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12 pages, 525 KB  
Article
Prognostic Value of Systemic Immune-Inflammation Index in Mucosal Malignant Melanoma
by Burak Paçacı, Erkam Kocaaslan, Ahmet Demirel, Fırat Akagündüz, Mustafa Alperen Tunç, Yeşim Ağyol, Ali Kaan Güren, Abdussamed Çelebi, Selver Işık, Ezgi Çoban, Nargiz Majidova, Nadiye Sever, Işık Paçacı, Buket Erkan Özmarasali, Adem Deligönül, Ali Fuat Gürbüz, Melek Karakurt Eryılmaz, Şüheda Ataş İpek, Nisanur Sarıyar Busery, Emre Yılmaz, Murat Sarı, İbrahim Vedat Bayoğlu, Osman Köstek and Nazım Can Demircanadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(2), 890; https://doi.org/10.3390/jcm15020890 (registering DOI) - 22 Jan 2026
Abstract
Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the [...] Read more.
Background: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. Methods: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. Results: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67–4.40; p < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12–3.14; p = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23–3.23; p = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32–6.94; p < 0.001) independently predicted a worse OS. Conclusions: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients. Full article
(This article belongs to the Section Oncology)
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12 pages, 963 KB  
Article
Training Healthcare Assistants for School-Based Care of Children Receiving Paediatric Palliative Care: A Post-Training Evaluation
by Anna Santini, Anna Marinetto, Enrica Grigolon, Alessandra Fasson, Mirella Schiavon, Igor D’angelo, Nicoletta Moro, Barbara Roverato, Pierina Lazzarin and Franca Benini
Children 2026, 13(1), 153; https://doi.org/10.3390/children13010153 (registering DOI) - 22 Jan 2026
Abstract
Background/Objectives: Children in paediatric palliative care often face school attendance barriers due to complex health needs. This study describes post-training perceptions of a training program by a pediatric hospice team to prepare school care assistants to safely include children with complex conditions, [...] Read more.
Background/Objectives: Children in paediatric palliative care often face school attendance barriers due to complex health needs. This study describes post-training perceptions of a training program by a pediatric hospice team to prepare school care assistants to safely include children with complex conditions, focusing on procedural skills, knowledge of the child, and family partnership. Methods: Care assistants who completed a structured course at the Paediatric Palliative Care Centre, University Hospital of Padua (2023–2024), were surveyed immediately after training. The program combined classroom instruction with hands-on simulation using high-fidelity mannequins and standard devices, including suction, pulse oximetry, ventilation, enteral feeding, and tracheostomy care. It also covered modules on urgent and emergency management, as well as family communication. An anonymous online questionnaire gathered socio-demographic data, prior training, clinical tasks performed, self-efficacy levels, and open-ended feedback. Quantitative results were analyzed descriptively, while qualitative comments were subjected to thematic analysis. Results: Of 130 invited assistants, 105 participated (81%). Participants reported strong perceived confidence: 85% selected the upper end of the 5-point scale (“very” or “extremely”) for routine-management ability, and 60% selected these same response options for emergency-management ability. In the most severe events recalled, 60.5% of incidents were resolved autonomously, 7.6% involved contacting emergency services, and 3.8% involved community or hospice nurses. Seventy-five percent judged the course comprehensive; thematic analysis of 102 comments identified satisfaction, requests for regular refreshers, stronger practical components, and requests for targeted topics. Conclusions: Immediately after the session, participants tended to select the upper end of the self-assurance item for both routine and emergency tasks. Combining core emergency procedures with personalized, child-specific modules and family-partnership training may support safety, trust, and inclusion. Regular refreshers and skills checks are advised. Full article
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27 pages, 2933 KB  
Article
Design Principles for Work-Integrated Safety Training (WIST) in Gamified Immersive Learning Environments
by Jesse Katende, Amir Haj-Bolouri, Stefan Nilsson, Lu Cao and Matti Rossi
Virtual Worlds 2026, 5(1), 5; https://doi.org/10.3390/virtualworlds5010005 (registering DOI) - 21 Jan 2026
Abstract
Immersive virtual reality is increasingly used for safety training, yet many initiatives remain technology-led pilots that enhance scenario realism and engagement without explaining how training becomes embedded in everyday work (e.g., alignment with SOPs, assessment routines, scheduling, and accountable debrief practices) or how [...] Read more.
