Journal of Personalized Medicine最新文献

{"title":"Pharmacogenomics and Opioid Efficacy in Sickle Cell Disease: Is the Field Ready for Precision Prescribing?","authors":"Cheedy Jaja, Daniel M Sop, Andrew Campbell, Wally R Smith","doi":"10.3390/jpm16080424","DOIUrl":"10.3390/jpm16080424","url":null,"abstract":"<p><p>Pain is a leading cause of morbidity and healthcare utilization in sickle cell disease (SCD), and opioids remain central to treating vaso-occlusive and chronic pain. Yet opioid response varies widely, raising the question of whether pharmacogenetic testing should inform opioid prescribing. Our review examined the PubMed literature on pharmacogenomics and opioid efficacy in SCD. We focus on CYP2D6 as the clearest current pharmacogenetic signal for codeine and tramadol, and assess SCD-specific implementation studies, preemptive testing, and African pharmacoequity. The current evidence supports targeted CYP2D6-informed prescribing in selected contexts rather than universal testing for all opioids, while highlighting the need to integrate genotype with pain phenotype, drug-drug interactions, liver function, and clinically grounded implementation studies, and better characterize African and African-ancestry pharmacogene variation.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-MS/MS Profiling of Blood Serum Reveals Disease-Enriched Peptides in Metabolic Syndrome.","authors":"Alma Nurtazina, Valeriia Koss, Ivan Voitsekhovskiy, Maxat Toishimanov, Daulet Dautov, Kairat Karibayev, Victoria Shender, Georgij Arapidi","doi":"10.3390/jpm16080425","DOIUrl":"10.3390/jpm16080425","url":null,"abstract":"<p><p><b>Background:</b> Metabolic syndrome (MetS) is a heterogeneous cardiometabolic group of conditions in which early disturbances of glucose homeostasis are not always adequately captured by routine clinical tests. <b>Methods:</b> In this pilot study, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based blood serum peptidomics was applied to identify circulating peptide signatures associated with MetS and progressive glycemic impairment. Serum samples from healthy donors and patients with MetS, including subgroups with normoglycemia, prediabetes, and diabetes mellitus, were subjected to peptide enrichment by ultrafiltration and solid-phase extraction prior to LC-MS/MS analysis. <b>Results:</b> Overall, 6754 unique peptides derived from 1820 precursor proteins were identified, and 32 peptides were significantly overrepresented in patients with MetS relative to healthy donors. Eight precursor proteins and five identified peptides showed significant positive correlations with glycemic stage, likely indicating progressive remodeling of the circulating serum peptidome during disease progression. A separate analysis of patients with prediabetes revealed additional candidate markers associated with early metabolic alterations. Moreover, multivariate logistic regression identified a four-peptide panel with good discriminatory performance for differentiating healthy donors from patients with MetS, yielding a leave-one-out cross-validated area under the curve of 0.91. <b>Conclusions:</b> Collectively, these findings indicate that serum peptidome profiling can reveal biologically and clinically relevant possible candidate biomarkers associated with MetS and early dysglycemia.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Optimized and Explainable Machine Learning Framework for Diabetes Prediction Using Marine Predators Algorithm and SHAP.","authors":"Alifa Nasrin, Muhammad Bin Asif, Ramasamy Naidu, Afzal Haq Asif, Muhammad Shahzad Chohan, Gausal Azam Khan, Md Arifuzzaman, Akm Azad, Muhammad Ali Martuza","doi":"10.3390/jpm16080423","DOIUrl":"10.3390/jpm16080423","url":null,"abstract":"<p><p><b>Background:</b> Diabetes mellitus affects over 500 million people worldwide, yet many machine learning prediction models remain difficult to interpret, limiting their clinical applicability. This study proposes an explainable machine learning framework integrating the Marine Predators Algorithm (MPA) for hyperparameter optimization with SHAP-based explainability to diabetes prediction. <b>Methods:</b> Logistic Regression (LR), Random Forest (RF), and MPA-optimized XGBoost were evaluated using a publicly available Kaggle diabetes dataset of approximately 100,000 records. Statistical significance was assessed using Wilcoxon signed-rank tests with Bonferroni correction for fold-wise cross-validation results, while McNemar's and DeLong's tests were employed for paired comparison of independent test-set predictions and ROC-AUC values, respectively. Performance was assessed using accuracy, precision, recall, F1-score, specificity, ROC-AUC, and Brier score. SHAP was used to provide global and local model explanations. <b>Results:</b> The MPA-optimized XGBoost model achieved the highest performance, with 96.72% accuracy, 97.70% precision, 95.70% recall, 96.71% F1-score, and 99.56% ROC-AUC, significantly