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Background: Electrocardiograms (EKGs) are essential tools in emergency medicine, often used to evaluate chest pain, dyspnea, and other symptoms suggestive of cardiac dysfunction. Yet, EKGs are not universally administered to all emergency department (ED) patients. Understanding and predicting which patients receive an EKG may offer insights into clinical decision making, resource allocation, and potential disparities in care. This study examines whether integrating structured clinical data with free-text patient narratives can improve prediction of EKG utilization in the ED. Methods: We conducted a retrospective observational study to predict electrocardiogram (EKG) utilization using data from 13,115 adult emergency department (ED) visits in the nationally representative 2021 National Hospital Ambulatory Medical Care Survey–Emergency Department (NHAMCS-ED), leveraging both structured features—demographics, vital signs, comorbidities, arrival mode, and triage acuity, with the most influential selected via Lasso regression—and unstructured patient narratives transformed into numerical embeddings using Clinical-BERT. Four supervised learning models—Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF) and Extreme Gradient Boosting (XGB)—were trained on three inputs (structured data only, text embeddings only, and a late-fusion combined model); hyperparameters were optimized by grid search with 5-fold cross-validation; performance was evaluated via AUROC, accuracy, sensitivity, specificity and precision; and interpretability was assessed using SHAP values and Permutation Feature Importance. Results: EKGs were administered in 30.6% of adult ED visits. Patients who received EKGs were more likely to be older, White, Medicare-insured, and to present with abnormal vital signs or higher triage severity. Across all models, the combined data approach yielded superior predictive performance. The SVM and LR achieved the highest area under the ROC curve (AUC = 0.860 and 0.861) when using both structured and unstructured data, compared to 0.772 with structured data alone and 0.823 and 0.822 with unstructured data alone. Similar improvements were observed in accuracy, sensitivity, and specificity. Conclusions: Integrating structured clinical data with patient narratives significantly enhances the ability to predict EKG utilization in the emergency department. These findings support a personalized medicine framework by demonstrating how multimodal data integration can enable individualized, real-time decision support in the ED. Full article

Background Sex disparity has been highlighted in personalized medicine for various human diseases including acute/chronic liver diseases. In the transplant community, greater graft failure risk in female-to-male liver transplantation (LT) has been repeatedly reported, and a recent study in living donor LT reported that the inferiority of female-to-male LT is shown only when donor age is ≤40 y. We aimed to analyze the United Network for Organ Sharing (UNOS) database to test if the poorer outcome of female-to-male LT changes by donor age of 40 y in deceased donor LT, as shown in living donor LT. Methods In this retrospective cohort study, 11,752 adult patients in the UNOS registry who underwent deceased donor LT between 2000–2023 were analyzed. Multivariable analysis was performed to adjust the effects from transplant years, graft ischemia time, disease severity, and others. The primary outcome was graft failure. Results Within the subgroup of recipients with ≤40 y donors, graft failure risk was significantly greater in female-to-male LT than others (vs. female-to-female, HR = 1.43 [1.16–1.76], p < 0.001; vs. male-to-female, HR = 1.46 [1.18–1.81], p < 0.001; vs. male-to-male, HR = 1.26 [1.16–1.49], p = 0.009). In contrast, within the subgroup of recipients with >40 y donors, the risk was comparable between female-to-male LT and other donor-recipient sex groups (vs. female-to-female, p = 0.907; vs. male-to-female, p = 0.781; vs. male-to-male, p = 0.937). We tested various cutoff donor ages and determined that 40 y is the best cutoff value to define the risk subgroup in female-to-male LT. Conclusions In the current study, we found that the sex disparity shown in living donor LT is also observed in deceased donor LT. That is, post-transplant graft failure risk was greater in female-to-male LT than other donor–recipient sex groups only when donor age was ≤40 y. In contrast, graft failure risk was comparable irrespective of donor-recipient sex combinations when donor age was >40 y. Full article

A healthy vasculature with well-regulated perfusion and pulsatility is essential for the brain. One vascular structure that has received little attention is the carotid siphon. The proximal portion of the siphon is stiff due to the narrow location in the skull base, whilst the distal portion is highly flexible. This flexible part in combination with the specific curves lead to lower pulsatility at the cost of energy deposition in the arterial wall. This deposited energy contributes to damage and calcification. Severe siphon calcification stiffens the distal part of the siphon, leading to less damping of the pulsatility. Increased blood flow pulsatility is a possible cause of stroke and cognitive disorders. In this review, based on comprehensive multimodality imaging, we first describe the anatomy and physiology of the carotid siphon. Subsequently, we review the in vivo imaging data, which indeed suggest that the siphon attenuates pulsatility. Finally, the data as available in the literature are shown to provide convincing evidence that severe siphon calcifications and the calcification pattern are linked to incident stroke and dementia. Interventional studies are required to test whether this association is causal and how an assessment of pulsatility and the siphon calcification pattern can improve personalized medicine, working to prevent and treat brain disease. Full article

