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18 pages, 1461 KB  
Article
Single-Bolus Sequential Triple-Rule-Out CT Angiography: Image Quality and Radiation Dose on Wide-Area Detector and Dual-Source CT
by Hyun Jung Kim, Jin Woo Kim, Sung-Jin Cha and Sung Min Ko
J. Clin. Med. 2026, 15(18), 7166; https://doi.org/10.3390/jcm15187166 - 15 Sep 2026
Abstract
Background/Objectives: Single-pass triple-rule-out computed tomography (CT) angiography (TRO-CTA) must compromise among differing pulmonary, coronary, and aortic contrast-transit times. Wide-area detector CT (WAD-CT) and dual-source CT (DSCT) offer different coverage, temporal resolution, and dose profiles, but direct comparative evidence for a sequential single-bolus [...] Read more.
Background/Objectives: Single-pass triple-rule-out computed tomography (CT) angiography (TRO-CTA) must compromise among differing pulmonary, coronary, and aortic contrast-transit times. Wide-area detector CT (WAD-CT) and dual-source CT (DSCT) offer different coverage, temporal resolution, and dose profiles, but direct comparative evidence for a sequential single-bolus strategy is limited in selected emergency patients with overlapping concern for acute coronary syndrome, pulmonary embolism, or acute aortic syndrome. We compared territory-specific image quality and radiation dose; diagnostic accuracy was not assessed. Methods: This retrospective study included 114 adults (WAD-CT, n = 60; DSCT, n = 54). After test-bolus timing, one weight-based diagnostic bolus was used for sequential pulmonary, electrocardiography-synchronized coronary, and non-gated aortic acquisitions. Attenuation, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), blinded dual-reader quality scores, and radiation dose were compared by territory. Results: Mean overall scores across the two readers were ≥3 for every examination in all phases. WAD-CT showed higher pulmonary trunk SNR (19.5 ± 8.9 vs. 14.3 ± 3.8; p = 0.002), higher ascending aortic SNR (24.9 ± 11.4 vs. 14.2 ± 3.0; p < 0.001), lower coronary and aortic noise, and 38.1% lower total estimated dose (6.40 ± 1.72 vs. 10.34 ± 6.91 mSv; p < 0.001). DSCT showed higher right coronary attenuation (671.8 ± 186.7 vs. 466.4 ± 128.9 Hounsfield units; p < 0.001), no significant difference in right coronary SNR (p = 0.681), and less aortic-root pulsation artifact (p < 0.001). Pulmonary- and coronary-phase overall scores were comparable. Conclusions: Both protocols provided acceptable territory-level image quality from one diagnostic bolus. WAD-CT provided lower coronary and aortic noise and estimated radiation dose, whereas DSCT provided higher coronary attenuation and less aortic-root pulsation artifact. Diagnostic accuracy and performance in subsegmental pulmonary arteries and distal or small coronary branches remain unestablished. Full article
(This article belongs to the Special Issue Advances in Cardiovascular Computed Tomography (CT))
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27 pages, 1524 KB  
Review
Neurological Manifestations of Long COVID: Current Evidence, Emerging Concepts, and Future Perspectives
by Marina Bralic, Frederic-Ivan Silconi, Vladimira Vuletic and Slavica Kovacic
J. Clin. Med. 2026, 15(18), 7163; https://doi.org/10.3390/jcm15187163 - 15 Sep 2026
Abstract
Six years after the onset of the COVID-19 pandemic, many individuals continue to experience persistent neurological symptoms that extend beyond the acute phase of infection, affecting daily life, work, and overall functioning, thereby representing a substantial long-term health burden. Cognitive impairment, fatigue, headache, [...] Read more.
Six years after the onset of the COVID-19 pandemic, many individuals continue to experience persistent neurological symptoms that extend beyond the acute phase of infection, affecting daily life, work, and overall functioning, thereby representing a substantial long-term health burden. Cognitive impairment, fatigue, headache, and autonomic dysfunction are among the most frequently reported neurological features, often persisting despite the absence of clear diagnostic findings. Although Long COVID is recognized as a distinct clinical entity, the underlying pathophysiological mechanisms remain incompletely understood. This narrative review provides a critical synthesis of current literature regarding the clinical presentations, potential mechanisms, and biomarkers associated with neurological involvement in Long COVID. Reflecting the high heterogeneity of the available evidence, it is important to note that no neurological biomarker or disease-modifying therapy has yet been clinically validated. Ultimately, characterizing these pathways may help define disease heterogeneity, support patient stratification, and guide future personalized therapeutic approaches. Full article
(This article belongs to the Section Clinical Neurology)
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54 pages, 1275 KB  
Review
Microbiome-Based Therapeutics in Oncology: Expanding Indications Beyond C. difficile
by Ayham Al-Omari, Abdallah Kheshman, Peter Morkos, Katherine Davanzo and Lea Monday
Onco 2026, 6(3), 47; https://doi.org/10.3390/onco6030047 - 14 Sep 2026
Abstract
The intestinal microbiome has emerged as a clinically significant modulator of outcomes across multiple domains of cancer care. In hematopoietic stem cell transplantation (HSCT), loss of microbial diversity and depletion of short-chain fatty acid-producing commensals are independently associated with graft-versus-host disease (GvHD), bloodstream [...] Read more.
