Aging is associated with reduced inhibitory control, leading to challenges in attention, decision-making, and everyday cognitive tasks. To better understand these difficulties, it is important to adopt well-designed experimental approaches that specifically assess inhibitory control mechanisms. A commonly used tool to assess how inhibitory control changes with age is the Stroop Color and Word Test, which evaluates the capacity to suppress automatic responses in favor of appropriate behavior.
In the present study, a sample of 91 healthy individuals was examined to investigate how cognitive functions underlying Stroop task performance vary across the adult lifespan. Pearson correlations were computed between participants’ age and response times (RTs) recorded in each of the three Stroop conditions, as well as the mean RTs across all conditions. Furthermore, to assess whether these behavioral patterns were mirrored at the neurophysiological level, power spectral density (PSD) analyses were performed on resting-state electroencephalographic recordings.
In all cases, Pearson correlations were strongly significant, with stronger effects observed as task difficulty increased. At the neurophysiological level, a correlation emerged between RTs and PSD in the occipital region within the alpha 2 frequency band, which, like the behavioral effects, became progressively stronger with increasing task difficulty. In contrast, no significant correlations were observed for the alpha 1 band, suggesting that these neurophysiological changes are specific to higher alpha frequencies linked to increased cognitive demands and inhibitory control processes.
These findings contribute to a better understanding of the neural mechanisms underlying age-related declines in inhibitory control and may inform the development of interventions aimed at mitigating cognitive deficits in older adults.
Aging is associated with reduced inhibitory control, leading to challenges in attention, decision-making, and everyday cognitive tasks. To better understand these difficulties, it is important to adopt well-designed experimental approaches that specifically assess inhibitory control mechanisms. A commonly used tool to assess how inhibitory control changes with age is the Stroop Color and Word Test, which evaluates the capacity to suppress automatic responses in favor of appropriate behavior.
In the present study, a sample of 91 healthy individuals was examined to investigate how cognitive functions underlying Stroop task performance vary across the adult lifespan. Pearson correlations were computed between participants’ age and response times (RTs) recorded in each of the three Stroop conditions, as well as the mean RTs across all conditions. Furthermore, to assess whether these behavioral patterns were mirrored at the neurophysiological level, power spectral density (PSD) analyses were performed on resting-state electroencephalographic recordings.
In all cases, Pearson correlations were strongly significant, with stronger effects observed as task difficulty increased. At the neurophysiological level, a correlation emerged between RTs and PSD in the occipital region within the alpha 2 frequency band, which, like the behavioral effects, became progressively stronger with increasing task difficulty. In contrast, no significant correlations were observed for the alpha 1 band, suggesting that these neurophysiological changes are specific to higher alpha frequencies linked to increased cognitive demands and inhibitory control processes.
These findings contribute to a better understanding of the neural mechanisms underlying age-related declines in inhibitory control and may inform the development of interventions aimed at mitigating cognitive deficits in older adults.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is characterized by a high recurrence rate, limited treatment options, and frequent resistance to systemic therapy. A key factor in this resistance is the persistent activation of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that normally protects against oxidative stress but, in malignant hepatocytes, suppresses ferroptosis by restricting lipid peroxidation. This dual function positions NRF2 as a key target for therapeutic modulation in HCC. Recent preclinical studies demonstrate that NRF2 maintains tumor survival by regulating antioxidant and iron management pathways, such as GPX4, SLC7A11, and ferritin, which together mitigate lipid peroxidation and prevent ferroptotic cell death. Multiple pharmacological strategies have been evaluated to counteract this effect, including direct NRF2 inhibitors such as camptothecin (CPT) and brusatol, preoperative modulators such as metformin and picropodophyllin (PPP), and natural compounds such as tiliroside, bavaquine, and arenobufagin. These interventions often show synergistic activity with sorafenib and other standard treatments, while postoperative effectors such as CYP4F11 and the NRF2-SLC7A11-GPX4 axis have emerged as promising additional intervention points. Despite compelling results in vitro and animal model results, several challenges limit its application to clinical practice. These include the lack of dedicated clinical trials, the limited specificity of available inhibitors, tumor heterogeneity, and potential safety concerns in cirrhotic livers. Future research focuses on the development of selective NRF2 modulators, hepatocyte-targeted approaches such as proteolysis-targeted chimeras (PROTACs) and GalNAc-conjugated oligonucleotides, and biomarker-based patient stratification using genomic, immunohistochemical, and transcriptomic indicators of NRF2 activation. Taken together, contextual NRF2 modulation represents a promising strategy to restore sensitivity to ferroptosis, overcome drug resistance, and improve outcomes in HCC patients.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is characterized by a high recurrence rate, limited treatment options, and frequent resistance to systemic therapy. A key factor in this resistance is the persistent activation of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that normally protects against oxidative stress but, in malignant hepatocytes, suppresses ferroptosis by restricting lipid peroxidation. This dual function positions NRF2 as a key target for therapeutic modulation in HCC. Recent preclinical studies demonstrate that NRF2 maintains tumor survival by regulating antioxidant and iron management pathways, such as GPX4, SLC7A11, and ferritin, which together mitigate lipid peroxidation and prevent ferroptotic cell death. Multiple pharmacological strategies have been evaluated to counteract this effect, including direct NRF2 inhibitors such as camptothecin (CPT) and brusatol, preoperative modulators such as metformin and picropodophyllin (PPP), and natural compounds such as tiliroside, bavaquine, and arenobufagin. These interventions often show synergistic activity with sorafenib and other standard treatments, while postoperative effectors such as CYP4F11 and the NRF2-SLC7A11-GPX4 axis have emerged as promising additional intervention points. Despite compelling results in vitro and animal model results, several challenges limit its application to clinical practice. These include the lack of dedicated clinical trials, the limited specificity of available inhibitors, tumor heterogeneity, and potential safety concerns in cirrhotic livers. Future research focuses on the development of selective NRF2 modulators, hepatocyte-targeted approaches such as proteolysis-targeted chimeras (PROTACs) and GalNAc-conjugated oligonucleotides, and biomarker-based patient stratification using genomic, immunohistochemical, and transcriptomic indicators of NRF2 activation. Taken together, contextual NRF2 modulation represents a promising strategy to restore sensitivity to ferroptosis, overcome drug resistance, and improve outcomes in HCC patients.