Cardiovascular disease (CVD) remains Europe’s leading cause of mortality, responsible for >45% of deaths. Beyond established risk factors (hypertension, diabetes, dyslipidaemia, smoking, obesity), psychosocial elements—depression, anxiety, financial stress, personality traits, and trauma—significantly influence CVD development and progression. Behavioural Cardiology addresses this connection by systematically incorporating psychosocial factors into prevention and rehabilitation protocols. This review examines the HEARTBEAT model, developed by Greece’s first Behavioural Cardiology Unit, which aligns with current European guidelines. The model serves dual purposes: primary prevention (targeting at-risk individuals) and secondary prevention (treating established CVD patients). It is a personalised medicine approach that integrates psychosocial profiling with traditional risk assessment, utilising tailored evaluation tools, caregiver input, and multidisciplinary collaboration to address personality traits, emotional states, socioeconomic circumstances, and cultural contexts. The model emphasises three critical implementation aspects: (1) digital health integration, (2) cost-effectiveness analysis, and (3) healthcare system adaptability. Compared to international approaches, it highlights research gaps in psychosocial interventions and advocates for culturally sensitive adaptations, particularly in resource-limited settings. Special consideration is given to older populations requiring tailored care strategies. Ultimately, Behavioural Cardiology represents a transformative systems-based approach bridging psychology, lifestyle medicine, and cardiovascular treatment. This integration may prove pivotal for optimising chronic disease management through personalised interventions that address both biological and psychosocial determinants of cardiovascular health. Full article

Background: The long-term clinical and laboratory results of a 33-year follow-up of a Greek family with abetalipoproteinemia (ABL) are described. Case Report: The patients (two brothers and their sister, aged 57, 49, and 62 years, respectively) are still alive, being under close surveillance. In two of the three patients, diarrhea appeared in early infancy, while in the third, it appeared during adolescence. CNS symptomatology worsened after the second decade of life. At the same time, night blindness appeared in the advanced stages of the disease, resulting in almost complete loss of vision in one of the male patients and severe impairment in the other. The diagnosis was based on the clinical picture, ophthalmological findings, serum lipid estimations, and presence of peripheral acanthocytosis. All patients exhibited typical serum lipidemic profile, ophthalmological findings, and acanthocytes in the peripheral blood. During the follow-up period, strict dietary modifications were applied, including the substitution of fat with medium-chain triglycerides (MCT oil). After 33 years since the initial diagnosis, all patients are alive without any sign of liver dysfunction despite continuous use of MCT oil. However, symptoms from the central nervous system and vision impairment worsened. Conclusion: The course of these patients suggests that the application of a modified diet, including MCT oil, along with close surveillance, could prolong the survival of patients without significant side effects from the liver. Full article

Background: Minimally invasive cardiac surgery (MICS) via right minithoracotomy is a safe, reproducible approach with excellent outcomes and reduced costs compared to median sternotomy. Despite careful patient selection, conversion to sternotomy occurs in 1–3% of cases and is associated with significantly higher morbidity and mortality. Small body habitus, particularly a short anteroposterior (AP) diameter, may increase the risk of conversion, but this has not been previously studied. This study aims to identify preoperative factors associated with conversion to improve patient selection for MICS. As cardiovascular surgery becomes increasingly personalized, identifying anatomical factors that predict technical complexity is essential. Methods: This retrospective study included 254 adult patients who underwent elective MICS between 2015 and 2024 at a tertiary hospital. Patient characteristics, computed tomography (CT) scans, intraoperative parameters, and postoperative outcomes were reviewed. AP diameter was defined as the distance from the posterior sternum to the anterior vertebral body at the mitral valve level on CT. Statistical analyses included Mann−Whitney and Fisher’s exact/chi-square tests. Results: Conversion to sternotomy occurred in 1.6% of patients (n = 4). All converted patients were female. The converted group had a significantly shorter median AP diameter (100 mm vs. 124 mm, p = 0.020). Conversion was associated with higher rates of stroke and infection (25.0% vs. 0.8%, p = 0.047 for both), but no significant differences in hospital stay, bleeding, or renal failure. Conclusions: An AP diameter of less than 100 mm was associated with a higher risk of conversion to sternotomy in MICS. Incorporating simple, reproducible preoperative imaging metrics into surgical planning may advance precision-guided cardiac surgery and optimize patient outcomes. Full article