The intestinal microbiome has emerged as a clinically significant modulator of outcomes across multiple domains of cancer care. In hematopoietic stem cell transplantation (HSCT), loss of microbial diversity and depletion of short-chain fatty acid-producing commensals are independently associated with graft-versus-host disease (GvHD), bloodstream infections, transplant-related mortality, and overall survival. Mechanistic studies have identified interconnected pathways—including butyrate-mediated epithelial protection, tryptophan-derived aryl hydrocarbon receptor signaling, bile acid metabolism, and Paneth cell–intestinal stem cell interactions—through which microbial communities regulate intestinal barrier integrity and immune homeostasis. These insights have provided the biological rationale for therapeutic strategies aimed at restoring microbial ecology. Fecal microbiota transplantation (FMT) has demonstrated promising clinical activity in steroid-refractory acute GvHD, with one meta-analysis reporting a pooled clinical remission rate of 64% (95% CI, 51–77%) across prospective single-arm studies, and proprietary live biotherapeutic products (LBPs) such as MaaT013 met the primary endpoint of the single-arm phase III ARES trial, achieving a day-28 gastrointestinal overall response rate of 62%; however, the CHMP adopted a negative opinion on its conditional marketing authorization application in June 2026, citing limitations of the single-arm design, and a re-examination is pending. In parallel, gut microbiome composition has been associated with immune checkpoint inhibitor (ICI) response, and early-phase FMT studies suggest that microbiome modulation may restore sensitivity to anti-PD-1 therapy in some patients with refractory melanoma and may enhance treatment responses in first-line ICI settings; however, these findings derive primarily from small, uncontrolled or early-phase studies. Defined single-strain approaches, notably Clostridium butyricum MIYAIRI 588 (CBM588), have shown encouraging secondary clinical efficacy signals in two small, randomized phase I trials in metastatic renal cell carcinoma, including significantly prolonged progression-free survival in one trial and a higher objective response rate in another; however, neither trial met its prespecified primary microbiome endpoint of increased Bifidobacterium spp. abundance. Emerging evidence further links antibiotic-induced dysbiosis to impaired chimeric antigen receptor T-cell (CAR-T) therapy outcomes, while short-chain fatty acids have been identified as direct enhancers of CAR-T cell effector function. This review synthesizes the current evidence for microbiome-based therapeutics across HSCT, GvHD, ICI therapy, CAR-T cell therapy, and infection prevention, and addresses cross-cutting translational challenges including antibiotic stewardship, donor selection, safety in immunocompromised populations, and pharmacomicrobiomics. While randomized controlled trial data remain limited and many approaches are investigational, the convergence of mechanistic, observational, and early interventional evidence positions microbiome restoration as a promising frontier in precision oncology. Full article
21 pages, 3834 KB  
Article
Anatomy- and Time-Based Post-Processing with CT Perfusion-Derived Time–Vessel Maps to Reduce Incorrect Occlusion Detections in Late-Phase CT Angiography
by Andrés Martínez Mora, Mahsa Mojtahedi, Lucas de Vries, Michael Baumgartner, Yannick Kirchhoff, Maximilian Zenk, Katharina Eckstein, Jessica Kächele, Gianluca Brugnara, Martin Bendszus, Alexander Radbruch, Yvo Roos, Wim van Zwam, Robert van Oostenbrugge, Diederik W. J. Dippel, Bart J. Emmer, Charles Majoie, Philipp Vollmuth, Clara I. Sánchez, Klaus H. Maier-Hein and Henk A. Marqueringadd Show full author list remove Hide full author list
Diagnostics 2026, 16(18), 2972; https://doi.org/10.3390/diagnostics16182972 - 14 Sep 2026
Abstract
Background/Objectives: Computer-aided vessel occlusion detection for acute ischemic stroke is typically developed on early-phase CT angiography (CTA). In late-phase CTA, enhanced venous contrast can mimic arterial occlusions and lead to incorrect occlusion detections. To counteract this, we propose a constraint-based post-processing framework that [...] Read more.