outperforming LR and RF (<i>p</i> < 0.001). The model demonstrated good calibration with a Brier score of 0.0262. SHAP analysis identified HbA1c level, blood glucose level, and age as the most influential predictors, while interaction analysis indicated a synergistic relationship between HbA1c and blood glucose. <b>Conclusions:</b> The proposed framework demonstrated strong predictive performance and interpretable model behavior on the publicly available diabetes dataset used in this study. These findings indicate the potential of MPA-based optimization combined with SHAP explainability for supporting transparent machine learning research in diabetes prediction. However, additional external validation using independent clinical datasets is required before considering the framework for clinical decision support or real-world deployment.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active Surveillance for Low- and Favourable Intermediate-Risk Prostate Cancer: A Single-Centre Cohort Study on Discontinuation Rates and Quality-of-Life Outcomes.","authors":"Ioannis Mykoniatis, Athanasios Papatzelos, Damianos Damon Dejan Nikolaou Nikolovski, Asterios Symeonidis, Christos Roidos, Chrysovalantis Toutziaris, Ioannis Vakalopoulos, Petros Sountoulides","doi":"10.3390/jpm16080420","DOIUrl":"10.3390/jpm16080420","url":null,"abstract":"<p><p><b>Background</b>: Active surveillance (AS) represents a cornerstone of personalized medicine in uro-oncology, offering an individualized management strategy for low- and selected favourable intermediate-risk prostate cancer that aligns treatment intensity with patient-specific risk profiles; however, real-world adherence data from southern European academic centres remain scarce. This study aimed to evaluate AS discontinuation rates, reasons for transition to active treatment, and quality of life (QoL) in a single-centre Greek university hospital cohort. <b>Methods</b>: This is an observational retropective cohort study of patients enrolled in an AS protocol at the First Department of Urology, Aristotle University of Thessaloniki, between October 2016 and July 2022. Treatment-free survival (TFS) was estimated using Kaplan-Meier analysis. Associations between AS discontinuation and age at diagnosis, PSA level, and Charlson Comorbidity Index (CCI) were explored using univariable and multivariable Cox proportional hazards regression. QoL, erectile function, and anxiety were assessed cross-sectionally in patients remaining on AS using SF-12, IIEF-6, STAI-6, and MAX-PC. <b>Results</b>: Thirty-six patients were included (32 low-risk; 4 favourable intermediate-risk), with a median age of 69.5 years, median PSA of 6.92 ng/mL, and median CCI of 3. After a median follow-up of 24 months (IQR 21-45), 19 patients (52.8%) transitioned to active treatment; the median time to treatment was 21 months (IQR 17-34). Among the 10 patients with a known reason for discontinuation, 6 (31.6% of all discontinued) showed histopathological or clinical disease progression, 3 (15.8%) had a PSA increase alone, and 1 (5.3%) transitioned due to urinary symptoms; the reason was unknown in 9 cases (47.4%). In exploratory Cox regression, PSA ≥ 7.0 ng/mL was the only factor with complete documented output significantly associated with transition to active treatment (univariable HR 3.70, 95% CI 1.35-10.1, <i>p</i> = 0.011; multivariable HR 3.93, 95% CI 1.42-10.9, <i>p</i> = 0.008). Cross-sectional QoL assessment in 10 patients remaining on AS demonstrated median scores above established population norms for SF-12 and below clinical anxiety thresholds on STAI-6 and MAX-PC. <b>Conclusions</b>: In this single-centre cohort, AS discontinuation occurred early and at a rate higher than that of established international programmes, consistent with the institution's initial AS experience. Higher PSA at diagnosis was the only factor with complete analytical documentation to be significantly associated with earlier transition.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interrelationship Between Sarcopenia, Frailty and Cardiovascular Disease-The Crucial Role of Obesity in Hypothesis Generation-A Narrative Review.","authors":"Alan Sinclair, Ffion James, Aswani Muraleedharan, Ahmed Abdelhafiz","doi":"10.3390/jpm16080422","DOIUrl":"10.3390/jpm16080422","url":null,"abstract":"<p><p><b>Introduction</b>: Sarcopenia and frailty are emerging independent risk factors for cardiovascular disease. Sarcopenia represents a decline in function associated with reduced muscle mass. Frailty, defined as a phenotype or the multiple stress model, is associated with weakness and a decline in organ reserve with vulnerability to disease. Frailty and sarcopenia may overlap and have shared clinical risk factors including age and malnutrition. <b>Methods</b>: We performed a literature review of published studies on frailty and sarcopenia with respect to cardiovascular risk factors and body composition. <b>Results</b>: Studies demonstrated that obese sarcopenic or obese frail subjects had a higher prevalence of cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidaemia, smoking and sedentary lifestyle, which was highly associated with cardiovascular disease. On the other hand, anorexic malnourished frail participants with unintentional weight loss or sarcopenic subjects without obesity had a low prevalence of cardiovascular risk factors, which was less associated with cardiovascular disease. <b>Conclusions:</b> Obesity appears to play a crucial role in mediating the cardiovascular risk of both sarcopenic and frail patients.