bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, radiological and molecular characterization of intramedullary astrocytomas
Authors: Lebrun Laetitia , Meléndez Barbara , Blanchard Oriane , De Nève Nancy , Van Campenhout Claude , Lelotte Julie , Balériaux Danielle , Riva Matteo , Brotchi Jacques , Bruneau Michaël , De Witte Olivier , Decaestecker Christine , D’Haene Nicky , Salmon Isabelle 
Published: August 2020

AbstractIntramedullary astrocytomas (IMAs) are rare tumors, and few studies specific to the molecular alterations of IMAs have been performed. Recently, KIAA1549-BRAF fusions and the H3F3A p.K27M mutation have been described in low-grade (LG) and high-grade (HG) IMAs, respectively. In the present study, we collected clinico-radiological data and performed targeted next-generation sequencing for 61 IMAs (26 grade I pilocytic, 17 grade II diffuse, 3 LG, 3 grade III and 12 grade IV) to identify KIAA1549-BRAF fusions and mutations in 33 genes commonly implicated in gliomas and the 1p/19q regions. One hundred seventeen brain astrocytomas were analyzed for comparison. While we did not observe a difference in clinico-radiological features between LG and HG IMAs, we observed significantly different overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that the tumor grade was associated with better OS while EFS was strongly impacted by tumor grade and surgery, with higher rates of disease progression in cases in which only biopsy could be performed. For LG IMAs, EFS was only impacted by surgery and not by grade. The most common mutations found in IMAs involved TP53, H3F3A p.K27M and ATRX. As in the brain, grade I pilocytic IMAs frequently harbored KIAA1549-BRAF fusions but with different fusion types. Non-canonical IDH mutations were observed in only 2 grade II diffuse IMAs. No EGFR or TERT promoter alterations were found in IDH wild-type grade II diffuse IMAs. These latter tumors seem to have a good prognosis, and only 2 cases underwent anaplastic evolution. All of the HG IMAs presented at least one molecular alteration, with the most frequent one being the H3F3A p.K27M mutation. The H3F3A p.K27M mutation showed significant associations with OS and EFS after multivariate analysis. This study emphasizes that IMAs have distinct clinico-radiological, natural evolution and molecular landscapes from brain astrocytomas.
Microglia depletion diminishes key elements of the leukotriene pathway in the brain of Alzheimer’s Disease mice
Authors: Michael J. , Unger M. S. , Poupardin R. , Schernthaner P. , Mrowetz H. , Attems J. , Aigner L. 
Published: August 2020

AbstractLeukotrienes (LTs) contribute to the neuropathology of chronic neurodegenerative disorders including Alzheimer’s Disease (AD), where they mediate neuroinflammation and neuronal cell-death. In consequence, blocking the action of Leukotrienes (LTs) ameliorates pathologies and improves cognitive function in animal models of neurodegeneration. Surprisingly, the source of Leukotrienes (LTs) in the brain is largely unknown. Here, we identified the Leukotriene (LT) synthesis rate-limiting enzyme 5-Lipoxygenase (5-Lox) primarily in neurons and to a lesser extent in a subpopulation of microglia in human Alzheimer´s Disease (AD) hippocampus brain sections and in brains of APP Swedish PS1 dE9 (APP-PS1) mice, a transgenic model for Alzheimer´s Disease (AD) pathology. The 5-Lipoxygenase (5-Lox) activating protein (FLAP), which anchors 5-Lipoxygenase (5-Lox) to the membrane and mediates the contact to the substrate arachidonic acid, was confined exclusively to microglia with the entire microglia population expressing 5-Lipoxygenase activating protein (FLAP). To define the contribution of microglia in the Leukotriene (LT) biosynthesis pathway, we ablated microglia using the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in wildtype (WT) and APP-PS1 mice. Microglia ablation not only diminished the expression of FLAP and of the Leukotriene (LT) receptor Cysteinylleukotriene receptor 1 (CysLTR1), as expected based on their microglia cell type-specific expression, but also drastically reduced 5-Lipoxygenase (5-Lox) mRNA expression in the brain and its protein expression in neurons, in particular in wildtype (WT) mice. In conclusion i) microglia are key in Leukotriene (LT) biosynthesis, and ii) they regulate neuronal 5-Lipoxygenase (5-Lox) expression implying a yet unknown signaling mechanism between neurons and microglia.
Co-expression of NMDA-receptor subunits NR1, NR2A, and NR2B in dysplastic neurons of teratomas in patients with paraneoplastic NMDA-receptor-encephalitis: a retrospective clinico-pathology study of 159 patients
Authors: Jiang Xin-Yue , Lei Song , Zhang Le , Liu Xu , Lin Min-Tao , Blumcke Ingmar , Piao Yue-Shan , Zhou Dong , Li Jin-Mei 
Published: August 2020