Current treatment for medulloblastoma involves craniospinal irradiation (CSI) with a radiation boost to the posterior fossa and adjuvant chemotherapy following surgical resection. Due to neurotoxic effects of CSI—particularly its impact on cognitive function and intelligence quotient (IQ)—recent efforts have focused on reducing CSI dosage. This systematic review compares standard-dose CSI (SDCSI) versus low-dose CSI (LDCSI) in terms of relapse rate, event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).
A systematic search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened studies for eligibility and extracted data on study design, patient demographics, CSI dosage, chemotherapy regimens, EFS, OS, relapse rates, and reported side effects.
Out of 749 identified studies, 24 met the inclusion criteria for this review. Reported 5-year EFS ranged from 27.3% to 83%, and 5-year OS ranged from 41 ± 8% to 94.7 ± 3.4%. Commonly reported adverse effects included hematologic toxicity, secondary malignancies, disease progression, nausea/vomiting, and cognitive impairment. IQ outcomes ranged from 71 to 98.6, with studies consistently showing that LDCSI was associated with a smaller decline in IQ compared to SDCSI. Factors such as age, molecular subgroup, and histological features were identified as important variables for risk stratification.
LDCSI combined with chemotherapy may provide sufficient treatment efficacy for medulloblastoma while mitigating neurocognitive decline. Future research should focus on optimizing chemotherapy regimens and refining treatment stratification based on molecular and histological subtypes, particularly in standard- versus high-risk patients.
Current treatment for medulloblastoma involves craniospinal irradiation (CSI) with a radiation boost to the posterior fossa and adjuvant chemotherapy following surgical resection. Due to neurotoxic effects of CSI—particularly its impact on cognitive function and intelligence quotient (IQ)—recent efforts have focused on reducing CSI dosage. This systematic review compares standard-dose CSI (SDCSI) versus low-dose CSI (LDCSI) in terms of relapse rate, event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).
A systematic search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened studies for eligibility and extracted data on study design, patient demographics, CSI dosage, chemotherapy regimens, EFS, OS, relapse rates, and reported side effects.
Out of 749 identified studies, 24 met the inclusion criteria for this review. Reported 5-year EFS ranged from 27.3% to 83%, and 5-year OS ranged from 41 ± 8% to 94.7 ± 3.4%. Commonly reported adverse effects included hematologic toxicity, secondary malignancies, disease progression, nausea/vomiting, and cognitive impairment. IQ outcomes ranged from 71 to 98.6, with studies consistently showing that LDCSI was associated with a smaller decline in IQ compared to SDCSI. Factors such as age, molecular subgroup, and histological features were identified as important variables for risk stratification.
LDCSI combined with chemotherapy may provide sufficient treatment efficacy for medulloblastoma while mitigating neurocognitive decline. Future research should focus on optimizing chemotherapy regimens and refining treatment stratification based on molecular and histological subtypes, particularly in standard- versus high-risk patients.
The transition from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) reflects a paradigm shift in hepatology and highlights the need for a more pathophysiologically based classification. The aim of this review is to critically examine the conceptual evolution from NAFLD to MASLD, highlighting the implications for pathogenesis, diagnosis, risk stratification, and therapeutic strategies within the broader context of systemic metabolic dysfunction. Unlike the exclusion-based NAFLD definition, MASLD is grounded in positive diagnostic criteria and recognizes hepatic steatosis as a manifestation of metabolic disease. This reclassification improves clinical risk assessment and aligns hepatic care with cardiometabolic management. MASLD is closely linked to insulin resistance, lipotoxicity, chronic inflammation, and gut dysbiosis, which contribute to cardiovascular disease, chronic kidney disease, type 2 diabetes, and hepatocellular carcinoma. Non-invasive tools (e.g., FIB-4, elastography, ELF score) and emerging biomarkers (e.g., miR-122, CK-18, FGF21) support early diagnosis and personalized approaches. Therapeutically, MASLD management includes lifestyle modification, antidiabetic agents (GLP-1 receptor agonists, SGLT2 inhibitors), PPAR agonists, and novel drugs such as resmetirom. This evolving framework demands integrated, multidisciplinary strategies to address the systemic burden and clinical heterogeneity of MASLD.
The transition from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) reflects a paradigm shift in hepatology and highlights the need for a more pathophysiologically based classification. The aim of this review is to critically examine the conceptual evolution from NAFLD to MASLD, highlighting the implications for pathogenesis, diagnosis, risk stratification, and therapeutic strategies within the broader context of systemic metabolic dysfunction. Unlike the exclusion-based NAFLD definition, MASLD is grounded in positive diagnostic criteria and recognizes hepatic steatosis as a manifestation of metabolic disease. This reclassification improves clinical risk assessment and aligns hepatic care with cardiometabolic management. MASLD is closely linked to insulin resistance, lipotoxicity, chronic inflammation, and gut dysbiosis, which contribute to cardiovascular disease, chronic kidney disease, type 2 diabetes, and hepatocellular carcinoma. Non-invasive tools (e.g., FIB-4, elastography, ELF score) and emerging biomarkers (e.g., miR-122, CK-18, FGF21) support early diagnosis and personalized approaches. Therapeutically, MASLD management includes lifestyle modification, antidiabetic agents (GLP-1 receptor agonists, SGLT2 inhibitors), PPAR agonists, and novel drugs such as resmetirom. This evolving framework demands integrated, multidisciplinary strategies to address the systemic burden and clinical heterogeneity of MASLD.
HIV/AIDS has changed from a deadly disease in the early 1990s to a chronic treatment following huge research efforts. HIV had a great impact due to the long period until its fatal consequences in the form of AIDS appeared. As a consequence, the spread of the disease was global. However, even now, after many years of extensive research, there is still no functional cure or eradication possible. This review provides an overview on HIV/AIDS covering a description of the disease, the mechanism of infection, HIV/AIDS symptoms, the current treatment options, the formation of latent reservoirs, and the efforts to provide a cure of HIV including CCR5Δ32/Δ32 donor stem cell transplantation, gene therapy, broadly neutralizing antibodies, HIV vaccination, chimeric antigen receptor cells, latency-addressing agents, and combination approaches.