Background/Objectives: Computer-aided vessel occlusion detection for acute ischemic stroke is typically developed on early-phase CT angiography (CTA). In late-phase CTA, enhanced venous contrast can mimic arterial occlusions and lead to incorrect occlusion detections. To counteract this, we propose a constraint-based post-processing framework that leverages anatomical and temporal vascular information from CT perfusion (CTP) scans. Methods: Vascular anatomy and relative contrast-arrival times were encoded as time–vessel maps. Three complementary constraints worked on these maps to remove incorrect detections based on distance-to-vessel truncation points, contrast-arrival time, and spatial priors. Constraints were fixed on a 32-case late-phase development subset and applied to an external held-out cohort of late-phase CTA (N = 354). To enable application without CTP, an auxiliary CTA-to-time–vessel map generator was designed to estimate maps directly from CTA. Results: In the external cohort, the framework reduced incorrect occlusions per scan from 3.9 (95% CI 3.6–4.2) to 2.1 (95% CI 1.9–2.3), preserving occlusion-level sensitivity at 80% (95% CI 69–91). The patient-level AUROC was 83 for the baseline versus 88 with post-processing. Improvements were also observed in detectors exposed to late-phase CTA, where post-processing reduced incorrect occlusions per scan from 2.8 to 1.9. As only 51 occlusion-positive cases were present in the external cohort, confidence intervals were wide. Consequently, these estimates should be interpreted with caution. Conclusions: Anatomically and temporally informed post-processing reduced incorrect occlusion detections in late-phase CTA without measurable loss of sensitivity, potentially improving robustness against CTA phase changes in external institutions. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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28 pages, 15736 KB  
Article
Head-to-Tail Cyclization and D-Amino Acid Substitution Redesign the Biological Activities of a Naturally Occurring Amphibian Peptide
by María Verónica Húmpola, Roque Spinelli, Ivan Sanchís, Milagros de Orellana, Fernando Albericio and Álvaro Sebastian Siano
Molecules 2026, 31(18), 3240; https://doi.org/10.3390/molecules31183240 - 14 Sep 2026
Abstract
Peptide engineering has emerged as a powerful strategy to optimize naturally occurring peptides. Here, the amphibian skin peptide Hp-1891 from Boana pulchella was selected as a model scaffold to investigate the effects of two complementary engineering approaches, namely site-specific D-amino acid substitution and [...] Read more.
Peptide engineering has emerged as a powerful strategy to optimize naturally occurring peptides. Here, the amphibian skin peptide Hp-1891 from Boana pulchella was selected as a model scaffold to investigate the effects of two complementary engineering approaches, namely site-specific D-amino acid substitution and head-to-tail cyclization. A library of twelve analogues was synthesized by 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis and evaluated for inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), together with antioxidant and hemolytic activities. Circular dichroism spectroscopy and molecular modeling were performed to investigate the structural basis of the observed biological effects. Head-to-tail cyclization consistently enhanced inhibition of AChE, BChE, and Mpro, whereas D-amino acid substitution exerted a greater influence on antioxidant activity and hemolysis. Among the analogue library, c-Hp-d2 emerged as the most promising multifunctional peptide, displaying enhanced inhibition of all three enzymes while maintaining reduced hemolytic activity compared with the native peptide. Structural analyses indicated that cyclization promoted conformational organization, whereas D-amino acid incorporation reduced α-helical propensity. These findings demonstrate that rational peptide engineering effectively reshapes the biological profile of amphibian peptides and highlight head-to-tail cyclization as a versatile strategy for generating multifunctional peptide scaffolds with therapeutic potential. Full article
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23 pages, 807 KB  
Article
Associations Between FTO (Fat Mass- and Obesity-Associated) Gene Allelic Load and Heart Rate Responses to Submaximal Exercise in Humans: A Cross-Sectional Study
by Habib Al Ashkar, Nora Kovacs, Karoly Nagy, Roza Adany and Peter Piko
Biology 2026, 15(18), 1607; https://doi.org/10.3390/biology15181607 - 11 Sep 2026
Viewed by 85
Abstract
Obesity is a widespread condition strongly linked to increased cardiovascular risk, and heart rate (HR) responses to physical activity are widely used physiological indicators of this relationship. Although the role of fat mass- and obesity-associated (FTO) gene variants in obesity risk [...] Read more.
