bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dermatomyositis-related intestinal dysmotility
Authors: Loftis Christine , White Rosa , Dulgheru Emilia C 
Published: November 2021

ABSTRACT
Dermatomyositis (DM) is an inflammatory myopathy (IIM) characterized by proximal muscle weakness and pathognomonic skin lesions. A 69-year-old woman with a recent diagnosis of DM 1 month prior, treated with corticosteroids and immunomodulators, presented to our inpatient rehabilitation with worsening dysphagia and constipation. At the time of our evaluation, physical examination was notable for erythematous papules over the metacarpophalangeal joints, proximal interphalangeal joints, elbows, and knees as well as a violaceous rash on the face. Muscle strength was diminished bilaterally with proximal distribution being affected greater than distal. Laboratory studies were notable for the creatine kinase (CK) level of 31 IU/l, antinuclear antibodies (ANA) by immunofluorescence of 1:80, and aldolase 4 u/l. The 11-antibody myositis panel was negative showed partially treated acquired IIM with perifascicular atrophy. During hospitalisation, she was found to have pulmonary embolism. She received enoxaparin 1 mg/kg subcutaneous BID. Soon after, she developed rectal bleeding. Colonoscopy showed a stercoral ulcer caused by chronic constipation. While dysphagia is common, being present in 25–50% of patients with DM, lower gastrointestinal problems involving the small and large intestine are rare and typically present as a late manifestation of the disease. Decreased peristalsis in the large colon can lead to constipation, impaction, and subsequent mucosal ulceration, and pressure necrosis induced by faecaloma formation. Although rare, our case highlights the importance of recognising gastrointestinal complications that DM can cause and the effects that those complications have on morbidity and mortality.
Music Therapy with Children Whose Mothers Are in Residential Treatment for Substance Use Disorders: A Program Evaluation
Authors: Pasiali Varvara , Benner Gretchen , Tisdale Ashley , Jones Gabrielle E , Tart Miriam , Crate Nicole 
Published: November 2021

Abstract
Children who experience multiple stressors may benefit from music therapy programming that addresses the development of social skills, self-expression, and coping mechanisms. Emerging evidence supports the use of improvisation techniques, group songwriting, and drumming activities to support self-regulation and increase social competence. In this article, we aimed to describe the inception and evaluate the implementation of a music therapy program for children at a residential treatment facility for women with substance use disorders (SUDs) at Dove’s Nest, a residential facility for women with SUDs. In this facility, children can reside with their mothers during the length of treatment. We collected pre/post data from children ages 5–11 (N = 20) who attended 8 nonconsecutive music therapy sessions by asking the mothers to complete the Home and Community Social Behavior Scale (HCSBS; Merrell, K. W., & Caldarella, P. (2008). Home & Community Social Behavior Scales user’s guide. Paul H. Brookes Publishing Company). Statistical analyses showed no significant changes on individual HCSBS subscale pre–post comparisons. The total number of scale items on HCSBS flagged as areas of concern was reduced both in social competence (31 pre to 6 post or a decrease of 80.65%) and antisocial behavior (34 pre to 17 post or a decrease of 50%) scales. Evaluation results indicated that even though the children assessed may score within average ranges for social competence and antisocial behaviors, they still exhibit a high number of areas of concern at baseline, particularly in the defiant/disruptive category, which warrants preventive interventions. Clinicians may need to focus on interventions that promote social integration, self-regulation, and assertiveness while addressing behaviors such as blaming and attention seeking.
LncACTdb 3.0: an updated database of experimentally supported ceRNA interactions and personalized networks contributing to precision medicine
Authors: Wang Peng , Guo Qiuyan , Qi Yue , Hao Yangyang , Gao Yue , Zhi Hui , Zhang Yuanfu , Sun Yue , Zhang Yakun , Xin Mengyu , Zhang Yunpeng , Ning Shangwei , Li Xia 
Published: November 2021

