bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regular Aerobic Exercise-Alleviated Dysregulation of CAMKIIα Carbonylation to Mitigate Parkinsonism via Homeostasis of Apoptosis With Autophagy
Authors: Liu Wenfeng , Fu Rang , Wang Zhiyuan , Liu Shaopeng , Tang Changfa , Li Li , Yin Dazhong 
Published: December 2019

Abstract
This study investigated carbonylation of proteins with oxidative modification profiling in the striatum of aging and Parkinson disease (PD) rats, as well as the long-term effects of regular aerobic exercise on the carbonylation process and the damaging effects of PD vs habitual sedentary behavior. Regular aerobic exercise improved the PD rats’ rotational behavior, increased tyrosine hydroxylase expression in both the striatum and substantia nigra pars compacta, and decreased α-synuclein expression significantly. Interestingly, apoptotic nuclei and autophagosomes were increased in the aerobic exercise PD rat striatum. Carbonylated protein Ca2+/calmodulin-dependent protein kinase alpha (CAMKIIα) was present in the middle-aged and aged groups but only in the sedentary, not the exercise, PD rat striatum. Notably, CAMKIIα was characterized by a 4-hydroxynonenal adduct. Regular aerobic exercise upregulated CAMKIIα expression level, activated the CAMK signaling pathway, and promoted the expression of autophagy markers Beclin1 and microtubule-associated proteins 1 A/1B light chain 3II. Aberrant carbonylation of CAMKII initiated age-related changes and might be useful as a potential biomarker of PD. Regular aerobic exercise alleviated protein carbonylation modification of CAMKIIα and regulated the CAMK signaling pathway, thereby affecting and regulating the homeostasis of apoptosis and autophagy in the striatum to alleviate the neurodegenerative process of PD lesions.
ADVANCING QUALITY COMPETITION IN BIG DATA MARKETS
Authors: Kuenzler Adrian 
Published: December 2019

Abstract
The European Commission in its decision in Google Search (Shopping) found that a dominant search engine abused its market power by giving preferential treatment to its own related services over those of rivals. Conventional market mechanisms, it is supposed, can no longer correct the harm arising from such conduct. But there is disagreement in legal scholarship as to what this harm actually represents. This article maintains that the practice of self-favouring is best understood as an attempt to ward off product quality degradations in digital markets, which are difficult to repair purely by means of the consumer’s sole ability to switch. Framed against Albert Hirschman’s well-known work on Exit, Voice, and Loyalty, the Commission’s ruling must be understood as recognition that rivalry stemming from smaller market actors will not necessarily prevent large platforms from degrading product quality, despite the consumer’s ability to gain access to a variety of services that are only a click away. The article explicates the market’s functioning and the available methods of recuperation against the backdrop of the available case law in this area, and expounds the Commission’s findings in light of Hirschman’s theory.
Hyphema in Open-Globe Versus Closed-Globe Injuries in Operation Iraqi Freedom and Enduring Freedom: 2001–2011
Authors: Miller Natalie R , Justin Grant A , Kim Won I , Brooks Daniel I , Ryan Denise S , Weichel Eric D , Colyer Marcus H 
Published: December 2019

AbstractIntroductionThe goal of this study is to update the incidence of hyphema in Operation Iraqi (OIF) and Enduring Freedom (OEF). We wanted to assess associated ocular injuries and final visual acuity (VA) in open-globe versus closed-globe injuries with a hyphema.Materials and MethodsWe performed a retrospective review of the Walter Reed Ocular Trauma Database (WRTOD) to identify U.S. Service members and DoD civilians with hyphema who were evacuated to Walter Reed Army Medical Center between 2001 and 2011. Primary outcome measures were the final VA and differences in concomitant ocular injuries in open-globe hyphema and closed-globe hyphema.Results168 of 890 eyes (18.9%) in the WROTD had a hyphema. Closed-globe injuries were noted in 64 (38.1%) eyes and open-globe injuries in 104 (61.9%) eyes. A final VA of less than 20/200 was noted in 88 eyes (51.8%). Eyes with hyphema were more likely to have traumatic cataract formation (odds ratio (OR) 6.2, 95% confidence interval (CI) 4.2–9.2, P &lt; 0.001), retinal detachment (OR 4.2, CI 2.8–6.4, P &lt; 0.001), angle recession (OR 8.1, CI 2.9–24.3, P &lt; 0.001), and final VA of less than 20/200 (OR 3.7, CI 2.6–5.4, P &lt; 0.001). Traumatic cataract formation (OR 7.4, CI 2.9–18.7, P &lt; 0.001), retinal detachment (OR 6.1, CI 2.1–17.5, P &lt; 0.001), and a final VA less than 20/200 (OR 6.1, CI 2.4–15.4 P &lt; 0.001) were statistically more likely to occur with an open-globe hyphema than with a closed-globe hyphema.ConclusionsClose follow-up in patients with hyphema is important due to the associated development of traumatic cataract and retinal detachment and poor final visual outcome.
Double dark matter vision: twice the number of compact-source lenses with narrow-line lensing and the WFC3 grism
Authors: Nierenberg A M , Gilman D , Treu T , Brammer G , Birrer S , Moustakas L , Agnello A , Anguita T , Fassnacht C D , Motta V , Peter A H G , Sluse D 
Published: December 2019