HIV/AIDS has changed from a deadly disease in the early 1990s to a chronic treatment following huge research efforts. HIV had a great impact due to the long period until its fatal consequences in the form of AIDS appeared. As a consequence, the spread of the disease was global. However, even now, after many years of extensive research, there is still no functional cure or eradication possible. This review provides an overview on HIV/AIDS covering a description of the disease, the mechanism of infection, HIV/AIDS symptoms, the current treatment options, the formation of latent reservoirs, and the efforts to provide a cure of HIV including CCR5Δ32/Δ32 donor stem cell transplantation, gene therapy, broadly neutralizing antibodies, HIV vaccination, chimeric antigen receptor cells, latency-addressing agents, and combination approaches.
Because of severe immunosuppression, coinfections continue to be a major cause of morbidity and mortality in HIV-infected patients. As the primary method currently used for diagnosing coinfections in HIV-infected patients, conventional microbiological tests (CMTs) often suffer from limitations such as prolonged processing times and low sensitivity, which may delay the initiation of appropriate treatment. This retrospective study aims to explore the applicability of metagenomic next-generation sequencing (mNGS) as a diagnostic tool compared with CMT.
A retrospective study was conducted on HIV-infected patients with coinfections admitted to Peking Union Medical College Hospital between November 2022 and November 2024. A receiver operating characteristic (ROC) curve was generated to evaluate the predictors and determine their sensitivities and specificities. The comprehensive final clinical diagnosis (FCD) was used as the reference standard for evaluating the diagnostic performance of CMT and mNGS. Then, treatment adjustments and outcomes after mNGS and CMT of the HIV-infected patients were also assessed.
The areas under the ROC curve (AUCs) for CMT and mNGS were 0.600 and 0.775, respectively. When mNGS was combined with CMT, the AUC was 0.833. The sensitivity and specificity of mNGS were 80% and 75%, whereas those of CMT were 20% and 100%. When mNGS was combined with CMT, the sensitivity increased to 86.67%. Among the 15 coinfected HIV patients, 8 patients underwent treatment adjustments on the basis of mNGS results and achieved effective treatment, whereas only 1 patient underwent treatment adjustments solely on the basis of CMT and achieved effective treatment.
Compared with CMT, mNGS has a better detection rate. mNGS provides an alternative and promising method for identifying coinfections in HIV-positive patients. Thus, the combination of mNGS and CMT is a better diagnostic strategy for coinfections in HIV patients.
Because of severe immunosuppression, coinfections continue to be a major cause of morbidity and mortality in HIV-infected patients. As the primary method currently used for diagnosing coinfections in HIV-infected patients, conventional microbiological tests (CMTs) often suffer from limitations such as prolonged processing times and low sensitivity, which may delay the initiation of appropriate treatment. This retrospective study aims to explore the applicability of metagenomic next-generation sequencing (mNGS) as a diagnostic tool compared with CMT.
A retrospective study was conducted on HIV-infected patients with coinfections admitted to Peking Union Medical College Hospital between November 2022 and November 2024. A receiver operating characteristic (ROC) curve was generated to evaluate the predictors and determine their sensitivities and specificities. The comprehensive final clinical diagnosis (FCD) was used as the reference standard for evaluating the diagnostic performance of CMT and mNGS. Then, treatment adjustments and outcomes after mNGS and CMT of the HIV-infected patients were also assessed.
The areas under the ROC curve (AUCs) for CMT and mNGS were 0.600 and 0.775, respectively. When mNGS was combined with CMT, the AUC was 0.833. The sensitivity and specificity of mNGS were 80% and 75%, whereas those of CMT were 20% and 100%. When mNGS was combined with CMT, the sensitivity increased to 86.67%. Among the 15 coinfected HIV patients, 8 patients underwent treatment adjustments on the basis of mNGS results and achieved effective treatment, whereas only 1 patient underwent treatment adjustments solely on the basis of CMT and achieved effective treatment.
Compared with CMT, mNGS has a better detection rate. mNGS provides an alternative and promising method for identifying coinfections in HIV-positive patients. Thus, the combination of mNGS and CMT is a better diagnostic strategy for coinfections in HIV patients.
An increasingly popular therapeutic approach for the treatment of cancer is the modification of signaling pathways mediated by oxidative stress. Epigenetic dysregulation serves as a key characteristic of human cancer, as almost half of all cancer cases involve mutations in epigenetic regulators like microRNAs (miRNAs). These small non-coding RNAs play a crucial role by generating functional RNA molecules that range from 18 to 25 nucleotides. miRNAs are essential for regulating gene expression at the mRNA level, but they have also been demonstrated in recent studies to influence the growth and development of cancer. miRNAs play a significant role in the generation of reactive oxygen species (ROS) and in various processes influenced by ROS. Therefore, exploring the relationship between ROS and miRNAs is becoming increasingly crucial, as it holds the potential to advance the development of effective cancer therapies and prevention strategies. This article aims to provide a comprehensive overview of the key characteristics and functional roles of miRNAs that are linked to oxidative stress in different cancers, paving the way for future research and therapeutic innovations. However, a lot of concerns and uncertainties regarding ROS-miRNAs and antioxidant defense systems still need to be resolved despite a great deal of research in this field.
An increasingly popular therapeutic approach for the treatment of cancer is the modification of signaling pathways mediated by oxidative stress. Epigenetic dysregulation serves as a key characteristic of human cancer, as almost half of all cancer cases involve mutations in epigenetic regulators like microRNAs (miRNAs). These small non-coding RNAs play a crucial role by generating functional RNA molecules that range from 18 to 25 nucleotides. miRNAs are essential for regulating gene expression at the mRNA level, but they have also been demonstrated in recent studies to influence the growth and development of cancer. miRNAs play a significant role in the generation of reactive oxygen species (ROS) and in various processes influenced by ROS. Therefore, exploring the relationship between ROS and miRNAs is becoming increasingly crucial, as it holds the potential to advance the development of effective cancer therapies and prevention strategies. This article aims to provide a comprehensive overview of the key characteristics and functional roles of miRNAs that are linked to oxidative stress in different cancers, paving the way for future research and therapeutic innovations. However, a lot of concerns and uncertainties regarding ROS-miRNAs and antioxidant defense systems still need to be resolved despite a great deal of research in this field.