Abstract
Objective
To comprehensively describe the pathological features of neurons in patients with ovarian teratomas and paraneoplastic anti-NMDAR encephalitis (anti-NMDARE), emphasizing on NMDA-receptor expression and infiltrating lymphocytes.

Methods
A retrospective study was performed in a large series of 159 patients from the West China Hospital. We retrospectively identified 12 patients with paraneoplastic anti-NMDARE (11 case with ovarian teratomas and 1 case with mixed germ cell tumor), which were compared to 35 patients with teratomas and no encephalitis and to 147 patients with anti-NMDARE and no evidence for tumors. Patient history and outcome were reviewed from the clinical charts and compared between all three groups. Histopathological examination, including double-immunofluorescence of NMDAR subunits and IgG was performed in all teratoma tissues. Magnetic Luminex Assay Human Premixed Multi-Analyte Kit was performed to investigate cytokines profile of CSF.

Results
Patients with paraneoplastic anti-NMDARE had a more severe clinical presentation, i.e. they required more mechanical ventilation and intensive care (p < 0.001). Though immunotherapy was initiated earlier in this group, repeated intravenous immunoglobulin administration (IVIG) was more common (p = 0.002) and with higher cerebrospinal fluid (CSF) antibody titres (p = 0.004). Following tumor resection, the outcome did not differ between groups. A peculiar population of floating-frog like dysplastic neurons were observed only in teratomas of patients with paraneoplastic anti-NMDARE, co-expressing NR1, NR2A, NR2B subunits and IgG. Also, CD20 positive B-cells were more common in anti-NMDARE teratomas. In CSF of paraneoplastic anti-NMDARE patients, TNF-α, IL-10 and GM-CSF concentrations were higher than in negative symptom control and VEGF-A and IL-1a were lower than in anti-NMDARE patients (0.25 < p < 0.05).

Conclusions
Patients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE. Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE.
The many faces of Reigate Stone: an assessment of variability in historic masonry based on Medieval London’s principal freestone
Authors: Michette Martin , Viles Heather , Vlachou Constantina , Angus Ian 
Published: August 2020

Abstract
Reigate Stone was used in high profile projects across London during a key growth period and represents an important chapter of architectural heritage. Historic Reigate masonry is subject to inherent variability. It is prone to rapid decay; however, highly decayed and well-preserved stones are frequently adjacent. This inherent variability in masonry can present a challenge to the design of conservation strategies by obscuring or complicating the identification of decay processes. This paper presents a model for assessing the combined impact of construction economies and mineralogical variability (Graphical abstract), by synthesising archival research on the history of Reigate Stone with experimental analysis of its properties. The limitations of the local geography coupled with the demands of the medieval building industry are shown to have introduced inherent variability into the built fabric at an early stage. Later socio-economic factors are shown to have compounded these by contributing to selective recycling, replacement and contamination of Reigate Stone. These historic factors augmented pre-existing mineralogical variability. This variability makes classification according to commonly used stone types difficult. Experimental analysis correlates variable cementing components with hygro-physical properties related to resilience. Calcite content influences strength properties and capillarity; clay content influences moisture adsorption and retention; opal-CT forms a weakly cemented, porous matrix. These presented different decay pathways to a range of environmental mechanisms and agents of decay. The findings suggest that inherent mineralogical variability, environmental changes, and historic contingency must all be considered in the design of ongoing Reigate Stone conservation strategies.
Changing times, changing needs: enhancing the utility of international large-scale assessments
Authors: Kirsch Irwin , Braun Henry 
Published: August 2020

