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Purpose: Hydrocephalus presents diagnostic and management challenges due to its heterogeneity. The ASPECT Hydrocephalus System, introduced in 2023, offers a comprehensive approach to describing patients with hydrocephalus. This study investigates the clinical applicability of the ASPECT Hydrocephalus System compared to the International Classification of Disease (ICD-10) and demonstrates its utility., Methods: Two hundred pediatric and adult patients with hydrocephalus treated at Copenhagen University Hospital between September 2019 and 2020 were described according to the ASPECT Hydrocephalus System. The latest brain imaging served as assessment point., Results: Forty-seven percent of patients had more than one ICD-10 code assigned, and 40.5% of patients had an unspecific ICD-10 code as the most recent. It was possible to apply factor A (anatomy), S (symptomatology), P (previous interventions), C (complications) and T (time of onset) to all patients. Factor E (etiology) categorized 15% of patients as 'unknown'. Combining factor A and S showed a similar incidence of acute high-pressure symptoms in patients with and without ventriculomegaly on imaging (39.7% vs 39.3%), demonstrating how symptoms and neuro-radiological findings do not necessarily correlate., Conclusion: The ASPECT Hydrocephalus System's applicability and utility were demonstrated in a large, diverse patient population. Except for 'Etiology', all factors could be applied to the entire population showing the system's robustness. While limitations in ICD-10 may force clinicians to choose between clinical measures, the ASPECT Hydrocephalus System allows comprehensive patient characterization, potentially aiding in clinical decision-making and research. Its use depends on registration quality. Application in prospective cohorts is warranted to assure feasibility., (© 2024. The Author(s).)

Background Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction in patients with liver cirrhosis and recurrent symptoms of portal hypertension is primarily assessed with US and confirmed with invasive catheter venography, which can be used to measure the portosystemic pressure gradient (PSPG) to identify TIPS-refractory portal hypertension. To avoid the risks and costs of invasive catheter venography, noninvasive PSPG evaluation strategies are needed. Purpose To demonstrate the feasibility of the combination of four-dimensional (4D) flow MRI with computational fluid dynamics (CFD) for noninvasive PSPG assessment in participants with cirrhosis and TIPS. Materials and Methods Abdominal 4D flow MRI was performed prospectively in participants with cirrhosis and TIPS between January 2019 and September 2020. Flow rates were measured within the TIPS and inferior vena cava (IVC). The portal vein (PV), TIPS, right hepatic vein, and IVC were segmented on MRI scans to create a CFD mesh. The PV and infrahepatic IVC were defined as inflows for 4D flow MRI-derived flow rates. The suprahepatic IVC was defined as the outflow. CFD simulations were used to noninvasively estimate PSPG as the difference between the simulated pressures in the PV and suprahepatic IVC. Invasive venographic measurements of the PSPG served as the reference standard, and Pearson correlation analysis was conducted to evaluate the relationship between noninvasive estimates and invasive measurements. Results In all 20 participants with cirrhosis (mean age, 58 years ± 9 [SD]; 11 men), 4D flow MRI-based CFD simulations enabled visualization of flow velocities and pressure distributions within the segmented vasculature and TIPS. Noninvasive estimates and invasive measures of PSPG were strongly correlated ( r = 0.77; P < .001). The 4D flow MRI-based CFD simulations correctly classified the presence or absence of a post-TIPS PSPG greater than 12 mm Hg in 16 of 20 participants (80%). Conclusion The combination of 4D flow MRI and CFD was feasible for noninvasive PSPG assessment in participants with cirrhosis, portal hypertension, and TIPS. © RSNA, 2024 See also the editorial by Motosugi and Watanabe in this issue.

Objectives: Optic neuritis is a common clinical presentation in patients suffering from multiple sclerosis (MS). Even though optic neuritis is not part of the MS diagnostic criteria, the diagnosis and consideration of differential diagnoses are important in clinical routine. For the evaluation of the optic nerves with MRI, T2-weighted images with fat suppression, known as short tau inversion recovery sequences (STIR), are often used. Besides that, double inversion recovery (DIR) sequences are being used increasingly in MS patients, especially to determine cortical lesions. The Aim of this study was to evaluate the 3D-DIR for the detection of lesions in the optic nerves in MS patients., Methods: MR examinations of 45 MS-patients containing both STIR and DIR images were independently assessed by two neuroradiologic experienced radiologists, blinded to clinical data. A third neuroradiologic, an experienced radiologist, evaluated the images together, also considering clinical data. These results were considered ground truth and statistically compared to the results of the single readings. To objectify our findings, ROI measurements of affected and unaffected optic nerve segments were made, and a contrast ratio (CR) was calculated., Result: DIR images are statistically equivalent to STIR images concerning the detection of lesions in the optic nerve (p < 0.001). The sensitivity of DIR images (84.7 %) and STIR images (77 %), as well as the specificity (92.2 % and 91.2 %), are comparable. The interrater reliability was substantial for both sequences (κ = 0,73) as well as separated for the STIR images (κ = 0.744) and the DIR images (κ = 0.707). The objective analysis revealed significantly higher CRs in DIR images (p < 0.001)., Conclusion: 3D DIR images showed similar sensitivity and specificity for detecting optic nerve lesions in comparison to dedicated 2D images of the optic nerve. When 3D DIR images are part of the routine scan protocol for evaluating MS patients, additional 2D imaging of the optic nerve is no longer necessary., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The French healthcare system has been affected by the COVID-19 pandemic in 2020, including cancer care., Methods: In order to evaluate the impact of this pandemic on cancer incidence, the Isere Departmental Cancer Registry compared the actual 2020 incidence of melanoma, breast, colorectal, prostate and lung cancers with the expected 2020 incidence based on data collected by the Registry between 2015 and 2019, taking into account periods of lockdown and reopening. When available, cancer stages and/or prognostic scores were recorded., Results: During the period of initial confinement, a 54%, 50% and 36,8% drop in incidence was observed for breast, prostate and colorectal cancer respectively. Although their annual incidence remained stable, a worsening trend emerged as a decline in the number of low stages/scores at diagnosis in favour of higher stages/scores towards the end of 2020. In contrast, a significant 17,8% drop was observed in annual incidence of melanoma, particularly for Breslow scores < 1 (-27,4%). However, this trend was noticeable before the lockdown, as well as the 14% reduction in the incidence of lung cancer in women, but not in men., Conclusion: The incidence of certain cancers was caught up over the year but the COVID-19 pandemic seems to be associated with a change in their severity at diagnosis throughout 2020. The downward trends in female lung cancer and melanoma incidence point to complex underlying phenomena. Further analysis is still needed to assess the global impact of the COVID-19 pandemic on cancer incidence., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: 4D flow MRI-derived variables from Marfan patients are highly heterogeneous. Our aim was to identify distinct Marfan patient subgroups based on aortic 4D flow MRI and Z-score for stratification of distinct hemodynamic profiles and clinical features by means of hierarchical cluster analysis., Materials and Methods: One hundred Marfan patients underwent baseline aortic 4D flow MRI at 3 T. Z-scores, degree of helical and vortical flow, wall shear stress, flow displacement, and peak velocity were determined in the ascending aorta. Sex, age, BMI, antihypertensive medication, and dural ectasia were recorded. Hierarchical cluster analysis was performed using 4D flow MRI variables and Z-scores as input., Results: Cluster analysis resulted in three distinct clusters characterized by different Z-scores (mean ± SD); cluster 1: 0.4 ± 1.1 vs. cluster 2: 3.1 ± 1.1 vs. cluster 3: 3.6 ± 1.9. The three clusters delivered differences in helical and vortical flow patterns (global p = 0.003 and p < 0.001, respectively), wall shear stress (0.49 ± 0.11 vs. 0.44 ± 0.12 vs. 0.37 ± 0.09 N/m 2 , global p < 0.001), flow displacement (0.11 ± 0.05 vs. 0.16 ± 0.08 vs. 0.15 ± 0.07, global p = 0.006), and peak velocity (76.3 ± 9.0 vs. 60.1 ± 7.3 vs. 56.0 ± 7.8 cm/s, global p < 0.001). Patients in cluster 1 and 2 were relevantly younger than in cluster 3 (32.3 ± 13.8 vs. 32.8 ± 12.6 vs. 40.2 ± 15.0 years, all pairwise ∆p < 0.0297)., Conclusion: Hierarchical cluster analysis based on aortic 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients, each characterized by specific hemodynamic profiles and clinical features. Follow-up of our patients is warranted to assess if 4D flow MRI- and Z-score-based stratification can predict future aortic diameter growth and ultimately improve outcomes., Clinical Relevance Statement: A combination of Z-score and 4D flow MRI-derived parameters may help identify subgroups of Marfan patients representing different stages or phenotypes of aortic disease, which require specific management strategies., Key Points: Four-dimensional (4D) flow MRI-derived variables of Marfan patients are highly heterogeneous across varying Z-scores. Cluster analysis based on 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients. A combination of Z-score and 4D flow MRI-derived parameters may identify different stages of aortic disease in Marfan patients., (© 2024. The Author(s).)