Coronary artery bypass grafting (CABG) remains a cornerstone in the management of complex coronary artery disease, particularly in patients with multivessel involvement, diabetes, or left main disease. As surgical practice enters a new era of precision medicine and digital innovation, the need to reimagine CABG—beyond its traditional framework—has never been more pressing. This review explores the future of CABG across three central themes: innovation, individualization, and integration. Technological advancements such as robotic-assisted procedures, hybrid revascularization strategies, and artificial intelligence-driven decision support are reshaping operative planning and execution. Concurrently, biological innovations—including regenerative therapies and tissue-engineered grafts—are expanding the therapeutic envelope, offering potential solutions for anatomically complex or high-risk patients. Personalized medicine is gaining traction through genomic profiling, biomarker-guided risk stratification, and machine learning-based outcome prediction. Enhanced recovery after surgery (ERAS) protocols and telemedicine-enabled follow-up are redefining postoperative care, emphasizing early mobilization, opioid minimization, and remote monitoring. Ethical and economic considerations remain pivotal as these innovations transition into practice. Issues of equitable access, algorithmic transparency, and cost-effectiveness must be addressed to ensure responsible integration. In parallel, the professional development landscape for cardiac surgeons is evolving, with calls for structured training in advanced techniques and interdisciplinary collaboration. Future research priorities include validation of regenerative adjuncts, predictive analytics, and advanced conduit strategies, alongside investigations into health equity and subspecialization. Ultimately, achieving durable, patient-centered outcomes in the next phase of CABG requires a system-level shift that embraces innovation while safeguarding safety, accessibility, and sustainability. This article provides a comprehensive, forward-facing overview of these themes, identifying key directions for clinical practice, research, and education in the evolving world of coronary revascularization.
Coronary artery bypass grafting (CABG) remains a cornerstone in the management of complex coronary artery disease, particularly in patients with multivessel involvement, diabetes, or left main disease. As surgical practice enters a new era of precision medicine and digital innovation, the need to reimagine CABG—beyond its traditional framework—has never been more pressing. This review explores the future of CABG across three central themes: innovation, individualization, and integration. Technological advancements such as robotic-assisted procedures, hybrid revascularization strategies, and artificial intelligence-driven decision support are reshaping operative planning and execution. Concurrently, biological innovations—including regenerative therapies and tissue-engineered grafts—are expanding the therapeutic envelope, offering potential solutions for anatomically complex or high-risk patients. Personalized medicine is gaining traction through genomic profiling, biomarker-guided risk stratification, and machine learning-based outcome prediction. Enhanced recovery after surgery (ERAS) protocols and telemedicine-enabled follow-up are redefining postoperative care, emphasizing early mobilization, opioid minimization, and remote monitoring. Ethical and economic considerations remain pivotal as these innovations transition into practice. Issues of equitable access, algorithmic transparency, and cost-effectiveness must be addressed to ensure responsible integration. In parallel, the professional development landscape for cardiac surgeons is evolving, with calls for structured training in advanced techniques and interdisciplinary collaboration. Future research priorities include validation of regenerative adjuncts, predictive analytics, and advanced conduit strategies, alongside investigations into health equity and subspecialization. Ultimately, achieving durable, patient-centered outcomes in the next phase of CABG requires a system-level shift that embraces innovation while safeguarding safety, accessibility, and sustainability. This article provides a comprehensive, forward-facing overview of these themes, identifying key directions for clinical practice, research, and education in the evolving world of coronary revascularization.
Abnormalities in sperm parameters can result from genetic variations in DNA repair genes. The base excision repair (BER) pathway is responsible for maintaining DNA integrity. Single-nucleotide polymorphisms (SNPs) in BER genes may influence sperm DNA fragmentation (SDF) and other seminal fluid parameters. Therefore, we conducted a study to investigate the impact of SNPs in BER genes, specifically XRCC1, OGG1, MUTYH, and APEX1, on SDF and seminal fluid parameters in a selected male population from the Gaza Strip.
The case-control study included 75 men with elevated SDF and 74 men with normal SDF. Semen samples underwent conventional semen analysis and the SDF test. DNA extracted from the samples was genotyped for the selected polymorphisms using the allele-specific polymerase chain reaction (AS-PCR) technique. Genotypes and allele frequencies were compared between the case and control groups using standard statistical methods.
In terms of SDF, the XRCC1 rs25487 polymorphism showed a significant difference between cases and controls, with the C allele and the CC genotype being more prevalent (P-value = 0.004) in the control group. Additionally, the MUTYH rs3219489 polymorphism also had a significant difference, with the GC genotype being more frequent (P-value = 0.025) in the control group. However, OGG1 and APEX1 polymorphisms did not show a significant difference between the two groups. The examined polymorphisms were not significantly related to conventional semen parameters.
This study highlights the effects of genetic variations in DNA repair genes, specifically XRCC1 and MUTYH, on SDF. Further studies with a larger sample size are necessary to confirm these findings and explore the impact of these SNPs on reproductive potential.
Abnormalities in sperm parameters can result from genetic variations in DNA repair genes. The base excision repair (BER) pathway is responsible for maintaining DNA integrity. Single-nucleotide polymorphisms (SNPs) in BER genes may influence sperm DNA fragmentation (SDF) and other seminal fluid parameters. Therefore, we conducted a study to investigate the impact of SNPs in BER genes, specifically XRCC1, OGG1, MUTYH, and APEX1, on SDF and seminal fluid parameters in a selected male population from the Gaza Strip.
The case-control study included 75 men with elevated SDF and 74 men with normal SDF. Semen samples underwent conventional semen analysis and the SDF test. DNA extracted from the samples was genotyped for the selected polymorphisms using the allele-specific polymerase chain reaction (AS-PCR) technique. Genotypes and allele frequencies were compared between the case and control groups using standard statistical methods.
In terms of SDF, the XRCC1 rs25487 polymorphism showed a significant difference between cases and controls, with the C allele and the CC genotype being more prevalent (P-value = 0.004) in the control group. Additionally, the MUTYH rs3219489 polymorphism also had a significant difference, with the GC genotype being more frequent (P-value = 0.025) in the control group. However, OGG1 and APEX1 polymorphisms did not show a significant difference between the two groups. The examined polymorphisms were not significantly related to conventional semen parameters.
This study highlights the effects of genetic variations in DNA repair genes, specifically XRCC1 and MUTYH, on SDF. Further studies with a larger sample size are necessary to confirm these findings and explore the impact of these SNPs on reproductive potential.
This case report documents the successful endodontic retreatment of a mandibular first molar exhibiting four mesial root canals in a 20-year-old male patient—an exceptionally rare anatomical configuration. Following the extraction of the perforated distal root, careful clinical exploration revealed two supplementary canals demonstrating apical convergence with the primary canals. The treatment protocol incorporated ultrasonically activated irrigation, precision rotary instrumentation, and warm vertical compaction obturation with bioceramic sealer. This case underscores the critical importance of thorough anatomical exploration in complex root canal systems.