AbstractMounting concerns about the levels and distributions of human capital, as well as how they are associated with outcomes for individuals and societies, have contributed to an increase in the number of national and international surveys. These surveys not only examine skills among school-age and adult populations, they also facilitate evaluation of the relationships among these skills and various background factors. At this juncture, the main ILSAs are making the transition to becoming fully digitally based assessments (DBAs). With the transition rapidly progressing, this is a propitious moment to consider the history of large-scale national and international assessments and to reflect on both what has contributed to their increased salience and growth, and how best to enhance their constructive impact on both policy and policy research in the future. We argue this can be done by utilizing a comprehensive, multidimensional framework that establishes a set of design criteria against which these assessments, present and future can be evaluated. The original framework was proposed more than 30 years ago by Messick (European Journal of Psychology of Education II 2:157–165, 1987) when all large-scale assessments were developed and delivered with paper-based instruments. Messick’s framework provided an organizational structure for how to think about and evaluate the potential utility of all large-scale assessments. After presenting a brief historical perspective on the development and growth of large-scale assessments, we review and extend Messick’s original framework. We then describe how the transition to DBAs can impact each of the framework’s three criteria. We also offer recommendations on how ILSAs’ development and innovations can best be deployed so that they are of greater utility to policy makers and other stakeholders worldwide.
Repeated occurrence of surface-sediment remobilization along the landward slope of the Japan Trench by great earthquakes
Authors: Ikehara Ken , Usami Kazuko , Kanamatsu Toshiya 
Published: August 2020

AbstractDeep-sea turbidites have been utilized to understand the history of past large earthquakes. Surface-sediment remobilization is considered to be a mechanism for the initiation of earthquake-induced turbidity currents, based on the studies on the event deposits formed by recent great earthquakes, such as the 2011 Tohoku-oki earthquake, although submarine slope failure has been considered to be a major contributor. However, it is still unclear that the surface-sediment remobilization has actually occurred in past great earthquakes. We examined a sediment core recovered from the mid-slope terrace (MST) along the Japan Trench to find evidence of past earthquake-induced surface-sediment remobilization. Coupled radiocarbon dates for turbidite and hemipelagic muds in the core show small age differences (less than a few 100 years) and suggest that initiation of turbidity currents caused by the earthquake-induced surface-sediment remobilization has occurred repeatedly during the last 2300 years. On the other hand, two turbidites among the examined 11 turbidites show relatively large age differences (~ 5000 years) that indicate the occurrence of large sea-floor disturbances such as submarine slope failures. The sedimentological (i.e., of diatomaceous nature and high sedimentation rates) and tectonic (i.e., continuous subsidence and isolated small basins) settings of the MST sedimentary basins provide favorable conditions for the repeated initiation of turbidity currents and for deposition and preservation of fine-grained turbidites. The MST small basin is a suitable site for examining deep-sea turbidite paleoseismology.
It is not ‘business as usual’ for orthopaedic surgeons in May 2020– the Austrian-German-Swiss experience
Authors: Liebensteiner M. C. , Khosravi I. , Hirschmann M. T. , Heuberer P. R. ,   The Board of the AGA - Society of Arthroscopy and Joint-Surgery, HEUBERER Philipp , NIEMEYER Philipp , LILL Helmut , LAMPERT Christoph , DIRISAMER Florian , BRAUN Sepp , BUCHHORN Tomas , ATTAL René E. L. , JUNG Christian , MÜLLER Andreas Marc , SCHEFFLER Sven , ZELLNER Johannes , ANGELE Peter , Saffarini M. , Thaler M. 
Published: August 2020

Abstract
Purpose
To document the status-quo of orthopaedic health-care services as the COVID-19 pandemic recedes, and to determine the rate of resumption of orthopaedic surgery in the German-speaking countries in May 2020.

