Mariana Araújo-Pereira

Basic sciences remain a cornerstone of medical education, but the terms of the debate about their importance have changed. The central risk is no longer their formal exclusion from medical curricula but their curricular invisibility: the gradual dilution of mechanistic reasoning within integrated, technology-mediated, and institutionally unequal training environments. In this Viewpoint, we revisit the past, present, and future of basic science teaching to argue that reform must protect conceptual progression, curricular visibility, and clinical transfer. Active learning, curricular integration, digital tools, and AI may strengthen scientific literacy, but only when they are anchored in faculty development, institutional support, and explicit commitments to rigor and equity.

Human nature is paradoxical. People often recognize problems but hesitate to act, preferring the familiarity of discomfort to the uncertainty of change. This reluctance to embrace the unknown is not just a personal tendency; it extends to science and society at large, where progress is often stalled by fear of disruption. To overcome stagnation, it is increasingly important to educate and develop problem solvers, or in other words, dissolvers of chaos—those who transform disorder into understanding, uncertainty into insight. This conceptual commentary explores the mindset of problem solvers, examining how they approach complexity not as an obstacle, but as a puzzle to be solved. Just as assembling a jigsaw puzzle requires patience, adaptability, and the ability to identify connections, solving real-world problems demands a willingness to navigate uncertainty, persist through failure, and engage in deep, iterative thinking. We examine historical and anecdotal examples of resistance to change, discuss the cognitive and social barriers that discourage deep problem-solving, and propose strategies for fostering a new generation of problem solvers. By shifting perspective, from seeing problems as obstacles to recognizing them as opportunities to build new knowledge, bit by bit, we can cultivate individuals who not only navigate complexity but embrace it as the foundation of progress.

The omics sciences represent a revolution for clinical studies, offering integrative approaches to analyzing biological data with unprecedented depth. From the discovery of the double-helix structure of DNA to the CRISPR-Cas9 gene editing tool, passing through the evolution of sequencing platforms and the exponential advance of computing power and in silico tools, omics has progressed in its role of leading innovative solutions for old challenges in health sciences. In this review, we describe different omics, the history of their techniques and technologies, data analysis and up-to-date visualization tools used for clinical data in research and health systems. We also discuss how omics are currently being applied in diagnosis, precision and personalized medicine. For the future, omics vow to underpin the majority of decisions made by health professionals, allowing individualized treatments based on Big Data and personal biological information.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) persists as serious global health concern with more than a million deaths and 10 million new cases in 2024 [1]. Recent TB research continues to evolve at the intersection of diagnostics, host-pathogen interactions, host immunity, as well as clinical complexity and therapeutic innovations. This research topic contains original and review articles from studies that collectively illustrate how advances in molecular technologies, evolutionary trade-offs in immune defense and underscores the importance of considering sex as a biological variable in genetic association studies in the context of infectious diseases.Sex-specific immune regulation was also central to the study by Hertz et.al, who demonstrated that B cell-derived interleukin-10 (IL-10) promotes TB susceptibility in a mouse model, with effects most pronounced in males. Deletion of IL-10 specifically in B cells resulted in delayed disease progression, lower lung bacterial loads, and prolonged survival, accompanied by increased interferon gamma (IFN-γ) production and remodeling of pulmonary immune cell populations. Transcriptomic analyses revealed broad sex-dependent immune reprogramming, implicating pathways such as Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) signaling. These findings reposition B cells as key regulators of TB immunity and suggest that immunomodulatory interventions may require sex-adapted strategies to achieve maximal benefit.Functional immune profiling in human populations complements these mechanistic insights. Oo et.al, characterized peripheral blood mononuclear cells (PBMCs) from individuals with active TB disease, latent infection, and healthy controls in an endemic setting. Using mycobacterial growth inhibition assays alongside flow cytometry, the study showed that cells from patients with active disease exhibited enhanced capacity to restrict mycobacterial growth, associated with increased natural killer (NK) cells and robust TNF responses from CD4⁺ and CD8⁺ T cells. Specific cytokine profiles correlated inversely with bacterial replication, suggesting that qualitative features of immune responses may serve as correlates of protection against TB and inform vaccine development or patient stratification.In another study, Zhu et.al, report distinct gene expression profile of CD3+/IFNγ+ T cells from the PBMCs of healthy individuals when stimulated with BCG vaccine or Mtb. In these cells, BCG stimulation upregulated IL-2 resulted in a positive feedback loop that amplifies the cell population expressing IFNγ. This study highlights the role of IL2 by CD3+/IFNγ+ T cells in anti-TB immunity.Nutritional and metabolic factors further modulate immune responses to TB. Moideen et.al, documented significant alterations in serum mineral concentrations among patients with pulmonary disease, including elevated copper levels and increased copper-to-zinc and copper-to-selenium ratios, alongside reduced zinc and selenium. These imbalances correlated with both pro-and anti-inflammatory cytokines and normalized following anti-tuberculous therapy, implicating mineral ratios as integrative biomarkers of systemic inflammation. The findings highlight the potential of nutritional interventions as adjuncts to therapy, while also cautioning that causal relationships and optimal supplementation strategies require longitudinal validation.Beyond host susceptibility, therapeutic innovation increasingly emphasizes host-directed strategies. Sabeel et.al, investigated the immunomodulatory effects of atorvastatin in infected PBMCs and demonstrated dose-dependent suppression of intracellular mycobacterial growth. Mechanistically, atorvastatin enhanced phagosome maturation, induced autophagy, and promoted apoptosis through pathways linked to inhibition of the mevalonate cascade. Selective reduction of IL-1β without broad cytokine suppression suggested a targeted anti-inflammatory effect. These findings support the repurposing of statins as adjunctive host-directed therapies and provide a mechanistic rationale for clinical trials integrating immunological endpoints.Pathogen-centered biology remains equally critical for long-term control. Zhang et.al, integrated the available evidence on the PE/PPE protein family of Mtb, which plays central roles in immune modulation, nutrient acquisition, and virulence. These proteins interact with host receptors, disrupt phagosome maturation, and influence cytokine networks and cell death pathways. Their immunogenic properties have already been leveraged in vaccine candidates showing promise in clinical trials, as well as in diagnostic assays distinguishing latent from active disease. However, functional redundancy and antigenic variability pose challenges, emphasizing the need for high-resolution structural and systems-level analyses to guide rational vaccine and diagnostic design.Clinical practice in TB often reveals complexities that transcend experimental models. Tang et.al, reported a rare neonatal case of concurrent TB and pertussis in a 47-day-old infant, diagnosed through comprehensive molecular testing of bronchoalveolar lavage fluid (BAL). Successful management of this case required carefully balanced antimicrobial regimens and vigilant monitoring for toxicity. This clinical presentation underscores the importance of broad diagnostic evaluation in infants with atypical respiratory disease and highlights the vulnerability of early life to overlapping infections.Similarly, Tian et.al, described the first documented coexistence of papillary renal cell carcinoma with ipsilateral renal TB. Radiologic findings suggested malignancy, but definitive diagnosis relied on postoperative histopathology and molecular testing. This case illustrates how renal TB can mimic or coexist with cancer, complicating diagnosis and management, and reinforces the indispensable role of tissue-based...

