Hadronic vacuum polarization contribution to the muon g−2g-2 in holographic QCD

We evaluate the leading-order hadronic vacuum polarization contribution to the anomalous magnetic moment of the muon with two light flavors in minimal hard-wall and soft-wall holographic QCD models, as well as in simple generalizations thereof, and compare with the rather precise results available from dispersive and lattice approaches. While holographic QCD cannot be expected to shed light on the existing small discrepancies between the latter, this comparison in turn provides useful information on the holographic models, which have been used to evaluate hadronic light-by-light contributions where errors in data-driven and lattice approaches are more sizable. In particular, in the hard-wall model that has recently been used to implement the Melnikov-Vainshtein short-distance constraint on hadronic light-by-light contributions, a matching of the hadronic vacuum polarization to the data-driven approach points to the same correction of parameters that has been proposed recently in order to account for next-to-leading order effects.Comment: REVTEX, 18 pages, 3 figures, 3 tables; v2: references adde

Two-Loop Infrared Renormalization with On-shell Methods

Within the framework proposed by Caron-Huot and Wilhelm, we give a recipe for computing infrared anomalous dimensions purely on-shell, efficiently up to two loops in any massless theory. After introducing the general formalism and reviewing the one-loop recipe, we extract a practical formula that relates two-loop infrared anomalous dimensions to certain two- and three-particle phase space integrals with tree-level form factors of conserved operators. We finally provide several examples of the use of the two-loop formula and comment on some of its formal aspects, especially the cancellation of `one-loop squared' spurious terms.Comment: 12 pages, 3 figure

Melatonin Moderates the Triangle of Chronic Pain, Sleep Architecture and Immunometabolic Traffic

Preclinical as well as human studies indicate that melatonin is essential for a physiological sleep state, promotes analgesia and is involved in immunometabolic signaling by regulating neuroinflammatory pathways. Experimental and clinical neuromodulation studies for chronic pain treatment suggest that neurostimulation therapies such as spinal cord stimulation, vagus nerve stimulation and dorsal root ganglion stimulation have an impact on circulating inflammatory mediators in blood, cerebrospinal fluid and saliva. Herein, we provide an overview of current literature relevant for the shared pathways of sleep, pain and immunometabolism and elaborate the impact of melatonin on the crossroad of sleep, chronic pain and immunometabolism. Furthermore, we discuss the potential of melatonin as an adjunct to neurostimulation therapies. In this narrative review, we addressed these questions using the following search terms: melatonin, sleep, immunometabolism, obesity, chronic pain, neuromodulation, neurostimulation, neuroinflammation, molecular inflammatory phenotyping. So far, the majority of the published literature is derived from experimental studies and studies specifically assessing these relationships in context to neurostimulation are sparse. Thus, the adjunct potential of melatonin in clinical neurostimulation has not been evaluated under the umbrella of randomized-controlled trials and deserves increased attention as melatonin interacts and shares pathways relevant for noninvasive and invasive neurostimulation therapies

Prediction of the Topography of the Corticospinal Tract on T1-Weighted MR Images Using Deep-Learning-Based Segmentation

Introduction: Tractography is an invaluable tool in the planning of tumor surgery in the vicinity of functionally eloquent areas of the brain as well as in the research of normal development or of various diseases. The aim of our study was to compare the performance of a deep-learning-based image segmentation for the prediction of the topography of white matter tracts on T1-weighted MR images to the performance of a manual segmentation. Methods: T1-weighted MR images of 190 healthy subjects from 6 different datasets were utilized in this study. Using deterministic diffusion tensor imaging, we first reconstructed the corticospinal tract on both sides. After training a segmentation model on 90 subjects of the PIOP2 dataset using the nnU-Net in a cloud-based environment with graphical processing unit (Google Colab), we evaluated its performance using 100 subjects from 6 different datasets. Results: Our algorithm created a segmentation model that predicted the topography of the corticospinal pathway on T1-weighted images in healthy subjects. The average dice score was 0.5479 (0.3513–0.7184) on the validation dataset. Conclusions: Deep-learning-based segmentation could be applicable in the future to predict the location of white matter pathways in T1-weighted scans

Immunometabolic Profiling of Chronic Subdural Hematoma through Untargeted Mass Spectrometry Analysis: Preliminary Findings of a Novel Approach