Obesity is a widespread condition strongly linked to increased cardiovascular risk, and heart rate (HR) responses to physical activity are widely used physiological indicators of this relationship. Although the role of fat mass- and obesity-associated (FTO) gene variants in obesity risk is well established, their potential associations with HR changes during and after physical activity (independent of adiposity) have not yet been fully elucidated. This study examined whether common FTO polymorphisms (rs9939609, rs1121980, rs1558902, and rs9941349) and an exploratory FTO multi-variant score (MVSFTO), representing regional variation across the high-LD FTO locus, are associated with HR responses to a brief submaximal exercise stimulus. A population-based cohort of Hungarian adults (n = 660) completed the YMCA 3-min step test, with HR measured at rest, at first-minute post-exercise (HRaft), and at 5- (HR5min) and 10-min recovery (HR10min). Acute HR response (ΔHR) and percent of predicted maximal HR (HRmax%) were calculated. Linear regression analyses showed no association between any FTO variant and resting HR (all p > 0.05). In contrast, all four candidate SNPs demonstrated significant negative associations with HRaft (β ≈ −3.6 to −4.2, all p ≤ 0.005), ΔHR (β ≈ −3.7 to −3.9, p ≤ 0.005), and HRmax% (β ≈ −2.5, p = 0.001). The MVSFTO revealed even more pronounced and consistent associations: higher MVSFTO burden was associated with lower HRaft (β = −4.19, p = 0.001), HR5min (β = −2.06, p = 0.004), HR10min (β = −1.15, p = 0.009), ΔHR (β = −4.04, p = 0.001), and HRmax% (β = −2.47, p = 0.001). Exploratory four-way mediation decompositions and saturated structural equation models indicated that these inverse associations remained statistically robust after multivariable adjustment for measured BMI and leisure-time physical activity (all direct paths p ≤ 0.001). Furthermore, multi-trait latent cluster analysis identified distinct phenotypic profiles consistent with these findings, showing that individuals with high MVSFTO burden and moderate physical activity exhibit blunted exercise HR reactivity across recovery phases. Rather than establishing biological causality or clinical cardiovascular benefit, these observational findings demonstrate that regional FTO locus variation captured by the multi-variant score is statistically associated with inter-individual variability in short-term post-exercise HR reactivity, providing hypothesis-generating insights that warrant validation in prospective cohorts and interventional exercise trials. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
12 pages, 1038 KB  
Article
Persistent Focal Myocardial 18F-FDG Uptake Discordant with CMR Oedema on Hybrid PET/MRI Six Months After Acute Myocarditis
by Guillaume Reverdito and Hichem Sakhi
Diagnostics 2026, 16(18), 2941; https://doi.org/10.3390/diagnostics16182941 - 11 Sep 2026
Viewed by 129
Abstract
Background: Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) enables simultaneous assessment of myocardial metabolism and CMR tissue characteristics. We investigated whether integrated 18F-FDG PET/MRI could identify persistent metabolic abnormalities approximately 6 months after acute myocarditis, including abnormalities discordant with concomitant CMR [...] Read more.
Background: Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) enables simultaneous assessment of myocardial metabolism and CMR tissue characteristics. We investigated whether integrated 18F-FDG PET/MRI could identify persistent metabolic abnormalities approximately 6 months after acute myocarditis, including abnormalities discordant with concomitant CMR oedema markers. Methods: In this retrospective single-centre study, 20 consecutive patients with a previous episode of acute myocarditis underwent integrated cardiac 18F-FDG PET/MRI approximately 6 months after the acute event. Focal myocardial FDG uptake, myocardial SUVmax and SUVmean, target-to-background ratios, T2 mapping, late gadolinium enhancement (LGE), and ventricular function were assessed within the hybrid examination. Results: Hybrid PET/MRI was performed at a median of 202 days (interquartile range [IQR], 173–221) after the acute episode. Four patients (20%) had non-diagnostic PET because of inadequate myocardial glucose suppression. Among 16 evaluable patients, four (25%) remained PET-positive with focal myocardial FDG uptake. Their myocardial SUVmax was 2.85 (IQR, 2.58–3.25) versus 1.65 (IQR, 1.38–1.80) in PET-negative patients (p = 0.001), and the myocardium-to-blood-pool ratio was 1.03 (IQR, 1.00–1.19) versus 0.82 (IQR, 0.75–0.86), respectively (p = 0.003). None of the four PET-positive patients had myocardial oedema on concomitant T2 mapping, whereas all had persistent LGE. One PET-negative patient showed persistent CMR oedema. Conclusions: Integrated PET/MRI identified persistent focal metabolic abnormalities in 25% of evaluable patients approximately 6 months after acute myocarditis, despite absent concomitant CMR oedema. Although the cohort is small and contemporary longitudinal clinical characterisation is limited, these hybrid-imaging findings support further investigation of PET/MRI as a tool for phenotyping the post-acute phase of myocarditis. Full article
(This article belongs to the Special Issue Advancements in Cardiovascular Imaging)
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13 pages, 3164 KB  
Case Report
Imatinib-Associated Interstitial Lung Disease with a Fibrotic NSIP Pattern on Transbronchial Lung Cryobiopsy: A Case Report and Review of the Literature
by Pier-Valerio Mari, Lorenzo Carriera, Filippo Lococo, Stefano Margaritora, Simone Ielo, Veronica Ojetti, Giulio Onelli, Fabrizio Liberati and Vittorio Pietrangeli
Reports 2026, 9(3), 303; https://doi.org/10.3390/reports9030303 - 10 Sep 2026
Viewed by 80
Abstract
Background and Clinical Significance: Interstitial lung disease (ILD) is an uncommon but potentially serious complication of imatinib. Its histopathological characterization has so far relied on surgical biopsy or transbronchial forceps sampling, and no case characterized by transbronchial lung cryobiopsy (TBLC) has been [...] Read more.
