bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMOD-29. STANDARDIZED GENERATION OF TUMOR-ORGANOIDS AS NOVEL DRUG SCREENING MODEL IN MENINGIOMA
Authors: Jungwirth Gerhard , Yu Tao , Junguo Cao , Lotsch Catharina , Unterberg Andreas , Herold-Mende Christel 
Published: November 2021

Abstract
Tumor-organoids (TOs) are novel, complex three-dimensional ex vivo tissue cultures that under optimal conditions accurately reflect genotype and phenotype of the original tissue with preserved cellular heterogeneity and morphology. They may serve as a new and exciting model for studying cancer biology and directing personalized therapies. The aim of our study was to establish TOs from meningioma (MGM) and to test their usability for large-scale drug screenings. We were capable of forming several hundred TO equal in size by controlled reaggregation of freshly prepared single cell suspension of MGM tissue samples. In total, standardized TOs from 60 patients were formed, including eight grade II and three grade III MGMs. TOs reaggregated within 3 days resulting in a reducted diameter by 50%. Thereafter, TO size remained stable throughout a 14 days observation period. TOs consisted of largely viable cells, whereas dead cells were predominantly found outside of the organoid. H&E stainings confirmed the successful establishment of dense tissue-like structures. Next, we assessed the suitability and reliability of TOs for a robust large-scale drug testing by employing nine highly potent compounds, derived from a drug screening performed on several MGM cell lines. First, we tested if drug responses depend on TO size. Interestingly, drug responses to these drugs remained identical independent of their sizes. Based on a sufficient representation of low abundance cell types such as T-cells and macrophages an overall number of 25.000 cells/TO was selected for further experiments revealing FDA-approved HDAC inhibitors as highly effective drugs in most of the TOs with a mean z-AUC score of -1.33. Taken together, we developed a protocol to generate standardized TO from MGM containing low abundant cell types of the tumor microenvironment in a representative manner. Robust and reliable drug responses suggest patient-derived TOs as a novel drug testing model in meningioma research.
BRMP-04. AI-based biomarker of the peritumoral region using tissue microstructure
Authors: Samani Zahra Riahi , Parker Drew , Wolf Ronald , Brem Steven , Verma Ragini 
Published: November 2021

Abstract

PURPOSE
Glioblastomas, the most common malignant brain tumor [BS1], infiltrate into peritumoral brain structures, making clinical management challenging. An unmet need is to develop a biomarker that reliably characterize infiltration in the peritumoral region, where surgical biopsy or resection may be hazardous. Diffusion tensor imaging (DTI) with multicompartment modeling can characterize extracellular free water, providing unique information of the tissue microstructure that is able to capture this heterogeneity. We propose a novel biomarker based on peritumoral tissue microstructure, using deep-learning on DTI-based free water map.

METHOD
Peritumoral regions were automatically segmented for 136 patients with brain tumors (86 glioblastomas and 50 metastases, ages 23–87 years, 65 females). We trained a Convolutional Neural Network (CNN) on free-water maps using automatically defined patches in the peritumoral area from glioblastomas and metastases, labeled as low free-water and high free-water to extract a microstructural index for each voxel. To extract the biomarker, we grouped peritumoral voxels into connected components (CCs) where adjacent voxels have high (&gt;0.9) microstructural index values. Two independent test sets related to two clinically significant problems were evaluated: i) metastases vs. glioblastomas; ii) glioma patients categorized into short and long survival groups and the number of CCs were statistically compared.

RESULT
Two-sample t-tests showed significant group difference in the number of CCs between metastases and glioblastomas (p&lt; 0.05), and short and long-survivals (p&lt;0.05) with higher number of CCs in metastases and long-survivals, which suggests smaller number of voxels in CCs.

CONCLUSION
The proposed biomarker based on CCs of microstructural index captures the differences in infiltration of the peritumoral region, showing larger CCs in glioblastomas and short-survivals corresponding to higher infiltration.