Purpose: This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic., Methods: A survey was conducted at German study sites participating in the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS). Hospitals certified by the German Society of Infectious diseases (DGI) were identified as ID centers. We compared care provision and the involvement of ID specialists between ID and non-ID hospitals. Then we applied a multivariable regression model to analyse how clinical ID care influenced the mortality of COVID-19 patients in the LEOSS cohort., Results: Of the 40 participating hospitals in the study, 35% (14/40) were identified as ID centers. Among those, clinical ID care structures were more commonly established, and ID specialists were always involved in pandemic management and the care of COVID-19 patients. Overall, 68% (27/40) of the hospitals involved ID specialists in the crisis management team, 78% (31/40) in normal inpatient care, and 80% (28/35) in intensive care. Multivariable analysis revealed that COVID-19 patients in ID centers had a lower mortality risk compared to those in non-ID centers (odds ratio: 0.61 (95% CI 0.40-0.93), p = 0.021)., Conclusion: ID specialists played a crucial role in pandemic management and inpatient care., (© 2024. The Author(s).)

Pulsed light (PL) inactivates microorganisms by UV-rich, high-irradiance and short time pulses (250 μs) of white light with wavelengths from 200 nm to 1100 nm. PL is applied for disinfection of food packaging material and food-contact equipment. Spores of seven Bacillus ssp. strains and one Geobacillus stearothermophilus strain and conidia of filamentous fungi (One strain of Aspergillus brasiliensis, A. carbonarius and Penicillium rubens) were submitted to PL (fluence from 0.23 J/cm 2 to 4.0 J/cm 2 ) and UVC (at λ = 254 nm; fluence from 0.01 J/cm 2 to 3.0 J/cm 2 ). One PL flash at 3 J/cm 2 allowed at least 3 log-reduction of all tested microorganisms. The emetic B. cereus strain F4810/72 was the most resistant of the tested spore-forming bacteria. The PL fluence to 3 log-reduction (F 3 PL ) of its spores suspended in water was 2.9 J/cm 2 and F 3 UVC was 0.21 J/cm 2 , higher than F 3 PL and F 3 UVC of spores of B. pumilus SAFR-032 2.0 J/cm 2 and 0.15 J/cm 2 , respectively), yet reported as a highly UV-resistant spore-forming bacterium. PL and UVC sensitivity of bacterial spores was correlated. Aspergillus spp. conidia suspended in water were poorly sensitive to PL. In contrast, PL inactivated Aspergillus spp. conidia spread on a dry surface more efficiently than UVC. The F 2 PL of A. brasiliensis DSM1988 was 0.39 J/cm 2 and F 2 UVC was 0.83 J/cm 2 . The resistance of spore-forming bacteria to PL could be reasonably predicted from the knowledge of their UVC resistance. In contrast, the sensitivity of fungal conidia to PL must be specifically explored., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Endovascular treatment (ET) options for acute stroke due to distal middle cerebral artery occlusions are rapidly evolving, but data on outcome and safety are sparse. We therefore performed an analysis of patients undergoing ET for primary M3 occlusions in routine clinical practice in a nationwide registry., Methods: Patients enrolled between 01/20 and 12/21 in the prospective, multicenter German Stroke Registry-Endovascular Treatment (GSR-ET) were screened for mechanical thrombectomy performed for primary M3 occlusion. We analyzed neurological deficit as measured by the National Institute of Health Stroke Scale (NIHSS), symptomatic intracranial hemorrhage (sICH), thrombectomy technique, successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3) and functional outcome as measured by the modified Rankin Scale (mRS) at discharge and 90 days., Results: Out of 5574 patients, 11 patients (0.2%, median age 80 years, 54.5% female) underwent ET for primary M3 occlusion. All patients had pre-admission mRS ≤ 1, median NIHSS on admission was 8, and successful reperfusion was achieved in 6/11 patients (54.5%). While no vasospasm, dissection or perforation was reported, symptomatic intracranial hemorrhage occurred in 2 patients (18.2%). Favorable outcome (mRS ≤ 2) was achieved in 6/11 patients (54.5%) at 90-day follow-up., Conclusions: ET for primary M3 occlusions is rarely performed. While technically feasible, the procedure's potential benefits must be carefully weighed against its associated risks, including clinically relevant complications. Caution and further research is needed to optimize patient selection for this intervention., Trial Registration: GSR-ET; ClinicalTrials.gov Identifier: NCT03356392; Trial Registration Date: 11/29/2017., (© 2024. The Author(s).)

White lupin (Lupinus albus L.) is a high-protein grain legume alternative to soybean in Central Europe, but its cultivation is risky due to the fungal disease anthracnose that can cause severe yield damage. In addition, management of seed alkaloids is critical for human nutrition and animal feed. We report on a white lupin collection of genebank accessions, advanced breeding lines and cultivars that was genotyped and phenotypically characterized for anthracnose resistance and seed alkaloids and protein levels. Using genotyping by sequencing (GBS), SeqSNP-targeted GBS, BiomarkX genotyping and Sanger sequencing, a genetic resource of genome-wide SNPs for white lupin was established. We determined anthracnose resistance in two years field trials at four locations with infection rows and measured seed alkaloids and protein levels by near-infrared spectroscopy (NIRS). Few white lupin breeding lines showed anthracnose resistance comparable or better than Celina and Frieda, currently the best commercial cultivars in Germany. NIRS estimates for seed alkaloids and protein levels revealed variation in the white lupin collection. Using genome-wide association studies (GWAS), we identified SNPs significantly associated with anthracnose resistance in the field representing known and new genomic regions. We confirmed the pauper locus and detected new SNP markers significantly associated with seed alkaloids. For the first time, we present loci associated with total grain protein content. Finally, we tested the potential of genomic prediction (GP) in predicting the phenotype of these three quantitative traits. Application of results and resources are discussed in the context of fostering breeding programs for white lupin., (© 2024. The Author(s).)