Background and Clinical Significance: Interstitial lung disease (ILD) is an uncommon but potentially serious complication of imatinib. Its histopathological characterization has so far relied on surgical biopsy or transbronchial forceps sampling, and no case characterized by transbronchial lung cryobiopsy (TBLC) has been reported. The single previous description of a non-specific interstitial pneumonia (NSIP) pattern with imatinib came from a surgical specimen and was cellular in type, with complete radiological resolution after withdrawal. Case Presentation: A 69-year-old never-smoker began imatinib 400 mg daily for Philadelphia chromosome-positive chronic myeloid leukemia; chest computed tomography performed immediately beforehand was normal. Approximately three months later, she developed dyspnea, dry cough and a cutaneous rash, progressing to acute respiratory failure with forced vital capacity 49% and diffusing capacity 30% of predicted. Avian exposure had ceased one month before symptom onset, and she had never received amiodarone. Although serum precipitins were unavailable, hypersensitivity pneumonitis was considered less likely given the temporal relationship but could not be definitively excluded. TBLC yielded specimens showing fibrotic thickening of the alveolar septa by hyaline collagen deposition with a focal lymphomonocytic infiltrate, corresponding to a fibrotic NSIP pattern. After drug withdrawal and administration of corticosteroids, forced vital capacity rose to 82% of predicted. Multidisciplinary discussion concluded that this was drug-induced ILD, graded probable on the Naranjo scale. Imatinib was subsequently replaced by bosutinib for insufficient molecular response, without pulmonary recurrence. Conclusions: Imatinib-associated ILD may present with an organizing-pneumonia-like radiological pattern followed by a fibrosing pattern, with cryobiopsy performed later demonstrating fibrotic NSIP. Because no tissue was obtained during the acute phase, this sequence remains a hypothesis rather than a demonstrated evolution. Cryobiopsy can be performed safely when surgical biopsy is not appropriate. Full article
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17 pages, 1811 KB  
Article
Clinical and Radiological Outcomes of Organising Pneumonia Secondary to COVID-19: A 2-Year Longitudinal Cohort Study
by Oswaldo Antonio Caguana-Vélez, Diana Badenes-Bonet, Xavier Duran, Flavio Zuccarino, Didac Ramal, Santiago Carbullanca, Judit Villar-García, Diego A. Rodríguez-Chiaradía and Eva Balcells
J. Clin. Med. 2026, 15(18), 6999; https://doi.org/10.3390/jcm15186999 - 10 Sep 2026
Viewed by 148
Abstract
Background: Organising pneumonia secondary to COVID-19 (OP-COVID-19) is a recognised inflammatory complication of SARS-CoV-2 infection. We assessed the 2-year clinical, radiological, and functional evolution of patients hospitalised with OP-COVID-19 and identified factors independently associated with long-term fibrotic-like lesions. Methods: This ambispective [...] Read more.
Background: Organising pneumonia secondary to COVID-19 (OP-COVID-19) is a recognised inflammatory complication of SARS-CoV-2 infection. We assessed the 2-year clinical, radiological, and functional evolution of patients hospitalised with OP-COVID-19 and identified factors independently associated with long-term fibrotic-like lesions. Methods: This ambispective longitudinal study included adults consecutively hospitalised with OP-COVID-19 from March 2020 to February 2021. Diagnosis was based on clinical assessment and high-resolution computed tomography (HRCT). Patients underwent standardised follow-up at 3, 6, 12, and 24 months after hospital discharge, including clinical assessment, chest HRCT, pulmonary function tests, and the six-minute walk test. Longitudinal radiological changes were assessed using paired comparisons, and exploratory multivariable logistic regression identified factors independently associated with long-term fibrotic-like lesions. Results: OP-COVID-19 was diagnosed in 271 patients (4.9%), and 228 were included in the follow-up cohort. Inflammatory HRCT abnormalities resolved progressively, with paired comparisons showing a significant reduction in consolidations, peribronchovascular opacities, crazy-paving pattern, reversed halo sign, and perilobular opacities at 3–6 months compared with the initial HRCT (p < 0.05 for all). Among the 221 patients with an ascertainable final radiological outcome, persistent pulmonary abnormalities were observed in 14.9%, including fibrotic-like lesions in 10.4%. No statistically detectable late radiological progression was observed among patients undergoing extended imaging follow-up. The need for respiratory support during the acute phase (odds ratio [OR] 5.79, 95% confidence interval [CI] 1.81–18.52), bronchial dilatation (OR 3.50, 95% CI 1.10–11.11), and architectural distortion and/or volume loss on initial HRCT (OR 4.72, 95% CI 1.80–12.35) were independently associated with long-term fibrotic-like abnormalities. Pulmonary function was largely preserved, with mildly reduced diffusing capacity for carbon monoxide (DLCO) in the assessed subsets. Conclusions: OP-COVID-19 has a favourable long-term prognosis, with progressive resolution of inflammatory abnormalities in most patients. Fibrotic-like lesions occur in a minority of patients and are associated with greater initial disease severity and early structural abnormalities on HRCT. These findings support risk-stratified follow-up for patients with OP-COVID-19. Full article
(This article belongs to the Special Issue Pneumonia: From Diagnosis to Treatment)
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13 pages, 12757 KB  
Article
Joint Trajectories of Death Anxiety and Experiential Avoidance After Cancer Diagnosis: A Longitudinal Study
by Yiguo Deng, Furong Chen, Siyu Li, Qihan Zhang, Jiaying Li and Zengjie Ye
Curr. Oncol. 2026, 33(9), 546; https://doi.org/10.3390/curroncol33090546 - 9 Sep 2026
Viewed by 112
Abstract
Background: Despite the observed association between death anxiety and experiential avoidance, their joint short-term trajectories in patients with newly diagnosed cancer remain unclear. This study aimed to identify joint trajectories of death anxiety and experiential avoidance during early cancer care. Methods: This secondary [...] Read more.