ABSTRACT
The magnifications of compact-source lenses are extremely sensitive to the presence of low-mass dark matter haloes along the entire sightline from the source to the observer. Traditionally, the study of dark matter structure in compact-source strong gravitational lenses has been limited to radio-loud systems, as the radio emission is extended and thus unaffected by microlensing which can mimic the signal of dark matter structure. An alternate approach is to measure quasar nuclear-narrow-line emission, which is free from microlensing and present in virtually all quasar lenses. In this paper, we double the number of systems which can be used for gravitational lensing analyses by presenting measurements of narrow-line emission from a sample of eight quadruply imaged quasar lens systems, WGD J0405−3308, HS 0810+2554, RX J0911+0551, SDSS J1330+1810, PS J1606−2333, WFI 2026−4536, WFI 2033−4723, and WGD J2038−4008. We describe our updated grism spectral modelling pipeline, which we use to measure narrow-line fluxes with uncertainties of 2–10 per cent, presented here. We fit the lensed image positions with smooth mass models and demonstrate that these models fail to produce the observed distribution of image fluxes over the entire sample of lenses. Furthermore, typical deviations are larger than those expected from macromodel uncertainties. This discrepancy indicates the presence of perturbations caused by small-scale dark matter structure. The interpretation of this result in terms of dark matter models is presented in a companion paper.
MUSE-ALMA haloes V: physical properties and environment of z ≤ 1.4 H i quasar absorbers
Authors: Hamanowicz Aleksandra , Péroux Céline , Zwaan Martin A , Rahmani Hadi , Pettini Max , York Donald G , Klitsch Anne , Augustin Ramona , Krogager Jens-Kristian , Kulkarni Varsha , Fresco Alejandra , Biggs Andrew D , Milliard Bruno , Vernet Joël D R 
Published: December 2019

ABSTRACT
We present results of the MUSE-ALMA haloes, an ongoing study of the circumgalactic medium (CGM) of low-redshift galaxies (z ≤ 1.4), currently comprising 14 strong H i absorbers in 5 quasar fields. We detect 43 galaxies associated with absorbers down to star formation rate (SFR) limits of 0.01–0.1 M⊙ yr−1, found within impact parameters (b) of 250 kpc from the quasar sightline. Excluding the targeted absorbers, we report a high detection rate of 89 per cent and find that most absorption systems are associated with pairs or groups of galaxies (3–11 members). We note that galaxies with the smallest impact parameters are not necessarily the closest to the absorbing gas in velocity space. Using a multiwavelength data set (UVES/HIRES, HST, MUSE), we combine metal and H i column densities, allowing for derivation of the lower limits of neutral gas metallicity as well as emission-line diagnostics (SFR, metallicities) of the ionized gas in the galaxies. We find that groups of associated galaxies follow the canonical relations of N(H i)–b and Wr(2796)–b, defining a region in parameter space below which no absorbers are detected. The metallicity of the ISM of associated galaxies, when measured, is higher than the metallicity limits of the absorber. In summary, our findings suggest that the physical properties of the CGM of complex group environments would benefit from associating the kinematics of individual absorbing components with each galaxy member.
ACTR-25. RETHINKING THE DOGMA: HOW IMPORTANT IS TREATMENT OF THE CSF IN PATIENTS WITH PRIMARY CNS LYMPHOMA (PCNSL)?
Authors: Aregawi Dawit , Korfel Agnieszka , Schlegel Uwe , Glantz Michael 
Published: December 2019

Abstract

INTRODUCTION
PCNSL constitutes a small but important fraction of adult malignant primary brain tumors. These tumors frequently and often dramatically respond to high-dose methotrexate-containing regimens, but almost inevitably recur. Following initial treatment and at the time of recurrence, no widely accepted treatment paradigm exists. In particular, no consensus exists regarding the need to treat the CSF at the time of PCNSL diagnosis.