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated with Secondary Pulmonary Hypertension Among Hospitalized Females: An Artificial Neural Network Analysis of a National US Cohort.","authors":"Adil Sarvar Mohammed, Sai Priyanka Mellacheruvu, Zainab Gandhi, Sai Prasanna Lekkala, Suvidha Manne, Umera Yasmeen, Iramunisa Begum, Rupak Desai, Shrinivas Kambali, Lakshmi Sai Meghana Kodali, Shiny Teja Kolli, Shaylika Chauhan, Shweta Kambali","doi":"10.3390/jpm16080421","DOIUrl":"10.3390/jpm16080421","url":null,"abstract":"<p><p><b>Background</b>: Non-group 1 pulmonary hypertension, also known as secondary pulmonary hypertension (SPH), is predominantly observed among females. However, there is a significant lack of data concerning factors associated with hospitalization among patients diagnosed with SPH. This study aims to provide clinicians with vital insights for the identification of high-risk groups and for the more effective management of contributory risk factors within the female population affected by SPH. <b>Methods</b>: Using the 2019 National Inpatient Sample, we identified female admissions with SPH (n = 648,190), accounting for 3.8% of the total 17,236,228 female admissions. An Artificial Neural Network (ANN) analysis was conducted to evaluate predictive factors. We randomly allocated 3,319,543 patients into training and testing datasets at a ratio of 70:30, comprising 2,323,696 (70%) for training and 995,847 (30%) for testing, to calibrate and validate the performance of the ANN algorithm. Model performance was assessed by comparing misclassification rates between training and testing sets and by the area under the receiver operating characteristic curve (AUC); only internal validation was performed. <b>Results</b>: Females hospitalized with SPH were generally of older age, with a median of 75 years compared to 58 years, and more frequently identified as White (67.7% versus 65.5%) or Black (20.5% versus 15.5%) relative to those without SPH. They also demonstrated a higher prevalence of most atherosclerotic cardiovascular disease (ASCVD) risk factors or their equivalents, including complicated hypertension (50.6% versus 17.8%), diabetes with chronic complications (30.6% versus 13.7%), and hyperlipidemia (50.8% versus 29.2%), as well as other comorbidities such as COPD (43.4% versus 20.2%) and CKD (43.3% versus 14.0%), and exhibited increased all-cause mortality (4.5% versus 1.8%) (<i>p</i> < 0.001). Our ANN model achieved an AUC of 0.823, indicating good predictive capability. The rates of incorrect predictions were comparable in both the testing and training cohorts, at 3.8% each. The factors most strongly associated with a coded SPH diagnosis included age at admission, complicated hypertension, chronic kidney disease, chronic obstructive pulmonary disease, uncomplicated hypertension, prior VTE, race, arthropathies, and AIDS. <b>Conclusions</b>: Our ANN model identified demographic and comorbidity factors associated with a coded SPH diagnosis among hospitalized females, with good discrimination (AUC = 0.823). Because the model classifies the presence of an existing diagnosis rather than predicting future hospitalization, and was validated only internally, external and prospective validation is required before clinical application. Once validated, these factors could support individualized, sex-specific risk stratification for high-risk female populations, consistent with the goals of personalized medicine.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism, Morphology and Function of the Anterior Abdominal Wall Musculature in Ventral Hernias and After Repair: A Narrative Review and Research Agenda.","authors":"Sergey Yu Muraviev, Zakhar A Akulov, Maria A Sukhanova, Miroslava O Pilipenko, Evgeniy A Tarabrin, Zelimkhan G M Berikkhanov, Milena Yu Ivanova, Andrey M Nikolaev, Vadim S Razumovsky, Vladislav S Rakintsev, Aleksey G Kotelnikov, Sara Nourmahal, Alexey L Shestakov","doi":"10.3390/jpm16080419","DOIUrl":"10.3390/jpm16080419","url":null,"abstract":"<p><p><b>Objectives:</b> To assess whether muscle morphology and metabolism can inform personalised care in ventral hernias and to define which parts of a proposed postoperative remodelling model are supported by direct evidence. <b>Methods:</b> We conducted a structured narrative review of PubMed/MEDLINE, Scopus and Web of