Updated Perspective Research Articles

Targeting of the 8-oxodG Base Excision Repair Pathway for Cancer Therapy

Genomic integrity is critical for cellular homeostasis, preventing the accumulation of mutations that can drive diseases such as cancer. Among the mechanisms safeguarding genomic stability, the Base Excision Repair (BER) pathway plays a pivotal role in counteracting oxidative DNA damage caused by reactive oxygen species. Central to this pathway are enzymes like 8-oxoguanine glycosylase 1 (OGG1), which recognize and excise 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesions, thereby initiating a series of repair processes that restore DNA integrity. BER inhibitors have recently been identified as a promising approach in cancer therapy, increasing the sensitivity of cancer cells to radiotherapy and chemotherapy. By exploiting tumor-specific DNA repair dependencies and synthetic lethal interactions, these inhibitors could be used to selectively target cancer cells while sparing normal cells. This review provides a robust reference for scientific researchers, offering an updated perspective on small-molecule inhibitors targeting the 8-oxodG-BER pathway and highlighting their potential role in expanding cancer treatment strategies.

Textbook Selection in Nursing Education: An Updated Perspective.

Evidence-based guidelines about textbook selection for nursing didactic courses are lacking. Therefore, this study explored the priorities of faculty in baccalaureate nursing programs for selecting primary textbooks. The study aimed to identify the ranking of essential characteristics in nursing textbooks, including content, general characteristics, supplemental resources, organization, and specific considerations about electronic textbooks. Using a cross-sectional design, a descriptive survey was conducted among faculty members across the United States. Results from 59 faculty participants demonstrated a strong preference for textbooks emphasizing clinical judgment and application to practice, with content being the top priority. Additionally, instructor resources, such as test banks and teaching strategies, were prioritized within supplemental resources. Few participants reported formal training in textbook selection, indicating a potential area for nursing education improvement. The study found the need for further research and development of structured guidelines to aid in the textbook selection process.

Updated diagnostic and therapeutic management for membranous nephropathy.

Pioneering contributions in membranous nephropathy over the last decade have greatly enhanced our comprehension of its pathogenesis, diagnosis, and treatments, igniting renewed interest in this entity. This review provides an updated perspective on the diagnosis and therapeutic management of membranous nephropathy. The identification of antiphospholipase A2 receptor (PLA2R) antibodies in 50-80% of membranous nephropathy patients was a key breakthrough. High or increasing PLA2R antibody levels are linked to persistent nephrotic syndrome and the need for targeted treatment. Given the high specificity of PLA2R antibodies, a kidney biopsy may not be required for pure nephrotic syndrome cases with no comorbidities. Over the years, various target antigens and associated conditions have been identified in membranous nephropathy patients, leading to a reclassification of membranous nephropathy. Treatment approaches vary based on baseline characteristics and changes in proteinuria and PLA2R titers. Rituximab has emerged as the first-line therapy for most patients without severe risk factors, with other emerging therapies under development. Advances in the diagnosis and treatment of membranous nephropathy have moved the management towards a more precision-based approach, though further studies and new therapies are needed for a comprehensive management strategy.

Current Trend and Outcomes on Immunonutrition in Medical and Surgical Fields: An Updated Perspective

Immunonutrition, which involves the targeted use of specific nutrients to enhance immune function and mitigate inflammation, has recently become a mainstay for both medical and surgical benefits. This review explores the evolution, mechanisms, and clinical applications of immunonutrition, with a focus on essential nutrients, such as omega-3 fatty acids, glutamine, arginine, and vitamins. These immunonutrients modulate immune responses, reduce pro-inflammatory cytokines, and support tissue repair. Clinical evidence indicates that immunonutrition reduces postoperative complications, shortens the duration of hospitalisation, and lowers the rate of infection, mainly in high-risk surgical patients and those with cancer or chronic diseases. In this regard, nutrients such as glutamine and omega-3 fatty acids have improved the nutritional status and recovery of cancer patients, while omega-3 fatty acids and antioxidant vitamins have exerted an anti-inflammatory effect, improving heart health in patients with cardiovascular disease. Immunonutrition has bright prospects in the management of infectious diseases, where certain nutrients, including vitamin D and zinc, aid in fighting immune defences and reducing the severity of infection. Future studies should investigate the molecular mechanisms underlying immunonutrition and its role in personalised nutrition. This could revolutionise dietary interventions based on genetic and proteomic profiling.