Immersive virtual reality is increasingly used for safety training, yet many initiatives remain technology-led pilots that enhance scenario realism and engagement without explaining how training becomes embedded in everyday work (e.g., alignment with SOPs, assessment routines, scheduling, and accountable debrief practices) or how skills reliably transfer back to duty. This paper addresses that gap by introducing Work-Integrated Safety Training (WIST) as a socio-technical training approach that couples IVR-based immersion with work-integrated routines to develop competence in safety-critical, passenger-facing work. Using Action Design Research (ADR) with Sweden’s national rail operator (SJ), we iteratively designed and evaluated a gamified immersive prototype for onboard conflict management, drawing on interviews, incident reports, co-design workshops, and in situ evaluations. We formalize four transferable design principles—specified with mechanisms and boundary conditions that guide how immersive training can (i) scaffold composure before intervention, (ii) make dynamic risk legible through interpretable cues, (iii) support SOP-aligned adaptive communication with replay-based reflection, and (iv) strengthen team coordination through role-specific checkpoints and psychologically safe debriefs. The paper contributes design knowledge for moving from isolated IVR demonstrations to work-integrated training systems that are implementable in organizations and testable in further longitudinal evaluation. Full article
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14 pages, 4548 KB  
Article
Comparison of Epiretinal Membrane Detection Rates Between Optos® and Clarus Ultra-Widefield Fundus Imaging Systems
by Satoshi Kuwayama, Yoshio Hirano, Arisa Shibata, Hiroaki Sugiyama, Nariko Soga, Kihei Yoshida, Takaaki Yuguchi, Ryo Kurobe, Akiyo Tsukada, Shuntaro Ogura, Hiroya Hashimoto and Tsutomu Yasukawa
J. Clin. Med. 2026, 15(2), 883; https://doi.org/10.3390/jcm15020883 (registering DOI) - 21 Jan 2026
Abstract
Background: Ultra-widefield (UWF) images are frequently used for fundus examinations during medical screening. Optos® generates pseudo-color images using only red and green lasers, which may reduce the visibility of retinal interface lesions. In contrast, Clarus™ incorporates blue light, suggesting potential superiority in [...] Read more.
Background: Ultra-widefield (UWF) images are frequently used for fundus examinations during medical screening. Optos® generates pseudo-color images using only red and green lasers, which may reduce the visibility of retinal interface lesions. In contrast, Clarus™ incorporates blue light, suggesting potential superiority in epiretinal membrane (ERM) detection. Methods: This retrospective study included 233 patients (408 eyes; 816 UWF images per device) who underwent simultaneous Optos® and Clarus™ imaging plus optical coherence tomography (OCT) at our institution from March to April 2019. Ten blinded ophthalmologists assessed only the UWF images for ERM presence or absence. Diagnosis was confirmed by fundus examination and OCT. McNemar’s test compared detection accuracy. Results: Clarus™ consistently outperformed Optos®, with superior sensitivity [median 49% (range 42–70) vs. 14% (4–47); p = 0.002], correct judgment rate [85% (82–90) vs. 78% (44–88); p = 0.010], and lower unassessed rate [6% (2–13) vs. 13% (3–52); p = 0.002]. This superiority held across ERM stages, lens status, and ophthalmologist experience levels. Conclusions: This study demonstrated that Clarus™ significantly outperformed Optos® in ERM detection accuracy. These results suggest that true-color UWF systems like Clarus™ may be more useful for macular screening in routine practice and health examinations. Full article
(This article belongs to the Section Ophthalmology)
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20 pages, 1260 KB  
Review
Neuroimaging-Guided Insights into the Molecular and Network Mechanisms of Chronic Pain and Neuromodulation
by Chiahui Yen and Ming-Chang Chiang
Int. J. Mol. Sci. 2026, 27(2), 1080; https://doi.org/10.3390/ijms27021080 - 21 Jan 2026
Abstract
Chronic pain is a pervasive and debilitating condition that affects millions of individuals worldwide. Unlike acute pain, which serves a protective physiological role, chronic pain persists beyond routine tissue healing and often arises without a discernible peripheral cause. Accumulating evidence indicates that chronic [...] Read more.