Science from 1 January 2010 through 30 April 2026. Two authors selected 38 publications. Evidence was classified as direct when generated in ventral or incisional hernia cohorts and indirect when drawn from inguinal hernia, transplantation, geriatric, oncological, animal or general muscle studies. No quantitative synthesis was undertaken. <b>Results:</b> Direct studies document lateral muscle displacement, impaired abdominal wall function, inconsistent associations between low muscle mass and clinical outcomes, and CT-derived increases in muscle cross-sectional areas after transversus abdominis release (TAR). The evidence for anterior abdominal wall myosteatosis, biomarker-guided care and the three proposed remodelling trajectories remains largely indirect. In a 37-patient TAR series, the median rectus abdominis cross-sectional area increased by 16.1% (IQR 11.4-27.0%); muscle function and metabolic recovery were not measured. <b>Conclusions:</b> Routine CT can yield muscle area, attenuation and intermuscular adipose tissue measures without further imaging. No anterior abdominal wall-specific thresholds or biomarker cut-offs have been validated, so these measures should not determine current treatment in isolation. Prospective studies should test whether combined imaging, functional and clinical phenotyping improves the selection of prehabilitation and follow-up.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repigmentation Competence in Vitiligo: Integrating Immune, Regulatory, Regenerative, and Microenvironmental Axes.","authors":"Maria Efenesia Baffa, Roberto Maglie, Stefano Colabrese, Carlo Pipitò, Vincenzina Rubino, Sasha Visinoni, Lucrezia Cerchiai, Marzia Caproni, Emiliano Antiga","doi":"10.3390/jpm16080418","DOIUrl":"10.3390/jpm16080418","url":null,"abstract":"<p><p>Vitiligo is an autoimmune depigmenting disorder characterized by marked heterogeneity in therapeutic response, both between patients and among lesions within the same individual. While current therapies primarily target interferon-γ (IFN-γ)-driven inflammation, clinical outcomes remain variable and frequently incomplete, suggesting that additional lesion-specific biological factors contribute to repigmentation potential. In this narrative review, we propose the concept of <i>repigmentation competence</i> to describe the capacity of an individual lesion to achieve clinically meaningful repigmentation under therapy. We hypothesize that this competence emerges from the interaction of four interconnected biological axes: (i) cytokine network and immune memory, (ii) local immune regulation, (iii) regenerative capacity, and (iv) microenvironmental permissiveness. A targeted search of PubMed/MEDLINE and ClinicalTrials.gov up to March 2026 was conducted to identify translational studies, mechanistic models, and clinical trials relevant to these pathways. Evidence was synthesized thematically with emphasis on cytokine-mediated mechanisms and their interaction with regenerative and tissue-context processes. The IFN-γ/CXCL9/CXCL10 axis and tissue-resident memory T cells (TRM) represent the most clinically validated drivers of disease persistence, as demonstrated by the therapeutic efficacy of JAK inhibitors, although immune suppression alone often fails to achieve complete or durable repigmentation. In contrast, regulatory pathways involving PD-1/PD-L1 signaling, regulatory T cells (Tregs), IL-10, TGF-β, and IL-2-based strategies remain biologically compelling but only partially translated into effective therapies. Regenerative capacity has also emerged as an important determinant of treatment response, with growing evidence supporting the role of melanocyte stem cell niches, follicular regeneration, and Wnt/β-catenin signaling. Accordingly, regenerative approaches such as non-cultured epidermal cell suspension (NCES) are increasingly being integrated into combination therapeutic strategies. The lesional microenvironment remains the least therapeutically developed axis despite growing experimental evidence supporting its importance in melanocyte survival and migration. Collectively, these observations suggest that the variable efficacy of current therapies may reflect different combinations of lesion-specific biological constraints. The emerging benefit of combination strategies may therefore derive not simply from additive effects, but from the simultaneous engagement of multiple axes involved in repigmentation competence. Our review supports a shift from a predominantly drug-centered model toward a lesion-oriented framework integrating immune, regenerative, regulatory, and microenvironmental determinants of response.