bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobile health applications for older adults: a systematic review of interface and persuasive feature design
Authors: Liu Na , Yin Jiamin , Tan Sharon Swee-Lin , Ngiam Kee Yuan , Teo Hock Hai 
Published: July 2021

Abstract

Objective
Mobile-based interventions have the potential to promote healthy aging among older adults. However, the adoption and use of mobile health applications are often low due to inappropriate designs. The aim of this systematic review is to identify, synthesize, and report interface and persuasive feature design recommendations of mobile health applications for elderly users to facilitate adoption and improve health-related outcomes.

Materials and Methods
We searched PubMed, Embase, PsycINFO, CINAHL, and Scopus databases to identify studies that discussed and evaluated elderly-friendly interface and persuasive feature designs of mobile health applications using an elderly cohort.

Results
We included 74 studies in our analysis. Our analysis revealed a total of 9 elderly-friendly interface design recommendations: 3 recommendations were targeted at perceptual capabilities of elderly users, 2 at motor coordination problems, and 4 at cognitive and memory deterioration. We also compiled and reported 5 categories of persuasive features: reminders, social features, game elements, personalized interventions, and health education.

Discussion
Only 5 studies included design elements that were based on theories. Moreover, the majority of the included studies evaluated the application as a whole without examining end-user perceptions and the effectiveness of each single design feature. Finally, most studies had methodological limitations, and better research designs are needed to quantify the effectiveness of the application designs rigorously.

Conclusions
This review synthesizes elderly-friendly interface and persuasive feature design recommendations for mobile health applications from the existing literature and provides recommendations for future research in this area and guidelines for designers.
Pre-release dietary supplements of methoprene and raspberry ketone increase field abundance of sterile Queensland fruit flies (Diptera: Tephritidae)
Authors: Biswas Md Jamil Hossain , Mainali Bishwo P , Inskeep Jess R , Cross Dominic , Benelli Maurizio , Allen Andrew P , Taylor Phillip W , Rempoulakis Polychronis 
Published: July 2021

AbstractThe sterile insect technique (SIT) is a sustainable pest management tool based on the release of millions of sterile insects that suppress reproduction in targeted populations. Success of SIT depends on survival, maturation, dispersal, and mating of released sterile insects. Laboratory and field cage studies have demonstrated that dietary supplements of methoprene and raspberry ketone (RK) promote sexual maturation of adult Queensland fruit fly, Bactrocera tryoni (Froggatt), and may hence shorten the delay between release and maturity in the field. We investigated the effects of methoprene and RK dietary supplements on field abundance of sexually mature sterile Q-flies relative to untreated flies fed only sugar and yeast hydrolysate before release at 2 d of age. Compared with untreated flies, more methoprene- and RK-treated flies were recaptured in cuelure traps to which only sexually mature males are attracted. At distances of 100 and 200 m from the release point, recapture rates were higher for methoprene- and RK-treated flies than for untreated flies, but at 300 m recapture rates were low and were similar for treated and untreated flies. Rainfall, relative humidity, wind speed, and wind direction did not affect recapture rates, but temperature was positively correlated with recapture rates for all treatments. There was a strong correlation between the number of sterile and wild flies caught in traps, indicating co-location in the field. Dietary supplements of methoprene and RK can substantially increase abundance of sexually mature sterile male Q-flies in the field following release as 2-d-old immature adults.
Swirl sign in post-Roux-en-Y gastric bypass patients: a case series
Authors: Al-Mulla Ahmad E , Sultan Abdulla E , Imam Ehab S , Al-Huzaim Raghad A 
Published: July 2021

Abstract
Bariatric surgeries have been increasing with the rising numbers of obese patients. Roux-en-Y is one of the safest and effective bariatric procedures worldwide. Internal hernia is one of laparoscopic Roux-en-Y gastric bypass complications. Its vague symptoms and late presentation may lead to adverse outcomes. Swirl sign in computed tomography scan has proven to be a particular and sensitive finding to detecting internal hernia in patients with an ambiguous presentation.
Acetylcholine ameliorated hypoxia-induced oxidative stress and apoptosis in trophoblast cells via p38 MAPK/NF-κB pathway
Authors: Wang Zheng , Zhao Gongxiao , Zibrila Abdoulaye Issotina , Li Yubei , Liu Jinjun , Feng Weiyi 
Published: July 2021