METHODS
We identified three independent cohorts of adults with PCNSL in which some patients received intra-CSF chemotherapy as part of their initial therapy, and others did not. All patients were comparable with respect to demographic and disease characteristics (study-level data). Data on CSF involvement, response, relapse, and survival were extracted and summary statistics were calculated from these three studies using the inverse variance method and random effects model.

RESULTS
The three cohorts were treated with: HD MTX/rituximab/ifosfamide followed by either HD MTX/cytarabine/ifosfamide (group Ia), or cytarabine/thiotepa and autologous stem cell transplant (group Ib) (n=80); HDMTX/rituximab/vinca alkaloids/ifosfamide/cytarabine (group II) (n=48); or HD MTX/rituximab (group III). Intra-CSF chemotherapy consisted of MTX/cytarabine/prednisolone (group Ia only, n=43); MTX/cytarabine/prednisolone (group II, n=30); or liposomal cytarabine (group III, n=21). One- and two-year survivals were greater in the IT chemotherapy compared to the no-IT chemotherapy groups (RR 1.25 [1.16–1.34] and 1.20 [1.14–1.26] respectively, p&lt; 0.001 for both). Relapse involving the CSF was greater in the non-IT chemotherapy group (RR 2.31 [2.03–2.62], p&lt; 0.001). In one cohort, comparison of pre-treatment CSF cytology from ventricular vs lumbar sites was possible. CSF cytology was positive in 81% of ventricular specimens vs 14.3% of lumbar specimens (p&lt; 0.0001).

CONCLUSIONS
CSF involvement by tumor occurs in most patients with PCNSL. Including intra-CSF chemotherapy in the initial treatment regimen of these patients may improve overall survival and reduce the frequency of relapses involving the CSF. Well-designed prospective trials are warranted.
GENE-02. ESTABLISHING PERSONALIZED TREATMENT OPTIONS FOR RECURRENT HIGH-GRADE GLIOMAS
Authors: Hau Ann-Christin , Houben Linsey , Klein Eliane , Oudin Anais , Stieber Daniel , Flies Ben , Kaoma Tony , Azuaje Fransisco , Fritah Sabrina , Bjerkvig Rolf , Mittelbronn Michel , Hertel Frank , Golebiewska Anna , Niclou Simone 
Published: December 2019

Abstract

BACKGROUND
High grade glioma (HGG) patients develop resistance to standard treatment leading to disease progression and limited life expectancy. Recent advances in the molecular characterisation of treatment-naïve HGGs based on next generation sequencing and DNA methylation analyses have led to a better delineation of HGG-subtypes and identification of distinct genomic abnormalities opening opportunities for personalized treatment strategies.

METHODS
We collected 300 fresh glioma specimen with approximately 100 longitudinal samples of initial and recurrent tumors from 43 matched patients. We succeeded in generating a live-biobank of HGG patient-derived orthotopic xenografts (PDOX) and 3D tumor organoids that neatly recapitulates the mutational spectrum including structural DNA variations and methylation-based subtypes of gliomas. A highlight is the generation of 19 PDOXs of paired initial and relapse HGGs from 9 glioma patients, enabling high-throughput drug screens. We performed comprehensive molecular profiling using arrayCGH, DNA-methylation and targeted DNA sequencing on patient specimen and their derivatives, 3D tumor organoids and PDOXs.

RESULTS
Detailed analysis of the paired longitudinal samples indicated that PDOXs closely recapitulate the evolutionary trajectory of the parental tumors. Furthermore, targeted genomic sequencing of paired HGGs suggests that relapse tumors also accumulate somatic mutations in epigenetic effectors. Based on patient-derived material we carried out drug response screening on 3D tumor organoids using a compound library matching the majority of genes that were assessed with targeted sequencing. Differential drug responses between initial and recurrent tumors were observed and the prevailing primary drug response profiles were essentially recapitulad in the relapse setting.

CONCLUSIONS
Response assessment of treatment-naïve gliomas and their recurrences provides crucial information on the differential sensitivity between initial and relapsed HGGs and offers novel personalized therapeutic options for the relapse setting. Furthermore, in depth correlation of the profiled somatic molecular landscape with drug response will enable pharmacogenomic predictions of potential inhibitors in the clinical setting.
HOUT-17. UTILITIES OF RARE CANCERS LIKE MALIGNANT PLEURAL MESOTHELIOMA AND GLIOBLASTOMA MULTIFORME - DO THEY COMPARE?
Authors: Proescholdt Christina , Kelly Justin 
Published: December 2019

Abstract

BACKGROUND
Glioblastoma (GBM) is the most aggressive primary brain cancer in adults. Malignant pleural mesothelioma (MPM) is an invasive and generally fatal malignancy of the pleura mainly caused by exposure to asbestos fibers. TTFields treatment has been shown effective in both MPM and GBM with a comparable increase in median overall survival (OS). Differences in utility values however, could significantly influence assessment of cost-effectiveness for MPM and GBM, despite similar clinical efficacy.