The Role of Exercise in Steatotic Liver Diseases: An Updated Perspective

ABSTRACTBackgroundThe increasing prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly known as non‐alcoholic fatty liver disease (NAFLD), parallels the rise in sedentary lifestyles. MASLD is the most common form of steatotic liver disease (SLD), which represents the umbrella beneath which the vast majority of chronic liver diseases fall, including alcohol‐related liver disease and their overlap. These conditions are the leading contributors to chronic liver disease, significantly impacting global morbidity and mortality. Despite the emergence of new pharmacotherapies, exercise represents the foundation of MASLD treatment.ObjectiveThis review aims to provide an updated perspective on the role of exercise in the management of SLD, highlight its molecular and clinical benefits, and explore its benefits and safety in the stage of cirrhosis.MethodsEvidence from pre‐clinical and clinical studies was reviewed to evaluate the impact of exercise on SLD (mainly MASLD), advanced chronic liver disease stages, and its relevance in the context of evolving therapies such as Resmetirom and incretin‐based anti‐obesity medications.ConclusionExercise remains a cornerstone intervention in the management of MASLD, with suggested benefits even for patients who have progressed to cirrhosis. Personalized exercise regimens should be prioritized for all patients, including those receiving pharmacotherapy. Further research is needed to refine exercise protocols and investigate their impact on histologic and clinical outcomes, as well as their potential synergistic effects with emerging treatments.

Nuclear Structure, Size Regulation, and Role in Cell Migration.

The nucleus serves as a pivotal regulatory and control hub in the cell, governing numerous aspects of cellular functions, including DNA replication, transcription, and RNA processing. Therefore, any deviations in nuclear morphology, structure, or organization can strongly affect cellular activities. In this review, we provide an updated perspective on the structure and function of nuclear components, focusing on the linker of nucleoskeleton and cytoskeleton complex, the nuclear envelope, the nuclear lamina, and chromatin. Additionally, nuclear size should be considered a fundamental parameter for the cellular state. Its regulation is tightly linked to environmental changes, development, and various diseases, including cancer. Hence, we also provide a concise overview of different mechanisms by which nuclear size is determined, the emerging role of the nucleus as a mechanical sensor, and the implications of altered nuclear morphology on the physiology of diseased cells.

The role of osteoprotegerin (OPG) in exercise-induced skeletal muscle adaptation

Abstract Objectives The purpose of this narrative review is to offer an updated perspective on the current research on the glycoprotein Osteoprotegerin (OPG), including its potential therapeutic impact and mechanisms of action, and interaction with bone and muscle tissues. Content As health and social care advances people are living longer, with projections suggesting that in 2050 there will be 2 billion people who are aged over 60 years. Yet musculoskeletal health still declines into older age and as a result there is an increase in the proportion of older populations that spend more time with persistent disabilities. Although physical exercise is repeatedly demonstrated to minimise detrimental effects of ageing, it is not always a feasible intervention, and other directions must be considered. Summary and outlook OPG, a glycoprotein decoy receptor for the receptor activator of nuclear factor kappa-β ligand (RANKL) is a key regulator of bone formation yet emerging evidence has presented its potential to offer positive outcomes in regard to the preservation of skeletal muscle mass and function. Animal models have shown that OPG levels increase during exercise, and independently acts to restore losses of muscle strength and reduce bone resorption. Interventions to increase circulating OPG alongside exercise may act as a therapeutic target to combat the decline in quality of life in older age in humans. Further research is needed on the mechanisms of its action and interaction in humans in combination with exercise.