Background: Transcranial direct current stimulation (tDCS) has emerged as a promising neuromodulatory tool for language rehabilitation in chronic aphasia. However, the effects of bi-hemispheric, multisite stimulation remain largely unexplored, especially in people with chronic and treatment-resistant language impairments. The goal of this study is to look at the effects on behavior and brain activity of an individualized language training program that combines bi-hemispheric multisite anodal tDCS with personalized language training for Albert, a patient with long-standing, treatment-resistant non-fluent aphasia. Methods: Albert, a right-handed retired physician, had transcortical motor aphasia (TCMA) subsequent to a left-hemispheric ischemic stroke occurring more than six years before the operation. Even after years of traditional treatment, his expressive and receptive language deficits remained severe and persistent despite multiple rounds of traditional therapy. He had 15 sessions of bi-hemispheric multisite anodal tDCS aimed at bilateral dorsal language streams, administered simultaneously with language training customized to address his particular phonological and syntactic deficiencies. Psycholinguistic evaluations were performed at baseline, immediately following the intervention, and at 1, 2, 3, and 6 months post-intervention. Resting-state fMRI was conducted at baseline and following the intervention to evaluate alterations in functional connectivity (FC). Results: We noted statistically significant enhancements in auditory sentence comprehension and oral reading, particularly at the 1- and 3-month follow-ups. Neuroimaging showed decreased functional connectivity (FC) in the left inferior frontal and precentral regions (dorsal stream) and in maladaptive right superior temporal regions, alongside increased FC in left superior temporal areas (ventral stream). This pattern suggests that language networks may be reorganizing in a more efficient way. There was no significant improvement in phonological processing, which may indicate reduced connectivity in the left inferior frontal areas. Conclusions: This case underscores the potential of combining individualized, network-targeted language training with bi-hemispheric multisite tDCS to enhance recovery in chronic, treatment-resistant aphasia. The convergence of behavioral gains and neuroplasticity highlights the importance of precision neuromodulation approaches. However, findings are preliminary and warrant further validation through controlled studies to establish broader efficacy and sustainability of outcomes. Full article

Background: Genetic polymorphisms in the cyclooxygenase-2 (COX-2) gene may contribute to individual susceptibility to periodontal disease. A meta-analysis assessed the association between three COX-2 single-nucleotide polymorphisms (SNPs) namely, −765 G/C (rs20417), −1195 G/A (rs689466), and 8473 T/C (rs5275), and the risk of CP. Methods: Following the PRISMA 2020 guidelines, we conducted a comprehensive search of five electronic databases and additional sources. The eligible studies were observational (case–control or cohort) with genotypic data comparing individuals with periodontal disease and periodontally healthy controls. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS), and the certainty of evidence was evaluated via the GRADE framework. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under dominant genetic models. Results: Seven studies (n = 1467 participants) met the inclusion criteria. No eligible studies evaluated the 8473 T/C SNP. The meta-analysis of the −765 G/C variant revealed a significant association with periodontal disease (OR = 1.61; 95% CI: 1.12–2.32, p = 0.03; I² = 0%). For the −1195 G/A variant, the pooled OR was 1.86 (95% CI: 1.00–3.43, p = 0.05; I² = 35%), suggesting a borderline significant association. The certainty of evidence was graded as moderate for −765 G/C and low for −1195 G/A. Conclusions: The COX-2 −765 G/C polymorphism is significantly associated with increased CP risk, while the −1195 G/A variant shows a potential, though less certain, link. Larger, high-quality studies using standardized classifications are needed to confirm these associations. Full article

