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Is the freezing index a valid outcome to assess freezing of gait during turning in Parkinson's disease?
Full text linkIntroduction Freezing of gait (FOG) is a disabling symptom for people with Parkinson's disease (PwPD). Turning on the spot for one minute in alternating directions (360 turn) while performing a cognitive dual-task (DT) is a fast and sensitive way to provoke FOG. The FOG-index is a widely used wearable sensor-based algorithm to quantify FOG severity during turning. Despite that, the FOG-index's classification performance and criterion validity is not tested against the gold standard (i.e., video-rated time spent freezing). Therefore, this study aimed to evaluate the FOG-index's classification performance and criterion validity to assess FOG severity during 360 turn. Additionally, we investigated the FOG-index's optimal cutoff values to differentiate between PwPD with and without FOG. Results Twenty-eight patients self-reported FOG, while 104 were classified as a freezer by the experts. The FOG-index had limited classification agreement with the NFOGQ (AUC = 0.60, p = 0.115, sensitivity 46.4%, specificity 72.8%) and the experts (AUC = 0.65, p < 0.001, sensitivity 68.3%, specificity 61.7%). Only weak correlations were found between the algorithm outputs and expert ratings for FOG severity (rho = 0.13-0.38). Conclusion A surprisingly large discrepancy was found between self-reported and expert-rated FOG during the 360 turning task, indicating PwPD do not always notice FOG in daily life. The FOG-index achieved suboptimal classification performance and poor criterion validity to assess FOG severity. Regardless, 360 turning proved a sensitive task to elicit FOG. Further development of the FOG-index is warranted, and long-term follow-up studies are needed to assess the predictive value of the 360 turning task for classifying FOG conversion
Editorial: Time-series observations of ocean acidification: a key tool for documenting impacts on a changing planet
Full text linkEditorial on the Research Topic Time-series observations of ocean acidification: a key tool for documenting impacts on a changing planet Ocean acidification (OA) is a pressing global issue characterized by fundamental changes in ocean chemistry, including the reduction of pH levels, due to the absorption of increased atmospheric CO2. This phenomenon poses significant threats to marine ecosystems, affecting biodiversity, food security, and coastal economies. Time-series observations remain indispensable for documenting these changes, offering insights into the drivers and consequences of OA over temporal and spatial scales. This editorial summarizes the 17 studies in this Research Topic, highlighting the advancements in understanding OA dynamics and their broader implications
Comparison of 16S ribosomal RNA hypervariable regions in microbiome studies of anorexia nervosa
Full text linkIntroduction Short read sequencing of the 16S ribosomal RNA (rRNA) gene targeting specific hypervariable regions is widely employed to study the human gut microbiota. In these studies, the selection of particular 16S rRNA hypervariable regions is a crucial step. However, the results of such studies exhibit significant variability depending on the targeted hypervariable region. Methods In this study, we systematically evaluated the performance of hypervariable regions V1V2 and V3V4 in a longitudinal gut microbiome study of adolescent patients with anorexia nervosa (AN) and matched controls. Results The dominant genera, such as Bacteroides H, Faecalibacterium and Phocaeicola A 858004 were consistently detected in both hypervariable regions across timepoints. The within-sample longitudinal alpha diversity measures varied between the regions with the Chao1 index values being higher in the V1V2 region. The overall microbiome profiles based on beta diversity also differed between the regions. Bland-Altman analysis revealed a general lack of strong agreement between the two sequencing methods, except for a few taxa such as Faecalibacterium, Ruminococcus, Roseburia, Turicibacter and Anaerotruncus. While some results were similar across both hypervariable regions, most of the findings were sensitive to the chosen region. Conclusion This study underscores the importance of primer selection in microbiome studies of AN, as it can influence taxonomic resolution and diversity estimates along with downstream statistical analyses
Editorial: The multiple applications of marine-derived bioactives
Full text linkMarine biotechnology is a rapidly evolving field that focuses on the exploration and utilization of marine biological sources for development of products and services with societal benefits. The chemical constituents of marine organisms, especially secondary metabolites (i.e., marine natural products) that are designed for ecological functions in their ecosystems represent ideal candidates as drugs and other functional ingredients. However, despite the vast potential of marine biota, the ocean remains largely underexplored and undervalorized, presenting a significant opportunity for discovering alternative sources of drugs, agrochemicals, cosmeceuticals, nutraceuticals, bio-inspired materials and other industrially relevant chemical