This case report documents the successful endodontic retreatment of a mandibular first molar exhibiting four mesial root canals in a 20-year-old male patient—an exceptionally rare anatomical configuration. Following the extraction of the perforated distal root, careful clinical exploration revealed two supplementary canals demonstrating apical convergence with the primary canals. The treatment protocol incorporated ultrasonically activated irrigation, precision rotary instrumentation, and warm vertical compaction obturation with bioceramic sealer. This case underscores the critical importance of thorough anatomical exploration in complex root canal systems.
Cancer patients and their caregivers often face a high burden of physical and psychological symptoms, such as pain, fatigue, anxiety, insomnia, and emotional distress, which significantly impact quality of life. While pharmacological treatments remain central to oncology care, they may not fully address these complex needs and can introduce risks such as polypharmacy. Non-pharmacological interventions offer complementary strategies that are generally safe, cost-effective, and adaptable to various clinical and home settings. This review explores practical, evidence-based non-pharmacological interventions that can be integrated into supportive cancer care. These include aromatherapy, massage therapy, mindfulness practices, guided imagery, music and art therapy, and sleep hygiene techniques. Each approach is examined in terms of its mechanisms of action, symptom targets, delivery methods, and implementation considerations. For example, lavender and citrus essential oils have been shown to have anxiolytic and sedative effects through olfactory-limbic pathways. Massage therapy has been associated with reductions in pain, stress, and cortisol levels. Mindfulness-based practices and guided imagery can help regulate emotional distress and may have a positive influence on immune and inflammatory markers. Music and art therapy support emotional expression and coping, while sleep hygiene strategies improve sleep quality and reduce fatigue. These interventions can benefit both patients and caregivers by enhancing resilience, fostering emotional connection, and supporting holistic well-being. Healthcare professionals play a crucial role in guiding the safe and appropriate use of these non-pharmacological interventions. Integrating these approaches into routine care requires individualized planning, clinician training, and institutional support. As evidence grows, non-pharmacological interventions should be recognized as valuable components of comprehensive cancer care.
Cancer patients and their caregivers often face a high burden of physical and psychological symptoms, such as pain, fatigue, anxiety, insomnia, and emotional distress, which significantly impact quality of life. While pharmacological treatments remain central to oncology care, they may not fully address these complex needs and can introduce risks such as polypharmacy. Non-pharmacological interventions offer complementary strategies that are generally safe, cost-effective, and adaptable to various clinical and home settings. This review explores practical, evidence-based non-pharmacological interventions that can be integrated into supportive cancer care. These include aromatherapy, massage therapy, mindfulness practices, guided imagery, music and art therapy, and sleep hygiene techniques. Each approach is examined in terms of its mechanisms of action, symptom targets, delivery methods, and implementation considerations. For example, lavender and citrus essential oils have been shown to have anxiolytic and sedative effects through olfactory-limbic pathways. Massage therapy has been associated with reductions in pain, stress, and cortisol levels. Mindfulness-based practices and guided imagery can help regulate emotional distress and may have a positive influence on immune and inflammatory markers. Music and art therapy support emotional expression and coping, while sleep hygiene strategies improve sleep quality and reduce fatigue. These interventions can benefit both patients and caregivers by enhancing resilience, fostering emotional connection, and supporting holistic well-being. Healthcare professionals play a crucial role in guiding the safe and appropriate use of these non-pharmacological interventions. Integrating these approaches into routine care requires individualized planning, clinician training, and institutional support. As evidence grows, non-pharmacological interventions should be recognized as valuable components of comprehensive cancer care.
Mobile technology enables frequent, remote cognitive assessments, introducing new methodological opportunities and challenges. The study evaluated the feasibility of a high-frequency cognitive assessment schedule among older adults, in terms of total assessments and adherence to a prescribed schedule.
Thirty-three older adults were recruited from the Boston University Alzheimer’s Disease Research Center (mean age = 73.5 years; 27.3% cognitively impaired; 57.6% female; 81.8% White, 18.2% Black). Participants downloaded the DANA Brain Vital mobile application on their own mobile devices during a remote study visit, and were provided a schedule with seventeen assessments to complete over one year at varying frequencies. The first segment contained three subsegments to be completed within one week, the second segment consisted of weekly subsegments spanning three weeks, and the third and fourth segments consisted of monthly subsegments spanning five and six months, respectively. Three adherence types were defined to reflect incrementally broader adherence timescales: subsegment adherence (strict adherence to each prescribed assessment period), segment adherence (completing the required number of assessments within each broader segment), and cumulative adherence (completing the total number of assessments irrespective of timing).
Completion rates differed depending on the adherence timescale and corresponding adherence type. Using the strictest adherence definition (subsegment adherence), completion rates declined (from 93.9% to 72.7%, p = 0.05) during the fourth segment. However, when a broader adherence timescale was applied, completion rates did not decline. Overall completion rates increased as adherence timescale parameters were broadened from subsegment adherence (60.6%) to segment adherence (78.8%), to cumulative adherence (90.9%).
Older adults, including those with cognitive impairment, are able to complete remote cognitive assessments at a high-frequency, but may not necessarily adhere to prescribed schedules. Future high-frequency studies should consider adherence as a potential behavioral variable to complement cognitive test data, while recognizing the potential influence of adherence timescale on interpreting completion rates.
Mobile technology enables frequent, remote cognitive assessments, introducing new methodological opportunities and challenges. The study evaluated the feasibility of a high-frequency cognitive assessment schedule among older adults, in terms of total assessments and adherence to a prescribed schedule.
Thirty-three older adults were recruited from the Boston University Alzheimer’s Disease Research Center (mean age = 73.5 years; 27.3% cognitively impaired; 57.6% female; 81.8% White, 18.2% Black). Participants downloaded the DANA Brain Vital mobile application on their own mobile devices during a remote study visit, and were provided a schedule with seventeen assessments to complete over one year at varying frequencies. The first segment contained three subsegments to be completed within one week, the second segment consisted of weekly subsegments spanning three weeks, and the third and fourth segments consisted of monthly subsegments spanning five and six months, respectively. Three adherence types were defined to reflect incrementally broader adherence timescales: subsegment adherence (strict adherence to each prescribed assessment period), segment adherence (completing the required number of assessments within each broader segment), and cumulative adherence (completing the total number of assessments irrespective of timing).