CLINICAL IMPORTANCE
The proposed biomarker provides a novel insight into the peritumoral microenvironment and can be derived from clinically feasible DTI data, providing new possibilities for the diagnosis and treatment of glioblastoma.
CNTM-06. Individual Cerebrocerebellar Functional Network Analysis for Decoding the Symptomatological Dynamics of Posterior Fossa Syndrome
Authors: Chen Ko-Ting , Huang Sheng-Yao 
Published: November 2021

Abstract
Posterior fossa syndrome (PFS) consists of three types of symptom (motoric, linguistic, and neurobehavioral) in patients with posterior fossa pathologies. The evolutional mechanism of this high cognitive syndromic complex from cerebellar origin remains unconfirmed. Previous studies analyzing PFS patients mostly focused on the association between structural abnormalities that occur during PFS, of which proximal efferent cerebellar pathway (pECP) injury appears to be the most common pathogenesis. However, structural imaging may not be sensitive enough to determine the dynamic course of PFS, since the symptomatology is primarily an output of cerebral operation. On the other hand, a network neuroscience approach using a mathematical model to extract information from functional imaging to generate interregional connectivity provides abundant evidence that the cerebellum is influential in modulating cerebral functions. This study applied a network approach to children with PFS. Scaling of each symptom domain was used to quantify the dynamics of the syndrome. An individual cerebrocerebellar functional network analysis was then performed to determine the network dynamics during PFS. Cross-validation of clinical neurophysiology and functional neuroscience suggested the critical role of the pECP within PFS from the network analysis. The employed approach was therefore useful in determining the complex clinical symptoms using individual functional network analysis, which bridges the gap between structural neuroimaging and clinical neurophysiology.
FLGS-04. Fluorescence lifetime imaging (FLIm) is a dye-free, high sensitivity approach for fluorescence guided surgery in high-grade and low-grade gliomas
Authors: Bloch Orin , Garcia Alba Alfonso , Anbunesan Silvia Noble , Frusciante Roberto , Bec Julien , Marcu Laura 
Published: November 2021

Abstract

INTRODUCTION
Fluorescence-guided surgery can improve tumor identification and extent of surgical resection. 5-ALA is the standard for GBM, but is limited by lack of quantitative fluorescence, a need to work in the dark, and a lack of sensitivity for low grade tumors. We have developed a novel instrument for dye-free tissue autofluorescence lifetime imaging (FLIm) to identify glioma tissue during resection. This approach utilizes time-resolved autofluorescence measurements in narrow-band channels to assess markers of tissue metabolism. Compared to intensity-based imaging of exogenous fluorophores, FLIm has greater sensitivity without dependence on background lighting. The advantages of FLIm include quantitative tissue analysis, the ability to work under full light conditions, sensitivity for high and low grade gliomas, and the potential ability to identify IDH mutational status. In this study, we validated the use of FLIm for identification of glioma tissue at tumor resection margins.

METHODS
FLIm was used to image tissue margins during glioma resections and compared to microbiopsies from imaged regions to correlate fluorescence with histopathology.

RESULTS
FLIm was applied intraoperatively to 11 GBM and 5 LGG patients (7 imaged biopsies per patient). In GBM, tumor infiltration of cortex was associated with significantly decreased fluorescence lifetime (FL) in channels 2 (470/28nm;p&lt;0.05) and 3 (542/50nm;p&lt;0.002). In subcortical margins, FL was inversely proportional to the density of tumor in channels 2,3 (p&lt;0.05). When IDH wild-type GBMs were compared to IDH1-mutant tumors, FL was noted to be significantly longer in channel 1 (390/40nm;p&lt;0.05), and trended towards longer FL in channel 2, shorter FL in channel 3. In LGG, FL was significantly correlated with tumor density in channel 2 (p&lt;0.01).