Patient-Reported Outcomes Measurement Information System as a Clinical Tool for Capturing the Patient Perspective in Pediatric Inflammatory Bowel Disease: A Narrative Review.

Inflammatory bowel disease (IBD) is an immune-mediated chronic disease with a significant impact on quality of life. In pediatric patients, diagnosing and managing IBD is particularly challenging, and IBD often presents as a more severe and progressive disease. Patient-reported outcomes (PROs) are measures of treatment and disease management outcomes reported by patients and/or caregivers. These measures evaluate several aspects of disease management from the patient/caregiver perspective, emphasizing the patient's real-life experience with the disease and its treatment. PROs represent a model of patient-centered care, facilitating better-informed healthcare decisions. The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to promote the use of PROs among patients with chronic conditions. Its primary objective is to provide PROs for research and clinical practice throughout the lifespan. The PROMIS is a non-disease-specific instrument for both adults and pediatric patients assessing domains of physical, psychological, and social health, as well as quality of life (QOL). These instruments are designed to be applicable to a wide range of chronic diseases. Despite the initial expectation concerning PROs in assessing pediatric IBD outcomes, objective data in this area have only recently begun to emerge. This narrative review, based on a selection of reliable articles recognized by PubMed and Cochrane Library, aimed to identify and summarize previously published evidence of the usefulness of PROs, particularly the PROMIS, in IBD patients and in the pediatric population. We present an updated perspective, including identification of their general applications and most relevant previous studies, in the mentioned areas and identify knowledge gaps.

Update on the connectivity of the paraventricular nucleus of the thalamus and its position within limbic corticostriatal circuits.

The paraventricular nucleus of the thalamus (PVT) is generating interest because of evidence establishing a role for this midline thalamic nucleus in behavior. Early tracing studies demonstrated that afferent fibers from the PVT and limbic cortex converge with dopamine fibers within subcompartments of the ventral striatum. Subsequent tracing studies expanded on these observations by establishing that the PVT provides a dense projection to a continuum of striatal-like regions that include the nucleus accumbens and the extended amygdala. These findings have been complemented by recent tracing evidence examining the organization of the PVT's efferent and afferent connections. An updated view of the organization of projection neurons in PVT is provided with a focus on the input-output relationship of these neurons. The review emphasizes recent findings demonstrating that the PVT is composed of intermixed populations of neurons with axons that collateralize to densely innervate limbic striatal regions while being reciprocally connected with limbic cortical areas that innervate the same regions of the striatum. An updated perspective of the PVT's anatomical relationship with limbic corticostriatal circuits is presented to stimulate research on how the PVT regulates behavioral responses associated with emotion and motivation.

Review on the role of autophagy in the toxicity of nanoparticles and the signaling pathways involved.

As the development of nanotechnology, the application of nanoproducts and the advancement of nanomedicine, the contact of nanoparticles (NPs) with human body is becoming increasingly prevalent. This escalation elevates the risk of NPs exposure for workers, consumers, researchers, and both aquatic and terrestrial organisms throughout the production, usage, and disposal stages. Consequently, evaluating nanotoxicity remains critically important, though standardized assessment criteria are still lacking. The diverse and complex properties of NPs further complicate the understanding of their toxicological mechanisms. Autophagy, a fundamental cellular process, exhibits dual functions-both pro-survival and pro-death. This review offers an updated perspective on the dual roles of autophagy in nanotoxicity and examines the factors influencing autophagic responses. However, no definitive framework exists for predicting NPs-induced autophagy. Beyond the conventional autophagy pathways, the review highlights specific transcription factors activated by NPs and explores metabolic reprogramming. Particular attention is given to NPs-induced selective autophagy, including mitophagy, ER-phagy, ferritinophagy, lysophagy, and lipophagy. Additionally, the review investigates autophagy's involvement in NPs-mediated biological processes such as ferroptosis, inflammation, macrophage polarization, epithelial-mesenchymal transition, tumor cell proliferation and drug resistance, as well as liver and kidney injury, neurotoxicity, and other diseases. In summary, this review presents a novel update on selective autophagy-mediated nanotoxicity and elucidates the broader interactions of autophagy in NPs-induced biological processes. Collectively, these insights offer valuable strategies for mitigating nanotoxicity through autophagy modulation and advancing the development of NPs in biomedical applications.