Completion rates differed depending on the adherence timescale and corresponding adherence type. Using the strictest adherence definition (subsegment adherence), completion rates declined (from 93.9% to 72.7%, p = 0.05) during the fourth segment. However, when a broader adherence timescale was applied, completion rates did not decline. Overall completion rates increased as adherence timescale parameters were broadened from subsegment adherence (60.6%) to segment adherence (78.8%), to cumulative adherence (90.9%).
Older adults, including those with cognitive impairment, are able to complete remote cognitive assessments at a high-frequency, but may not necessarily adhere to prescribed schedules. Future high-frequency studies should consider adherence as a potential behavioral variable to complement cognitive test data, while recognizing the potential influence of adherence timescale on interpreting completion rates.
Mushrooms are non-photosynthetic organisms produced as distinctive spore bearing fruiting bodies of filamentous macro-fungi. More than 14,000 mushroom species have been recognized, of which around 2,200 are edible. Scientists have extensively studied the extracts of different mushroom fruit bodies over the past few decades to identify the biologically active medicinal and nutraceutical components having different health benefits. Mushroom is also considered a functional food owing to the presence of low-fat and high-fiber contents useful in maintaining metabolic health. An expansive patent search since 2019 was conducted to review the information on mushrooms and their bioactive constituents using multiple patent databases. This review aims to highlight the pharmacological effects and potential therapeutic implications of mushroom bioactive substances as published in patent literature. Such information would assist researchers to explore the detailed processes and interactions involved by which the mushroom chemical components exert different medicinal properties, thereby increasing their credibility in clinical applications.
Mushrooms are non-photosynthetic organisms produced as distinctive spore bearing fruiting bodies of filamentous macro-fungi. More than 14,000 mushroom species have been recognized, of which around 2,200 are edible. Scientists have extensively studied the extracts of different mushroom fruit bodies over the past few decades to identify the biologically active medicinal and nutraceutical components having different health benefits. Mushroom is also considered a functional food owing to the presence of low-fat and high-fiber contents useful in maintaining metabolic health. An expansive patent search since 2019 was conducted to review the information on mushrooms and their bioactive constituents using multiple patent databases. This review aims to highlight the pharmacological effects and potential therapeutic implications of mushroom bioactive substances as published in patent literature. Such information would assist researchers to explore the detailed processes and interactions involved by which the mushroom chemical components exert different medicinal properties, thereby increasing their credibility in clinical applications.
Streptococcus pneumoniae is a leading cause of respiratory infections and invasive disease. Although its burden in children is well-known, adult asymptomatic carriage remains under-investigated, particularly in tropical regions.
This meta-analysis, registered in PROSPERO (CRD420244559641) and adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, searched PubMed, ScienceDirect, and Epistemonikos for studies published in the past decade. Eligible studies on adult carriage were included in the PECOS framework. Data were independently extracted by multiple reviewers and pooled using a random-effects meta-analysis. Subgroup analyses evaluated differences by sex, comorbidities [e.g., human immunodeficiency virus (HIV), diabetes], and behavioral factors (e.g., contact with children). Geospatial variations were mapped using RStudio and ggplot2, and study quality was appraised via the Joanna Briggs Institute tools.
Thirty-two studies (n = 56,409) revealed a pooled carriage prevalence of 17% (95% CI: 0.12–0.23). Carriage was higher in females (57% vs. 47% in males) and in HIV-positive individuals (78%), while type 2 diabetes was linked to lower carriage (6%). Elevated rates were mapped in Gambia, Fiji, and Malawi. Non-vaccine serotypes (68%) predominated over vaccine serotypes (32%).
Adult S. pneumoniae carriage is globally significant and heterogeneous, underscoring the need for targeted surveillance and vaccination strategies, especially in tropical, high-density settings.
Streptococcus pneumoniae is a leading cause of respiratory infections and invasive disease. Although its burden in children is well-known, adult asymptomatic carriage remains under-investigated, particularly in tropical regions.
This meta-analysis, registered in PROSPERO (CRD420244559641) and adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, searched PubMed, ScienceDirect, and Epistemonikos for studies published in the past decade. Eligible studies on adult carriage were included in the PECOS framework. Data were independently extracted by multiple reviewers and pooled using a random-effects meta-analysis. Subgroup analyses evaluated differences by sex, comorbidities [e.g., human immunodeficiency virus (HIV), diabetes], and behavioral factors (e.g., contact with children). Geospatial variations were mapped using RStudio and ggplot2, and study quality was appraised via the Joanna Briggs Institute tools.
Thirty-two studies (n = 56,409) revealed a pooled carriage prevalence of 17% (95% CI: 0.12–0.23). Carriage was higher in females (57% vs. 47% in males) and in HIV-positive individuals (78%), while type 2 diabetes was linked to lower carriage (6%). Elevated rates were mapped in Gambia, Fiji, and Malawi. Non-vaccine serotypes (68%) predominated over vaccine serotypes (32%).
Adult S. pneumoniae carriage is globally significant and heterogeneous, underscoring the need for targeted surveillance and vaccination strategies, especially in tropical, high-density settings.
Patients who have lupus nephritis are usually asymptomatic. A few lupus nephritis patients may experience edema, hypertension, nocturia, polyuria, and foamy urine. Foamy urine or nocturia are early indicators of proteinuria, indicating tubular or glomerular dysfunction. Membranous-like glomerulopathy with masked IgG kappa deposits (MMMD) represents a form of immune complex deposition marked by concealed IgG kappa-restricted deposits, which are located in the subepithelial and mesangial areas as seen on electron microscopy. We report a rare case of a 26-year-old Hispanic woman with a history of systemic lupus erythematosus (SLE) diagnosed in 2015, who was initially evaluated for proteinuria and underwent a renal biopsy in 2019. The biopsy demonstrated membranous glomerulonephritis consistent with class V lupus nephritis. The patient volunteered to participate in a clinical trial for lupus nephritis in mid-2023. The second renal biopsy done at this visit (4 years after the initial renal biopsy) reported membranous glomerulonephritis, consistent with lupus class V and MMMD. Given the new finding of MMMD, a search for monoclonal gammopathy was initiated by looking for flow cytometry, serum protein electrophoresis (SPEP), and serum-free light chains, all of which were reported as negative. As the workup for monoclonal gammopathy and monoclonal gammopathy of renal significance (MGRS) was negative, MMMD was considered a secondary manifestation of lupus nephritis, a rare renal presentation of the condition.