CONCLUSIONS
FLIm is a dye-free, quantitative alternative to 5-ALA for fluorescence guided glioma resections with sensitivity to high and low-grade tumors, and the ability to predict IDH mutations in GBM. Further validation studies are on-going.
ITVT-02. Elucidating the pleiotropic effects of verteporfin photodynamic therapy in preclinical glioblastoma models
Authors: Price Gabrielle , Anastasiadou Maria , Sudhir Sweta , Bouras Alexandros , Tsankova Nadejda , Hadjipanayis Constantinos 
Published: November 2021

Abstract
Glioblastoma (GBM) ranks the highest in mortality rate, incidence, and aggressiveness of primary brain tumor types. The highly malignant nature of GBM makes it difficult for mainstay treatments to have an effect beyond stabilizing the disease. Deregulation of receptor tyrosine kinase (RTKs), such as EGFR and PI3K, have been implicated in GBM tumorigenesis. The expression of EGFR has been linked to hippo pathway transcriptional co-activators YAP and TAZ that bind to TEAD co-factors to drive the transcription of target genes. The convergence of EGFR signaling and the hippo pathway regulates stem cell programs, including proliferation, survival, and self-renewal. Verteporfin (VP), an FDA-approved macular degeneration therapy, has antitumor effects in in vitro and in vivo GBM preclinical models and phase I/II clinical trials for patients with EGFR mutated/amplified GBM by abrogating YAP/TAZ-TEAD interactions. As a porphyrin derivative, VP can exert therapeutic and photodynamic effects in the presence of 689 nm light; however, the efficacy of VP-PDT has not been explored in GBM. Our results indicate that VP-PDT reduces cell viability to a greater extent than solitary VP treatment (viability — 0.7 uM VP: 97%, 0.7 uM VP-PDT: 46%). The antitumor effects of VP-PDT are two pronged involving 1) inhibition of live cell dynamics, including migration and intravasation, by downregulating hippo pathway constituents YAP, TAZ and TEAD and transcriptional target EGFR and 2) induction of programmed cell death by reactive oxygen species. Our results suggest that VP-PDT can be a potential avenue for treating these incurable tumors.
ITVT-06. Application of artificial intelligence and radiomics for the analysis of intraoperative ultrasound images of brain tumors
Authors: Cepeda Santiago 
Published: November 2021

Abstract

BACKGROUND
Intraoperative ultrasound (ioUS) images of brain tumors contain information that has not yet been exploited. The present work aims to analyze images in both B-mode and strain-elastography using techniques based on artificial intelligence and radiomics. We pretend to assess the capacity for differentiating glioblastomas (GBM) from solitary brain metastases (SBM) and also to assess the ability to predict the overall survival (OS) in GBM.

METHODS
We performed a retrospective analysis of patients who underwent craniotomy between March 2018 to June 2020 with GBM and SBM diagnoses. Cases with an ioUS study were included. In the first group of patients, an analysis based on deep learning was performed. An existing neural network (Inception V3) was used to classify tumors into GBM and SBM. The models were evaluated using the area under the curve (AUC), classification accuracy, and precision. In the second group, radiomic features from the tumor region were extracted. Radiomic features associated with OS were selected employing univariate correlations. Then, a survival analysis was conducted using Cox regression.

RESULTS
For the classification task, a total of 36 patients were included. 26 GBM and 10 SBM. Models were built using a total of 812 ultrasound images. For B-mode, AUC and accuracy values ranged from 0.790 to 0.943 and from 72 to 89 % respectively. For elastography, AUC and accuracy values ranged from 0.847 to 0.985 and from 79 to 95 % respectively. Sixteen patients were available for the survival analysis. A total of 52 radiomic features were extracted. Two texture features from B-mode (Conventional mean and GLZLM_SZLGE) and one texture feature from strain-elastography (GLZLM_LZHGE) were significantly associated with OS.

