proteomics, and metabolomics) that facilitate the design and optimisation of next-generation microbial formulations. Their significance lies in enabling precision nutrition and the development of functional foods tailored to individual host requirements. This review also discusses strategies for microbial strain engineering, synbiotic formulation, and the application of high-throughput omics approaches to better understand host-microbe interactions. Furthermore, it highlights applications in managing gut-related disorders and improving food quality. While addressing challenges such as biosafety concerns, regulatory limitations, and environmental implications, the review emphasises the potential of designer probiotics and synbiotics as innovative tools for precision-guided health through dietary interventions. Overall, this emerging field provides a sustainable approach to advancing nutrition and microbiome-based therapies by bridging precision health with food science.

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With the rising global prevalence of obesity and type 2 diabetes, metabolic disorders have become major drivers of cardiovascular morbidity and mortality worldwide. Cardiovascular-kidney-metabolic (CKM) syndrome encompasses obesity, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD), all of which share common pathophysiological pathways. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a novel class of antihyperglycemic agents, have demonstrated pleiotropic effects—including weight reduction, blood pressure lowering, albuminuria reduction, decreased major adverse cardiovascular events (MACE), and slowed progression of renal dysfunction. These benefits position GLP-1RAs as a potential cornerstone therapy for CKM syndrome. This review synthesizes recent advances in GLP-1RA research within the CKM framework, explores their underlying mechanisms, and offers insights to refine diagnostic and therapeutic strategies for cardiometabolic diseases.

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Climate change (CC) affects our health in ways especially when it comes to liver diseases. Rising temperatures and changing weather patterns are altering the spread and severity of liver diseases. CC can affect health, especially liver diseases, in direct and indirect ways. Hepatic infections such as viral hepatitis and schistosomiasis, metabolic dysfunction-associated steatotic liver disease (MASLD), hepatocellular carcinoma, and acute on chronic liver failure (ACLF) are examples. The movement of infected individuals from areas where diseases are endemic, prompted by ecological disasters, introduces these diseases to previously unexposed regions. CC serves as an early warning for shifts and the necessity to re-evaluate hepatic diseases, which is crucial for health policymakers. Ambient temperature and its variability have a major influence on the pathogenesis of MASLD, demonstrating nonlinear exposure–response relationships. Long-term temperature exposure follows a reverse J-shaped pattern, while temperature variability shows a U-shaped association, with both extremes independently increasing disease susceptibility. Prolonged exposure to cold and fluctuations in temperature could worsen various liver diseases. Gaining a deeper insight into these CC-related risks for our patients and practice is essential to optimize their care both now and in the warmer temperatures ahead. Incorporating climate resilience into public health initiatives may aid in alleviating the growing prevalence of liver diseases linked to CC. Aside from increasing awareness, which should take precedence, there is a pressing need to investigate innovative ways to frame the educational message and eliminate financial incentives that contribute to environmental damage. Common climate strategies for healthcare systems include reducing and managing waste, utilizing cleaner and less energy, offering and endorsing planet-friendly food options, and addressing transportation issues related to accessing healthcare facilities, such as transitioning in-person appointments to virtual consultations when possible, encouraging green-endoscopy practices, and participating in conferences virtually can be beneficial.

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Obesity is a rapidly growing global health concern. The pathogenesis is complex and cannot be fully explained by lifestyle factors alone. The increasing attention towards this concern has finally been directed towards environmental contributors which may influence metabolic regulation. Microplastics and nano-plastics (MNPs) are ubiquitous environmental pollutants that have recently been detected in food, drinking water, air, and human biological samples, raising concerns about their potential role in metabolic disorders, including obesity. Chronic exposure to MNPs may interfere with metabolic homeostasis through multiple biological pathways. Emerging evidence, including both experimental and animal studies, reports alterations in lipid metabolism, body weight, insulin sensitivity, and inflammatory responses following MNPs exposure. This review synthesizes current evidence linking MNPs to obesity, highlighting key exposure pathways, mechanistic insights, and gaps in existing research. Understanding the metabolic implications of MNPs exposure is essential for advancing obesity research and informing future public health strategies. Further well-designed human studies are needed to clarify causal relationships and guide preventive interventions.