Patients who have lupus nephritis are usually asymptomatic. A few lupus nephritis patients may experience edema, hypertension, nocturia, polyuria, and foamy urine. Foamy urine or nocturia are early indicators of proteinuria, indicating tubular or glomerular dysfunction. Membranous-like glomerulopathy with masked IgG kappa deposits (MMMD) represents a form of immune complex deposition marked by concealed IgG kappa-restricted deposits, which are located in the subepithelial and mesangial areas as seen on electron microscopy. We report a rare case of a 26-year-old Hispanic woman with a history of systemic lupus erythematosus (SLE) diagnosed in 2015, who was initially evaluated for proteinuria and underwent a renal biopsy in 2019. The biopsy demonstrated membranous glomerulonephritis consistent with class V lupus nephritis. The patient volunteered to participate in a clinical trial for lupus nephritis in mid-2023. The second renal biopsy done at this visit (4 years after the initial renal biopsy) reported membranous glomerulonephritis, consistent with lupus class V and MMMD. Given the new finding of MMMD, a search for monoclonal gammopathy was initiated by looking for flow cytometry, serum protein electrophoresis (SPEP), and serum-free light chains, all of which were reported as negative. As the workup for monoclonal gammopathy and monoclonal gammopathy of renal significance (MGRS) was negative, MMMD was considered a secondary manifestation of lupus nephritis, a rare renal presentation of the condition.
Cancer immunotherapy is one of the renowned therapeutic approaches worldwide, where its intervention has scaled further than conventional therapy. This review targets oncology researchers, immunotherapy clinicians, and public health policymakers and aims to address novel strategies for overcoming the barriers that exploit the implementation of interleukin-12 (IL-12) in cancer immunotherapy. Moreover, it emphasizes the translational challenges and clinical implications for global health interventions. IL-12 cytokine therapy is a specialized type of cancer immunotherapy that involves the systemic or local administration of IL-12 to the targeted tumor microenvironment. Over the years, IL-12 therapy has shown a promising approach in its therapeutic potential in the treatment of various cancer diseases. The molecular structure of IL-12 depicts its potential for stimulating the immune system. IL-12 enhances the production of interferon-gamma (IFN-γ), a specialized cytokine used for the potential treatment of malignant melanoma and other cancer diseases. However, despite its potent antitumor effects, IL-12 therapy has been limited by considerable toxicity observed in preclinical studies, raising concerns about its safety profile. To fully harness IL-12’s therapeutic potential, researchers should prioritize translational studies that mitigate toxicity and improve delivery mechanisms. This includes innovative approaches such as vector-based delivery systems (e.g., viral vectors and nanoparticle carriers), localized gene therapy platforms, and synergistic combination regimens that reduce systemic exposure while enhancing efficacy. Policymakers should promote flexible regulatory frameworks to accommodate adaptive clinical trial designs, while funding bodies are encouraged to support high-impact translational research that accelerates the safe clinical application of IL-12 and similar immunotherapeutic agents.
Cancer immunotherapy is one of the renowned therapeutic approaches worldwide, where its intervention has scaled further than conventional therapy. This review targets oncology researchers, immunotherapy clinicians, and public health policymakers and aims to address novel strategies for overcoming the barriers that exploit the implementation of interleukin-12 (IL-12) in cancer immunotherapy. Moreover, it emphasizes the translational challenges and clinical implications for global health interventions. IL-12 cytokine therapy is a specialized type of cancer immunotherapy that involves the systemic or local administration of IL-12 to the targeted tumor microenvironment. Over the years, IL-12 therapy has shown a promising approach in its therapeutic potential in the treatment of various cancer diseases. The molecular structure of IL-12 depicts its potential for stimulating the immune system. IL-12 enhances the production of interferon-gamma (IFN-γ), a specialized cytokine used for the potential treatment of malignant melanoma and other cancer diseases. However, despite its potent antitumor effects, IL-12 therapy has been limited by considerable toxicity observed in preclinical studies, raising concerns about its safety profile. To fully harness IL-12’s therapeutic potential, researchers should prioritize translational studies that mitigate toxicity and improve delivery mechanisms. This includes innovative approaches such as vector-based delivery systems (e.g., viral vectors and nanoparticle carriers), localized gene therapy platforms, and synergistic combination regimens that reduce systemic exposure while enhancing efficacy. Policymakers should promote flexible regulatory frameworks to accommodate adaptive clinical trial designs, while funding bodies are encouraged to support high-impact translational research that accelerates the safe clinical application of IL-12 and similar immunotherapeutic agents.
Apical extrusion of debris during root canal preparation can lead to inflammation, flare-ups, and delayed recovery. Therefore, instrumentation techniques that minimize debris extrusion are crucial. This study aimed to compare the apical extrusion of debris by four single-file, full-sequence rotary systems with different tapers.
In this in vitro study, 68 human maxillary lateral incisor teeth with identical root lengths and canal curvatures of less than 10 degrees were used. The teeth were randomly assigned to four experimental groups (n = 17) based on the instrument type: One-Shaped (25, 0.06), 2-Shaped (25, 0.04), Hyflex (25, 0.08), and Neoniti A1 (25, 0.08). Canal preparation was performed according to the manufacturer’s instructions for each file. Extruded debris was collected in pre-weighed vials, and after drying in an incubator, the amount of debris was determined by measuring the weight difference of the vials before and after preparation. Data were analyzed using SPSS 20, with a one-way analysis of covariance (ANOVA) and Tukey’s post hoc test at a significance level of 0.05.
The amount of extruded debris in the One-Shaped file was significantly higher than the extruded debris amount in Neoniti A1 (p = 0.049), Hyfex (p = 0.013), and the 2-Shaped file (p = 0.003).
The null hypothesis was not invalidated due to significant differences in debris extrusion between the instruments observed in the present investigation. Within the limitations of the present study, the One-Shaped file was associated with higher debris extrusion due to the taper design and other system-specific characteristics. Clinical studies are required to assess whether these findings have an impact on the clinical outcome.
Apical extrusion of debris during root canal preparation can lead to inflammation, flare-ups, and delayed recovery. Therefore, instrumentation techniques that minimize debris extrusion are crucial. This study aimed to compare the apical extrusion of debris by four single-file, full-sequence rotary systems with different tapers.