Background: Despite the observed association between death anxiety and experiential avoidance, their joint short-term trajectories in patients with newly diagnosed cancer remain unclear. This study aimed to identify joint trajectories of death anxiety and experiential avoidance during early cancer care. Methods: This secondary longitudinal analysis included 266 adults with newly diagnosed cancer recruited at Hunan Cancer Hospital, China, between April and September 2022. Death anxiety and experiential avoidance were assessed using the 15-item Templer Death Anxiety Scale (DAS) and the seven-item Acceptance and Action Questionnaire-II (AAQ-II), respectively, at hospital admission, discharge, and one month after discharge. This interval represented the acute adaptation phase after diagnosis and treatment initiation. Outcome-specific trajectory models informed a fully crossed dual-trajectory model. Results: Participants (mean age, 48.33 ± 11.18 years; 53.8% male) followed three jointly re-estimated declining DAS trajectories (low, 37.3%; moderate, 26.5%; high, 36.3%) and two declining AAQ-II trajectories (low, 70.6%; high, 29.4%). In the dual-trajectory model (entropy = 0.849), the probability of high-AAQ-II increased across low, moderate, and high-DAS trajectories (8.5%, 18.7%, and 58.6%), and 72.3% of the high-AAQ-II trajectory followed the high-DAS trajectory. A high-DAS/low-AAQ-II combination accounted for 15.0%, indicating incomplete correspondence. Conclusions: During early care after cancer diagnosis, high-AAQ-II membership was concentrated in higher DAS trajectories, whereas high-DAS could also accompany low-AAQ-II. Full article
(This article belongs to the Special Issue The Psychosocial Impact of Cancers and Supportive Care Interventions)
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22 pages, 5687 KB  
Article
Investigating Neuropharmacological Features of the Cortical Activity of Cannabidiol GWP42003 P—A Phase 1 Clinical Trial
by Viviana Santoro, Po-Yu Fong, Andrea Biondi, Isabella Premoli, Harry Clark, Lorenzo Rocchi and Mark P. Richardson
Brain Sci. 2026, 16(9), 957; https://doi.org/10.3390/brainsci16090957 - 9 Sep 2026
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Abstract
Background/Objectives: Despite the clinical efficacy of cannabidiol (CBD) in treating certain epilepsies, its in vivo neuropharmacological mechanisms remain incompletely understood. This Phase 1 clinical trial aimed to evaluate the acute effects of a single oral dose of highly purified CBD (GWP42003-P) on [...] Read more.
Background/Objectives: Despite the clinical efficacy of cannabidiol (CBD) in treating certain epilepsies, its in vivo neuropharmacological mechanisms remain incompletely understood. This Phase 1 clinical trial aimed to evaluate the acute effects of a single oral dose of highly purified CBD (GWP42003-P) on cortical excitability. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) and electromyography (TMS-EMG) were utilized as assessment tools. Methods: In a randomized, double-blind, placebo-controlled crossover trial, 15 healthy male participants received a single 1500 mg dose of GWP42003-P or placebo. Cortical activity metrics, including resting and active motor thresholds (RMT, AMT), short intracortical inhibition (SICI), TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP), and inter-trial phase clustering (ITPC), were recorded pre-dose and at 1, 4, and 6 h post-dose. Results: RMT and AMT significantly decreased over time following CBD administration, though without a significant Condition × Time interaction. While primary analyses showed no condition-driven alterations for SICI, TEPs, or TRSP, secondary longitudinal modeling revealed a transient reduction in beta-band desynchronization 1 h post-dose, aligning with peak plasma concentration. The drug condition also exhibited a qualitative, non-significant trend toward increased alpha ITPC and decreased delta ITPC at 4 and 6 h post-dose compared to placebo. Conclusions: A single acute 1500 mg dose of GWP42003-P did not produce statistically significant alterations in widespread cortical excitability in healthy adult males. However, the transient blunting of beta desynchronization at peak concentration may reflect CBD’s distinct, non-classical neuromodulatory profile. Overall, these largely null findings suggest that acute CBD administration lacks a robust, direct modulatory effect on cortical networks. Capturing its precise neuropharmacological mechanisms will likely require future investigations utilizing chronic dosing paradigms or clinical patient populations. Full article
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18 pages, 16967 KB  
Article
Serum Urate and Renal Dysfunction: Bidirectional Genetic Associations, External Validation, and Exploratory Multi-Omics Characterization of Antithrombin (SERPINC1) in Hyperuricemic Nephropathy
by Lei Jin and Feng Wang
Genes 2026, 17(9), 1084; https://doi.org/10.3390/genes17091084 - 9 Sep 2026
Viewed by 161
Abstract
Background: Hyperuricemic nephropathy (UAN) involves a systemic thromboinflammatory axis, yet the role of antithrombin (AT, SERPINC1) remains incompletely defined. While AT has anticoagulant and anti-inflammatory properties, whether it contributes to UAN as a disease-responsive molecular node remains uncertain. Methods: We integrated two-sample MR [...] Read more.