Pestiviruses, within the family Flaviviridae, are economically important viruses of livestock. In recent years, new pestiviruses have been reported in domestic animals and non-cloven-hoofed animals. Among them, atypical porcine pestivirus (APPV) and Norway rat pestivirus (NRPV) have relatively little sequence conservation in their surface glycoprotein E2. Despite E2 being the main target for neutralizing antibodies and necessary for cell attachment and viral fusion, the mechanism of viral entry remains elusive. To gain further insights into the pestivirus E2 mechanism of action and to assess its diversity within the genus, we report X-ray structures of the pestivirus E2 proteins from APPV and NRPV. Despite the highly divergent structures, both are able to dimerize through their C-terminal domain and contain a solvent-exposed β-hairpin reported to be involved in host receptor binding. Functional analysis of this β-hairpin in the context of BVDV revealed its ability to rescue viral infectivity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Neurofibromatosis type 1 (NF1) is associated with the development of benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumors. Recently described atypical neurofibromas (ANF) are considered pre-malignant precursor lesions to MPNSTs. Previous studies indicate that diffusion-weighted magnetic resonance imaging (DW-MRI) can reliably discriminate MPNSTs from BPNSTs. We therefore investigated the diagnostic accuracy of DW-MRI for the discrimination of benign, atypical, and malignant peripheral nerve sheath tumors., Methods: In this prospective explorative single-center phase II diagnostic study, 44 NF1 patients (23 male; 30.1 ± 11.8 years) underwent DW-MRI ( b -values 0-800 s/mm²) at 3T. Two radiologists independently assessed mean and minimum apparent diffusion coefficients (ADC mean/min ) in areas of largest tumor diameters and ADC dark in areas of lowest signal intensity by manual contouring of the tumor margins of 60 BPNSTs, 13 ANFs, and 21 MPNSTs. Follow-up of ≥ 24 months (BPNSTs) or histopathological evaluation (ANFs + MPNSTs) served as diagnostic reference standard. Diagnostic ADC-based cut-off values for discrimination of the three tumor groups were chosen to yield the highest possible specificity while maintaining a clinically acceptable sensitivity., Results: ADC values of pre-malignant ANFs clustered between BPNSTs and MPNSTs. Best BPNST vs. ANF + MPNST discrimination was obtained using ADC dark at a cut-off value of 1.6 × 10 -3 mm 2 /s (85.3% sensitivity, 93.3% specificity), corresponding to an AUC of 94.3% (95% confidence interval: 85.2-98.0). Regarding BPNST + ANF vs. MPNST, best discrimination was obtained using an ADC dark cut-off value of 1.4 × 10 -3 mm 2 /s (83.3% sensitivity, 94.5% specificity)., Conclusions: DW-MRI using ADC dark allows specific and noninvasive discrimination of benign, atypical, and malignant nerve sheath tumors in NF1., Competing Interests: The authors report no conflict of interest. All authors have approved the final version of the article., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background:  An abdominal aortic aneurysm (AAA) is defined as a localized dilatation of the abdominal aorta of ≥ 3 cm. With a prevalence of 4-8 %, AAA is one of the most common vascular diseases in Western society. Radiological imaging is an elementary component in the diagnosis, monitoring, and treatment planning of AAA patients., Method:  This is a narrative review article on preoperative imaging strategies of AAA, incorporating expert opinions based on the current literature and standard-of-care practices from our own center. Examples are provided to illustrate clinical cases from our institution., Results and Conclusion:  Radiological imaging plays a pivotal role in the initial diagnosis and monitoring of patients with AAA. Ultrasound is the mainstay imaging modality for AAA screening and surveillance. Contrast-enhanced CT angiography is currently considered the gold standard for preoperative imaging and image-based treatment planning in AAA repair. New non-contrast MR angiography techniques are robustly applicable and allow precise determination of aortic diameters, which is of critical importance, particularly with regard to current diameter-based surgical treatment guidelines. 3D imaging with multiplanar reformation and automatic centerline positioning enables more accurate assessment of the maximum aortic diameter. Modern imaging techniques such as 4D flow MRI have the potential to further improve individualized risk stratification in patients with AAA., Key Points:   · Ultrasound is the mainstay imaging modality for AAA screening and monitoring. · Contrast-enhanced CT angiography is the gold standard for preoperative imaging in AAA repair. · Non-contrast MR angiography allows for accurate monitoring of aortic diameters in AAA patients. · Measurement of aortic diameters is more accurate with 3D-CT/MRI compared to ultrasound. · Research seeks new quantitative imaging biomarkers for AAA risk stratification, e. g., using 4D flow MRI., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Gastrointestinal bleeding, as a potentially life-threatening condition, is typically diagnosed by radiation-based imaging modalities like computed tomography or more invasively catheter-based angiography. Endoscopy enables examination of the upper gastrointestinal tract and the colon but not of the entire small bowel. Magnetic Particle Imaging (MPI) enables non-invasive, volumetric imaging without ionizing radiation. The aim of this study was to evaluate the feasibility of detecting gastrointestinal bleeding by single- and multi-contrast MPI using human-sized organs. A 3D-printed small bowel phantom and porcine small bowel specimens were prepared with a defect within the bowel wall as the source of a bleeding. For multi-contrast MPI, the bowel lumen was filled with an intestinal tracer representing an orally administered tracer. MPI was performed to evaluate the fluid exchange between the vascular compartment of the bowel wall and the lumen while a blood pool tracer was applied. Leakage of the blood pool tracer was observed to the bowel lumen. Multi-contrast MPI enabled co-registration of both tracers at the same location within the bowel lumen indicating gastrointestinal bleeding. Single- and multi-contrast MPI are feasible to visualize gastrointestinal bleeding. Therefore, MPI might emerge as a useful tool for radiation-free detection of bleeding within the entire gastrointestinal tract., (© 2023. The Author(s).)

Background and Purpose: The new p64 flow diverter with hydrophilic polymer coating (HPC) was designed to reduce thrombogenicity. To date, it is unclear how antithrombogenic surface modifications affect neoendothelialization and thrombus formation in patients with unruptured intracranial aneurysms. The purpose of this study was to evaluate the safety and effectiveness of the p64MW-HPC in the treatment of unruptured aneurysms of small to giant size and of both the anterior and posterior circulation., Materials and Methods: Between March 2020 and October 2022 all patients with unruptured intracranial aneurysms treated with the p64MW-HPC were included at five neurovascular centers. Demographic data, aneurysm characteristics, antiplatelet therapy, procedural complications, and clinical and angiographic outcomes were recorded., Results: A total of 100 patients with 100 unruptured intracranial aneurysms met the inclusion criteria. Eighty-three aneurysms were classified as saccular, 12 aneurysms were fusiform, 4 aneurysms dissecting, and 1 aneurysm was blister-like. Dual antiplatelet therapy with Clopidogrel and Aspirin was given in 68 cases, and with Ticagrelor and Aspirin in 24 cases. Technical issues with deployment were encountered in 14 cases (torsion ( n  = 3), foreshortening ( n  = 8), and incomplete opening ( n  = 3)). Ischemic stroke occurred in a total of seven cases. In one patient a wire perforation and subsequent severe ICH occurred. Complete aneurysm occlusion at angiographic follow-up (mean time = 7 months) was seen in 73% and adequate occlusion in 93%., Conclusion: This study is the largest multicenter study to date documenting the safety and effectiveness of the new antithrombogenic p64MW-HPC in the treatment of unruptured intracranial aneurysms of the anterior and posterior circulation., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DF: Medtronic—Consulting, Proctoring, Cerenovous—Consulting, Microvention—Consulting, Proctoring, Research Support, Penumbra—Research Support, Stryker—Consulting, Research Support, Balt USA—Consulting, Research Support, Siemens—Research Support, MENTICE-Vascular Simulations—Consultant, Neurogami—Stock Holder, Consultant, Marblehead—Consultant, Stock Holder, RAPID.AI—Consultant, RAPID Medical—Consultant, Qapel Medical—Honorarium, Consultant, Arsenal Medical—Consultant, Phenox Medical—Consultant, Scientia Medical—SAB, Consultant, Stock Holder, NVMed—SAB, Stockholder, Perfuze—SAB, Consultant, Vesalio—Consultant. JK: Phenox—Consulting. MH: speaker, consultant, and proctoring honoraria for Microvention, Phenox, Stryker, Cerenovus, Medtronic, Balt.

Background: Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots., Methods: A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥ 50%. Features with consensus and rated ≥ 3 out of 4 on the certainty scale were included in the definition of a challenging clot., Results: Three DELPHI rounds were performed. Panelists achieved consensus on 16/30 questions, of which 8 were rated 3 or 4 on the certainty scale, namely white-colored clots (mean certainty score 3.1), calcified clots under histology (3.7) and imaging (3.7), stiff clots (3.0), sticky/adherent clots (3.1), hard clots (3.1), difficult to pass clots (3.1) and clots that are resistant to pulling (3.0). Most panelists considered switching endovascular treatment (EVT) techniques after 2-3 unsuccessful attempts., Conclusion: This DELPHI consensus identified 8 distinct features of a challenging clot. The varying degree of certainty amongst the panelists emphasizes the need for more pragmatic studies to enable accurate a priori identification of such occlusions prior to EVT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Neuronal differentiation is regulated by neuronal activity. Here, we analyzed dendritic and axonal growth of Basket cells (BCs) and non-Basket cells (non-BCs) using sparse transfection of channelrhodopsin-YFP and repetitive optogenetic stimulation in slice cultures of rat visual cortex. Neocortical interneurons often display axon-carrying dendrites (AcDs). We found that the AcDs of BCs and non-BCs were, on average, the most complex dendrites. Further, the AcD configuration had an influence on BC axonal development. Axons originating from an AcD formed denser arborizations with more terminal endings within the dendritic field of the parent cell. Intriguingly, this occurred already in unstimulated BCs, and complexity was not increased further by optogenetic stimulation. However, optogenetic stimulation exerted a growth-promoting effect on axons emerging from BC somata. The axons of non-BCs neither responded to the AcD configuration nor to the optogenetic stimulation. The results suggest that the formation of locally dense BC plexuses is regulated by spontaneous activity. Moreover, in the AcD configuration, the AcD and the axon it carries mutually support each other's growth., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Purpose: While MRI has become the imaging modality of choice in the diagnosis of sellar tumors, no systematic attempt has yet been made to align radiological reporting of findings with the information needed by the various medical disciplines dealing with these patients. Therefore, we aimed to determine the prevailing preferences in this regard through a nationwide expert survey., Methods: First, an interdisciplinary literature-based catalog of potential reporting elements for sellar tumor MRI examinations was created. Subsequently, a web-based survey regarding the clinical relevance of these items was conducted among board certified members of the German Society of Neurosurgery, German Society of Radiation Oncology, and the Pituitary Working Group of the German Society of Endocrinology., Results: A total of 95 experts (40 neurosurgeons, 28 radiation oncologists, and 27 endocrinologists) completed the survey. The description of the exact tumor location, size, and involvement of the anatomic structures adjacent to the sella turcica (optic chiasm, cavernous sinus, and skull base), occlusive hydrocephalus, relationship to the pituitary gland and infundibulum, and certain structural characteristics of the mass (cyst formation, hemorrhage, and necrosis) was rated most important (> 75% agreement). In contrast, the characterization of anatomic features of the nasal cavity and sphenoid sinus as well as the findings of advanced MRI techniques (e.g., perfusion and diffusion imaging) was considered relevant by less than 50% of respondents., Conclusion: To optimally address the information needs of the interdisciplinary treatment team, MRI reports of sellar masses should primarily focus on the accurate description of tumor location, size, internal structure, and involvement of adjacent anatomic compartments., (© 2023. The Author(s).)