Methods
A prospective online survey was sent out to 4234 surgeons of the AGA - Society of Arthroscopy and Joint-Surgery (Gesellschaft für Arthroskopie und Gelenkchirurgie, AGA). The survey was created using SurveyMonkey software and consisted of 23 questions relating to the reduction of orthopaedic services at the participating centres and the impact that the pandemic is having on each surgeon.

Results
A total of 890 orthopaedic surgeons responded to the online survey. Approximately 90% of them experienced a reduction in their surgical caseload and patient contact. 38.7% stated that their institutions returned to providing diagnostic arthroscopies. 54.5% reported that they went back to performing anterior cruciate ligament reconstructions (ACLR), 62.6% were performing arthroscopic meniscus procedures, and 55.8% had resumed performing shoulder arthroscopy. Only 31.9% of the surgeons were able to perform elective total joint arthroplasty. 60% of the participants stated that they had suffered substantial financial loss due to the pandemic.

Conclusion
A gradual resumption of orthopaedic health-care services was observed in May 2020. Typical orthopaedic surgical procedures like ACLR, shoulder arthroscopy and elective total joint arthroplasty were reported to be currently performed by 54%, 56% and 32% of surgeons, respectively. Despite signs of improvement, it appears that there is a prolonged curtailment of orthopaedic health-care at present in the middle of Europe.
A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis
Authors: Fisher Jane , Pavan Chiara , Ohlmeier Luisa S. , Nilson Bo , Lundgaard Iben , Linder Adam , Bentzer Peter 
Published: August 2020

AbstractBackgroundAcute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae.MethodsWe developed and tested a functional observational battery to quantify the severity of a variety of relevant neurological and clinical symptoms in a rat model of bacterial meningitis. The functional observational battery included symptoms relating to general clinical signs, gait and posture abnormalities, involuntary motor movements, focal neurological signs, and neuromotor abnormalities which were scored according to severity and summed to obtain a combined clinical and neurological score. To test the functional observational battery, adult Sprague-Dawley rats were infected by intracisternal injection of a clinical isolate ofStreptococcus pneumoniae. Rats were evaluated for 6 days following the infection.ResultsPneumococcal meningitis was not lethal in this model; however, it induced severe neurological symptoms. Most common symptoms were hearing loss (75% of infected vs 0% of control rats;p= 0.0003), involuntary motor movements (75% of infected vs 0% of control rats;p= 0.0003), and gait and posture abnormality (67% of infected vs 0% of control rats;p= 0.0013). Infected rats had a higher combined score when determined by the functional observational battery than control rats at all time points (24 h 12.7 ± 4.0 vs 4.0 ± 2.0; 48 h 17.3 ± 7.1 vs 3.4 ± 1.8; 6 days 17.8 ± 7.4 vs 1.7 ± 2.4;p< 0.0001 for all).ConclusionsThe functional observational battery described here detects clinically relevant neurological sequelae of bacterial meningitis and could be a useful tool when testing new therapeutics in rat models of meningitis.
Diffusion-Weighted Imaging (DWI) derived from PET/MRI for lymph node assessment in patients with Head and Neck Squamous Cell Carcinoma (HNSCC)
Authors: Freihat Omar , Pinter Tamas , Kedves András , Sipos Dávid , Cselik Zsolt , Repa Imre , Kovács Árpád 
Published: August 2020