Background: Hyperuricemic nephropathy (UAN) involves a systemic thromboinflammatory axis, yet the role of antithrombin (AT, SERPINC1) remains incompletely defined. While AT has anticoagulant and anti-inflammatory properties, whether it contributes to UAN as a disease-responsive molecular node remains uncertain. Methods: We integrated two-sample MR of serum urate and renal traits with complementary sensitivity analyses, cis-eQTL and pQTL analyses of SERPINC1, and exploratory transcriptomic, proteomic, metabolomic, and coexpression analyses. The available data were used to assess genetic associations and to distinguish genetic evidence from cross-dataset molecular patterns. Results: Genetically predicted serum urate showed positive or negative associations with BUN and eGFR, respectively, but the primary analyses showed substantial heterogeneity. Reverse-direction estimates were also associated with serum urate, representing reciprocal genetic relationships between related renal traits and urate rather than proof of a temporal feedback cycle. Available data did not demonstrate mediation through genetically predicted whole-blood SERPINC1 expression. Three deCODE cis-pQTL instruments gave inconsistent renal estimates: nominally lower BUN (β = −0.0290, p = 0.047), null eGFR (β = −0.0036, p = 0.472), and higher CKD risk (β = +0.3361, p = 0.020) with directional pleiotropy evidence. Exploratory multi-omics analyses showed higher PBMC SERPINC1 expression during acute gout and a nominal urinary proteomic difference that did not survive multiple-testing correction (FDR = 0.998). Conclusions: SERPINC1 is best interpreted as a responsive molecular feature requiring further validation, rather than as a demonstrated genetic mediator or renal-protective therapeutic target. The transcriptomic and urinary findings represent cross-dataset, stage-associated observations and should not be interpreted as proven sequential phases. Full article
(This article belongs to the Special Issue Genetic and Genomic Insights into the Pathogenesis of Kidney Disease)
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13 pages, 495 KB  
Article
Post-Acute Nasal Expression of ACE2, TMPRSS2, FURIN, and NRP1 in Relation to COVID-19 Severity: A Multicenter Cross-Sectional Study
by Ana María Piqueras-Sánchez, José Francisco López-Gil, Diego Hellín-Meseguer, Juan Cabezas-Herrera, Ginés Francisco Blesa-Llaona, José Meseguer-Cabezas, Enrique Bernal-Morell, Alfredo Minguela-Puras, Francisco Mateo Piqueras-Pérez and José Antonio Díaz-Manzano
Diagnostics 2026, 16(18), 2896; https://doi.org/10.3390/diagnostics16182896 - 9 Sep 2026
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Abstract
Background/Objectives: Host factors angiotensin-converting enzyme 2 (ACE2), transmembrane protease-serine 2 (TMPRSS2), furin paired basic amino acid cleaving enzyme (FURIN), and neuropilin-1 (NRP1) facilitate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry, but it is unclear whether their upper-airway expression after recovery is [...] Read more.
Background/Objectives: Host factors angiotensin-converting enzyme 2 (ACE2), transmembrane protease-serine 2 (TMPRSS2), furin paired basic amino acid cleaving enzyme (FURIN), and neuropilin-1 (NRP1) facilitate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry, but it is unclear whether their upper-airway expression after recovery is associated with the severity of the preceding acute illness. We examined the association between post-acute expression of these genes and previous coronavirus disease 2019 (COVID-19) severity. Methods: This multicenter cross-sectional study included 104 adults with polymerase chain reaction (PCR)-confirmed COVID-19 during the first two pandemic waves in Murcia, Spain. Nasal and/or oropharyngeal swabs were collected in the post-acute phase, at a median of 75 days after symptom onset, and transcript levels were quantified by quantitative real-time PCR. Severity was categorized using the World Health Organization (WHO) Clinical Progression Scale, and associations were evaluated using logistic regression adjusted for age, sex, and race/ethnicity. Results: In the primary analyses using continuous expression measures, none of the four genes was significantly associated with severity. In exploratory tertile-based analyses, the intermediate ACE2 tertile (odds ratio [OR] = 0.17, 95% confidence interval [CI] 0.05–0.61; p = 0.007) and intermediate NRP1 tertile (OR = 0.29, 95% CI 0.10–0.88; p = 0.030) were associated with lower odds of severe disease; no significant associations were observed for the high tertiles or for FURIN or TMPRSS2. Conclusions: Primary adjusted analyses did not reveal statistically significant associations between post-acute nasal expression of ACE2, TMPRSS2, FURIN, or NRP1 and COVID-19 severity. Because expression was measured after clinical recovery, these associations cannot be interpreted as predictors of acute severity and may instead reflect persistent molecular remodeling after more severe disease; reverse causation cannot be excluded. Longitudinal studies with acute-phase and serial post-acute sampling and healthy controls are needed. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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14 pages, 1795 KB  
Article
News Fluorescence-Based Polarization Immunoassays as a Frontline Test for the Rapid Detection of Acute and Late Phase Lyme-Borreliosis Disease
by Joao P. R. S. Carvalho, Monica E. T. Alcón-Chino, Paloma Napoleão-Pêgo, Guilherme C. Lechuga, Isis C. Prado, Mariana S. Freitas, Jessica A. Waterman, Karyne Rangel and Salvatore G. De-Simone
Molecules 2026, 31(18), 3152; https://doi.org/10.3390/molecules31183152 - 8 Sep 2026
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Abstract
Lyme borreliosis (LB) is a tick-borne disease caused by a diverse and expanding group of spirochetes characterized by complex biology and advanced immune evasion mechanisms. It presents a wide range of clinical symptoms affecting multiple organ systems and can lead to persistent complications. [...] Read more.