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Pembrolizumab, a programmed cell death protein 1 inhibitor, has had a substantial impact on cancer treatment across multiple malignancies, but is associated with immune-related cardiovascular toxicities that pose significant clinical challenges. Complications such as myocarditis, arrhythmias, and cardiomyopathy are emerging as significant entities with high morbidity and mortality. This article is a narrative review and was not designed or conducted as a systematic review. No formal systematic review protocol was followed and attempts to identify or include all published studies on this topic were not undertaken. The goal is to provide a clinically oriented synthesis of the current literature on pembrolizumab-associated cardiotoxicity. A literature search was conducted using PubMed, Medline, and Google Scholar databases for articles published between January 2014 and March 2025. Search terms included ‘pembrolizumab,’ ‘PD-1 inhibitor,’ ‘immune checkpoint inhibitor,’ ‘cardiotoxicity,’ ‘myocarditis,’ ‘pericarditis,’ ‘arrhythmia,’ and ‘cardiac adverse events,’ used individually and in combination. Inclusion criteria encompassed English-language clinical trials, observational studies, systematic reviews, meta-analyses, pharmacovigilance analyses, clinical practice guidelines, and case reports involving human subjects. Non-English publications, preclinical studies without clinical correlates, and editorials without original data were excluded. Reference lists of identified articles were manually reviewed to identify additional relevant publications. Study selection was performed by a single author. Pembrolizumab-induced myocarditis, although rare, carries a high mortality rate and typically presents within the first few weeks of treatment, including a relative risk of myocarditis ~4.5 with combination immune checkpoint inhibitor therapy. Proposed mechanisms of this cardiotoxicity, though not settled, include shared antigenic targets between tumor and cardiac tissue and impaired immune tolerance. Current management relies on prompt recognition, immunosuppression with high-dose IV methylprednisolone as first-line therapy, and additional immunomodulatory agents for refractory cases. Emerging evidence from case reports and small cohort studies suggests potential benefit from abatacept with ruxolitinib in steroid-refractory cases; however, prospective validation is needed. Baseline cardiac screening and serial monitoring of cardiac biomarkers including high-sensitivity troponin and NT-proBNP, and a multidisciplinary cardio-oncology approach are essential for early detection and optimal outcomes.

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Autism spectrum disorder (ASD) is a clinically heterogeneous neurodevelopmental condition characterized by core social communication deficits and restricted/repetitive behaviors. The majority of cases present with certain medical and psychiatric comorbidities. These include epilepsy, gastrointestinal disorders, attention-deficit/hyperactivity disorder, anxiety, and metabolic dysregulation. While animal models are indispensable in pre-clinical research and studying ASD’s pathobiology, there remains a need to address these comorbidities while modelling major ASD clinical domains. The paper describes a spectrum of animal models for ASD and its comorbid disorders, with a focus on ASD & epilepsy co-occurrence.

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Precision oncology has revolutionized cancer care in high-income countries, but its implementation in Latin American low-resource settings faces profound bioethical dilemmas. This study analyzes these challenges through the lens of social justice and equity. An integrative review was conducted following the Whittemore and Knafl framework. A systematic search was performed across PubMed, Scopus, SciELO, and LILACS (2015–2025). Thematic synthesis was applied to integrate empirical data with normative bioethical theories. Four major analytical themes were identified: 1) The innovation paradox and financial toxicity, where prohibitive pricing (exceeding 100,000 USD/year) violates distributive justice and leads to a biological penalty in survival; 2) Infrastructure deficits and epistemic injustice, highlighted by a 9.4% access rate to next-generation sequencing (NGS) and the risks of applying Eurocentric genomic data to admixed LA populations; 3) Research vulnerability, where clinical trials serve as survival strategies, compromising autonomy and informed consent; and 4) The judicialization dilemma, where individual court orders for high-cost drugs threaten systemic sustainability and equity. To prevent a genomic apartheid, Latin America must transition toward genomic sovereignty and frugal precision oncology. Bioethical frameworks in the region must prioritize protection ethics and social justice to ensure that scientific innovation does not exacerbate existing health inequities.

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Primary bone sarcomas are rare and biologically heterogeneous malignancies for which therapeutic progress remains limited, particularly in metastatic and recurrent disease. Advances in genomic and molecular profiling have revealed substantial inter- and intratumoral heterogeneity across the major subtypes, including osteosarcoma, Ewing sarcoma and chondrosarcoma, challenging conventional histology-driven treatment strategies. Precision medicine approaches are being increasingly explored to better capture this biological complexity and guide individualized therapeutic decision-making. This review examines emerging precision oncology strategies in bone sarcomas, including molecular diagnostics, targeted therapeutic approaches, three-dimensional functional modeling systems, and liquid biopsy technologies for dynamic disease monitoring. Together, these platforms provide biologically informed frameworks for patient-specific treatment and longitudinal assessment of tumor evolution. However, clinical implementation remains limited by genomic complexity, small patient cohorts, and methodological variability across experimental platforms. The integration of multi-layered precision models combining genomic stratification, functional drug sensitivity testing and circulating biomarker monitoring may enable more adaptive and individualized management strategies. Such approaches have the potential to improve therapeutic selection and ultimately advance outcomes for patients with primary bone sarcomas.

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Human γδ T cells represent a minor subset of lymphocytes present in the peripheral blood. This lymphocyte subset is mainly localized within the mucosae of airways and gut. In the latter context, γδ T cells can represent a key immune cell subset involved both in regulating intestinal homeostasis and in responding to pathogens and colorectal carcinoma (CRC) growth. γδ T cell subsets such as the Vδ2⁺ respond to phosphate antigens produced by bacteria, while Vδ1⁺ cells can exert an immune response after mucosal stress stimuli. γδ T cells do not recognize as classical αβ⁺ T cells the peptide antigens in the context of major histocompatibility complex (MHC). γδ T cells may play a complementary role with αβ⁺ T cells in mucosal immunity at the gastrointestinal barrier. Colon γδ T cells can exhibit antitumor properties and regulatory functions. Indeed, human γδ T cell subsets present in the gut bear some activatory receptors, such as NKG2D and DNAX Accessory Molecule (DNAM)-1, leading to the elimination of CRC cells. By contrast, γδ T cells producing interleukin (IL)-17, transforming growth factor β, and amphiregulin show pro-tumor activity. This dual property of γδ T cells poses challenges for their use as an immunotherapeutic tool, while the MHC-independent recognition of antigens can support their use as off-the-shelf allogeneic cells.