Background & Aims: Cirrhosis is associated with an increased surgical morbidity and mortality. Portal hypertension and the surgery type have been established as critical determinants of postoperative outcome. We aim to evaluate the hypothesis that preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with cirrhosis is associated with a lower incidence of in-house mortality/liver transplantation (LT) after surgery., Methods: A retrospective database search for the years 2010-2020 was carried out. We identified 64 patients with cirrhosis who underwent surgery within 3 months after TIPS placement and 131 patients with cirrhosis who underwent surgery without it (controls). Operations were categorised into low-risk and high-risk procedures. The primary endpoint was in-house mortality/LT. We analysed the influence of high-risk surgery, preoperative TIPS placement, age, sex, baseline creatinine, presence of ascites, Chronic Liver Failure Consortium Acute Decompensation (CLIF-C AD), American Society of Anesthesiologists (ASA), and model for end-stage liver disease (MELD) scores on in-house mortality/LT by multivariable Cox proportional hazards regression., Results: In both the TIPS and the control cohort, most patients presented with a Child-Pugh B stage (37/64, 58% vs. 70/131, 53%) at the time of surgery, but the median MELD score was higher in the TIPS cohort (14 vs. 11 points). Low-risk and high-risk procedures amounted to 47% and 53% in both cohorts. The incidence of in-house mortality/LT was lower in the TIPS cohort (12/64, 19% vs. 52/131, 40%), also when further subdivided into low-risk (0/30, 0% vs. 10/61, 16%) and high-risk surgery (12/34, 35% vs. 42/70, 60%). Preoperative TIPS placement was associated with a lower rate for postoperative in-house mortality/LT (hazard ratio 0.44, 95% CI 0.19-1.00) on multivariable analysis., Conclusions: A preoperative TIPS might be associated with reduced postoperative in-house mortality in selected patients with cirrhosis., Impact and Implications: Patients with cirrhosis are at risk for more complications and a higher mortality after surgical procedures. A transjugular intrahepatic portosystemic shunt (TIPS) is used to treat complications of cirrhosis, but it is unclear if it also helps to lower the risk of surgery. This study takes a look at complications and mortality of patients undergoing surgery with or without a TIPS, and we found that patients with a TIPS develop less complications and have an improved survival. Therefore, a preoperative TIPS should be considered in selected patients, especially if indicated by ascites., Competing Interests: The authors have no conflict of interest to declare regarding the work under consideration for publication. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

Objective: Presurgical high-density electric source imaging (hdESI) of interictal epileptic discharges (IEDs) is only used by few epilepsy centers. One obstacle is the time-consuming workflow both for recording as well as for visual review. Therefore, we analyzed the effect of (a) an automated IED detection and (b) the number of IEDs on the accuracy of hdESI and time-effectiveness., Methods: In 22 patients with pharmacoresistant focal epilepsy receiving epilepsy surgery (Engel 1) we retrospectively detected IEDs both visually and semi-automatically using the EEG analysis software Persyst in 256-channel EEGs. The amount of IEDs, the Euclidean distance between hdESI maximum and resection zone, and the operator time were compared. Additionally, we evaluated the intra-individual effect of IED quantity on the distance between hdESI maximum of all IEDs and hdESI maximum when only a reduced amount of IEDs were included., Results: There was no significant difference in the number of IEDs between visually versus semi-automatically marked IEDs (74 ± 56 IEDs/patient vs 116 ± 115 IEDs/patient). The detection method of the IEDs had no significant effect on the mean distances between resection zone and hdESI maximum (visual: 26.07 ± 31.12 mm vs semi-automated: 33.6 ± 34.75 mm). However, the mean time needed to review the full datasets semi-automatically was shorter by 275 ± 46 min (305 ± 72 min vs 30 ± 26 min, P < 0.001). The distance between hdESI of the full versus reduced amount of IEDs of the same patient was smaller than 1 cm when at least a mean of 33 IEDs were analyzed. There was a significantly shorter intraindividual distance between resection zone and hdESI maximum when 30 IEDs were analyzed as compared to the analysis of only 10 IEDs (P < 0.001)., Significance: Semi-automatized processing and limiting the amount of IEDs analyzed (~30-40 IEDs per cluster) appear to be time-saving clinical tools to increase the practicability of hdESI in the presurgical work-up., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Acute abdominal pain (colic) is one of the major equine health threats worldwide and often necessitates intensive veterinary medical care and surgical intervention. Equine coronavirus (ECoV) infections can cause colic in horses but are rarely considered as a differential diagnosis. To determine the frequency of otherwise undetected ECoV infections in horses with acute colic, fresh fecal samples of 105 horses with acute colic and 36 healthy control horses were screened for viruses belonging to the Betacoronavirus 1 species by RT-PCR as well as for gastrointestinal helminths and bacteria commonly associated with colic. Horses with colic excreted significantly fewer strongyle eggs than horses without colic. The prevalence of anaerobic, spore-forming, gram-positive bacteria ( Clostridium perfringens and Clostridioides difficile ) was significantly higher in the feces of horses with colic. Six horses with colic (5.7%) and one horse from the control group (2.8%) tested positive for Betacoronaviruses. Coronavirus-positive samples were sequenced to classify the virus by molecular phylogeny (N gene). Interestingly, in three out of six coronavirus-positive horses with colic, sequences closely related to bovine coronaviruses (BCoV) were found. The pathogenic potential of BCoV in horses remains unclear and warrants further investigation.

Spontaneous or experimentally evoked activity can lead to changes in length and/or branching of neocortical pyramidal cell dendrites. For instance, an early postnatal overexpression of certain AMPA or kainate glutamate receptor subunits leads to larger amplitudes of depolarizing events driven by spontaneous activity, and this increases apical dendritic complexity. Whether stimulation frequency has a role is less clear. In this study, we report that the expression of channelrhodopsin2-eYFP was followed by a 5-day optogenetic stimulation from DIV 5-10 or 11-15 in organotypic cultures of rat visual cortex-evoked dendritic remodeling. Stimulation at 0.05 Hz, at a frequency range of spontaneous calcium oscillations known to occur in the early postnatal neocortex in vivo until eye opening, had no effect. Stimulation with 0.5 Hz, a frequency at which the cortex in vivo adopts after eye opening, unexpectedly caused shorter and somewhat less branched apical dendrites of infragranular pyramidal neurons. The outcome resembles the remodeling of corticothalamic and callosal projection neurons of layers VI and V, which in the adult have apical dendrites no longer terminating in layer I. Exposure to 2.5 Hz, a frequency not occurring naturally during the time windows, evoked dendritic damage. The results suggested that optogenetic stimulation at a biologically meaningful frequency for the selected developmental stage can influence dendrite growth, but contrary to expectation, the optogenetic stimulation decreased dendritic growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gonda, Köhler, Haase, Czubay, Räk, Riedel and Wahle.)

Objectives: To compare the accuracy and precision of 3D-Dixon and 2D-SSFP MR-imaging for assessment of aortic diameter in Marfan patients., Methods: This prospective single-center study investigated respiratory-gated 3D-Dixon and breath-hold 2D-SSFP non-contrast MR-imaging at 3 T in 47 Marfan patients (36.0 ± 13.2 years, 28♀,19♂). Two radiologists performed individual diameter measurements at five levels of the thoracic aorta and evaluated image quality on a four-grade scale (1 = poor, 4 = excellent) and artifacts (1 = severe, 4 = none). Aortic root diameters acquired by echocardiography served as a reference standard. Intraclass correlation coefficient, Bland-Altman analyses, F-test, t-test, and regression analyses were used to assess agreement between observers and methods., Results: Greatest aortic diameters were observed at the level of the sinuses of Valsalva (SOV) for 3D-Dixon (38.2 ± 6.8 mm) and 2D-SSFP (38.3 ± 7.1 mm) (p = 0.53). Intra- and interobserver correlation of diameter measurements was excellent at all aortic levels for both 3D-Dixon (r = 0.94-0.99 and r = 0.94-0.98) and 2D-SSFP (r = 0.96-1.00 and r = 0.95-0.99). 3D-Dixon-derived and 2D-SSFP-derived diameter measurements at the level of the SOV revealed a strong correlation with echocardiographic measurements (r = 0.92, p < 0.001 and r = 0.93, p < 0.001, respectively). The estimated mean image quality at the level of SOV was higher for 2D-SSFP compared to that for 3D-Dixon (3.3 (95%-CI: 3.1-3.5) vs. 2.9 (95%-CI: 2.7-3.1)) (p < 0.001). Imaging artifacts were less at all aortic levels for 3D-Dixon compared to 2D-SSFP (3.4-3.8 vs. 2.8-3.1) (all p < 0.002)., Conclusion: Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP MR-imaging provide accurate and precise aortic diameter measurements. We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations of the aortic root., Key Points: • Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP imaging provide accurate and precise aortic diameter measurements in patients suffering from Marfan syndrome. • Imaging artifacts are stronger in 2D-SFFP imaging than in 3D-Dixon imaging. • We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations., (© 2022. The Author(s).)