Lyme borreliosis (LB) is a tick-borne disease caused by a diverse and expanding group of spirochetes characterized by complex biology and advanced immune evasion mechanisms. It presents a wide range of clinical symptoms affecting multiple organ systems and can lead to persistent complications. The pathogenesis of LB remains incompletely understood, and diagnosis typically relies on serologic assays to detect antibodies against LB. However, the standard two-tiered testing (STTT) algorithm is limited by cross-reactivity, low sensitivity, and delayed results, hindering timely and accurate diagnosis. Although molecular tests are considered the gold standard, their reliance on centralized laboratories can delay critical treatment decisions. This underscores the urgent need for rapid, reliable diagnostic tools, particularly for use at the point of hospital admission. Point-of-care serological and direct antigen testing can provide actionable information, supporting decentralized healthcare systems in diagnosing complex diseases, such as LB. In this study, we developed two fluorescent polarization immunoassays (FPIAs) using IgM and IgG LB-specific synthetic epitopes/peptides to evaluate their diagnostic potential. These FPIAs showed high sensitivity and specificity in detecting IgM or IgG anti-LB antibodies in patient sera within minutes. The fluorescently labeled synthetic peptides produced significant polarization differences between infected and healthy samples, allowing clear discrimination. The FPIA-LB functions as a one-step assay, eliminating the need for secondary antibodies or complex protocols. This work highlights the FPIA technique as a robust, rapid, and efficient tool for LB diagnosis, offering a promising advance in improving early detection and patient outcomes, which could save lives and reduce long-term health complications. Full article
(This article belongs to the Special Issue Electrochemical Biosensors: From Design to Application, 2nd Edition)
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9 pages, 519 KB  
Article
Cognitive Outcomes in Pediatric Arteriovenous Malformation with Cerebral Hemorrhage: A Case Series
by Tomoko Uchida, Daisuke Matsuzawa, Ryo Tanabe, Kasumi Nagasawa, Mitsuko Ishii, Michiyo Ehara, Tadashi Shiohama and Hiromichi Hamada
Children 2026, 13(9), 1207; https://doi.org/10.3390/children13091207 - 7 Sep 2026
Viewed by 129
Abstract
Background: Arteriovenous malformation (AVM) is a leading cause of pediatric hemorrhagic stroke. While immediate management and short-term outcomes have been well-documented, research on long-term cognitive recovery after AVM hemorrhage remains limited, and outcomes are often difficult to predict. Methods: We report [...] Read more.
Background: Arteriovenous malformation (AVM) is a leading cause of pediatric hemorrhagic stroke. While immediate management and short-term outcomes have been well-documented, research on long-term cognitive recovery after AVM hemorrhage remains limited, and outcomes are often difficult to predict. Methods: We report the long-term cognitive recovery outcomes of 20 pediatric cases (12 boys, 8 girls) who underwent rehabilitation and cognitive function assessments during the recovery phase at our center following acute treatment for intracranial hemorrhage due to AVM. The mean age at onset was 11.0 ± 3.1 years (range: 6.3–16.6 years). The primary outcome was resumption of the premorbid educational trajectory, and we evaluated its relationship with the initial Full-Scale IQ (FIQ) recorded after onset. Results: Motor recovery was favorable (90% achieved independent walking), but cognitive outcomes were generally poor, with 60% exhibiting persistent dysfunction. Eight patients (40%) resumed their premorbid educational trajectory. Of the 8 patients whose FIQ reached 80 or above within the first 6 months post-onset, 6 (75%) subsequently resumed that trajectory, compared with 2 of the 12 patients whose early FIQ remained below 80 (odds ratio 15.0, 95% CI 1.65–136.2, p = 0.019; sensitivity 75%, specificity 83%). A normal-range FIQ was necessary but not sufficient: all 8 patients who resumed their premorbid trajectory reached an FIQ ≥ 80, yet 4 of the 12 patients who reached an FIQ ≥ 80 did not resume it. Conclusions: Although FIQ continued to improve for years in many patients, late gains were rarely sufficient to reach the normal range when the early assessment was low. Cognitive status in the early recovery phase was therefore associated with long-term educational continuity, and assessment within the first 6 months post-onset may inform planning without awaiting prolonged spontaneous recovery. Full article
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