In this in vitro study, 68 human maxillary lateral incisor teeth with identical root lengths and canal curvatures of less than 10 degrees were used. The teeth were randomly assigned to four experimental groups (n = 17) based on the instrument type: One-Shaped (25, 0.06), 2-Shaped (25, 0.04), Hyflex (25, 0.08), and Neoniti A1 (25, 0.08). Canal preparation was performed according to the manufacturer’s instructions for each file. Extruded debris was collected in pre-weighed vials, and after drying in an incubator, the amount of debris was determined by measuring the weight difference of the vials before and after preparation. Data were analyzed using SPSS 20, with a one-way analysis of covariance (ANOVA) and Tukey’s post hoc test at a significance level of 0.05.
The amount of extruded debris in the One-Shaped file was significantly higher than the extruded debris amount in Neoniti A1 (p = 0.049), Hyfex (p = 0.013), and the 2-Shaped file (p = 0.003).
The null hypothesis was not invalidated due to significant differences in debris extrusion between the instruments observed in the present investigation. Within the limitations of the present study, the One-Shaped file was associated with higher debris extrusion due to the taper design and other system-specific characteristics. Clinical studies are required to assess whether these findings have an impact on the clinical outcome.
Hypertension (HTN) has significant long-term cardiovascular risks and is becoming increasingly prevalent in the pediatric population. Apart from making the diagnosis of HTN and initiating treatment, sustained adherence to lifestyle modifications is the mainstay of pediatric HTN management. Little is described regarding compliance to lifestyle recommendations as treatment for HTN despite current guidelines outlining specific dietary and physical activity recommendations that are suggested to be equated to medical prescriptions. This is possibly because there are more objective metrics such as pharmacy pick-up/refill data that can more accurately track medication compliance. The purpose of this review is to provide the general pediatrician with a standardized framework for the management of pediatric HTN with a focus on objective tools that will enable a pragmatic approach to evaluating patient compliance. Adherence to lifestyle modifications focusing on diet and physical activity may potentially impact blood pressure control beyond drug therapy compliance. Concise flowsheets and tables are provided to aid the pediatrician’s workflow in a busy clinic whilst providing essential objective data to assess patient compliance and provide nutrition and physical activity prescriptions. In this review, we outline our current understanding of lifestyle modification and medication prescription compliance trends among youths with HTN and offer real-world tools to implement in any pediatric clinic to better understand and improve patient compliance.
Hypertension (HTN) has significant long-term cardiovascular risks and is becoming increasingly prevalent in the pediatric population. Apart from making the diagnosis of HTN and initiating treatment, sustained adherence to lifestyle modifications is the mainstay of pediatric HTN management. Little is described regarding compliance to lifestyle recommendations as treatment for HTN despite current guidelines outlining specific dietary and physical activity recommendations that are suggested to be equated to medical prescriptions. This is possibly because there are more objective metrics such as pharmacy pick-up/refill data that can more accurately track medication compliance. The purpose of this review is to provide the general pediatrician with a standardized framework for the management of pediatric HTN with a focus on objective tools that will enable a pragmatic approach to evaluating patient compliance. Adherence to lifestyle modifications focusing on diet and physical activity may potentially impact blood pressure control beyond drug therapy compliance. Concise flowsheets and tables are provided to aid the pediatrician’s workflow in a busy clinic whilst providing essential objective data to assess patient compliance and provide nutrition and physical activity prescriptions. In this review, we outline our current understanding of lifestyle modification and medication prescription compliance trends among youths with HTN and offer real-world tools to implement in any pediatric clinic to better understand and improve patient compliance.
This review summarizes recent developments in circulating tumor DNA (ctDNA)-based liquid biopsy for the detection and monitoring of minimal residual disease (MRD) in early-stage solid tumors. MRD assessment has emerged as a promising biomarker for predicting recurrence and guiding adjuvant therapy, particularly in non-small cell lung cancer (NSCLC). Advances in ultra-sensitive next-generation sequencing (NGS), digital PCR, and methylation-based assays have enabled detection of molecular relapse with variant allele frequencies as low as 0.004%. Numerous prospective studies have demonstrated that ctDNA positivity after curative-intent treatment is strongly associated with early relapse and can precede radiographic recurrence by several months. While ctDNA-based MRD testing has begun to influence clinical decision-making in selected settings—particularly in research-driven centers and prospective trials—its broader clinical implementation remains limited by challenges related to assay standardization, pre-analytical variability, and interpretation of MRD positivity. Ongoing efforts to establish consensus thresholds, filter clonal hematopoiesis, and validate predictive value in large-scale trials are essential for routine adoption. This review discusses both the current state and the future direction of MRD-guided oncology, highlighting emerging strategies such as longitudinal ctDNA monitoring, artificial intelligence-based interpretation, and multi-omics integration. Together, these developments may enable more precise and adaptive treatment strategies in the perioperative setting, ultimately facilitating the transition of MRD assessment from investigational use to clinical standard-of-care.
This review summarizes recent developments in circulating tumor DNA (ctDNA)-based liquid biopsy for the detection and monitoring of minimal residual disease (MRD) in early-stage solid tumors. MRD assessment has emerged as a promising biomarker for predicting recurrence and guiding adjuvant therapy, particularly in non-small cell lung cancer (NSCLC). Advances in ultra-sensitive next-generation sequencing (NGS), digital PCR, and methylation-based assays have enabled detection of molecular relapse with variant allele frequencies as low as 0.004%. Numerous prospective studies have demonstrated that ctDNA positivity after curative-intent treatment is strongly associated with early relapse and can precede radiographic recurrence by several months. While ctDNA-based MRD testing has begun to influence clinical decision-making in selected settings—particularly in research-driven centers and prospective trials—its broader clinical implementation remains limited by challenges related to assay standardization, pre-analytical variability, and interpretation of MRD positivity. Ongoing efforts to establish consensus thresholds, filter clonal hematopoiesis, and validate predictive value in large-scale trials are essential for routine adoption. This review discusses both the current state and the future direction of MRD-guided oncology, highlighting emerging strategies such as longitudinal ctDNA monitoring, artificial intelligence-based interpretation, and multi-omics integration. Together, these developments may enable more precise and adaptive treatment strategies in the perioperative setting, ultimately facilitating the transition of MRD assessment from investigational use to clinical standard-of-care.
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