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is feasible for portal blood flow evaluation after placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with liver cirrhosis. However, clinical acceptance of 4D flow CMR in TIPS patients is limited due to the lack of validation studies. The purpose of this study was to validate 4D flow CMR-derived measurements in TIPS stent grafts using a three-dimensional (3D)-printed flow phantom., Methods: A translucent flow phantom of the portal vasculature was 3D-printed. The phantom consisted of the superior mesenteric vein and the splenic vein draining into the portal vein, the TIPS-tract, and the hepatic vein. A TIPS stent graft (Gore® Viatorr®) was positioned within the TIPS-tract. Superior mesenteric vein and splenic vein served as inlets for blood-mimicking fluid. 4D flow CMR acquisitions were performed at 3T at preset flow rates of 0.8 to 2.8 l/min using velocity encoding of both 1.0 and 2.0 m/s. Flow rates and velocities were measured at predefined levels in the portal vasculature and within the stent graft. Accuracy of 4D flow CMR was assessed through linear regression with reference measurements obtained by flow sensors and two-dimensional (2D) phase contrast (PC) CMR. Intra- and interobserver agreement were assessed through Bland-Altman analyses., Results: At a velocity encoding of 2.0 m/s, 4D flow CMR-derived flow rates and velocities showed an excellent correlation with preset flow rates and 2D PC CMR-derived flow velocities at all vascular levels and within the stent graft (all r ≥ 0.958, p ≤ 0.003). At a velocity encoding of 1.0 m/s, aliasing artifacts were present within the stent graft at flow rates ≥ 2.0 l/min. 4D flow CMR-derived measurements revealed high intra- and interobserver agreement., Conclusions: The in vitro accuracy and precision of 4D flow CMR is unaffected by the presence of TIPS stent grafts, suggesting that 4D flow CMR may be used to monitor TIPS patency in patients with liver cirrhosis., (© 2023. The Author(s).)

The emergence of recombinant PRRSV strains has been observed for more than a decade. These recombinant viruses are characterized by a genome that contains genetic material from at least two different parental strains. Due to the advanced sequencing techniques and a growing number of data bank entries, the role of PRRSV recombinants has become increasingly important since they are sometimes associated with clinical outbreaks. Chimeric viruses observed more recently are products of PRRSV wild-type and vaccine strains. Here, we report on three PRRSV-1 isolates from geographically distant farms with differing clinical manifestations. A sequencing and recombination analysis revealed that these strains are crossovers between different wild-type strains and the same modified live virus vaccine strain. Interestingly, the recombination breakpoint of all analyzed isolates appears at the beginning of open reading frame 5 (ORF5). RNA structure predictions indicate a conserved stem loop in close proximity to the recombination hotspot, which is a plausible cause of a polymerase template switch during RNA replication. Further research into the mechanisms of the stem loop is needed to help understand the PRRSV recombination process and the role of MLVs as parental strains.

With Regulation (EU) No. 536/2014 on clinical trials on medicinal products for human use, which became applicable on 31 January 2022, full harmonisation of the authorisation and monitoring procedures of clinical trials with medicinal products in the European Union (EU) and the European Economic Area (EEA) has been achieved. In addition to an entirely paperless application procedure, communication between all parties involved is done through the Clinical Trials Information System (CTIS), which was developed specifically for the Regulation and through which all non-proprietary information and content of the clinical trial application and results are also made available to the public. As was already the case under the old legal framework, the authorisation of a clinical trial is granted by each Member State concerned; however, the assessment of the common part of the dossier of a clinical trial that is conducted in more than one Member State is jointly done by the respective Member States under the coordinating lead of a reporting Member State. The present article outlines the authorisation procedure with its deadline concept and addresses further aspects of the Regulation, such as details on the protection of the trial subjects, safety reporting and transparency rules., (© 2022. The Author(s).)

Introduction: Human respiratory syncytial virus (hRSV) is an important cause of lower respiratory tract infections in the pediatric and the geriatric population worldwide. There is a substantial economic burden resulting from hRSV disease during winter. Although no vaccines have been approved for human use, prophylactic therapies are available for high-risk populations. Choosing the proper animal models to evaluate different vaccine prototypes or pharmacological treatments is essential for developing efficient therapies against hRSV., Areas Covered: This article describes the relevance of using different animal models to evaluate the effect of antiviral drugs, pharmacological molecules, vaccine prototypes, and antibodies in the protection against hRSV. The animal models covered are rodents, mustelids, bovines, and nonhuman primates. Animals included were chosen based on the available literature and their role in the development of the drugs discussed in this manuscript., Expert Opinion: Choosing the correct animal model is critical for exploring and testing treatments that could decrease the impact of hRSV in high-risk populations. Mice will continue to be the most used preclinical model to evaluate this. However, researchers must also explore the use of other models such as nonhuman primates, as they are more similar to humans, prior to escalating into clinical trials.

While fractures of the distal femur are often considered as fragility fractures, detailed knowledge of the bone microarchitecture at this skeletal site is largely unavailable. Initial evaluation of a patient cohort with distal femur fractures showed a markedly increased occurrence in elderly women. The purpose of this study was to determine the extent to which demographic characteristics of distal femur fractures are reflected by general age- and sex-specific variations in local microarchitectural parameters. Fifty cadaveric femora were collected from 25 subjects (12 females, 13 males, age 25-97 years). A volume of interest within 3 cm proximal to the condyles was analyzed using high-resolution peripheral quantitative computed tomography (HR-pQCT), which revealed impaired trabecular and cortical bone microarchitecture in women compared to men as well as in osteoporotic compared to normal or osteopenic subjects, as classified by dual-energy X-ray absorptiometry (DXA) T-score. Linear regression analyzes showed negative associations between age and HR-pQCT parameters in women (e.g., cortical thickness -14 µm/year, 95% CI: -21 to -7 µm/year), but not in men (e.g., cortical thickness 1 µm/year, 95% CI: -12 to 14 µm/year). HR-pQCT parameters showed strong positive associations with areal bone mineral density (aBMD) determined by DXA at the hip in both sexes. Taken together, our findings suggest that female sex, advanced age, and low aBMD represent major risk factors for impaired microarchitecture at the distal femur. Both the diagnostic value of DXA for predicting distal femur fractures and the efficacy of bone-specific agents on fracture risk reduction should be investigated in the future., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most relevant porcine pathogens worldwide. Active control of the disease relies on modified live virus vaccines (MLVs), as most inactivated vaccines provide very limited protection. Neutralizing antibodies occur late in infection; therefore, CD8 + T cells are considered important correlates of protection and are a frequent focus of investigation. Our aim was to identify viral peptides naturally bound by the class I major histocompatibility complex (MHC-I) and to confirm their ability to stimulate CD8 + T cells. For this purpose, we immunoprecipitated MHC-I/peptide complexes of PRRSV (strain AUT15-33) -infected cells (SLA-I Lr-Hp 35.0/24 mod) to isolate the viral epitopes and analyzed them with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Furthermore, we employed these identified peptides to stimulate peripheral blood mononuclear cells (PBMCs) of previously PRRSV-infected pigs and measured the PRRSV-specific CD8 + T-cell response with an intracellular cytokine staining (ICS). Our data revealed that PRRSV non-structural proteins (NSPs), encoded in open reading frame 1a and 1b (ORF1), present the major source of MHC-I-presented peptides. Additionally, we show that our identified epitopes are able to trigger IFNγ responses in vitro . These findings are a basis for understanding the proteasomal degradation of PRRSV proteins, the cellular ability to display them via MHC-I, and their potential to restimulate CD8 + T cells.