CONCLUSIONS
Automated processing of ioUS images through deep learning can generate high-precision classification algorithms. Radiomic tumor region features in B-mode and elastography appear to be significantly associated with OS in GBM.
TWMP-01. RESECTION OF SUPPLEMENTARY MOTOR AREA GLIOMAS: REVISITING SUPPLEMENTARY MOTOR SYNDROME AND THE ROLE OF THE FRONTAL ASLANT TRACT
Authors: Young Jacob , Gogos Andrew , Aabedi Alex , Morshed Ramin , Pereira Matheus , Lashof-Regas Samuel , Mansoori Ziba , Luks Tracy , Hervey-Jumper Shawn , Villanueva-Meyer Javier , Berger Mitchel 
Published: November 2021

Abstract

INTRODUCTION
The supplemental motor area (SMA) is an eloquent region that is frequently a site for gliomas or the region is included in the resection trajectory to deeper lesions.

METHODS
Patient, tumor and outcome data were collected retrospectively from the UCSF tumor registry for patients who underwent surgical resection for newly diagnosed supratentorial diffuse glioma (WHO Grade II - IV) between 2010 and 2019 in the SMA region and the extent of SMA resection was determined by volumetric assessment. Tumors were registered to a standard brain atlas to create a frequency heat map of tumor volumes and resection cavities.

RESULTS
Although the volume of tumor within the SMA region did not correlate with the development of SMA syndrome, patients with SMA syndrome had larger resection cavities in the SMA region (25.4% SMA resection vs. 14.2% SMA resection, p = 0.039). The size of the resection cavity in the SMA region did not correlate with the severity of the SMA syndrome. Patients who developed SMA syndrome had cavities that were located more posteriorly in the SMA region and in the cingulate. When the frontal aslant tract (FAT) was preserved, 50% of patients developed SMA syndrome post-operatively; whereas 100% of patients who had disruption of the FAT during surgery developed SMA syndrome (p = 0.06). There was no difference in the overall survival for newly diagnosed glioblastoma patients with SMA syndrome compared to those without SMA syndrome (1.6 years vs. 3.0 years, p = 0.33).

CONCLUSION
For patients with SMA gliomas, larger resections and resections involving the posterior SMA region and posterior cingulate gyrus increased the likelihood of a post-operative SMA syndrome. Although SMA syndrome occurred in all cases where the FAT was resected, FAT preservation does not reliably avoid SMA syndrome post-operatively.
A phase II study of laser interstitial thermal therapy combined with doxorubicin in patients with recurrent glioblastoma
Authors: Butt Omar H , Zhou Alice Y , Huang Jiayi , Leidig William A , Silberstein Alice E , Chheda Milan G , Johanns Tanner M , Ansstas George , Liu Jingxia , Talcott Grayson , Nakiwala Ruth , Shimony Joshua S , Kim Albert H , Leuthardt Eric C , Tran David D , Campian Jian L 
Published: November 2021

Abstract

Background
The blood-brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability.

Methods
Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6–8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared to historical controls treated with bevacizumab salvage therapy (n = 50) or LITT with standard BBB-permeable salvage therapy (n = 28). Cox proportional-hazards models examined the contribution of age, gender, MGMT promoter status, and IDH-mutation status on any PFS and OS. Adverse events were also cataloged.

Results
The Late Arm and all patients (Early Arm + Late Arm) demonstrated significant improvement in OS compared to historical controls treated with bevacizumab (p &lt; 0.001) and LITT with standard salvage therapy (p &lt; 0.05). No significant difference in any PFS was observed between either arm and historical controls. Low-dose doxorubicin was well tolerated with comparable adverse event rates between the arms.

Conclusions
Low-dose doxorubicin given after LITT is well tolerated and correlated with higher OS compared to historical controls treated with bevacizumab or LITT with standard salvage chemotherapy. A larger study is needed to further characterize survival and progression patterns.
Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases
Authors: Chen Huimin , Wu Xiaohan , Xu Chunjin , Lin Jian , Liu Zhanju 
Published: November 2021

AbstractNeutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation, hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.
Coordination and Continuous Stochastic Choice
Authors: Morris Stephen , Yang Ming 
Published: November 2021