Chronic pain is a pervasive and debilitating condition that affects millions of individuals worldwide. Unlike acute pain, which serves a protective physiological role, chronic pain persists beyond routine tissue healing and often arises without a discernible peripheral cause. Accumulating evidence indicates that chronic pain is not merely a symptom but a disorder of the central nervous system, underpinned by interacting molecular, neurochemical, and network-level alterations. Molecular neuroimaging using PET and MR spectroscopy has revealed dysregulated excitatory–inhibitory balance (glutamate/GABA), altered monoaminergic and opioidergic signaling, and neuroimmune activation (e.g., TSPO-indexed glial activation) in key pain-related regions such as the insula, anterior cingulate cortex, thalamus, and prefrontal cortex. Converging multimodal imaging—including functional MRI, diffusion MRI, and EEG/MEG—demonstrates aberrant activity and connectivity across the default mode, salience, and sensorimotor networks, alongside structural remodeling in cortical and subcortical circuits. Parallel advances in neuromodulation, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), deep brain stimulation (DBS), and emerging biomarker-guided closed-loop approaches, provide tools to perturb these maladaptive circuits and to test mechanistic hypotheses in vivo. This review integrates neuroimaging findings with molecular and systems-level mechanistic insights into chronic pain and its modulation, highlighting how imaging markers can link biochemical signatures to neural dynamics and guide precision pain management and individualized therapeutic strategies. Full article
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18 pages, 2071 KB  
Article
Dynamic Modeling and Calibration of an Industrial Delayed Coking Drum Model for Digital Twin Applications
by Vladimir V. Bukhtoyarov, Ivan S. Nekrasov, Alexey A. Gorodov, Yadviga A. Tynchenko, Oleg A. Kolenchukov and Fedor A. Buryukin
Processes 2026, 14(2), 375; https://doi.org/10.3390/pr14020375 - 21 Jan 2026
Abstract
The increasing share of heavy and high-sulfur crude oils in refinery feed slates worldwide highlights the need for models of delayed coking units (DCUs) that are both physically meaningful and computationally efficient. In this study, we develop and calibrate a simplified yet dynamic [...] Read more.
The increasing share of heavy and high-sulfur crude oils in refinery feed slates worldwide highlights the need for models of delayed coking units (DCUs) that are both physically meaningful and computationally efficient. In this study, we develop and calibrate a simplified yet dynamic one-dimensional model of an industrial coke drum intended for integration into digital twin frameworks. The model includes a three-phase representation of the drum contents, a temperature-dependent global kinetic scheme for vacuum residue cracking, and lumped descriptions of heat transfer and phase holdups. Only three physically interpretable parameters—the kinetic scaling factors for distillate and coke formation and an effective wall temperature—were calibrated using routinely measured plant data, namely the overhead vapor and drum head temperatures and the final coke bed height. The calibrated model reproduces the temporal evolution of the top head and overhead temperatures and the final bed height with mean relative errors of a few percent, while capturing the more complex bottom-head temperature dynamics qualitatively. Scenario simulations illustrate how the coking severity (represented here by the effective wall temperature) affects the coke yield, bed growth, and cycle duration. Overall, the results indicate that low-order dynamic models can provide a practical balance between physical fidelity and computational speed, making them suitable as mechanistic cores for digital twins and optimization tools in delayed coking operations. Full article
10 pages, 419 KB  
Article
Comparison of a Single-Shot Antibiotic Protocol Compared to a Conventional 5-Day Antibiotic Protocol in Equine Diagnostic Laparotomy Regarding Pre- and Postoperative Colonization with Multi-Drug-Resistant Indicator Pathogens
by Sabita Diana Stöckle, Dania Annika Kannapin, Roswitha Merle, Antina Lübke-Becker and Heidrun Gehlen
Antibiotics 2026, 15(1), 106; https://doi.org/10.3390/antibiotics15010106 - 21 Jan 2026
Abstract
Objective: The emergence and spread of multi-drug-resistant (MDR) bacteria pose a growing threat in veterinary medicine, particularly in equine hospitals. This study investigated the colonization and infection dynamics of horses undergoing emergency laparotomy with two distinct antibiotic protocols (single-shot versus 5-day protocol) during [...] Read more.