Atypical porcine pestiviruses (APPV; Pestivirus K ) are a recently discovered, very divergent species of the genus Pestivirus within the family Flaviviridae . The presence of APPV in piglet-producing farms is associated with the occurrence of so-called "shaking piglets," suffering from mild to severe congenital tremor type A-II. Previous studies showed that the cellular protein DNAJC14 is an essential cofactor of the NS2 autoprotease of all classical pestiviruses. Consequently, genetically engineered DNAJC14 knockout cell lines were resistant to all tested noncytopathogenic (non-cp) pestiviruses. Surprisingly, we found that the non-cp APPV can replicate in these cells in the absence of DNAJC14, suggesting a divergent mechanism of polyprotein processing. A complete laboratory system for the study of APPV was established to learn more about the replication of this unusual virus. The inactivation of the APPV NS2 autoprotease using reverse genetics resulted in nonreplicative genomes. To further investigate whether a regulation of the NS2-3 cleavage is also existing in APPV, we constructed synthetic viral genomes with deletions and duplications leading to the NS2 independent release of mature NS3. As observed with other pestiviruses, the increase of mature NS3 resulted in elevated viral RNA replication levels and increased protein expression. Our data suggest that APPV exhibit a divergent mechanism for the regulation of the NS2 autoprotease activity most likely utilizing a different cellular protein for the adjustment of replication levels. IMPORTANCE DNAJC14 is an essential cofactor of the pestiviral NS2 autoprotease, limiting replication to tolerable levels as a prerequisite for the noncytopathogenic biotype of pestiviruses. Surprisingly, we found that the atypical porcine pestivirus (APPV) is able to replicate in the absence of DNAJC14. We further investigated the NS2-3 processing of APPV using a molecular clone, monoclonal antibodies, and DNAJC14 knockout cells. We identified two potential active site residues of the NS2 autoprotease and could demonstrate that the release of NS3 by the NS2 autoprotease is essential for APPV replication. Defective interfering genomes and viral genomes with duplicated NS3 sequences that produce mature NS3 independent of the NS2 autoprotease activity showed increased replication and antigen expression. It seems likely that an alternative cellular cofactor controls NS2-3 cleavage and thus replication of APPV. The replication-optimized synthetic APPV genomes might be suitable live vaccine candidates, whose establishment and testing warrant further research.

Background and Objective: Structured reporting of MRI examinations using consensus-based content categories has the potential to improve interdisciplinary communication in neuro-oncology. Therefore, the aim of this study was to determine the essential reporting categories in the imaging of gliomas from a clinical perspective within the setting of a nationwide survey of members of medical societies working in neuro-oncology., Materials and Methods: An online questionnaire was created based on an interdisciplinary developed catalog of possible MRI reporting elements. Subsequently, specialist members of the German Societies of Neurosurgery, Radiation Oncology, Hematology and Medical Oncology, Neurology, and Neuropathology were invited to evaluate the items with regard to their clinical relevance., Results: A total of 171 specialists from Germany participated in the survey (81 neurosurgeons, 66 radiation therapists, and 24 other neuro-oncology experts). Number and anatomic extent of tumors in the contrast-enhanced T1 and 2D T2 sequences (98.8% vs. 97.1%) as well as newly diagnosed lesions at follow-up (T1 + contrast 98.2%; T2 94.7%) were overall most frequently considered crucial. In addition, the experts particularly rated the description of ependymal and/or leptomeningeal tumor dissemination (93.6%) and signs of mass effect including occlusive hydrocephalus and parenchymal mass shifts (> 75.0% each) as essential. Standard mention of intratumoral calcifications, hemorrhages, tumor vascular architecture, or advanced imaging modalities such as MR perfusion, diffusion, tractography, and proton spectroscopy were considered fundamental to their everyday practice by only a minority of neuro-oncology colleagues., Conclusion: A referring physician-oriented minimum content standard for MRI examinations in primary brain tumor patients should include as clinically relevant core elements the exact anatomic spread of the lesion(s), including ependymal and meningeal involvement, and the pertinent signs of mass effect., (© 2022. The Author(s).)

Reproductive disorders induced by porcine reproductive and respiratory syndrome virus (PRRSV) cause high economic losses in the pig industry worldwide. In this study, we aimed to phenotypically characterize a virulent PRRSV-1 subtype 1 isolate (AUT15-33) in a reproductive model. Furthermore, the protective effect of a heterologous modified live virus vaccine (ReproCyc® PRRS EU) was evaluated. In addition, PRRSV AUT15-33 was genotypically compared to other well-characterized isolates. Sixteen gilts were equally divided into four groups: a vaccinated and infected group (V-I), a vaccinated and non-infected group (V-NI), a non-vaccinated and infected group (NV-I), and a non-vaccinated and non-infected (NV-NI) group. After PRRSV infection on gestation day 84, all gilts were clinically examined on a daily basis, and blood samples were taken at five timepoints. Necropsy was performed 3 weeks after infection. The fetal preservation status was assessed, and PRRSV RNA concentrations were measured in the blood and tissue samples from all gilts and fetuses. After infection, all four gilts in the NV-I group were viremic throughout 17 days post-infection (dpi), whereas two gilts in the V-I group were viremic at only one timepoint at 6 dpi. The viral load was significantly higher in gilt serum, tracheobronchial lymph nodes, uterine lymph nodes, maternal endometrium, and fetal placenta of NV-I gilts compared to the V-I ones ( p < 0.05). Moreover, the preservation status of the fetuses derived from NV-I gilts was significantly impaired (55.9% of viable fetuses) compared to the other groups ( p < 0.001). Upon comparison with other known isolates, the phylogenetic analyses revealed the closest relation to a well-characterized PRRSV-1 subtype 1 field isolate from Belgium. In conclusion, the high virulence of AUT15-33 was phenotypically confirmed in an experimental reproductive model. The vaccination of the gilts showed promising results in reducing viremia, fetal damage, and transplacental transmission of the PRRSV-1 strain characterized in this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kreutzmann, Stadler, Knecht, Sassu, Ruczizka, Zablotski, Vatzia, Balka, Zaruba, Chen, Riedel, Rümenapf and Ladinig.)

Background: The implementation of a collective terminology in radiological reporting such as the RSNA radiological lexicon (RadLex) yields many benefits including unambiguous communication of findings, improved education, and fostering data mining for research purposes. While some fields in general radiology have already been evaluated so far, this is the first exploratory approach to assess the applicability of the RadLex terminology to glioblastoma (GBM) MRI reporting., Methods: Preoperative brain MRI reports of 20 consecutive patients with newly diagnosed GBM (mean age 68.4 ± 10.8 years; 12 males) between January and October 2010 were retrospectively identified. All terms related to the tumor as well as their frequencies of mention were extracted from the MRI reports by two independent neuroradiologists. Every item was subsequently analyzed with respect to an equivalent RadLex representation and classified into one of four groups as follows: 1. verbatim RadLex entity, 2. synonymous/multiple equivalent(s), 3. combination of RadLex concepts, or 4. no RadLex equivalent. Additionally, verbatim entities were categorized using the hierarchical RadLex Tree Browser., Results: A total of 160 radiological terms were gathered. 123/160 (76.9%) items showed literal RadLex equivalents, 9/160 (5.6%) items had synonymous (non-verbatim) or multiple counterparts, 21/160 (13.1%) items were represented by means of a combination of concepts, and 7/160 (4.4%) entities could not eventually be transferred adequately into the RadLex ontology., Conclusions: Our results suggest a sufficient term coverage of the RadLex terminology for GBM MRI reporting. If applied extensively, it may improve communication of radiological findings and facilitate data mining for large-scale research purposes., (© 2022. The Author(s).)

During the annual hunt in a privately owned Austrian game population in fall 2019 and 2020, 64 red deer ( Cervus elaphus ), 5 fallow deer ( Dama dama ), 6 mouflon ( Ovis gmelini musimon ), and 95 wild boars ( Sus scrofa ) were shot and sampled for PCR testing. Pools of spleen, lung, and tonsillar swabs were screened for specific nucleic acids of porcine circoviruses. Wild ruminants were additionally tested for herpesviruses and pestiviruses, and wild boars were screened for pseudorabies virus (PrV) and porcine lymphotropic herpesviruses (PLHV-1-3). PCV2 was detectable in 5% (3 of 64) of red deer and 75% (71 of 95) of wild boar samples. In addition, 24 wild boar samples (25%) but none of the ruminants tested positive for PCV3 specific nucleic acids. Herpesviruses were detected in 15 (20%) ruminant samples. Sequence analyses showed the closest relationships to fallow deer herpesvirus and elk gammaherpesvirus. In wild boars, PLHV-1 was detectable in 10 (11%), PLHV-2 in 44 (46%), and PLHV-3 in 66 (69%) of animals, including 36 double and 3 triple infections. No pestiviruses were detectable in any ruminant samples, and all wild boar samples were negative in PrV-PCR. Our data demonstrate a high prevalence of PCV2 and PLHVs in an Austrian game population, confirm the presence of PCV3 in Austrian wild boars, and indicate a low risk of spillover of notifiable animal diseases into the domestic animal population.