The Effect of IL-17A and Combined Mechanical Injury on Meniscal Tissue Integrity In Vitro
Full text linkObjectives: Meniscal integrity is crucial for knee joint stability and the prevention of osteoarthritis (OA) development. Recent studies suggested that mechanical overload and interleukin (IL)-17A may be important intertwined players in meniscal degeneration, but a direct impact of IL-17A on the meniscus has not been investigated. Therefore, the aim of this study was to analyze the effect of IL-17A on meniscal tissue with and without combined mechanical injury (MI). After three days of incubation in a serum-free medium, the proteoglycan release (sGAG; DMMB assay), mRNA level of matrix-degrading enzymes (qRT-PCR), aggrecan degradation (NITEGE immunostaining), and cell death (histomorphometry of nuclear blebbing/apoptosis and condensed nuclei/unspecified cell death) were determined. Statistics: one- and two-way ANOVA with Tukey's multiple comparisons or Kruskal-Wallis with post hoc testing. [...] Signals for the ADAMTS4-related aggrecan neoepitope NITEGE were elevated by IL-17A in superficial areas of the excised tissue and by MI in superficial and deeper areas. The combination of both stimuli intensified this signal further. MI increased the number of cells with condensed nuclei significantly and induced apoptosis in a small proportion of cells. IL-17A had no significant impact on the amount of condensed or apoptotic nuclei. Conclusions: Our findings emphasize an interaction between inflammatory cytokine IL-17A signaling and mechanical stress since IL-17A induced matrix degeneration in meniscal tissue, which intensified in combination with a trauma. The latter might create a post-traumatic environment that promotes meniscal degeneration and subsequently osteoarthritis progression
Role of Lee Wave Turbulence in the Dispersion of Sediment Plumes
Full text linkSediment plumes threatening benthic ecosystems are one of the environmental hazards associated with seafloor interventions such as bottom trawling, cabling, dredging, and marine mining operations. This study focuses on sediment plume release from hypothetical future deep-sea mining activities, emphasizing its interaction with turbulent ocean currents in regions characterized by complex seafloor topography. In such environments, turbulent lee waves may significantly enhance the scattering of released sediments, pointing to the clear need for appropriate impact assessment frameworks. Global-scale models are limited in their ability to resolve sufficiently high Reynolds numbers to accurately represent turbulence generated by seafloor topography. To overcome these limitations and effectively assess lee wave dynamics, models must incorporate the full physics of turbulence without simplifying the Navier–Stokes equations and must operate with significantly finer spatial discretization while maintaining a domain large enough to capture the full topographic signal. Considering a seamount in the Lofoten Basin of the Norwegian Sea as an example, we present a novel numerical analysis that explores the interplay between lee wave turbulence and sediment plume dispersion using a high-resolution Large Eddy Simulation (LES) framework. We show that the turbulence occurs within semi-horizontal channels that emerge beyond the topographic highs and extend into sheet-like tails close to the seafloor. In scenarios simulating sediment release from various sites on the seamount, our model predicts distinct behavior patterns for different particle sizes. Particles with larger settling velocities tend to deposit onto the seafloor within 50–200 m of release sites. Conversely, particles with lower settling velocities are more susceptible to turbulent transport, potentially traveling greater distances while experiencing faster dilution. [...
Diagnostic Value of Opportunistic CT-Based Bone Density Assessment in Patients with and Without Sacral Insufficiency Fractures
Full text linkBackground/Objectives: This retrospective observational cohort examined whether opportunistic CT-derived Hounsfield units (HU) of the lumbar spine and proximal femur together with serum 25-OH-vitamin D can predict sacral insufficiency fractures (SIF) and osteoporosis. No interventional procedures were performed. Methods: Consecutive suspected SIF cases over 3 years (n = 253) were assigned to SIF (n = 98) or controls without SIF or spine/hip fractures (n = 155). HU were measured using ellipsoidal ROIs at L1-L3 and an irregular area ROI across the entire proximal femoral cancellous bone; vitamin D was quantified; ROC analyses assessed discrimination. HU cut-points were referenced via HU-to-QCT/CTXA conversions. Results: SIF patients had markedly lower HU than controls (lumbar 44.84 vs. 105.66 HU; femoral 47.0 vs. 148.0 HU). Diagnostic performance was excellent (AUC 0.98 for SIF discrimination using lumbar HU; AUC 0.98 for osteoporosis prediction using femoral HU). Vitamin D deficiency (<20 ng/mL) was highly prevalent (92.9%) with lower means in SIF (3.72 vs. 8.24 ng/mL). Within SIF, patients with hip fracture had femoral HU ≈ 14.2 vs. 70.6 without hip fracture; effect sizes were very large. Conclusions: Opportunistic HU assessment from routine CT provides a rapid, reproducible surrogate of bone density that distinguishes SIF with near-perfect accuracy and identifies osteoporosis. HU thresholds around ~96-98 are consistent with osteoporotic ranges and can be implemented to trigger metabolic evaluation and early osteoanabolic therapy where appropriate