Abstract
LncACTdb 3.0 is a comprehensive database of experimentally supported interactions among competing endogenous RNA (ceRNA) and the corresponding personalized networks contributing to precision medicine. LncACTdb 3.0 is freely available at http://bio-bigdata.hrbmu.edu.cn/LncACTdb or http://www.bio-bigdata.net/LncACTdb. We have updated the LncACTdb 3.0 database with several new features, including (i) 5669 experimentally validated ceRNA interactions across 25 species and 537 diseases/phenotypes through manual curation of published literature, (ii) personalized ceRNA interactions and networks for 16 228 patients from 62 datasets in TCGA and GEO, (iii) sub-cellular and extracellular vesicle locations of ceRNA manually curated from literature and data sources, (iv) more than 10 000 experimentally supported long noncoding RNA (lncRNA) biomarkers associated with tumor diagnosis and therapy, and (v) lncRNA/mRNA/miRNA expression profiles with clinical and pathological information of thousands of cancer patients. A panel of improved tools has been developed to explore the effects of ceRNA on individuals with specific pathological backgrounds. For example, a network tool provides a comprehensive view of lncRNA-related, patient-specific, and custom-designed ceRNA networks. LncACTdb 3.0 will provide novel insights for further studies of complex diseases at the individual level and will facilitate the development of precision medicine to treat such diseases.
TRF2 promotes dynamic and stepwise looping of POT1 bound telomeric overhang
Authors: Paul Tapas , Liou Wilson , Cai Xinyi , Opresko Patricia L , Myong Sua 
Published: November 2021

Abstract
Human telomeres are protected by shelterin proteins, but how telomeres maintain a dynamic structure remains elusive. Here, we report an unexpected activity of POT1 in imparting conformational dynamics of the telomere overhang, even at a monomer level. Strikingly, such POT1-induced overhang dynamics is greatly enhanced when TRF2 engages with the telomere duplex. Interestingly, TRF2, but not TRF2ΔB, recruits POT1-bound overhangs to the telomere ds/ss junction and induces a discrete stepwise movement up and down the axis of telomere duplex. The same steps are observed regardless of the length of the POT1-bound overhang, suggesting a tightly regulated conformational dynamic coordinated by TRF2 and POT1. TPP1 and TIN2 which physically connect POT1 and TRF2 act to generate a smooth movement along the axis of the telomere duplex. Our results suggest a plausible mechanism wherein telomeres maintain a dynamic structure orchestrated by shelterin.
TissueNexus: a database of human tissue functional gene networks built with a large compendium of curated RNA-seq data
Authors: Lin Cui-Xiang , Li Hong-Dong , Deng Chao , Guan Yuanfang , Wang Jianxin 
Published: November 2021

Abstract
Mapping gene interactions within tissues/cell types plays a crucial role in understanding the genetic basis of human physiology and disease. Tissue functional gene networks (FGNs) are essential models for mapping complex gene interactions. We present TissueNexus, a database of 49 human tissue/cell line FGNs constructed by integrating heterogeneous genomic data. We adopted an advanced machine learning approach for data integration because Bayesian classifiers, which is the main approach used for constructing existing tissue gene networks, cannot capture the interaction and nonlinearity of genomic features well. A total of 1,341 RNA-seq datasets containing 52,087 samples were integrated for all of these networks. Because the tissue label for RNA-seq data may be annotated with different names or be missing, we performed intensive hand-curation to improve quality. We further developed a user-friendly database for network search, visualization, and functional analysis. We illustrate the application of TissueNexus in prioritizing disease genes. The database is publicly available at https://www.diseaselinks.com/TissueNexus/.
mmCSM-NA: accurately predicting effects of single and multiple mutations on protein–nucleic acid binding affinity
Authors: Nguyen Thanh Binh , Myung Yoochan , de Sá Alex G C , Pires Douglas E V , Ascher David B 
Published: November 2021