Background/Objectives: Traumatic brain injury (TBI), especially mild TBI (mTBI), is frequently caused by traffic accidents, falls, or sports injuries. Although computed tomography (CT) is the gold standard for diagnosis, overuse can lead to unnecessary radiation exposure, increased healthcare costs, and emergency department saturation. Blood-based biomarkers have emerged as potential tools to optimize CT scan use. This systematic review aims to evaluate recent evidence on the role of specific blood biomarkers in guiding CT decisions in patients with mTBI. Methods: A systematic search was conducted in the PubMed, Cochrane, and CINAHL databases for studies published between 2020 and 2024. Inclusion criteria focused on adult patients with mTBI evaluated using both CT imaging and at least one of the following biomarkers: glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B). After screening, six studies were included in the final review. Results: All included studies reported high sensitivity and negative predictive value for the selected biomarkers in detecting clinically relevant intracranial lesions. GFAP and UCH-L1, particularly in combination, consistently identified low-risk patients who could potentially forgo CT scans. While S100B also showed high sensitivity, discrepancies in cutoff values across studies highlighted the need for harmonization. Conclusions: Blood biomarkers such as GFAP, UCH-L1, and S100B demonstrate strong potential to reduce unnecessary CT imaging in mTBI by identifying patients at low risk of significant brain injury. Future research should focus on standardizing biomarker thresholds and validating protocols to support their integration into clinical practice guidelines. Full article

Background/Objectives: Targeting individuals with certain characteristics provides improved precision in many healthcare applications. An alert mechanism for COPD exacerbations has recently been validated. It has been argued that its efficacy improves considerably with stratification. This paper provides an in-depth analysis of the cough data of the stratified cohort to identify options for and the feasibility of improved precision in the alert mechanism for the intended patient group. Methods: The alert system was extended using a system complementary to the existing one to accommodate observed rapid changes in cough trends. The designed system was tested in a post hoc analysis of the data. The trend data were inspected to consider their meaningfulness for patients and caregivers. Results: While stratification was effective in reducing misses, the augmented alert system improved the sensitivity and number of early alerts for the acute exacerbation of COPD (AE-COPD). The combination of stratification and the augmented mechanism led to sensitivity of 86%, with a false alert rate in the order of 1.5 per year in the target group. The alert system is rule-based, operating on interpretable signals that may provide patients or their caregivers with better insights into the respiratory condition. Conclusions: The augmented alert system operating based on cough trends has the promise of increased precision in detecting AE-COPD in the target group. Since the design and testing of the augmented system were based on the same data, the system needs to be validated. Signals within the alert system are potentially useful for improved self-management in the target group. Full article

Objectives: To investigate the reliability and validity of the Singer Reflux Symptom Score (sRSS), a new patient-reported outcome questionnaire documenting the severity of reflux symptoms in singing voice is proposed. Methods: Amateur and professional singers consulting the European Reflux Clinic for laryngopharyngeal reflux disease (LPRD) symptoms and findings were prospectively recruited from January 2022 to February 2023. The diagnosis was based on a Reflux Symptom Score (RSS) > 13 and Reflux Sign Assessment (RSA) > 14. A control group of asymptomatic singer subjects was recruited from the University of Mons. The sRSS was rated within a 7-day period to assess test–retest reliability. Internal consistency was measured using Cronbach’s α in patients and controls. A correlation analysis was performed between sRSS and Singing Voice Handicap Index (sVHI) to evaluate convergent validity. Responsiveness to change was evaluated through pre- to post-treatment sRSS changes. The sRSS threshold for suggesting a significant impact of LPRD on singing voice was determined by receiver operating characteristic (ROC) analysis. Results: Thirty-three singers with suspected LPRD (51.5% female; mean age: 51.8 ± 17.2 years) were consecutively recruited. Difficulty reaching high notes and vocal fatigue were the most prevalent LPRD-related singing complaints. The sRSS demonstrated high internal consistency (Cronbach-α = 0.832), test–retest reliability, and external validity (correlation with sVHI: r = 0.654; p = 0.015). Singers with suspected LPRD reported a significant higher sRSS compared to 68 controls. sRSS item and total scores significantly reduced from pre-treatment to 3 months post-treatment except for the abnormal voice breathiness item. ROC analysis revealed superior diagnostic accuracy for sRSS (AUC = 0.971) compared to sRSS-quality of life (AUC = 0.926), with an optimal cutoff at sRSS > 38.5 (sensitivity: 90.3%; specificity: 85.0%). Conclusions: The sRSS is a reliable and valid singer-reported outcome questionnaire for documenting singing symptoms associated with LPRD leading to personalized management of Singers. Future large-cohort studies are needed to evaluate its specificity for LPRD compared to other vocal fold disorders in singers. Full article