UNSTRUCTURED Basic sciences remain a cornerstone of medical education, yet how they should be taught has become increasingly debated. In this viewpoint, we reflect on how basic science teaching has changed over time and argue that traditional, memorization-driven approaches are no longer sufficient for contemporary medical training. We discuss the need for more integrated, practical, and student-centered strategies while reaffirming that science must remain central to the education of future physicians. We contend that meaningful improvement depends on faculty development, institutional support, and a sustained commitment to scientific rigor, curricular integration, and educational equity.

Background: Non-sputum biomarkers to monitor tuberculosis treatment and predict poor outcomes are lacking. We evaluated host-blood transcriptomic signatures for treatment monitoring and prognosis (death, treatment failure, recurrence) in adults with pulmonary tuberculosis. Methods: Adults with culture-confirmed, drug-susceptible pulmonary tuberculosis were enrolled at five Brazilian sites. Whole-blood PAXgene samples were collected at baseline, month 2 (M2), and end of treatment (EoT). Treatment failure was defined as sputum culture positivity at month 5 or later. Participants were followed for 24 months from treatment initiation for clinical or microbiological tuberculosis recurrence. Unfavourable outcomes were matched ∼1:3 to recurrence-free cure. Twenty-two published blood transcriptomic signatures were measured by microfluidic RT-qPCR and benchmarked against the WHO Target Product Profile (TPP) criteria. Main results: We matched 263 participants with recurrence-free cure to 33 with treatment failure, 24 who died (tuberculosis/unknown cause), and 9 with recurrence. Signature scores generally declined from baseline to EoT. Multiple signatures measured at baseline and M2 predicted recurrence (AUC range 0.71-0.91), with waning performance when measured at EoT (AUC range 0.42-0.89). Against the WHO TPP, 2/22 signatures met minimum criteria at baseline, 13/22 at M2, and none at EoT. Prediction of treatment failure was poor across timepoints (AUC < 0.70). In contrast, several signatures measured at baseline predicted death during treatment or follow-up (AUC ≥ 0.80). Conclusions: Blood transcriptomic signatures tracked treatment response and predicted recurrence and death, meeting WHO TPP benchmarks at baseline and M2. These findings support prospective, biomarker-guided trials to individualise tuberculosis therapy—shortening regimens for early responders and intensifying care for high-risk patients.

This viewpoint reflects on how Generation Z (born between 1995 and 2009), shaped by constant digital engagement, a growing awareness of mental health, and a dopamine-driven environment, is transforming medical education and practice. We explore, from a reflective and interdisciplinary perspective, how the defining characteristics of Generation Z, such as their familiarity with technology, demand for emotional safety, and resistance to traditional hierarchies, might reshape the ways we teach, learn, and practice medicine. Drawing on neuroscience, psychology, sociology, and the medical education literature, this viewpoint emphasizes the need to move beyond knowledge transmission and foster self-regulation, critical thinking, and ethical judgment. We call for a deliberate and compassionate adaptation of medical education to cultivate the skills required for a profession increasingly practiced in a context of overstimulation and complexity.