AbstractWhile protein–nucleic acid interactions are pivotal for many crucial biological processes, limited experimental data has made the development of computational approaches to characterise these interactions a challenge. Consequently, most approaches to understand the effects of missense mutations on protein-nucleic acid affinity have focused on single-point mutations and have presented a limited performance on independent data sets. To overcome this, we have curated the largest dataset of experimentally measured effects of mutations on nucleic acid binding affinity to date, encompassing 856 single-point mutations and 141 multiple-point mutations across 155 experimentally solved complexes. This was used in combination with an optimized version of our graph-based signatures to develop mmCSM-NA (http://biosig.unimelb.edu.au/mmcsm_na), the first scalable method capable of quantitatively and accurately predicting the effects of multiple-point mutations on nucleic acid binding affinities. mmCSM-NA obtained a Pearson's correlation of up to 0.67 (RMSE of 1.06 Kcal/mol) on single-point mutations under cross-validation, and up to 0.65 on independent non-redundant datasets of multiple-point mutations (RMSE of 1.12 kcal/mol), outperforming similar tools. mmCSM-NA is freely available as an easy-to-use web-server and API. We believe it will be an invaluable tool to shed light on the role of mutations affecting protein–nucleic acid interactions in diseases.
What it is like to be a bit: an integrated information decomposition account of emergent mental phenomena
Authors: Luppi Andrea I , Mediano Pedro A M , Rosas Fernando E , Harrison David J , Carhart-Harris Robin L , Bor Daniel , Stamatakis Emmanuel A 
Published: November 2021

Abstract
A central question in neuroscience concerns the relationship between consciousness and its physical substrate. Here, we argue that a richer characterization of consciousness can be obtained by viewing it as constituted of distinct information-theoretic elements. In other words, we propose a shift from quantification of consciousness—viewed as integrated information—to its decomposition. Through this approach, termed Integrated Information Decomposition (ΦID), we lay out a formal argument that whether the consciousness of a given system is an emergent phenomenon depends on its information-theoretic composition—providing a principled answer to the long-standing dispute on the relationship between consciousness and emergence. Furthermore, we show that two organisms may attain the same amount of integrated information, yet differ in their information-theoretic composition. Building on ΦID’s revised understanding of integrated information, termed ΦR, we also introduce the notion of ΦR-ing ratio to quantify how efficiently an entity uses information for conscious processing. A combination of ΦR and ΦR-ing ratio may provide an important way to compare the neural basis of different aspects of consciousness. Decomposition of consciousness enables us to identify qualitatively different ‘modes of consciousness’, establishing a common space for mapping the phenomenology of different conscious states. We outline both theoretical and empirical avenues to carry out such mapping between phenomenology and information-theoretic modes, starting from a central feature of everyday consciousness: selfhood. Overall, ΦID yields rich new ways to explore the relationship between information, consciousness, and its emergence from neural dynamics.
EPCO-14. MULTIFACETED TRANSCRIPTOMIC AND PROTEOMIC ANALYSES IDENTIFIED PUTATIVE ALTERNATIVE SPLICING-DERIVED CELL SURFACE ANTIGENS IN GLIOMA
Authors: Nejo Takahide , Kwok Darwin , Leung Kevin , Wang Lin , Wang Albert , Watchmaker Payal , Diebold David , Driks Hannah , Wells Jim , Diaz Aaron , Costello Joseph , Okada Hideho 
Published: November 2021

Abstract

BACKGROUND
To develop effective immunotherapy for gliomas, it is crucial to expand the repertoire of targetable antigens. Recent studies have suggested that alternative splicing (AS), or its deriving tumor-specific junctions (“neojunctions”), could generate cryptic amino acid sequences that can be a source of neoantigens. In this study, we investigated neojunctions based on multifaceted transcriptomic and proteomic analyses, seeking the potential cell surface antigens that may be targeted by CAR.