Abstract
Hypoxia-induced oxidative stress and apoptosis of trophoblast are involved in the pathogenesis of preeclampsia (PE). Extensive research reports that the principal vagal neurotransmitter acetylcholine (ACh) shows anti-oxidative and anti-apoptotic effects in various diseases models. However, the role of ACh in hypoxic trophoblast remains unknown. Here, we examined the apoptotic levels of human placenta and explored the role(s) of ACh on cobalt chloride (CoCl2)-treated (trophoblast-derived) HTR-8/SVneo cells for mimicking hypoxic injuries. Cell counting kit-8 (CCK-8), dihydroethidium (DHE) probe, western blotting, immunofluorescence staining, migration and invasion assay were employed in the current study. Our data showed that placentas from PE women exhibited increased level of reactive oxygen species (ROS) and apoptotic index than those in normal pregnancy. Our in vitro study showed that CoCl2 enhanced ROS generation and apoptosis in HTR-8/SVneo cells through the activation of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-κB (NF-κB) pathway. ACh significantly decreased hypoxia-induced ROS generation and the resulting apoptosis, accompanied by lowered phosphorylation of p38 MAPK and NF-κB. Western blotting analysis further confirmed that ACh decreased the ratio of pp38 MAPK/p38 MAPK, p-NF-κB/NF-κB, Bax/Bcl-2 and cleaved Caspase-3/Caspase-3. Besides, ACh promoted cell invasion and migration ability under hypoxic conditions. Atropine, the muscarinic receptor antagonist, abolished ACh’s effects mentioned above. Overall, our data showed that ACh exerted protective effects on hypoxia-induced oxidative stress and apoptosis in trophoblast cells via muscarinic receptors, indicating that improved vagal activity may be of therapeutic value in PE management.
ECOA-2. Immuno-sensitization of Glioblastoma to NY-ESO-1 Targeting via Promoter Demethylation
Authors: Lai Thomas , Treger Janet , Rao Jingyou , Li Tie , Lai Albert , Prins Robert , Everson Richard 
Published: July 2021

Abstract

Introduction
The immunotherapeutic targeting of New York-esophageal squamous cell carcinoma (NY-ESO-1) and other cancer/testis antigens (CTA) is an appealing strategy for the treatment of malignant gliomas because CTA are not expressed in most normal adult tissues and their expression can be induced in tumors for targeting by T-cells. Basally, NY-ESO-1 is often poorly expressed in glioblastoma (GBM), presumably through promoter methylation. Mechanisms governing the expression of CTA have been explored in other cancers; however, neither the prevalence of NY-ESO-1 downregulation in GBM patient tumors nor the presumed mechanism of downregulation by promoter methylation in GBM has been formally established.

Methods
We characterized baseline CpG methylation of NY-ESO-1 in 30 bulk patient GBM samples, 10 patient-derived gliomaspheres, and three established tumor cell lines using bisulfite sequencing. We induced NY-ESO-1 expression in vitro in U251 human GBM cells using the hypomethylating agent decitabine (DAC). We investigated the epigenetic response of DAC-treated U251 with bisulfite sequencing and NY-ESO-1 expression with quantitative real-time PCR. Lastly, we performed single-cell RNA sequencing on DAC-treated GBM U251 to evaluate tumor subpopulations that upregulate NY-ESO-1 and other co-expressed CTA after DAC treatment.

Results
Baseline NY-ESO-1 expression is associated with promoter methylation in the majority of GBM. Treatment of cells with 1 µM DAC every day for 4 days explicitly demethylated the promoter region of NY-ESO-1 and resulted in a 1000-fold increase in mRNA expression. DAC treatment upregulates NY-ESO-1 coordinately with other cancer/testis antigens CTAG2 and MAGEA4 as demonstrated by single-cell RNA sequencing.

Conclusion
Exposure of U251 to DAC results in promoter demethylation in NY-ESO-1 and increased expression of CTA. DAC treatment may therefore render GBM susceptible to targeting of these antigens by T-cells, revealing a feasible strategy of NY-ESO-1 and co-expressed CTA promoter demethylation to sensitize GBM to immunotherapy.
OMRT-8. Precision targeting of cellular pathways with complementary diagnostics
Authors: Siddaway Robert , Nobre Liana , Milos Scott , Johnson Monique , Ryall Scott , Sheth Javal , Ku Michelle , Tabori Uri , Hawkins Cynthia 
Published: July 2021

Abstract
Precision medicine tailors treatment for each patient by identifying the molecular drivers of their disease. This can allow more effective tumour targeting, avoid harmful standard chemotherapeutic side-effects, and offer savings to the healthcare system through not treating patients who are unlikely to respond to a specific agent. Treatment regimes are usually designed by identifying DNA-level alterations and selecting drugs tailored to that mutation. However, cancer is not a one-pathway disease and not all patients with particular mutations will respond to treatment, while patients without canonical pathway-activating mutations are excluded from potentially life-saving treatment. To address this, we have developed a NanoString assay combining proteomic and transcriptomic profiles of 4 key actionable, cancer-related pathways (MAPK, PI3K, NFκB and JAK/STAT). We used RNA-Seq data from gold standard cell lines with defined pathway changes to identify minimal gene sets indicative of pathway activation, and integrated them with phospho protein measurements to generate a pathway activation score. The combined panel was run on isogenic cell lines as well as glioma samples with both known and unknown driving alterations. We found pathway activation to be more variable than expected based on DNA alterations alone, implying that consideration of proteomic and/or transcriptomic-level information is important for future therapeutic decision-making.
OMRT-14. Small molecule circadian clock compounds exhibit potential as a novel therapy paradigm for glioblastoma
Authors: Chan Priscilla , Hirota Tsuyoshi , Qu Meng , Zhang Guoxin , Shah Khalid , Wakimoto Hiroaki , Kamenecka Theodore , Solt Laura , Rich Jeremy , Kay Steve 
Published: July 2021