Objective: The emergence and spread of multi-drug-resistant (MDR) bacteria pose a growing threat in veterinary medicine, particularly in equine hospitals. This study investigated the colonization and infection dynamics of horses undergoing emergency laparotomy with two distinct antibiotic protocols (single-shot versus 5-day protocol) during hospitalization. Methods: Nasal swabs and fecal samples were collected from 67 horses undergoing emergency laparotomy at clinic admission as well as on postoperative days 3 and 10. These were screened for multi-drug-resistant indicator pathogens. As multi-drug-resistant indicator pathogens, methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E), and bacteria belonging to the Acinetobacter baumannii complex were defined. Results: Preoperatively, 6.2% of horses tested positive for MRSA and 13% for ESBL-E. An increase in colonization was observed on day 3 postoperatively, with 62.1% of nasal swabs and 86.4% of fecal samples testing positive for MDR organisms. On day 10, 53.4% of nasal swabs and 62.5% of fecal samples tested positive for indicator pathogens. Surgical site infection developed in five horses, two of which tested positive for MRSA in both nasal and wound samples during hospitalization, supporting the potential role of nasal carriage as a source of infection. Furthermore, all horses tested positive for ESBL-E during at least one time-point during hospitalization, and Enterobacterales (MDR in two surgical site infections (SSI)) were involved in all surgical site infections. No significant differences were observed between the two antibiotic treatment groups regarding colonization rates with indicator pathogens during hospitalization. However, the results indicate that hospitalization itself contributes to increased colonization with resistant bacteria. A clear limitation of the study is the restricted number of sampled horses and the lack of environmental contamination data. Non-sampled hospitalized horses with and without antibiotic treatment may have acted as reservoirs for MDR bacteria. Conclusion: The findings emphasize the need for routine environmental monitoring and strict adherence to hygiene protocols in equine clinics to reduce the risk of nosocomial transmission. Ongoing surveillance and infection control strategies are essential to mitigate the spread of MDR pathogens in veterinary settings. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Bacterial Isolates of Animal Origin)
12 pages, 1222 KB  
Article
Impact of Deep-Learning-Based Respiratory Motion Correction on [18F] FDG PET/CT Test–Retest Reliability and Consistency of Tumor Quantification in Patients with Lung Cancer
by Shijia Weng, Limei Jiang, Runze Wu, Yuanyan Cao, Yuan Li and Qian Wang
Biomedicines 2026, 14(1), 245; https://doi.org/10.3390/biomedicines14010245 - 21 Jan 2026
Abstract
Objectives: Respiratory motion degrades the quantitative accuracy and test–retest (TRT) reliability of fluorine-18 fluorodeoxyglucose ([18F] FDG) positron emission tomography (PET)/computed tomography (CT) in lung cancer. This study investigated whether a deep-learning-based respiratory motion correction (RMC) method improves the TRT reliability and [...] Read more.
Objectives: Respiratory motion degrades the quantitative accuracy and test–retest (TRT) reliability of fluorine-18 fluorodeoxyglucose ([18F] FDG) positron emission tomography (PET)/computed tomography (CT) in lung cancer. This study investigated whether a deep-learning-based respiratory motion correction (RMC) method improves the TRT reliability and image quality of [18F] FDG PET tumor quantification compared with non-motion-corrected (NMC) reconstructions. Methods: Thirty-one patients with primary lung cancer underwent three PET acquisitions: whole body free breathing (Scan1), thoracic free breathing (Scan2), and thoracic controlled breathing (ScanCB). Each dataset was reconstructed with and without RMC. Visual assessments of liver motion artifacts, lesion clarity, and PET-CT co-registration were scored. Lung tumors were segmented to derive standardized uptake value max (SUVmax), SUVmean, metabolic tumor volume (MTV), PET-derived lesion length (PLL), and total lesion glycolysis (TLG). Visual image scores and TRT reliability of tumor quantification were compared using Kruskal–Wallis one-way analysis of variance and intraclass correlation coefficients (ICCs). Results: RMC reconstructions achieved higher visual scores of lesion clarity and PET-CT co-registration across all lung lobes and significantly reduced liver motion artifacts compared with NMC reconstructions. Differences in SUVmax, SUVmean, PLL, MTV, and TLG between Scan2 and ScanCB were significantly smaller with RMC than with NMC. ICCs for SUVmax, SUVmean, MTV, and TLG were higher between scans with RMC than NMC reconstructions, indicating improved TRT reliability. Conclusions: The deep-learning-based RMC method improved the image quality and TRT reproducibility of [18F] FDG PET/CT quantification in lung cancer, supporting its potential for routine adoption in therapy-response assessments. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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11 pages, 215 KB  
Article
Routine Ketorolac Use for Postoperative Pain Does Not Increase Bleeding Risk After Hysterectomy
by Grace M. Pipes, Rebecca J. Schneyer, Kacey M. Hamilton, Ogechukwu Ezike, Katharine Ciesielski, Kelly N. Wright, Raanan Meyer and Matthew T. Siedhoff
J. Clin. Med. 2026, 15(2), 869; https://doi.org/10.3390/jcm15020869 - 21 Jan 2026
Abstract
Background/Objective: Ketorolac is an effective alternative and addition to opioids for postoperative pain control; however, there is concern of perioperative bleeding risk with its use. Within gynecology, this risk has not yet been explored in the context of hysterectomy. This study aimed to [...] Read more.