METHODS
For screening, we analyzed bulk RNA-sequencing data of TCGA-GBM/LGG with high tumor purity (n = 429) and GTEx normal tissues (n = 9,166). Cohorts of spatially mapped intratumoral samples and longitudinally collected tumors were used to determine clonality and stability of the candidate neojunctions. Nanopore long-read amplicon sequencing was deployed to confirm the full-length transcript sequence. Their protein-level expression was explored by analyzing the Clinical Proteomic Tumor Analysis Consortium (CPTAC)-GBM proteomics dataset.

RESULTS
In the screening analysis comparing TCGA and GTEx datasets, we identified 218 neojunctions with adequate expression, prevalence, and tumor-specificity. Of these, 12 were predicted to be cell-surface antigens. Eight of the 12, such as BCAN, DLL3, and PTPRZ1, were also observed in multiple cases of another validation dataset. In the analysis of tumors with spatially mapped intratumoral samples, 7 of the 12 were recurrently detected in no less than 50% of the samples in multiple cases. In addition, 5 of the 12 were found to be conserved in primary and recurrent pairs of tumors in multiple cases. Full-length transcript sequencing corroborated our predictions based on short reads, and also demonstrated more complex AS patterns. Finally, CPTAC-GBM proteomics analysis identified one cryptic peptide that substantiated the corresponding transcriptome-based prediction. CONCLUSION: We identified neojunctions with the potential to generate cell-surface antigens. These multifaceted transcriptomic and proteomic analyses provide the rationale to pursue the development of immunotherapy targeting neojunction-derived antigens.
BIOM-09. MYO-INOSITOL LEVELS ON MR SPECTROSCOPY CAN PREDICT FAILURE OF ANTI-ANGIOGENIC TREATMENT IN RECURRENT GLIOBLASTOMA
Authors: El-Abtah Mohamed , Wenke Michael , Talati Pratik , Fu Melanie , Kim Daniel , Weerasekera Akila , He Julian , Vaynrub Anna , Vangel Mark , Rapalino Otto , Andronesi Ovidiu , Arrillaga-Romany Isabel , Forst Deborah , Yen Yi-Fen , Rosen Bruce , Batchelor Tracy , Gonzalez Ramon , Dietrich Jorg , Gerstner Elizabeth , Ratai Eva-Maria 
Published: November 2021

Abstract

BACKGROUND
Recurrent glioblastoma (rGBM) patients are often treated with anti-angiogenic agents such as bevacizumab (BEV). Despite therapeutic promise, conventional MR methods fail to determine which patients may not benefit. PURPOSE: The purpose of this study was to utilize magnetic resonance spectroscopic imaging (MRSI) with intermediate and short echo time to generate corrected Myo-inositol normalized by contralateral creatine (mI/c-Cr) in patients with rGBM treated with BEV and investigate whether it can predict survivorship prior to BEV initiation (baseline) and at 1-day, 4-weeks, and 8-weeks thereafter.

METHODS
We conducted a prospective, longitudinal study and evaluated spectroscopic data of myo-inositol (mI), a glial marker and osmoregulator within the brain, normalized to contralateral-creatine (mI/c-Cr) in the intratumoral, contralateral normal appearing white matter, and peritumoral volumes of rGBM patients. Area under the ROC curve (AUC) was calculated for all volumes at baseline, 1-day, 4-weeks, and 8-weeks after treatment to determine mI/c-Cr’s ability to predict survivorship.

RESULTS
21 participants (62 ± 12 years, 15 men) were evaluated. Lower mI/c-Cr in the tumor prior to and during BEV treatment predicted poor survivorship, with ROC analyses illustrating an AUC of 0.75 at baseline, 0.87 at 1-day, and 1 at 8 weeks. Lower levels of mI/c-Cr were also observed in the contralateral and the peritumoral volumes for shorter-term survivors. In the contralateral volume, lower mI/Cr was predictive of shorter-term survival at baseline and all other timepoints. Within the peritumoral volume, lower mI/c-Cr was predictive of shorter-term survival at baseline (AUC=0.80), 1-day (AUC=0.93), and 4-weeks (AUC=0.68).