The evidence for photobiomodulation in reducing postoperative pain after endodontic instrumentation is classified as low or very low certainty, indicating a need for further research. Longitudinal pain assessments over 24 h are crucial, and studies should explore these pain periods. Background/Objectives: This double-blind, randomized controlled clinical trial evaluated the effect of PBM on pain following single-visit endodontic treatment of maxillary molars at 4, 8, 12, and 24 h. Primary outcomes included pain at 24 h; secondary outcomes included pain at 4, 8, and 12 h, pain during palpation/percussion, OHIP-14 analysis, and frequencies of pain. Methods: Approved by the Research Ethics Committee (5.598.290) and registered in Clinical Trials (NCT06253767), the study recruited adults (21–70 years) requiring endodontic treatment in maxillary molars. Fifty-eight molars were randomly assigned to two groups: the PBM Group (n = 29), receiving conventional endodontic treatment with PBM (100 mW, 333 mW/cm², 9 J distributed at 3 points near root apices), and the control group (n = 29), receiving conventional treatment with PBM simulation. Pain was assessed using the Visual Analog Scale. Results: Statistical analyses used chi-square and Mann–Whitney tests, with explained variance (η²). Ten participants were excluded, leaving 48 patients for analysis. No significant differences were observed in postoperative pain at 24, 4, 8, or 12 h, or in palpation/percussion or OHIP-14 scores. Pain frequencies ranged from 12.5% to 25%. Conclusions: PBM does not influence post-treatment pain in maxillary molars under these conditions. These results emphasize the importance of relying on well-designed clinical trials to guide treatment decisions, and future research should focus on personalized dosimetry adapted to the anatomical characteristics of the treated dental region to enhance the accuracy and efficacy of therapeutic protocols. Full article

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported k_m value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure k_m. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the k_i value estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article

Heart failure (HF) poses a substantial global burden due to its high morbidity, mortality, and healthcare costs. Accurate prognostication is crucial for optimizing treatment, resource allocation, and patient counseling. Prognostic tools range from simple clinical scores such as ADHERE and MAGGIC to more complex models incorporating biomarkers (e.g., NT-proBNP, sST2), imaging, and artificial intelligence techniques. In acute HF, models like EHMRG and STRATIFY aid early triage, while in chronic HF, tools like SHFM and BCN Bio-HF support long-term management decisions. Despite their utility, most models are limited by poor generalizability, reliance on static inputs, lack of integration into electronic health records, and underuse in clinical practice. Novel approaches involving machine learning, multi-omics profiling, and remote monitoring hold promise for dynamic and individualized risk assessment. However, these innovations face challenges regarding interpretability, validation, and ethical implementation. For prognostic models to transition from theoretical promise to practical impact, they must be continuously updated, externally validated, and seamlessly embedded into clinical workflows. This review emphasizes the potential of prognostic models to transform HF care but cautions against uncritical adoption without robust evidence and practical integration. In the evolving landscape of HF management, prognostic models represent a hopeful avenue, provided their limitations are acknowledged and addressed through interdisciplinary collaboration and patient-centered innovation. Full article

Background: Patients diagnosed with melanoma are at increased risk of developing multiple primary melanomas (MPMs). Identifying clinical and genetic factors associated with MPM is critical for implementing personalized surveillance strategies. This study aims to describe the clinical, histopathological, and genetic characteristics of patients with MPM managed in a tertiary hospital and to contextualize findings within the current literature. Methods: We conducted a retrospective review of patients diagnosed with two or more primary melanomas between 2010 and 2023 at a tertiary dermatology unit. Demographic data, personal and family cancer history, phototype, melanoma characteristics, genetic testing, staging, treatments, and outcomes were collected. These data were compared with findings from the recent literature. Results: Thirteen patients (ten males, three females; median age: 59 years) were found to have a total of 33 melanomas. Most patients had Fitzpatrick phototype II and no immunosuppression. The number of melanomas per patient ranged from two to five. Synchronous lesions were observed in two patients. Common locations included the trunk and extremities. Histologically, 57% were in situ melanomas, and subsequent melanomas were generally thinner than the index lesion. Two patients showed progression to advanced disease. One patient was positive for MC1R mutation; the rest were negative or inconclusive. Additional phenotypic and environmental risk factors were extracted from patient records and are summarized as follows: Ten patients (76.9%) had Fitzpatrick skin phototype II, and three (23.1%) had phototype III. Chronic occupational sun exposure was reported in four patients (30.8%), while five (38.5%) recalled having suffered multiple sunburns during childhood or adolescence. Eight patients (61.5%) presented with a total nevus count exceeding 50, and five (38.5%) exhibited clinically atypical nevi. None of the patients reported use of tanning beds. Conclusions: Our findings are consistent with the existing literature indicating that patients with MPM often present with thinner subsequent melanomas and require long-term dermatologic follow-up. The inclusion of genetic testing and phenotypic risk factors enables stratified surveillance and supports the application of personalized medicine in melanoma management. Full article