METHODS
We reviewed the published literature adressing health state preference values or health utilities in both indications using a boolean search of the PubMed database. The results were compiled separately for both diseases and then compared to each other.

RESULTS
Estimates of health states preference values or utilities in GBM all refer to one single publication by the UK NICE. Healthy members of the NHS Value of Health Panel (VoHP) rated a total of nine descriptive health state scenarios using the standard gamble method for preference elicitation. Utilities for MPM were derived at individual patient level from the EQ-5 questionnaire collected during one trial. Other publications do not use specific mesothelioma heath state preference velues but assume applicability of utilities derived from a non small cell lung cancer (NSCLC) population.

CONCLUSIONS
GBM utilites use different health states for elicitation, while utilities used in MPM were elicited at patient level. GBM utilities can be used in a health state disease model but there are no similar published values for MPM. MPM utilities using the EQ-5 questionnaire however better describe individual utilities and their change during the course of disease. Despite similar costs and clinical efficacy of TTFields treatment for GBM and MPM, the difference in elicitation methods and sources of utilites may lead to significant disparities in cost effectiveness assessment and subsequent adoption of TTFields treatment in different indications.
PATH-13. SEX-LINKED TUMORAL MGMT STATUS AND OUTCOMES IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Barnett Addison , Saeed Bamashmos Anas , Ali Assad , Li Hong , Bosler David , Lathia Justin , Yeaney Gabrielle , Sagar Soumya , Yu Jennifer , Murphy Erin , Chao Samuel , Suh John , Mohammadi Alireza , Stevens Glen , Angelov Lilyana , Peereboom David , Barnett Gene , Ahluwalia Manmeet 
Published: December 2019

Abstract

INTRO/OBJECTIVE
Glioblastoma (GBM) and MGMT have been reported to have sexual dimorphism. The primary objective of this study was to analyze the impact and association between sex and MGMT status on progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed GBM.

METHODS
582 patients with newly diagnosed GBM who underwent first surgical intervention at a single tertiary care institution between 2012 and 2018 were reviewed. Adults with documented methylated (≥ 12) and un-methylated (≤ 7) MGMT status were included. A Kaplan-Meier and Cox proportional hazard models were used to analyze the association between sex and MGMT status on PFS and OS.

RESULTS
464 adult patients (median age 63.4, 36.6% female) had documented MGMT status. Overall rate of MGMT methylated patients was 42.5%, while females were more often methylated than males (52.1% vs 37.4%, p=0.004). MGMT methylated compared to un-methylated females (median: 12.8 vs 7.4 months; 1-yr: 53% vs 27%) had a greater PFS benefit than males (median: 9.6 vs 6.8 months; 1-yr: 44% vs 23%). OS was significantly improved in MGMT methylated compared to un-methylated patients among females (p=0.001) but not among males (p=0.22). Among MGMT methylated patients, females had significantly better OS compared to males (median: 18.7 vs 12.4 months; 2-yr OS: 36.8% vs 24.3%, p=0.03). Although statistically not significant, a similar pattern was observed on PFS (median: 12.8 vs 9.6 months; 1-yr PFS: 52.6% vs 44.4%). Compared to MGMT methylated females, MGMT methylated males had a PFS HR=1.22 (95% CI=0.80 – 1.85, p=0.36), and an OS HR=1.45 (95% CI=1.03 – 2.04, p=0.032).

CONCLUSION
MGMT methylation is more common in females and methylation had a larger impact on both PFS and OS in females compared to males. These analyses highlight the need to further investigate sex differences that can inform clinical management of GBM.
NIMG-21. FROM BEYOND THE MARGIN: HIGH ANGULAR RESOLUTION Q-SPACE MRI MAY DETECT GLIOBLASTOMA TUMOR CELL INVASION INTO BRAIN PARENCHYMA
Authors: Leary Owen , Toms Steven , Zepecki John , Merck Derek , Tapinos Nikos , Gilbert Richard 
Published: December 2019

Abstract

BACKGROUND
Invasion of glioblastoma tumor cells beyond the visible margins is hypothesized to mediate tumor spread and recurrence, and thereby affect poor survival. Radiomic biomarkers associated with the extent of tumor infiltration are virtually non-existent.