CONCLUSIONS
Lower levels of mI/c-Cr within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and anti-angiogenic treatment failure as early as one month before BEV treatment. Acquiring MRSI alongside conventional MR imaging modalities can convey critical information regarding tumor microenvironment that informs management of patients with rGBM.
BIOM-10. PRECLINICAL PLATFORM FOR THE IDENTIFICATION OF DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY-BASED BIOMARKERS OF BRAIN TUMOR METABOLISM
Authors: Batsios Georgios , Tran Meryssa , Taglang Céline , Gillespie Anne Marie , Ronen Sabrina , Costello Joseph , Viswanath Pavithra 
Published: November 2021

Abstract
Metabolic reprogramming is a fundamental hallmark of cancer, which can be exploited for non-invasive tumor imaging. Deuterium magnetic resonance spectroscopy (2H-MRS) recently emerged as a novel, translational method of interrogating flux from 2H-labeled substrates to metabolic products. However, to date, preclinical studies have been performed in vivo, an endeavor which suffers from low-throughput and potential wastage of animal life, especially when considering studies of treatment response. Developing in vitro assays for monitoring metabolism of 2H-labeled substrates will enhance throughput, lead to the rapid evaluation of new 2H-based probes and enable identification of treatment response biomarkers, thereby allowing the best 2H-based probes to be translated for further in vivo assessment. The goal of this study was to develop a preclinical cell-based platform for quantifying metabolism of 2H-labeled probes in brain tumor models. Since the Warburg effect, which is characterized by elevated glycolytic production of lactate, is a metabolic phenotype of cancer, including brain tumors, we examined metabolism of 2H-glucose or 2H-pyruvate in patient-derived glioblastoma (GBM6) and oligodendroglioma (BT88) cells and compared to normal human astrocytes (NHACONTROL). Following incubation in media containing [6,6’-2H]glucose or [U-2H]pyruvate, 2H-MR spectra obtained from live cell suspensions showed elevated 2H-lactate production in GBM6 and BT88 cells relative to NHACONTROL. Importantly, 2H-lactate production from [6,6’-2H]glucose or from [U-2H]pyruvate was reduced in GBM6 or BT88 cells subjected to irradiation and temozolomide, which is standard of care for glioma patients, pointing to the utility of this method for detecting response to therapy. Collectively, we have, for the first time, demonstrated the ability to quantify metabolism of 2H-MRS probes in live cell suspensions and validated the utility of our assay for differentiating tumor from normal cells and assessing response to therapy. Our studies will expedite the identification of novel 2H-MRS probes for imaging brain tumors and potentially other types of cancer.
BIOM-14. METABOLIC BIOMARKERS OF TERT-TARGETED THERAPY FOR HUMAN GLIOBLASTOMA DETECTED BY MAGNETIC RESONANCE SPECTROSCOPY
Authors: Minami Noriaki , Hong Donghyun , Stevers Nicholas , Batsios Georgios , Gillespie Anne Marie , Pieper Russell , Costello Joseph , Viswanath Pavithra , Ronen Sabrina 
Published: November 2021

Abstract

BACKGROUND
TERT promoter mutations that result in TERT expression are observed in over 80% of GBM. Moreover, the upstream transcription factor GABPB1 was recently identified as an ideal therapeutic target for tumors with TERT promoter mutations. In that context, non-invasive reliable biomarkers that can help detect TERT expression are needed. The aim of this research was to assess the value of MRS-detectable metabolic changes as biomarkers of TERT expression and TERT-targeted therapy in GBM.