Objective: Metabolomics has growing importance in the research of inflammatory processes. Chronic subdural hematoma (cSDH) is considered to be, at least in part, of inflammatory nature, but no metabolic analyses yet exist. Therefore, a mass spectrometry untargeted metabolic analysis was performed on hematoma samples from patients with cSDH. Methods: A prospective analytical cross-sectional study on the efficacy of subperiosteal drains in cSDH was performed. Newly diagnosed patients had the option of granting permission for the collection of a hematoma sample upon its removal. The samples were analyzed using liquid chromatography–mass spectrometry to obtain different types of metabolites from diverse biochemical classes. The statistical analysis included data cleaning, imputation, and log transformation, followed by PCA, PLS-DA, HCA, and ANOVA. The postoperative course of the disease was followed for 3 months. The metabolite concentrations in the hematoma fluid were compared based on whether a recurrence of the disease was recorded within this time frame. Results: Fifty-nine samples from patients who were operated on because of a cSDH were gathered. Among those, 8 samples were eliminated because of missing metabolites, and only 51 samples were analyzed further. Additionally, 39 samples were from patients who showed no recurrence over the course of a 3-month follow-up, and 12 samples were from a group with later recurrence. We recorded a noticeable drop (35%) in the concentration of acylcarnitines in the ”recurrence group“, where 10 of the 22 tested metabolites showed a significant reduction (p &lt; 0.05). Furthermore, a noticeable reduction in different Acyl-CoA-dehydrogenases was detected (VLCAD-deficiency p &lt; 0.05, MCAD-deficiency p = 0.07). No further changes were detected between both populations. Conclusions: The current study presents a new approach to the research of cSDH. The measurements presented us with new data, which, to date, are without any reference values. Therefore, it is difficult to interpret the information, and our conclusions should be considered to be only speculative. The results do, however, point in the direction of impaired fatty acid oxidation for cases with later recurrence. As fatty acid oxidation plays an important role in inflammatory energy metabolism, the results suggest that inflammatory processes could be aggravated in cases with recurrence. Because our findings are neither proven through further analyses nor offer an obvious therapy option, their implications would not change everyday practice in the management of cSDH. They do, however, present a further possibility of research that might, in the future, be relevant to the therapy.</jats:p

Physiological MRI Biomarkers in the Differentiation Between Glioblastomas and Solitary Brain Metastases

Purpose Glioblastomas (GB) and solitary brain metastases (BM) are the most common brain tumors in adults. GB and BM may appear similar in conventional magnetic resonance imaging (cMRI). Their management strategies, however, are quite different with significant consequences on clinical outcome. The aim of this study was to evaluate the usefulness of a previously presented physiological MRI approach scoping to obtain quantitative information about microvascular architecture and perfusion, neovascularization activity, and oxygen metabolism to differentiate GB from BM. Procedures Thirty-three consecutive patients with newly diagnosed, untreated, and histopathologically confirmed GB or BM were preoperatively examined with our physiological MRI approach as part of the cMRI protocol. Results Physiological MRI biomarker maps revealed several significant differences in the pathophysiology of GB and BM: Central necrosis was more hypoxic in GB than in BM (30 %; P = 0.036), which was associated with higher neovascularization activity (65 %; P = 0.043) and metabolic rate of oxygen (48 %; P = 0.004) in the adjacent contrast-enhancing viable tumor parts of GB. In peritumoral edema, GB infiltration caused neovascularization activity (93 %; P = 0.018) and higher microvascular perfusion (30 %; P = 0.022) associated with higher tissue oxygen tension (33 %; P = 0.020) and lower oxygen extraction from vasculature (32 %; P = 0.040). Conclusion Our physiological MRI approach, which requires only 7 min of extra data acquisition time, might be helpful to noninvasively distinguish GB and BM based on pathophysiological differences. However, further studies including more patients are required

Patients with Acute Limb Ischemia Might Benefit from Endovascular Therapy—A 17-Year Retrospective Single-Center Series of 985 Patients

Acute lower limb ischemia (ALI) is a common vascular emergency, requiring urgent revascularization by open or endovascular means. The aim of this retrospective study was to evaluate patient demographics, treatment and periprocedural variables affecting the outcome in ALI patients in a consecutive cohort in a tertiary referral center. Primary outcome events (POE) were 30-day (safety) and 180-day (efficacy) combined mortality and major amputation rates, respectively. Secondary outcomes were perioperative medical and surgical leg-related complications and the 5-year combined mortality and major amputation rate. Statistical analysis used descriptive and uni- and multivariable Cox regression analysis. In 985 patients (71 ± 9 years, 56% men) from 2004 to 2020, the 30-day and 180-day combined mortality and major amputation rates were 15% and 27%. Upon multivariable analysis, older age (30 d: aHR 1.17; 180 d: 1.27) and advanced Rutherford ischemia stage significantly worsened the safety and efficacy POE (30 d: TASC IIa aHR 3.29, TASC IIb aHR 3.93, TASC III aHR 7.79; 180 d: TASC IIa aHR 1.97, TASC IIb aHR 2.43, TASC III aHR 4.2), while endovascular treatment was associated with significant improved POE after 30 days (aHR 0.35) and 180 days (aHR 0.39), respectively. Looking at five consecutive patient quintiles, a significant increase in endovascular procedures especially in the last quintile could be observed (17.5% to 39.5%, p < 0.001). Simultaneously, the re-occlusion rate as well as the number of patients with any previous revascularization increased. In conclusion, despite a slightly increasing early re-occlusion rate, endovascular treatment might, if possible, be favorable in ALI treatment