The entry of BVDV into bovine cells was studied using CRIB cells (cells resistant to infection with bovine viral diarrhea virus [BVDV]) that have evolved from MDBK cells by a spontaneous loss of susceptibility to BVDV. Recently, larger genetic deletions were reported but no correlation of the affected genes and the resistance to BVDV infection could be established. The metalloprotease ADAM17 was reported as an essential attachment factor for the related classical swine fever virus (CSFV). To assess whether ADAM17 might be involved in the resistance of CRIB-1 cells to pestiviruses, we analyzed its expression in CRIB-1 and MDBK cells. While ADAM17 protein was detectable in MBDK cells, it was absent from CRIB-1 cells. No functional full-length ADAM17 mRNA could be detected in CRIB cells and genetic analysis revealed the presence of two defective alleles. Transcomplementation of functional ADAM17 derived from MDBK cells in CRIB-1 cells resulted in a nearly complete reversion of their resistance to pestiviral infection. Our results demonstrate that ADAM17 is a key cellular factor for the pestivirus resistance of CRIB-1 cells and establishes its essential role for a broader range of pestiviruses.

Linda virus (LindaV) was first identified in a pig farm in Styria, Austria in 2015 and associated with congenital tremor (CT) type A-II in newborn piglets. Since then, only one more LindaV affected farm was retrospectively discovered 10 km away from the initially affected farm. Here, we report the recent outbreak of a novel LindaV strain in a farrow-to-finish farm in the federal state Carinthia, Austria. No connection between this farm and the previously affected farms could be discovered. The outbreak was characterized by severe CT cases in several litters and high preweaning mortality. A herd visit two months after the onset of clinical symptoms followed by a diagnostic workup revealed the presence of several viremic six-week-old nursery pigs. These animals shed large amounts of virus via feces and saliva, implying an important epidemiological role for within- and between-herd virus transmission. The novel LindaV strain was isolated and genetically characterized. The findings underline a low prevalence of LindaV in the Austrian pig population and highlight the threat when introduced into a pig herd. Furthermore, the results urge the need to better understand the routes of persistence and transmission of this enigmatic pestivirus in the pig population.

Little is known about the consequences of viral infection for pregnant woman or for the fetus. This issue became important with the appearance of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The infection with SARS-CoV-2 causes a respiratory syndrome known as COVID-19. The fast spreading around the world and the fact that without a treatment or vaccine humans are completely exposed, converts emerging viral diseases in a significant risk for pregnant women and their infants. At this time, during SARS-CoV-2 pandemics pregnant women are not considered as a risk population and little is known about the effects of viral infections over the offspring although the amount of emerging evidence showing detrimental effects for the mother and the fetus. This issue highlights the importance to understand the effects of viral infections during pregnancy. In this work, we analyze the effects of viral infections, like SARS-CoV-2 and other related viruses during pregnancy over the mother and the consequences for the offspring.

Purpose: The field of obstetrics and gynecology (OB/GYN) is facing growing competition for young professionals in Germany, with high interest rates among female graduates and a declining proportion of male students who choose residency training in the field. The aim of this study is to analyze general and gender-dependent factors that influence the decision for or against specialty training in OB/GYN among medical students in Germany., Methods: Between February and November 2019, n = 346 medical students in their 5th and 6th year of undergraduate training at Heidelberg University received a questionnaire with 44 items., Results: n = 286 students (61.3 female; 38.7% male) participated in the study. 28% of the female students and 9% of the male students had considered OB/GYN for their specialty training. The students reported different general and gender-specific influencing factors in their choice of a specialty. Both genders desired a good work-life-balance, however, in comparison with their female colleagues, male students had heavily weighted factors related to their later careers and professional success, including competition among colleagues. Male students had gained little practical experience during compulsory internships (26.9% for females vs. 8.8% for males) or had chosen their final-year elective in OB/GYN (15.9% for females vs. 5.5% for males). Female students had worried about the negative effects of their sex on their career (35.4% for females vs. 5.9% for males)., Conclusion: OB/GYN must become more appealing and attractive to young female and male professionals alike. A better compatibility of career and family should go hand in hand with the implementation of differentiated, (extra) curricular teaching approaches that take the different preferences of female and male students into account., (© 2021. The Author(s).)

Objective: Traumatic brain injury (TBI) constitutes a major cause of trauma-related disability and mortality. The epidemiology and implications of associated cranial nerve injuries　(CNI)　in moderate to severe TBI are largely unknown. We aimed to determine the incidence of CNI in a large European cohort of TBI patients as well as clinical differences between TBI cases with and without concomitant CNI (CNI vs. control group) by means of a multinational trauma registry., Methods: The TraumaRegister DGU® was evaluated for trauma patients with head injuries ≥ 2 Abbreviated Injury Scale, who had to be treated on intensive care units after emergency admission to European hospitals between 2008 and 2017. CNI and control cases were compared with respect to demographic, clinical, and outcome variables., Results: 1.0% (946 of 91,196) of TBI patients presented with additional CNI. On average, CNI patients were younger than control cases (44.3 ± 20.6 vs. 51.8 ± 23.0 years) but did not differ regarding sex distribution (CNI 69.4% males vs. control 69.1%). Traffic accidents were encountered more frequently in CNI cases (52.3% vs. 46.7%; p < 0.001; chi-squared test) and falls more commonly in the control group (45.2% vs. 37.1%; p < 0.001). CNI patients suffered more frequently from concomitant face injuries (28.2% vs. 17.5%; p < 0.001) and skull base fractures (51.0% vs. 23.5%; p < 0.001). Despite similar mean Injury Severity Score (CNI 21.8 ± 11.3; control 21.1 ± 11.7) and Glasgow Coma Scale score (CNI 10.9 ± 4.2, control 11.1 ± 4.4), there was a considerably higher proportion of anisocoria in CNI patients (20.1% vs. 11.2%; p < 0.001). Following primary treatment, 50.8% of CNI and 35.5% of control cases showed moderate to severe disability (Glasgow Outcome Scale score 3-4; p < 0.001)., Conclusion: CNI rarely occur in the context of TBI. When present, they indicate a higher likelihood of functional impairment following primary care and complicating skull base fractures should be suspected., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The role of bovine CD46 in the host cell entry of BVDV has been established for more than a decade. By generating novel MDBK CD46 knock-out clones, we confirm previously reported data on the CD46 motives important for BVDV binding and the importance of the G479R exchange within BVDV E rns to gain independence of bovine CD46 during entry. The comparison of different knock-out genotypes revealed a high variability of cellular susceptibility for a BVDV encoding the G479R exchange. These data highlight the effect of clonal selection of knock-outs on virus susceptibility, which should be considered when planning knock-out experiments.

The purpose of this study was to identify key deficiencies in pediatric oncology early phase clinical trial protocols in Germany and to provide guidance for efficient trial protocol development. A systematic review of the response letters of German competent authorities (CAs) and Ethics Committees to phase I/II pediatric oncology trial submissions in the period from 2014 to 2019 was performed. Documents were requested from all five Society for Paediatric Oncology and Haematology in Germany (GPOH) phase I/II trial networks plus all nine German Innovative Therapies for Children with Consortium Cancer (ITCC) centers. A blinded dataset containing aggregated data from 33 studies was analyzed for validation. All deficiencies were reviewed, listed, and weighted using a structured matrix according to frequency, category, significance, and feasibility. In total, documents of 17 trials from 6 different sites were collected. Two hundred fifty deficiencies identified by the CAs were identified and categorized into eight categories. "Toxicity and safety" was the most prominent category (27.6%), followed by "Manufacturing and Import" (18%). The majority of deficiencies were categorized as minor and potential measures as easy to address, but an important group of major and difficult to implement deficiencies was also identified. The blinded validation dataset confirmed these findings. The majority of the EC deficiencies could be resolved by changing the wording in the patient-facing documents. In conclusion, this study was able to detect a pattern of key deficiencies. Most of the shortcomings can be anticipated by minor changes in the protocol and increased awareness can prevent time-consuming revisions, withdrawals, or even rejections. A corresponding guideline describing key regulatory aspects is provided., (© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Lyssaviruses are neurotropic rhabdoviruses thought to be restricted to mammalian hosts, and to originate from bats. The identification of lyssavirus sequences from amphibians and reptiles by metatranscriptomics thus comes as a surprise and challenges the mammalian origin of lyssaviruses. The novel sequences of the proposed American tree frog lyssavirus (ATFLV) and anole lizard lyssavirus (ALLV) reveal substantial phylogenetic distances from each other and from bat lyssaviruses, with ATFLV being the most distant. As virus isolation has not been successful yet, we have here studied the functionality of the authentic ATFLV- and ALLV-encoded glycoproteins in the context of rabies virus pseudotype particles. Cryogenic electron microscopy uncovered the incorporation of the plasmid-encoded G proteins in viral envelopes. Infection experiments revealed the infectivity of ATFLV and ALLV G-coated RABV pp for a broad spectrum of cell lines from humans, bats, and reptiles, demonstrating membrane fusion activities. As presumed, ATFLV and ALLV G RABV pp escaped neutralization by human rabies immune sera. The present findings support the existence of contagious lyssaviruses in poikilothermic animals, and reveal a broad cell tropism in vitro, similar to that of the rabies virus.