Background/Objective: Ketorolac is an effective alternative and addition to opioids for postoperative pain control; however, there is concern of perioperative bleeding risk with its use. Within gynecology, this risk has not yet been explored in the context of hysterectomy. This study aimed to evaluate the risk of postoperative bleeding complications with ketorolac administration in the context of hysterectomy. Methods: This was a retrospective cohort study that included all patients who underwent hysterectomy for benign indications between 2015 and 2024 at a quaternary care academic hospital. Inclusion criteria were any type of hysterectomy during the study period, while exclusion criteria were malignancy and peripartum status. Complication data for up to thirty days post operation were collected. Multivariable regression analysis, including age, American Society of Anesthesiology category, use of celecoxib before surgery, anticoagulant treatment, uterus size, surgical approach, increased surgical complexity, and lysis of adhesions, was performed to identify the adjusted odds of postoperative bleeding complications. The primary outcome was a composite of any postoperative bleeding complications by use of postoperative ketorolac, including postoperative transfusion, readmission, or reoperation for bleeding. Results: In total, 4236 patients underwent hysterectomy for benign indications during our study period, of which 76% (n = 3236) received ketorolac postoperatively. The composite postoperative bleeding rate was lower in the ketorolac group (2.1% vs. 4.1%, p = 0.001). There was no association between ketorolac use and risk of postoperative bleeding in multivariable regression analysis (aOR 1.02, 95% CI 0.36–2.88). There was no difference in overall intraoperative or perioperative complications (p = 0.070 for both). Major perioperative complications were less likely in the ketorolac group (p = 0.046). Additionally, there were no differences in postoperative complications except for ileus, which was less likely in the ketorolac group (p = 0.034). Conclusions: Ketorolac administration was not associated with a higher risk of bleeding complications after hysterectomy, including when celecoxib was used preoperatively as part of an enhanced recovery protocol. It may safely be administered as an opioid-sparing pain medication in this setting. Full article
17 pages, 556 KB  
Article
Directions and Perspectives for Preventive Activities in Primary Care—Patients’ Health-Promoting and Health-Risk Behaviours
by Anna Domańska, Sabina Lachowicz-Wiśniewska and Wioletta Żukiewicz-Sobczak
Nutrients 2026, 18(2), 346; https://doi.org/10.3390/nu18020346 - 21 Jan 2026
Abstract
Non-communicable diseases, particularly cardiovascular diseases (CVD) and metabolic syndrome (MS), remain a major challenge for primary health care (PHC). This study aimed to assess cardiometabolic risk and health behaviours in adult PHC patients using routine preventive screening. This prospective observational study included 506 [...] Read more.