AbstractBackgroundTo determine the usefulness of Diffusion Weighted Imaging (DWI) derived from PET/MRI in discriminating normal from metastatic lymph nodes and the correlation between the metastatic lymph nodes with the grade and the localization of the primary tumor.MethodsRetrospective study of 90 lymph nodes from 90 subjects; 65 patients who had proven histopathological metastatic lymph nodes from (HNSCC) who had undergone18F- PET/MRI for clinical staging and assessment and twenty-five lymph nodes were chosen from 25 healthy subjects. Apparent Diffusion Coefficient (ADC) map was generated from DWI withbvalues (0 and 800 s/mm2). ADC values of the metastatic lymph nodes were calculated and compared to the normal lymph nodes ADC values, ROC was used to determine the best cut-off values to differentiate between the two group. Metastatic lymph nodes ADC mean values were compared to primary tumor grade and localization.ResultsADCmean value of the metastatic lymph nodes in the overall sample (0.899 ± 0.98*10− 3 mm2/sec) was significantly lower than the normal lymph nodes’ ADCmean value (1.267 ± 0.88*10− 3 mm2/sec); (P = 0.001). The area under the curve (AUC) was 98.3%, sensitivity and specificity were 92.3 and 98.6%, respectively, when using a threshold value of (1.138 ± 0.75*10− 3 mm2/sec) to differentiate between both groups. Significant difference was found between metastatic lymph nodes (short-axis diameter < 10 mm), ADCmean (0.898 ± 0.72*10− 3 mm2/sec), and the benign lymph nodes ADCmean, (P = 0.001). No significant difference was found between ADCmean of the metastatic lymph nodes < 10 mm and the metastatic lymph nodes > 10 mm, ADCmean (0.899 ± 0.89*10− 3 mm2/sec), (P = 0.967). No significant differences were found between metastatic lymph nodes ADCmean values and different primary tumor grades or different primary tumor localization, (P > 0.05).ConclusionDWI-ADC is an effective and efficient imaging technique in differentiating between normal and malignant lymph nodes, and might be helpful to discriminate sub-centimeters lymph nodes.Trial registrationThe trial is registered in clinical trials underID:NCT04360993, registration date: 17/04/2020.
Potential impact and challenges associated with Parkinson’s disease patient care amidst the COVID-19 global pandemic
Authors: Elbeddini Ali , To Anthony , Tayefehchamani Yasamin , Wen Cindy 
Published: August 2020

AbstractBackgroundCOVID-19 has made itself known to health care providers and families across the world in a matter of months. While primarily a respiratory disorder, it has also been shown to cause neurological symptoms, which can be a concern for Parkinson’s disease (PD) patients. Although PD is not as common as other conditions such as cardiovascular diseases, it affects millions of patients around the world whose care has been affected by the global pandemic.ObjectivesThe aim of this review is to provide insight into the direct and indirect associations between COVID-19 and PD patient care.ResultsPotential direct effects of COVID-19 include possible neurodegeneration, concerns of symptom self-management with over-the-counter (OTC) products and ICU challenges that can arise in PD patients. In addition, a subset of PD patients may be at higher risk of severe COVID-19 infection. The indirect effects of the pandemic are associated with the social distancing measures and disruptions in health care systems and PD clinical trials, which may negatively affect PD patients’ mental wellbeing and create barriers in controlling their PD symptoms. On a more positive note, telemedical care is quickly emerging as a primary communication tool for virtual patient care. However, further research should be conducted to examine the applicability of telemedicine across the entire PD population, such as those with more severe symptoms living in less developed areas. With all the uncertainty during this time, it is hopeful to hear many promising COVID-19 treatments being researched, one of them being a PD drug therapy, amantadine.ConclusionHopefully, we can consider this pandemic an opportunity to strengthen the PD community and learn more about the impact of the SARS-COV-2 virus. This review provides an overview of the interaction between COVID-19 and PD patients and future investigational retrospective studies are suggested to validate the observations.