Abstract
Players receive a return to investment that is increasing in the proportion of others who invest and the state and incur a small cost for acquiring information about the state. Their information is reflected in a stochastic choice rule, specifying the probability of a signal leading to investment. If discontinuous stochastic choice rules are infinitely costly, there is a unique equilibrium as costs become small, in which actions are a best response to a uniform (Laplacian) belief over the proportion of others investing. Infeasibility of discontinuous stochastic choice rules captures the idea that it is impossible to perfectly distinguish states that are arbitrarily close together and is both empirically documented and satisfied by many natural micro-founded cost functionals on information. Our results generalize global game selection results and establish that they do not depend on the specific additive noise information structure.
Musculoskeletal pain in psoriasis—relation to inflammation and additional value of ultrasound in psoriatic arthritis classification
Authors: Felbo Sara Kamp , Terslev Lene , Juul Sørensen Inge , Hendricks Oliver , Kuettel Dorota , Lederballe Pedersen Rasmus , Chrysidis Stavros , Duer Anne , Zachariae Claus  , Skov Lone , Østergaard Mikkel 
Published: November 2021

Abstract

Objective
To investigate and compare clinical features and US signs of inflammation in joints and entheses in patients with psoriasis with and without musculoskeletal pain, and the additional value of US in classification of PsA. Furthermore, to explore the association between such findings and patient-reported outcomes (PROs) and the performance of screening-questionnaires for identifying patients with PsA.

Methods
Patients with psoriasis (n = 126) recruited from a nationwide survey were evaluated at one of four rheumatology departments. The evaluation included clinical examination, laboratory tests, radiography, greyscale and colour Doppler US of 48 joints and 12 entheses, PROs, and four screening questionnaires for PsA. Patients were classified with Classification for PsA (CASPAR), US-modified CASPAR, and US-only criteria.

Results
When subgroups of self-reported pain (63%), no pain (29%) and diagnosed PsA (9%) were compared, patients with pain had higher tenderness-related clinical scores (tender joints, entheses and FM points) and US greyscale sum-scores, compared with ‘no pain’ patients. PROs were negligibly moderately correlated with pain-related clinical scores (Spearman’s rho = 0.11–0.59, all patients), and negligibly weakly with US sum-scores (rho = 0.01–0.34). More patients could be classified as PsA when US synovitis/enthesitis was included as an entry criterion (US-modified CASPAR, 66% of all patients) compared with conventional CASPAR (35%) or US-only criteria (52%). Sensitivities of screening questionnaires were low for fulfilment of CASPAR (0.23–0.66), US-modified CASPAR (0.17–0.57), and US-only (0.20–0.57) criteria.

Conclusion
Self-reported pain in psoriasis is related to US inflammation. US-modified CASPAR criteria identified almost twice as many patients as conventional CASPAR criteria. Screening questionnaires showed limited value.
Inter-brain synchronization is weakened by the introduction of external punishment
Authors: Li Jianbiao , Pan Jingjing , Zhu Chengkang , Wang Yiwen 
Published: November 2021

Abstract
Punishment is a popular institution to enforce social norms in human society. However, how the punishment institution impacts the inter-brain neural signatures of two-person social interactions is still an open question. By performing electroencephalography recording of brain activity in two interacting parties as they simultaneously played both the revised repeated ultimatum game (rrUG) and the revised repeated dictator game (rrDG), this study focused on exploring how the introduction of external punishment influences inter-brain synchronization between the two parties. The data showed a significant negative effect of external punishment on inter-brain synchronization, with greater inter-brain synchronization observed in the rrDG than in the rrUG. We proposed a possible mechanism underlying this result. In the rrDG, the similar moral motivation of both proposers and responders results in inter-brain synchronization between them. However, in the rrUG, the introduction of external punishment crowds out the intrinsic moral motivation of the proposers, thereby undermining the inter-brain synchronization. Moreover, we found a significant positive correlation between the rejection rate from responders for disadvantageous inequal offer and inter-brain synchronization in the rrDG. These findings contribute to understanding the negative effect of punishment institution and shed light on the inter-brain mechanism underlying social interaction.