Non-communicable diseases, particularly cardiovascular diseases (CVD) and metabolic syndrome (MS), remain a major challenge for primary health care (PHC). This study aimed to assess cardiometabolic risk and health behaviours in adult PHC patients using routine preventive screening. This prospective observational study included 506 adults attending routine consultations in an urban PHC centre in Poland. Preventive assessment included anthropometric measurements (body weight, height, BMI, and waist circumference), blood pressure, lipid profile, and fasting glucose levels. Health behaviours were recorded using the standardised NFZ CHUK questionnaire. The 10-year CVD risk was estimated using the SCORE2 algorithm. Multivariable logistic regression was used to identify independent factors associated with high cardiovascular risk (SCORE2 ≥ 5%) and of a composite endpoint defined as the presence of any non-optimal biochemical parameter. Nearly half of the participants had excess body weight (overweight or obesity), and more than half met criteria for central obesity. Borderline or elevated total cholesterol was found in 47% of patients, abnormal LDL in 27%, low HDL-C (<40 mg/dL) in 80% (84% when applying sex-specific cut-offs), and impaired fasting glucose or diabetes in about 12%. High SCORE2 risk (≥5%) was observed in approximately 9% of the cohort. In multivariable models, SCORE2 components (age, sex, and smoking) were, as expected, associated with high SCORE2 risk, and obesity (BMI ≥ 30 kg/m2)—a factor not included in SCORE2—was additionally associated with higher risk. Additionally, age, male sex, and obesity also predicted the presence of at least one non-optimal biochemical marker. The prevalence of high SCORE2 risk increased from 1.2% in patients with 0–1 modifiable risk factor to 25.7% in those with 4–5 factors. Lower educational attainment was associated with a higher proportion of high-risk individuals in univariate analysis. Routine preventive activities in PHC enable the identification of important lipid and glucose abnormalities and the clustering of modifiable risk factors, even in a relatively young, highly educated population. Systematic cardiovascular screening and a focus on patients with accumulated risk factors should remain a priority in PHC to enable early identification of high-risk patients and timely implementation of lifestyle and therapeutic interventions. Full article
13 pages, 721 KB  
Article
Direct Relationship Between Heparin Binding to Midkine and Pleiotrophin and the Development of Acute Deep Vein Thrombosis
by Suna Aydin, İsmail Polat, Kevser Tural, Nurullah Duger, Kader Ugur, İbrahim Sahin, Suleyman Aydin and Do-Youn Lee
Biomedicines 2026, 14(1), 242; https://doi.org/10.3390/biomedicines14010242 - 21 Jan 2026
Abstract
Background/Objectives: The underlying molecular mechanisms of deep vein thrombosis (DVT), which continues to be a major global public health concern, remain unclear. A key component of anticoagulant therapy, heparin (HP) interacts with heparin-binding growth factors including pleiotrophin (PTN) and midkine (MK), both [...] Read more.
Background/Objectives: The underlying molecular mechanisms of deep vein thrombosis (DVT), which continues to be a major global public health concern, remain unclear. A key component of anticoagulant therapy, heparin (HP) interacts with heparin-binding growth factors including pleiotrophin (PTN) and midkine (MK), both of which have basic amino acid-rich domains that have a strong affinity for HP. The purpose of this study was to determine if changes in the levels of circulating HP, MK, and PTN are linked to the onset of acute DVT. Methods: Thirty patients diagnosed with acute DVT by venous Doppler ultrasonography (VDU) and 28 healthy controls with normal VDU findings were enrolled. Serum HP, MK, and PTN concentrations were measured using ELISA. In DVT patients, blood samples were obtained before and after routine subcutaneous low-molecular-weight heparin treatment; controls provided a single blood sample. ROC curve analysis was used to assess diagnostic performance. Results: Prior to treatment, patients with acute DVT exhibited significantly lower serum HP levels (p < 0.05) and significantly higher MK and PTN levels compared with healthy controls (both p < 0.05). Following heparin administration, serum HP levels increased significantly (p < 0.05), while MK and PTN levels showed a decreasing trend that did not reach statistical significance (p > 0.05). ROC curve analysis demonstrated limited diagnostic performance for HP (sensitivity 10.3%, specificity 68.8%), PTN (62.1%, 54.2%), and MK (82.8%, 35.4%). Conclusions: Decreased circulating HP and increased MK and PTN levels are characteristics of acute DVT that may indicate endogenous HP sequestration through binding to these growth factors. This imbalance could lead to less free HP being available, which would encourage the formation of thrombus. Therapeutic approaches that target MK- and PTN-mediated HP interactions may constitute a unique approach for the therapy of acute DVT, as evidenced by the partial normalization seen after exogenous heparin delivery. Full article
(This article belongs to the Section Cell Biology and Pathology)
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20 pages, 1483 KB  
Article
The Spherical Harmonic Representation of the Geoid
by Robert Tenzer, Wenjin Chen, Shengwang Yu and Zhengfeng Jin
Geomatics 2026, 6(1), 7; https://doi.org/10.3390/geomatics6010007 - 21 Jan 2026
Abstract
Global Gravitational Models (GGMs) describe the Earth’s external gravitational field by a set of spherical harmonic (Stokes) coefficients. These coefficients are routinely used to compute the geoid model, while disregarding the upper continental crustal (i.e., topographic) masses above the geoid. Strictly speaking, however, [...] Read more.