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Epilepsy is traditionally defined by recurrent seizures arising from abnormal neuronal excitability, yet growing evidence indicates that this view is incomplete. This narrative review examines epilepsy through the framework of neural–glial network instability, an integrative perspective that places neuronal dysfunction within a broader system shaped by glial regulation, calcium dysregulation, neuroinflammatory signaling, and circuit remodeling. The review first reframes epilepsy as a disorder of progressive instability in which failures of excitation–inhibition balance, extracellular homeostasis, inflammatory restraint, and adaptive plasticity shift neural networks from compensated function toward seizure-prone states. It then synthesizes neuronal mechanisms, including excitation–inhibition imbalance, GABAergic dysfunction, and altered intrinsic excitability, together with glial mechanisms involving astrocytic regulation of ionic and neurotransmitter environments, microglial inflammatory and synaptic responses, and oligodendroglial contributions to conduction and network coordination. Calcium dysregulation is considered a cross-cutting mechanism linking excitability, intracellular stress, gliotransmission, inflammation, and long-term remodeling. The review further examines how neuroinflammation and chronic circuit reorganization help convert transient disturbances into persistent epileptic networks. Together, this framework offers a more integrated account of seizure emergence, epileptogenesis, and chronic seizure susceptibility and points toward mechanism-informed therapeutic strategies aimed at restoring durable network stability.

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The link between brain energy consumption and neuronal aging has been explored at the cellular and molecular levels. The brain is described as a “selfish organ”, as previously indicated in recent publications, demanding energy from peripheral organs to avoid a reduction of its energy expenditure. Aging is the main risk factor for neurodegenerative disorders, like tauopathies, related to neuronal energy changes. Thus, preventing, delaying, or reversing those changes should be a suitable way to carry out neuroprotection. Finally, possible therapies using as targets neuronal proteins like folate receptor alpha, GDF15 receptor, or tau protein, which are related to mitochondrial function and dysfunction, are proposed.

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Breast cancer remains one of the leading causes of cancer-related mortality worldwide, and despite considerable advances in therapeutic strategies, the absence of reliable, minimally invasive diagnostic tools continues to limit early detection and real-time disease monitoring. Liquid biopsy has emerged as a transformative paradigm in oncology, offering the capacity to integrate tumor biology through the analysis of tumor-derived materials that circulate in peripheral blood and other biofluids. This review provides a comprehensive overview of the key analytes employed in liquid biopsy, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), extracellular vesicles (EVs), and protein biomarkers with particular emphasis on their translational relevance in breast cancer. Drawing on landmark clinical trials and foundational molecular studies, we highlight how these biomarkers capture spatial and temporal tumor heterogeneity in ways that conventional tissue biopsy cannot. Finally, we address the technical, clinical, and ethical challenges that still impede widespread adoption of liquid biopsy, and we outline a forward-looking research agenda oriented toward multi-omics integration and point-of-care diagnostics. Taken together, this review underscores the potential of liquid biopsy to complement existing diagnostic standards and improve how we screen for, monitor, and treat breast cancer across disease stages.

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Causal inference is grounded in contrasts between potential outcomes under alternative interventions. Randomized trials are the reference standard for estimating average causal effects because randomization renders treatment assignment independent of potential outcomes, eradicating confounding by design. However, many clinically important questions in rheumatology cannot feasibly be addressed through randomized experiments due to practical, ethical, or temporal constraints. In such settings, observational data can inform decisions. This paper argues that principles derived from randomized trials should continue to anchor causal reasoning and proposes the target trial framework as a structured approach to strengthen causal inference from observational data. By explicitly specifying the protocol of the hypothetical randomized trial that would answer the question and emulating it using real-world (observational) data, investigators can clarify eligibility criteria, treatment strategies, time zero, outcomes, causal contrasts, and identifying assumptions. By describing how each part of the target trial is emulated in observational data, they increase transparency, clarify the causal estimand, and make assumptions, limitations, and sources of bias explicit. This design-based perspective helps prevent common biases, including immortal time bias, selection of prevalent users, and inappropriate conditioning on post-treatment variables, and aligns reporting with clearly defined causal contrasts and effect measures. Ultimately, credibility of causal inference from observational data depends on whether the assignment mechanism is plausibly reconstructed, design choices are made without access to outcome data, and analyses target explicitly defined causal contrasts under stated assumptions, all of which are explicitly addressed within the target trial emulation framework.

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