A wide range of microbial pathogens is capable of entering the gastrointestinal tract, causing infectious diarrhea and colitis. A finely tuned balance between different cytokines is necessary to eradicate the microbial threat and to avoid infection complications. The current study identified IL-33 as a critical regulator of the immune response to the enteric pathogen Citrobacter rodentium. We observed that deficiency of the IL-33 signaling pathway attenuates bacterial-induced colitis. Conversely, boosting this pathway strongly aggravates the inflammatory response and makes the mice prone to systemic infection. Mechanistically, IL-33 mediates its detrimental effect by enhancing gut permeability and by limiting the induction of protective T helper 17 cells at the site of infection, thus impairing host defense mechanisms against the enteric pathogen. Importantly, IL-33-treated infected mice supplemented with IL-17A are able to resist the otherwise strong systemic spreading of the pathogen. These findings reveal a novel IL-33/IL-17A crosstalk that controls the pathogenesis of Citrobacter rodentium-driven infectious colitis. Manipulating the dynamics of cytokines may offer new therapeutic strategies to treat specific intestinal infections.

Studies show that psychiatric symptoms in adults and children are sometimes associated with serum neural autoantibodies. The significance of serum neural autoantibodies associated with psychiatric symptoms in children remains often unclear, but might be relevant for the extent and occurrence of psychiatric disease manifestation in later life, as well as therapy and outcome. For this narrative review, we sought articles listed in PubMed and published between 1988 and 2020 addressing the maternal-fetal transfer of neural autoantibodies and psychiatric disorders associated with serum neural autoantibodies. We identified six major subgroups of psychiatric disorders in children that are associated with serum neural autoantibodies: patients with attentional deficit hyperactivity disorder, autism spectrum disorder, obsessive compulsive disorder, Gilles de la Tourette syndrome, psychosis and catatonia. Furthermore, we summarized study findings from maternal-fetal transfer of Contactin-associated protein-like 2, N-methyl-D-aspartate receptor and fetal brain autoantibodies associated with behavioral effects in animals and humans. We hypothesize that the maternal transfer of serum neuronal autoantibodies during or after birth could result (1) in the ignition of an autoimmune-mediated inflammation having neurodevelopmental consequences for their children (autoimmune-priming-attack hypothesis) and (2) has a potential impact on the later manifestation of psychiatric disorders. Through this narrative review, we propose a diagnostic pathway for the clinical diagnosis of a potentially autoimmune origin of psychiatric symptoms in children while considering recent guidelines.

A novel pestivirus species, termed Lateral-shaking Inducing Neuro-Degenerative Agent virus (LindaV), was discovered in a piglet-producing farm in Austria in 2015 related to severe congenital tremor cases. Since the initial outbreak LindaV has not been found anywhere else. In this study, we determined the seroprevalence of LindaV infections in the domestic pig population of Austria. A fluorophore labeled infectious cDNA clone of LindaV (mCherry-LindaV) was generated and used in serum virus neutralization (SVN) assays for the detection of LindaV specific neutralizing antibodies in porcine serum samples. In total, 637 sera from sows and gilts from five federal states of Austria, collected between the years 2015 and 2020, were analyzed. We identified a single serum showing a high neutralizing antibody titer, that originated from a farm (Farm S2) in the proximity of the initially affected farm. The analysis of 57 additional sera from Farm S2 revealed a wider spread of LindaV in this pig herd. Furthermore, a second LindaV strain originating from this farm could be isolated in cell culture and was further characterized at the genetic level. Possible transmission routes and virus reservoir hosts of this emerging porcine virus need to be addressed in future studies.

Background: The study analyzes changes in lung function, pulmonary pressure and diffusing capacity of the lung in patients with mitral valve regurgitation (MR) treated by MitraClip implantation., Methods: A total of 43 patients (19 women and 24 men with an average age of 78.0 ± 6.6 years) who were able to perform pulmonary function testing including diffusing capacity of the lung for carbon monoxide (DLCO), vital capacity (VC), total lung capacity (TLC), residual volume (RV) and forced expiratory volume in 1 s (FEV1) before and 6 weeks after MitraClip implantation participated in this study. Furthermore, clinical and echocardiographic parameters including systolic pulmonary artery pressure (sPAP), left ventricular ejection fraction (LVEF) and left atrial diameter (LAD) measurements were recorded in all patients., Results: The procedure was performed successfully in all 43 patients leading to a reduction of MR in 97.7% of cases. One patient died on day 4 after the intervention most likely due to pulmonary artery embolism. Six weeks after the implantation 79.1% of patients showed a MR of at most mild to moderate. Furthermore, we could demonstrate a significant reduction of systolic pulmonary artery pressure during follow-up (from 48.8 ± 11.4 mmHg to 42.9 ± 9.0 mmHg (t(41) = - 2.6, p = 0.01). However, no changes in LVEF were detected. Comparing pre and post implant lung function tests, no significant alterations were seen for VC, TLC, DLCO and FEV1. Though, in a subgroup of patients with moderate to severe preexisting deterioration of DLCO at the baseline (max. 50%) the MitraClip procedure resulted in a significant improvement in DLCO (37.8% ± 9.0 to 41.6% ± 10.0, p < 0.001)., Conclusions: Treatment of MR with the MitraClip system successfully reduces MR severity in the vast majority of patients. Consecutively, a reduction in pulmonary pressure could be observed, however no changes in LVEF were obvious. Lung function tests remained unaltered during follow-up. However, in a subgroup of patients with severe preexisting deterioration of DLCO the MitraClip procedure resulted in a significant improvement in DLCO., Trial Registration: Name of the registry: Die Auswirkung der interventionellen Mitralklappenreparatur mit MitraClip-System auf die Ergebnisse der Lungenfunktionsmessung., Trial Registration Number: DRKS00022435; Date of registration: 09/07/2020 'Retrospectively registered'; URL of trial registry record: https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00022435 .

Degradation at the modular head-neck interface in total hip arthroplasty (THA) is predominately expressed in the form of corrosion and fretting, potentially causing peri-prosthetic failure by adverse reactions to metal debris. This retrieval study aimed to quantify variations in stem taper surface topographies and to assess the influence on the formation of corrosion and/or fretting in titanium alloy stem tapers combined with metal and ceramic heads. Four hip stem designs (Alloclassic, CLS, Bicontact and SL-Plus) were characterized using high-resolution 3D microscopy, and corrosion and fretting were rated using the Goldberg scoring scheme. Quantification of the taper surface topographies revealed a high variability in surface characteristics between threaded stem tapers: Alloclassic and CLS tapers feature deeply threaded trapezoid-shaped profiles with thread heights over 65 µm. The sawtooth-shaped Bicontact and triangular SL-Plus taper are characterized by low thread heights below 14 µm. Significantly lower corrosion and fretting scores were observed in lightly threaded compared to deeply threaded tapers in ceramic head combinations. No significant differences in corrosion or fretting scores with thread height were found in pairings with metal heads. Understanding the relationship between stem taper surface topography and the formation of corrosion and fretting could help to improve the performance of modern THAs and lead to longer-lasting clinical results.

For two decades, the genus pestivirus has been expanding and the host range now extends to rodents, bats and marine mammals. In this review, we focus on one of the most diverse pestiviruses, atypical porcine pestivirus or pestivirus K, comparing its special traits to what is already known at the structural and functional level from other pestiviruses.

Vaccines of outstanding efficiency, safety, and public acceptance are needed to halt the current SARS-CoV-2 pandemic. Concerns include potential side effects caused by the antigen itself and safety of viral DNA and RNA delivery vectors. The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which might cause vaccination-induced complications or enhancement of COVID-19 disease. Besides, encoding of a functional S in replication-competent virus vector vaccines may result in the emergence of viruses with altered or expanded tropism. Here, we have developed a safe single round rhabdovirus replicon vaccine platform for enhanced presentation of the S receptor-binding domain (RBD). Structure-guided design was employed to build a chimeric minispike comprising the globular RBD linked to a transmembrane stem-anchor sequence derived from rabies virus (RABV) glycoprotein (G). Vesicular stomatitis virus (VSV) and RABV replicons encoding the minispike not only allowed expression of the antigen at the cell surface but also incorporation into the envelope of secreted non-infectious particles, thus combining classic vector-driven antigen expression and particulate virus-like particle (VLP) presentation. A single dose of a prototype replicon vaccine complemented with VSV G, VSVΔG-minispike-eGFP (G), stimulated high titers of SARS-CoV-2 neutralizing antibodies in mice, equivalent to those found in COVID-19 patients, and protected transgenic K18-hACE2 mice from COVID-19-like disease. Homologous boost immunization further enhanced virus neutralizing activity. The results demonstrate that non-spreading rhabdovirus RNA replicons expressing minispike proteins represent effective and safe alternatives to vaccination approaches using replication-competent viruses and/or the entire S antigen., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AAH and KKC are listed as inventors on a rhabdovirus minispike patent application.