Non-Pharmacological Therapy in Heart Failure and Management of Heart Failure in Special Populations-A Review.

Non-pharmacological therapies play an essential role in the management of heart failure, complementing pharmacological treatments to mitigate disease progression and improve patient outcomes. This review provides an updated perspective on non-pharmacological interventions with a focus on lifestyle modifications, device therapies, and the management of heart failure in special populations, such as the elderly, women, and patients with comorbid conditions like renal dysfunction and diabetes. Key lifestyle interventions, including sodium and fluid restriction, dietary changes, and physical activity, are explored for their impact on symptom reduction, hospital readmissions, and quality of life. Device therapies like cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICD) are also evaluated for their effectiveness in reducing mortality in patients with advanced HF. Special attention is given to vulnerable populations, emphasizing the need for individualized approaches tailored to specific pathophysiological mechanisms and socioeconomic factors. By integrating these strategies, healthcare providers can optimize care and enhance patient adherence, reducing the overall burden of heart failure.

Mevalonate kinase deficiency: an updated clinical overview and revision of the SHARE recommendations.

Mevalonate kinase deficiency (MKD), a rare auto-inflammatory disorder, arises from mutations in the MVK gene, disrupting isoprenoid biosynthesis, and affecting cellular processes. This comprehensive review provides an updated perspective on MKD, including its aetiology, pathogenesis, diagnostic modalities, and therapeutic strategies. Based on recent research and clinical advances, our objective is to bridge the knowledge gaps in the 2015 SHARE guidelines. By describing molecular mechanisms, diagnostic dilemmas, and emerging therapies, this article should serve as a resource for clinicians and researchers, promoting a deeper understanding of MKD and guiding optimal patient care.

Malignant Pleural Effusion: Diagnosis and Treatment-Up-to-Date Perspective.

Malignant pleural effusion is the presence of malignant cells within the pleural fluid, representing the second most common cause of pleural exudate. Although diagnostic methods and management techniques for malignant pleural effusion have dramatically improved over the decades, the current treatment is still palliative, aiming to remove pleural fluid, possibly prevent its recurrence, and alleviate symptoms through a wide range of available procedures. Treatment should be tailored to the individual patient, considering comorbidities, size of the effusion, rate of fluid accumulation, underlying cardiac or respiratory conditions, rate of recurrence, presence of loculations or trapped lung, tumor characteristics, cancer type, and patient preferences. This manuscript aims to review the available literature and to present the latest evidence on malignant pleural effusion management in order to provide an updated perspective on its diagnosis and treatment.

PCSK9 Inhibitors: The Evolving Future.