METHODS
Seven subjects diagnosed with glioblastoma underwent high resolution “Q-Space” diffusion-weighted MRI sequences (Siemens 3T scanner, 64 gradient directions, b-value=1000s/mm2) during pre-operative MRI workup. For each subject, the largest tumor was manually segmented, and patterns of probabilistic inter-voxel coherence intersecting each segmentation generated as tractograms using DSI Studio (length=0–200mm, AT=30º). Separately, immunodeficient (Nu/J) mice were injected sub-hippocampally with patient-derived glioma stem cells (GSCs) using stereotactic guidance. Two months after injection, mice were sacrificed, resected brains were scanned on a Bruker 7T MRI using cryoprobe with T2-weighted and diffusion-weighted sequences (512 directions), and tumor-intersecting tractography displayed. 3D whole-brain reconstruction of the same xenograft model, stained with anti-human mitochondrial antibody, was performed for comparison. In one patient undergoing resection of fronto-temporal glioblastoma, BrainLab intraoperative navigation was used for stereotactic biopsy of extra-tumor parenchymal samples localized according to proximity to tumor-intersecting tractography. RNA-seq was performed on all samples using Illumina HiSeq2500 by a blinded analyst.

RESULTS
All human tumors (n=7) displayed region-specific long projecting tracts extending into brain parenchyma (Mean=23.2mm, SD=3.1mm). Maximum tract length varied from 80–130mm (Mean=102mm, SD=20.4mm). Xenograft models displayed similar tumor-intersecting tractography (n=3), with 3D reconstruction of stained GSCs replicating that pattern. RNAseq data revealed significant overrepresentation (≥2-fold) of 528 transcripts in projecting tumor tract-associated samples compared to samples obtained from the tumor mass itself and brain parenchyma unassociated with projecting tumor tracts. Functional classification revealed that 62% of these transcripts regulate cell motility as part of inter-related networks.

CONCLUSION
These imaging data, backed by region-specific transcriptomic evidence, suggest that Q-Space MRI may discriminate localizable patterns of inter-voxel coherence representing tumor-associated infiltration pathways in glioblastoma.
NCMP-16. IMMUNO-ONCOTHERAPY (IO) PROVOKED ENCEPHALITIS AND METASTATIC MIMICRY: PATIENT WITH HISTORY OF RENAL CELL CARCINOMA ON IO PRESENTS WITH SEIZURE, FIELD CUT, AND BRAIN MASS
Authors: Tosha Gatson Na , Patel Mayur , Grant Michelle , Woods Julie , Mongelluzzo Gino , Conger Andrew 
Published: December 2019

Abstract
With the success of immuno-oncotherapy (IO) to treat systemic cancers came the risk for multi-organ autoimmune inflammation (esophagitis, colitis, hypophysitis, pneumonitis, etc.). Immune-mediated encephalitis, however, has been only rarely described in patients treated on IO. Here we present the first case of a 70-year-old male with history of clear cell renal cell carcinoma (CCRCC, Fuhrman grade 4, April 2017) post-nephrectomy with early progressive pulmonary metastases treated with pazopanib before switching to single-agent nivolumab (February 2018) with demonstrated early response. Further progression (March 2019) added body irradiation and continued systemic nivolumab with questionable medication-induced dermatitis. Patient presented to ED in May 2019 with new-onset generalized tonic-clonic seizure, left visual field cut, and 4.6cm heterogeneous enhancing right occipital mass with vasogenic edema on brain MRI, presumed metastasis. However, unknown to the patient was a remote area of right occipital encephalomalacia (found on skull-based portion of staging PET, July 2018) presumed silent stroke or TBI endorsed 20-years-ago. Patient started anti-epileptic therapy and underwent negative CSF evaluation before neurosurgical resection. Tissue pathology concerning for lymphoproliferative malignancy versus reactive lymphocytic infiltrate with perivascular distribution of monomorphic CD4+ T-cell predominance (97%) and positive T-cell receptor (gamma, beta) gene rearrangement. While clonal T-cell populations are highly suggestive of T-cell malignancies, reactive conditions can also rarely show clonal T-cell populations. Patient underwent a negative systemic staging for lymphoma and IO was discontinued without immediate initiation of steroids. Follow up clinical evaluation reveal patient improved off IO therapy. Patient was determined to have reactive immune-mediated encephalitis secondary to IO therapy causing seizure mimicking brain metastasis of primary CCRCC. Interestingly, the prior area of encephalomalacia allowed for a cellular bed to collect, resembling brain mass. Upfront staging brain MRI prior to starting IO might have revealed susceptible area and could be considered in these patients