Global Gravitational Models (GGMs) describe the Earth’s external gravitational field by a set of spherical harmonic (Stokes) coefficients. These coefficients are routinely used to compute the geoid model, while disregarding the upper continental crustal (i.e., topographic) masses above the geoid. Strictly speaking, however, these coefficients can describe only gravity field quantities at (or above) the Earth’s surface to satisfy Laplace’s equation. Consequently, the GGM coefficients cannot be used to define the geoid surface rigorously without accounting for the internal convergence domain and the gravitational effect of topographic masses. In most technical and scientific applications, the computation of the geoid model directly from the GGM coefficients has been accepted under the assumption that errors due to disregarding the internal convergence domain (inside the topographic masses) are typically less than a few centimeters (i.e., at the level of global geoid model uncertainties). In this study, we demonstrate that these errors reach several decimeters and even meters, with maxima in Tibet and Himalayas exceeding ~4 m. Moreover, relatively large errors, reaching decimeters, are already detected in regions with a moderately elevated topography. In scientific applications requiring a high accuracy, such errors cannot be ignored. Instead, GGM coefficients describing the Earth’s external gravitational field have to be corrected for the effect of (topographic) masses distributed above the geoid surface to obtain spherical harmonic coefficients that explicitly define the geoid globally. The explicit definition of the global geoid model in the spectral domain is derived in this study and used to compile spherical harmonic coefficients of the geoid up to degree/order 2160 from the EIGEN-6C4 global gravitational model. Full article
17 pages, 989 KB  
Systematic Review
Neonatal Sepsis as Organ Dysfunction: Prognostic Accuracy and Clinical Utility of the nSOFA in the NICU—A Systematic Review
by Bogdan Cerbu, Marioara Boia, Manuela Pantea, Teodora Ignat, Mirabela Dima, Ileana Enatescu, Bogdan Rotea, Andra Rotea, Vlad David and Daniela Iacob
Diagnostics 2026, 16(2), 349; https://doi.org/10.3390/diagnostics16020349 - 21 Jan 2026
Abstract
Background and Objectives: Early recognition of life-threatening organ dysfunction is central to modern sepsis frameworks. We systematically reviewed the prognostic performance and clinical utility of the Neonatal Sequential Organ Failure Assessment (nSOFA) for mortality and major morbidity in NICU populations. The search identified [...] Read more.
Background and Objectives: Early recognition of life-threatening organ dysfunction is central to modern sepsis frameworks. We systematically reviewed the prognostic performance and clinical utility of the Neonatal Sequential Organ Failure Assessment (nSOFA) for mortality and major morbidity in NICU populations. The search identified 939 records across databases; after screening and full-text assessment, 16 studies met the inclusion criteria. Methods: Following PRISMA guidance, we searched major databases (2019–2025) for observational or interventional studies reporting discrimination or risk stratification using nSOFA in neonates. Populations included suspected/proven infection and condition-specific cohorts. Heterogeneity in timing, thresholds, and outcomes precluded meta-analysis. Results: A cumulative sample exceeding 25,000 neonates was identified across late- and early-onset infection, all-NICU admissions, necrotizing enterocolitis, respiratory distress, and very preterm screening cohorts. Across settings and timepoints, nSOFA demonstrated consistent, good-to-excellent mortality discrimination, with reported AUROCs ≥ 0.80 and upper ranges near 0.90–0.92; serial scoring within the first 6–12 h generally improved risk classification. Disease-specific applications (NEC, early-onset infection) showed similar discrimination for death or composite adverse outcomes. Conclusions: Evidence from diverse NICU contexts indicates that nSOFA is a pragmatic, EHR-ready organ dysfunction score with robust discrimination for mortality and serious morbidity, supporting routine, serial use for risk stratification and standardized endpoints in neonatal sepsis pathways, aligned with contemporary organ dysfunction–based pediatric criteria. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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15 pages, 242 KB  
Review
Real-World Evidence for Psychiatric Disorders from the German Disease Analyzer Database: A Narrative Review
by Karel Kostev, Marcel Konrad and Jens Bohlken
Brain Sci. 2026, 16(1), 115; https://doi.org/10.3390/brainsci16010115 - 21 Jan 2026
Abstract
The German IQVIA Disease Analyzer (DA) database has become an increasingly important source of real-world evidence for psychiatric research. Over the past decade, and particularly since 2020, DA-based studies have addressed a broad spectrum of psychiatric outcomes including depression, anxiety disorders, schizophrenia, bipolar [...] Read more.