PCSK9 inhibitors are a novel class of medications that lower LDL cholesterol (LDL-C) by increasing LDL receptor activity, promoting clearance of LDL-C from the bloodstream. Over the years, PCSK9 inhibitors have been explored as adjunct therapies to statins or as monotherapy in high-risk cardiovascular patients. This review aims to provide an updated perspective on PCSK9 inhibitors, assessing their clinical efficacy, safety, and significance, especially in light of recent clinical trials. The review examines the role of PCSK9 in cholesterol regulation and summarizes the results of major cardiovascular trials, including FOURIER, SPIRE-1, SPIRE-2, and ODYSSEY Outcomes. It also discusses emerging treatments like small interfering RNA (siRNA) therapies and evaluates PCSK9 inhibitor effects on LDL-C and lipoprotein(a) levels. Clinical trials have shown PCSK9 inhibitors reduce LDL-C by up to 60%. In the FOURIER trial, evolocumab reduced LDL-C by 59% and major cardiovascular events by 15%-20%. The SPIRE-2 trial, despite early termination, showed a 21% risk reduction in the primary composite endpoint with bococizumab. The ODYSSEY Outcomes trial reported a 57% LDL-C reduction with alirocumab, alongside a 15% reduction in adverse events. Emerging treatments like Inclisiran offer long-term LDL-C control with fewer doses. PCSK9 inhibitors are generally well-tolerated, with the most common side effect being injection site reactions. PCSK9 inhibitors significantly lower LDL-C and reduce cardiovascular events, offering promising therapies for high-risk patients, including those with familial hypercholesterolemia (FH) and those who cannot tolerate statins. Future research will focus on optimizing these inhibitors, integrating complementary therapies, and exploring gene-editing technologies to improve patient outcomes.

The Biological Roles of ZKSCAN3 (ZNF306) in the Hallmarks of Cancer: From Mechanisms to Therapeutics.

ZKSCAN3 (also known as ZNF306) plays a pivotal role in the regulation of various cellular processes that are fundamental to the development of cancer. It has been widely acknowledged as a key contributor to cancer progression, with its overexpression consistently reported in a broad spectrum of malignancies. Importantly, clinical studies have demonstrated a significant association between elevated ZKSCAN3 levels and adverse prognosis, as well as resistance to therapeutic drugs. Specifically, ZKSCAN3 promotes tumor progression by enhancing multiple hallmark features of cancer and promoting the acquisition of cancer-specific phenotypes. These effects manifest as increased tumor cell proliferation, invasion, and metastasis, accompanied by inhibiting tumor cell apoptosis and modulating autophagy. Consequently, ZKSCAN3 emerges as a promising prognostic marker, and targeting its inhibition represents a potential strategy for anti-tumor therapy. In this review, we provide an updated perspective on the role of ZKSCAN3 in governing tumor characteristics and the underlying molecular mechanisms. Furthermore, we underscore the clinical relevance of ZKSCAN3 and its potential implications for tumor prognosis and therapeutic strategies.

Non-Invasive Ultrasound Diagnostic Techniques for Steatotic Liver Disease and Focal Liver Lesions: 2D, Colour Doppler, 3D, Two-Dimensional Shear Wave Elastography (2D-SWE), and Ultrasound-Guided Attenuation Parameter (UGAP).

We conducted a comprehensive literature review to evaluate the efficacy of combining two-dimensional shear wave elastography (2D-SWE) and ultrasound-guided attenuation parameter (UGAP) in assessing the risk of progressive metabolic dysfunction-associated steatohepatitis (MASH). This narrative review explores the applications of liver ultrasound in diagnosing metabolic liver diseases, focusing on recent advancements in diagnostic techniques for steatotic liver disease (SLD). Liver ultrasound can detect a spectrum of SLD manifestations, from metabolic dysfunction-associated liver disease (MASLD) to fibrosis and cirrhosis. It is also possible to identify inflammation, hepatitis, hepatocellular carcinoma (HCC), and various other liver lesions. Innovative ultrasound applications, including elastography and UGAP, can significantly enhance the diagnostic capabilities of ultrasound in accurately interpreting liver diseases. Understanding the pathogenesis of liver diseases requires a thorough analysis of their etiology and progression in order to develop sound diagnostic and therapeutic approaches. Chronic liver diseases (CLD) vary in origin, with MASLD affecting approximately 20-25% of the general population. The insidious progression of CLD from inflammation to fibrosis and cirrhosis underscores the need for effective early detection methods. This review aims to highlight the evolving role of non-invasive ultrasound-based diagnostic tests in the early detection and staging of liver diseases. By synthesizing current evidence, we aim to provide an updated perspective on the utility of advanced ultrasound techniques in redefining the diagnostic landscape for metabolic liver diseases.