Magnetic resonance imaging biomarkers for clinical routine assessment of microvascular architecture in glioma

Knowledge about the topological and structural heterogeneity of the microvasculature is important for diagnosis and monitoring of glioma. A vessel caliber and type-dependent temporal shift in the magnetic resonance imaging signal forms the basis for vascular architecture mapping. This study introduced a clinically feasible approach for assessment of vascular pathologies in gliomas using vascular architecture mapping. Sixty consecutive patients with known or suspected gliomas were examined using vascular architecture mapping as part of the routine magnetic resonance imaging protocol. Maps of microvessel radius and density, which adapted to the vasculature-dependent temporal shift phenomenon, were calculated using a costume-made software tool. Microvessel radius and density were moderately to severely elevated in a heterogeneous, inversely correlated pattern within high-grade gliomas. Additionally, three new imaging biomarkers were introduced: Microvessel type indicator allowing differentiation between supplying arterial and draining venous microvasculature in high-grade gliomas. Vascular-induced bolus peak time shift may presumably be sensitive for early neovascularization in the infiltration zone. Surprisingly, curvature showed significant changes in peritumoral vasogenic edema which correlated with neovascularization in the tumor core of high-grade gliomas. These new magnetic resonance imaging biomarkers give insights into complexity and heterogeneity of vascular changes in glioma; however, histological validations in more well-defined patient populations are required

The Diagnostic and Therapeutic Role of Leptin and Its Receptor ObR in Glioblastoma Multiforme

Leptin has been recognized as a potential tumor growth promoter in various cancers including cranial tumor pathologies such as pituitary adenomas, meningiomas and gliomas. Despite recent advances in adjunctive therapy and the established surgical resection, chemo- and radiotherapy regimen, glioblastoma multiforme remains a particular diagnostic and therapeutic challenge among the intracranial tumor pathologies, with a poor long-term prognosis. Systemic inflammation and immune-metabolic signaling through diverse pathways are thought to impact the genesis and recurrence of brain tumors, and glioblastoma multiforme in particular. Among the various circulating mediators, leptin has gained especial diagnostic and therapeutic interest, although the precise relationship between leptin and glioblastoma biology remains largely unknown. In this narrative review (MEDLINE/OVID, SCOPUS, PubMed and manual searches of the bibliographies of known primary and review articles), we discuss the current literature using the following search terms: leptin, glioblastoma multiforme, carcinogenesis, immunometabolism, biomarkers, metformin, antidiabetic medication and metabolic disorders. An increasing body of experimental evidence implicates a relationship between the development and maintenance of gliomas (and brain tumors in general) with a dysregulated central and peripheral immune-metabolic network mediated by circulating adipokines, chemokines and cellular components, and in particular the leptin adipokine. In this review, we summarize the current evidence of the role of leptin in glioblastoma pathophysiology. In addition, we describe the status of alternative diagnostic tools and adjunctive therapeutics targeting leptin, leptin-receptors, antidiabetic drugs and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanism of action and the value of immune-metabolism molecular phenotyping (central and peripheral) in order to develop novel adjunctive diagnostics and therapeutics for newly diagnosed and recurrent glioblastoma patients

Treatment with Cyclic AMP Activators Reduces Glioblastoma Growth and Invasion as Assessed by Two-Photon Microscopy

(1) Background: Despite progress in surgery and radio-chemotherapy of glioblastoma (GB), the prognosis remains very poor. GB cells exhibit a preference for hypoxia to maintain their tumor-forming capacity. Enhancing oxidative phosphorylation—known as the anti-Warburg effect—with cyclic AMP activators has been demonstrated to drive GB cells from proliferation to differentiation thereby reducing tumor growth in a cell culture approach. Here we re-evaluate this treatment in a more clinically relevant model. (2) Methods: The effect of treatment with dibutyryl cyclic AMP (dbcAMP, 1 mM) and the cAMP activator forskolin (50µM) was assessed in a GB cell line (U87GFP+, 104 cells) co-cultured with mouse organotypic brain slices providing architecture and biochemical properties of normal brain tissue. Cell viability was determined by propidium-iodide, and gross metabolic effects were excluded in the extracellular medium. Tumor growth was quantified in terms of area, volume, and invasion at the start of culture, 48 h, 7 days, and 14 days after treatment. (3) Results: The tumor area was significantly reduced following dbcAMP or forskolin treatment (F2,249 = 5.968, p = 0.0029). 3D volumetric quantification utilizing two-photon fluorescence microscopy revealed that the treated tumors maintained a spheric shape while the untreated controls exhibited the GB typical invasive growth pattern. (4) Conclusions: Our data demonstrate that treatment with a cAMP analog/activator reduces GB growth and invasion