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Varicocele Truly Unilateral? Contralateral Involvement and Bilateral Testicular Effects in Male Infertility: A Narrative Review.","authors":"Aris Kaltsas, Andreas Koumenis, Evangelos N Symeonidis, Fotios Dimitriadis, Nikolaos Sofikitis","doi":"10.3390/jpm16080417","DOIUrl":"10.3390/jpm16080417","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Varicocele is usually clinically left-sided, but imaging and mechanistic studies suggest that contralateral venous reflux or bilateral testicular effects may be more common than physical examination indicates. This narrative review critically examines whether varicocele-associated infertility is better conceptualized as an asymmetric disorder with potential bilateral anatomical or functional involvement and considers the implications for diagnosis and treatment. <b>Methods:</b> PubMed/MEDLINE and Scopus were searched from inception to 21 June 2026 for studies on varicocele laterality, bilateral and subclinical disease, color Doppler ultrasonography, venography, and unilateral versus bilateral repair. Reference lists and contemporary clinical guidelines were also reviewed. Because the included studies differed substantially in patient selection, age, operator technique, diagnostic criteria, and reference standards, reported bilateral rates were not interpreted as head-to-head estimates of diagnostic sensitivity or as pooled prevalence estimates. <b>Results:</b> Physical examination identifies predominantly left-sided clinical disease. Bilateral involvement is reported more frequently when both sides are assessed using Doppler ultrasonography or venography, but estimates vary widely across referral-enriched and highly selected cohorts. Human and experimental evidence supports several mechanisms by which a clinically unilateral lesion may have bilateral functional effects, including shared scrotal hyperthermia, oxidative stress, endocrine disturbance, and venous cross-communication. Bilateral repair is consistent with standard treatment criteria when both varicoceles are clinically palpable. In men with a clinical left varicocele and non-palpable right-sided reflux, comparative evidence is mixed, and current guidelines do not support routine treatment of imaging-only disease. <b>Conclusions:</b> Varicocele is best viewed as an asymmetric disorder that may be anatomically or functionally bilateral in selected men, rather than as a universally bilateral disease. Deliberate bilateral clinical assessment and standardized bilateral ultrasonography when imaging is clinically indicated may improve phenotyping and operative planning. However, contralateral imaging abnormalities should not automatically be converted into a surgical indication.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Target Mapping to Advance Drug Repurposing for Cardiovascular Disease: A Perspective from an Explanted Heart Biobank.","authors":"Coco Ng, Gurpreet K Singhera, Ea Chung Chang, Amrit Samra, Katherine A Adolphs, Evan H Phillips, Jamil Bashir, Zachary Laksman, Honglin Luo, Gordon A Francis, Chi Lai, Ying Wang","doi":"10.3390/jpm16080416","DOIUrl":"10.3390/jpm16080416","url":null,"abstract":"<p><p><b>Background:</b> Although cardiovascular disease (CVD) significantly impacts the quality of life of millions of patients worldwide, the high costs of developing new drugs and conducting clinical trials for CVD hinder therapeutic development in this field. Repurposing approved drugs, of which the safety has already been tested can significantly reduce the time and cost required for treating CVD. From the perspective of pharmacology, repurposed drugs are selected to specifically target CVD patients carrying the matching drug targets, enabling tailored, personalized intervention. In the context of drug repurposing, therapeutic target mapping is a process used to assess the enrichment of molecules that can be affected by a drug in order to produce a therapeutic effect. <b>Methods:</b> This narrative review summarizes the workflows and challenges of performing therapeutic target mapping to assess the potential of repurposing existing drugs for treating CVD. We also share our perspective of how retrospective studies of human specimens can contribute to therapeutic target mapping based on experience from the Bruce McManus Cardiovascular Biobank (BMCB), a large explanted heart biobank located in Vancouver, Canada. The literature we discuss was identified by non-systematic searches of PubMed, using search terms \"human-derived specimens\", \"drug repurposing\", and \"cardiovascular disease\". We reviewed articles from 2012 to 2026 and prioritized studies conducted after 2019 to discuss recent advances in the field. <b>Conclusions:</b> Human specimens of high molecular quality are needed for evaluating the enrichment of drug targets in CVD. Therapeutic target mapping in diseased cardiovascular tissue requires integrated expertise from medical, translational, and applied sciences to identify suitable human specimens for molecular phenotyping, and to design hypothesis-driven approaches to validate the drugs suggested for repurposing.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13514999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}