The Potential of Artificial Intelligence to Improve Selection Criteria for Liver Transplantation in HCC
Full text linkSurvival in hepatocellular carcinoma (HCC) remains poor despite advances in therapy. Liver transplantation (LT) offers the best curative option, as it removes both the tumor and the underlying liver disease. However, due to the shortage of donor organs, patient selection and oncologic prognosis are crucial for fair organ allocation. While macrovascular invasion and extrahepatic spread are established contraindications, microvascular invasion and poor tumor differentiation have also emerged as negative prognostic factors. Current LT selection criteria mainly rely on simple imaging parameters such as tumor size and number, neglecting deeper imaging features. Recent studies have highlighted the potential of artificial intelligence (AI) and deep-learning methods for detecting aggressive tumor characteristics like microvascular invasion or poor differentiation—offering a “virtual biopsy.” Moreover, assessing tumor response to transarterial chemoembolization (TACE) may help predict post-transplant survival. This review summarizes diagnostic innovations and their potential impact on organ allocation in HCC
Incidence of Post-Procedural Conduction Disturbances and Rates of Permanent Pacemaker Implantation in Older and Newer Generations of Transcatheter Aortic Heart Valves
Full text linkObjective: This analysis compares new (G2) versus old (G1) generations of transcatheter heart valves (THVs) in transcatheter aortic valve replacement (TAVR) procedures, focusing on key outcomes: post-procedural conduction disturbance (CD) and permanent pacemaker implantation (PPMI). We aim to determine whether G2 valves reduce these specific complications and thereby improve patient outcomes compared with G1. Methods: From February 2015 to September 2022, 1468 patients underwent TAVR at the university clinic in Kiel. After applying exclusion criteria, a final cohort of 1182 patients were analysed. Among these, 782 patients underwent TAVR with G1, whereas 400 underwent TAVR with G2. The primary study endpoints were the occurrence of new CD and PPMI within 30 days post-procedure. The secondary endpoints included diverse post-TAVR events as defined by the safety criteria of Valve Academic Research Consortium 3 (VARC III). A statistical analysis compared outcomes between the G1 and G2 groups. Results: Out of 1182 patients, 12.1% required PPMI within 30 days. Rates showed no statistical difference between G2 and G1 for PPMI (10.3% vs. 13.0%, IPTW-weighted p = 0.31) or CD (15.3% vs. 21.48%, IPTW-weighted p = 0.08). Among G2, the Sapien 3 Ultra valve had the lowest PPMI rate (4.8%). Overall, G2 and G1 had similar post-procedural and 30-day mortality rates. Conclusion: G2 valves may reduce post-procedure CD, but the difference is not statistically significant. Differences between specific valve types—such as the Sapien 3 Ultra’s lower rates—are notable, but overall, PPMI and safety profiles remain similar between G1 and G2. Patient and procedural factors still play a significant role. Careful valve and patient selection is essential, and ongoing research will guide further improvements
Störung der hippocampalen Musterkomplettierung bei Patienten mit einer Multiplen Sklerose
Full text linkNeurokognitive Defizite lassen sich bei zahlreichen Multiple Sklerose Patienten beobachten. Einschränkungen des Gedächtnisses können unter anderem auf Schädigungen im Bereich des Hippocampus zurückgeführt werden. Dieser verhindert durch den Prozess der Musterseparation das überlappende Einspeichern ähnlicher Erinnerungen und gewährleistet gleichzeitig durch die Musterkomplettierung das Abrufen ganzheitlicher Erinnerungen aus Teilaspekten der ursprünglichen Erinnerung. Bereits gezeigt werden konnte eine Beeinträchtigung der Musterseparation bei Multiple Sklerose Patienten, inwieweit jedoch die Musterkomplettierung bei einer Erkrankung eine Mitbeteiligung aufweist, ist unklar. Das Ziel dieser Arbeit war es, die hippocampale Funktion und speziell die Musterkomplettierung bei Multiple Sklerose Patienten sowie etwaige Korrelate in der Bildgebung zu untersuchen. Dafür wurde bei 72 Multiple Sklerose Patienten und 72 gesunden Kontrollprobanden die Musterkomplettierung anhand des Memory Image Completion Task (MIC) erfasst. Mithilfe der Magnetresonanztomographie wurden die Läsionslast sowie das Hirnvolumen bestimmt. Die Musterkomplettierung war im gesamten Patientenkollektiv nicht signifikant eingeschränkt, jedoch wiesen die zum Zeitpunkt der Testungen bereits kognitiv beeinträchtigten Patienten Defizite in der Musterkomplettierung auf. Ein Zusammenhang mit der Musterkomplettierung konnte darüber hinaus für die Läsionslast und das Hirnvolumen beobachtet werden. Diese Ergebnisse sprechen für eine Störung der hippocampalen Kognition und der Musterkomplettierung bei Multiple Sklerose Patienten, die vor allem bei bereits bestehenden Kognitionseinschränkungen zu Tage tritt und mit strukturellen Schädigungen im Gehirn einhergeht