From stable teamwork to dynamic teaming in the ambulatory care diagnostic process.

Dynamic teaming is required whenever people must coordinate with one another in a fluid context, particularly when the fundamental structures of a team, such as membership, priorities, tasks, modes of communication, and location are in near-constant flux. This is certainly the case in the contemporary ambulatory care diagnostic process, where circumstances and conditions require a shifting cast of individuals to coordinate dynamically to ensure patient safety. This article offers an updated perspective on dynamic teaming commonly required during the ambulatory diagnostic process. Drawing upon team science, it clarifies the characteristics of dynamic diagnostic teams, identifies common risk points in the teaming process and the practical implications of these risks, considers the role of providers and patients in averting adverse outcomes, and provides a case example of the challenges of dynamic teaming during the diagnostic process. Based on this, futureresearch needs are offered as well as clinical practice recommendations related to team characteristics and breakdowns, team member knowledge/cognitions, teaming dynamics, and the patient as a team member.

Neuroscience in Pictures: 3. Schizophrenia

Schizophrenia is a complex, heritable brain disorder characterized by psychotic, negative, cognitive, mood, and motor symptoms. This pictorial review explores the multifaceted nature of schizophrenia, from its etiology to prevention strategies. We discuss the interplay of genetic and environmental risk factors, neurobiological underpinnings, and stepwise progression. Recent advances in understanding circuit-level pathophysiology and neurotransmitter systems beyond dopamine are highlighted along with neuropathological findings, particularly the exaggerated synaptic pruning hypothesis. Based on these developments, we present an updated perspective on pharmacological interventions. Finally, we outline preventative strategies across different stages, emphasizing early intervention. This overview, designed as a teaching resource, aims to provide trainees, clinicians and researchers with a current understanding of schizophrenia’s neurobiological underpinnings and the implications of such understanding to the evolving landscape of its diagnosis and management.

Cannabinoids and Genetic Epilepsy Models: A Review with Focus on CDKL5 Deficiency Disorder

Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers. The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBD’s antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids’ pharmacodynamics. This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid’s potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid’s therapeutic potential for CDD.

The effects of sodium-glucose cotransporter 2 inhibitors on the 'forgotten' right ventricle.

With the progress in diagnosis, treatment and imaging techniques, there is a growing recognition that impaired right ventricular (RV) function profoundly affects the prognosis of patients with heart failure (HF), irrespective of their left ventricular ejection fraction (LVEF). In addition, right HF (RHF) is a common complication associated with various diseases, including congenital heart disease, myocardial infarction (MI), pulmonary arterial hypertension (PAH) and dilated cardiomyopathy (DCM), and it can manifest at any time after left ventricular assist devices (LVADs). The sodium-glucose cotransporter 2 (SGLT2) inhibition by gliflozins has emerged as a cornerstone medicine for managing type 2 diabetes mellitus (T2DM) and HF, with an increasing focus on its potential to enhance RV function. In this review, we aim to present an updated perspective on the pleiotropic effects of gliflozins on the right ventricle and offer insights into the underlying mechanisms. We can ascertain their advantageous impact on the right ventricle by discussing the evidence obtained in animal models and monumental clinical trials. In light of the pathophysiological changes in RHF, we attempt to elucidate crucial mechanisms regarding their beneficial effects, including alleviation of RV overload, reduction of hyperinsulinaemia and inflammatory responses, regulation of nutrient signalling pathways and cellular energy metabolism, inhibition of oxidative stress and myocardial fibrosis, and maintenance of ion balance. Finally, this drug class's potential application and benefits in various clinical settings are described, along with a prospective outlook on future clinical practice and research directions.