METHODS
Genetically engineered GBM cells (NHARas/TERT) treated with TERT siRNA were compared to siCtrl-treated cells, and stable TERT and GABPB1 knock down GBM cells (U251, GBM1) were compared to shCtrl. 1H-MRS and 13C-MRS metabolic data was acquired from cell extracts using a Bruker 500MHz scanner. Hyperpolarized MRS studies of live cells used a HyperSense DNP polarizer and data was acquired using a Varian 500MHz scanner. Spectra were analyzed using Mnova and Matlab software. Multivariate data analysis was performed using SIMCA software.

RESULTS
Unbiased PCA analysis of 1H-MRS metabolic data showed separation of TERT or GABPB1 knock down and control cells. VIP predictive scores revealed that lactate and GSH were the top altered metabolites with a significant drop observed in both metabolites in every model following TERT silencing. Consistent with the reduction in GSH, spectrophotometric assays showed a significant drop in NADPH and NADH. 2-13C glucose flux analysis revealed that both glycolysis and PPP-related metabolites were reduced in TERT knock down cells. Hyperpolarized [1-13C]-pyruvate flux to lactate was also reduced, confirming that the glycolytic pathway was altered following TERT knock down.

CONCLUSION
1H MRS-detectable lactate and GSH, combined with hyperpolarized 13C MRS-detectable metabolic fluxes, could serve as metabolic biomarkers of TERT-targeted therapy for human GBM with TERT promoter mutations. These biomarkers could be translated to the clinical, improve the monitoring of GBM patients and advance precision medicine.
BIOM-26. SURVIVAL OUTCOMES AND PROGNOSTIC FACTORS IN PRIMARY GLIOBLASTOMA FROM A REAL-WORLD RETROSPECTIVE STUDY
Authors: Brown Nicholas , Ottaviani Diego , Tazare John , Gregson John , Kitchen Neil , Brandner Sebastian , Fersht Naomi , Mulholland Paul 
Published: November 2021

Abstract

INTRODUCTION
Glioblastoma has limited therapeutic options and is associated with a poor prognosis. Treatment, clinical outcomes, and prognostic factors remain poorly characterised outside of the selected population enrolled in clinical trials.

METHODS
Demographic, tumour molecular profiles, treatment, and survival data was collated for patients who underwent a biopsy or resection diagnostic of de novo glioblastoma at our centre between July 2011 and December 2015. We used multivariate proportional hazards models to examine the association of potential prognostic markers with survival.

RESULTS
490 patients were identified: 60% were male with a median age of 59 years. 60% of patients had surgical debulking, and 40% biopsy only. Subsequently, 56% had standard chemoradiotherapy, 25% non-standard chemo/radio-therapy, and 19% no further treatment; 22% of patients who had adjuvant therapy had surgery at relapse, 37% second-line chemotherapy, and 11% third-line chemotherapy. Median survival was 9.2 months (IQR 7.9-10.3 months), with survival at 12- and 24-months 41% and 13% respectively. In multivariate analysis, longer survival was associated with debulking surgery vs biopsy alone (14.9 vs 8 months) (HR 0.54 [95%CI 0.41-0.70]); subsequent treatment after diagnosis (HR 0.12 [0.08-0.16]) (standard chemoradiotherapy [16.9 months] vs non-standard regimens [9.2 months] vs none [2.0 months]); tumour MGMT promotor methylation (HR 0.71 [0.58-0.87]); and younger age (hazard ratio vs age&lt; 50: 1.70 [1.26-2.30] for ages 50-59; 3.53 [2.65-4.70] for ages 60-69; 4.82 [3.54-6.56] for ages 70+). IDH mutation was associated with longer survival (HR 0.64 [0.66-0.97] in univariate but not multivariate analysis.

CONCLUSION
Median survival for patients with glioblastoma is less than a year. Younger age, debulking surgery, treatment with chemoradiotherapy, and MGMT promotor methylation are independently associated with longer survival.