The German IQVIA Disease Analyzer (DA) database has become an increasingly important source of real-world evidence for psychiatric research. Over the past decade, and particularly since 2020, DA-based studies have addressed a broad spectrum of psychiatric outcomes including depression, anxiety disorders, schizophrenia, bipolar disorder, dementia, sleep disorders, and the mental health consequences of chronic somatic diseases and of contracting COVID-19. Using large, representative outpatient cohorts, these studies have examined factors associated with the incidence of psychiatric disorders, patterns of psychiatric and somatic comorbidity, treatment trajectories, and long-term outcomes under routine care conditions. The DA database’s longitudinal structure, nationwide coverage, and inclusion of multiple medical specialties enable it to capture psychiatric disorders throughout patient lifetimes and across different clinical contexts. This narrative review summarizes psychiatric research using the DA database that has been published since 2020, focusing on study design, main findings, methodological strengths and limitations, and implications for future psychiatric epidemiology and clinical research. Full article
(This article belongs to the Section Neuropsychiatry)
12 pages, 611 KB  
Article
Prognostic Performance of the Korean Triage and Acuity Scale Combined with the National Early Warning Score for Predicting Mortality and ICU Admission at Emergency Department Triage: A Retrospective Observational Study
by Jungtaek Park, Sang Hoon Oh, Ae Kyung Gong, Jee Yong Lim, Sun Hee Woo, Won Jung Jeong, Ji Hoon Kim, In Soo Kim and Soo Hyun Kim
Diagnostics 2026, 16(2), 345; https://doi.org/10.3390/diagnostics16020345 - 21 Jan 2026
Abstract
Objectives: This study aimed to compare the predictive performance of the Korean Triage and Acuity Scale (KTAS) and the National Early Warning Score (NEWS) for serious adverse events (SAEs), including mortality and intensive care unit (ICU) admission, during emergency department (ED) stay. [...] Read more.
Objectives: This study aimed to compare the predictive performance of the Korean Triage and Acuity Scale (KTAS) and the National Early Warning Score (NEWS) for serious adverse events (SAEs), including mortality and intensive care unit (ICU) admission, during emergency department (ED) stay. We also evaluated whether combining the two systems improves prediction accuracy. Methods: This retrospective study included adult patients (≥19 years) who presented to a university-affiliated ED between October and December 2024. KTAS and NEWS were assessed simultaneously at triage. NEWS2 was calculated retrospectively based on routinely documented vital signs and medical history without performing routine arterial blood gas analysis. The primary outcome was the occurrence of SAE during the ED stay. Predictive performance was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC), and logistic regression models were used to identify independent associations. Results: A total of 4216 patients were analyzed, of whom 255 (6.0%) experienced SAEs. All three scores—KTAS, NEWS and NEWS2—were independently associated with the occurrence of SAEs. The AUCs for KTAS, NEWS and NEWS2 were 0.75 (95% CI, 0.74–0.76), 0.73 (95% CI, 0.71–0.74) and 0.73 (95% CI, 0.71–0.74), respectively. Combining KTAS with NEWS or NEWS2 significantly improved predictive accuracy (AUC 0.81, 95% CI 0.79–0.82; p < 0.001). Conclusions: Both KTAS and NEWS/NEWS2 reliably predicted in-ED adverse outcomes, and their combination further enhanced prognostic performance. Integrating physiology-based early warning scores with structured triage systems may help identify high-risk ED patients earlier and optimize resource allocation. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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