Abstract
Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor type, claiming the lives of patients within 2 years of diagnosis. The major challenges in treating GBM are largely due to the biological characteristics of the tumor and the brain and pharmacokinetics of many drugs approved for other cancers. These tumors are located in areas that make it difficult to surgically resect without posing major issues and exposure to many drugs and therapies are limited due to the blood-brain barrier (BBB). GBMs also contain cancer stem cells, called GSCs, that have self-renewal and tumor initiating abilities, can secrete angiogenic factors, invade into the normal brain, and are chemoresistant and radioresistant. We found that GSCs have an exclusive dependence on core circadian clock transcription factors, Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK). These results suggest the potential for small molecule modulators of the circadian clock as a novel therapy paradigm for GBM treatment following surgical resection to prevent GSC infiltration and reoccurrence of the primary tumor. Here we found that multiple classes of clock compounds (Cryptochrome (CRY) stabilizers, REV-ERB agonists, Casein Kinase 1 (CK1) inhibitors, and Casein Kinase 2 (CK2) inhibitors) have the ability to elongate circadian periods in a clock reporter cell line. They also selectively and potently target patient-derived GSCs that range in sensitivity to temozolomide (TMZ) chemotherapy treatment while having limited effects on control cells both as single agents and in combination with each other. This data provides a platform for further exploration of synergistic effects of combining clock compounds with each other or with current GBM therapies, such as chemotherapy and radiation, with the ultimate goal of developing a clinical model of treatment.
OTEH-6. Algorithmic approach to characterize post-treatment recurrent glioma using RNA sequencing and quantitative histopathology
Authors: Argenziano Michael , Save Akshay , Boyett Deborah , Grinband Jack , Yoon Hyunsoo , Li Jing , Banu Matei , McKhann Guy , Sisti Michael , Swanson Kristin , Bruce Jeffrey , Canoll Peter 
Published: July 2021

Abstract

Introduction
Distinguishing between tumor and treatment effect in post-treatment glioma, although crucial for clinical management, is difficult because contrast-enhancing regions are mixtures of recurrent tumor and reactive tissue, and definitive histopathological criteria do not exist. This study disentangles the marked intra-tumoral heterogeneity in the treatment-recurrent setting by developing an unsupervised framework to algorithmically categorize intraoperative MRI-localized biopsies into three clinically-relevant tissue clusters based on joint analysis of RNA sequencing and histopathological data.

Methods
A retrospective cohort of 84 MRI-localized biopsies from 37 patients with post-treatment recurrent glioblastoma underwent mRNA extraction and quantification via PLATEseq protocol. For 48 of 84 biopsies, a neighboring piece of tissue underwent quantitative histopathology based on labeling index (LI) for SOX2, CD68, NeuN, Ki67, and H&E. Correlation between LIs and gene expression for these 48 samples was performed. Genes significantly correlated (p&lt;0.05) with ≥1 marker were used for hierarchical clustering of correlation matrix, identifying three mutually-exclusive tissue-specific gene sets. These sets were then used to perform ssGSEA to categorize each of 84 biopsies into one of three tissue types.

Results
Correlation analysis identified 7779 genes significantly correlated with ≥1 histopathological marker. Clustering revealed three gene sets associated with specific markers: SetA-3688 genes associated with SOX2/Ki67/H&E; SetB-2418 genes associated with CD68; SetC-1673 genes associated with NeuN. ssGSEA using these sets categorized each biopsy into one of three tissue types: 27 biopsies enriched in SetA, 28 in SetB, and 29 in SetC.

Conclusions
Using MRI-localized biopsies with both RNAseq and histopathological data, this algorithmic approach allows development of three orthogonal tissue-specific gene sets that can be applied to characterize the heterogeneity in post-treatment recurrent glioma: SetA: genes correlated with SOX2/Ki67/H&E, representing recurrent tumor; SetB: genes correlated with CD68 (microglia) representing reactive tissue consistent with treatment effect; SetC: genes correlated with NeuN (neurons), representing infiltrated brain.
OTEH-7. Molecular characterization of tumor stiffness in glioblastoma
Authors: Halldorsson Skarphedinn , Svensson Siri Fløgstad , Berg Henriette Engen , Wolrab Denise , Rise Frode , Wilkins Alistair , Wilson Steven Ray , Holcapek Michal , Emblem Kyrre Eeg , Vik-Mo Einar O 
Published: July 2021

Abstract
Tumor heterogeneity is one of the hallmarks of glioblastoma multiforme (GBM). Morphology within a given GBM tumor can be extremely variable where some regions of the tumor have a soft, gel-like structure while other areas are dense and fibrous. Abnormal mechanical stress and tissue stiffening caused by cancer proliferation are believed to affect vascularity by compressing structurally weak blood vessels and restricting the supply of nutrients and oxygen to the tissue. These effects contribute to a hypoxic microenvironment that promotes disease progression and chemoresistance. The genetic and molecular mechanisms that govern tissue stiffness within GBM tumors, however, are largely unknown. Magnetic Resonance Elastography (MRE) is an emerging technique for quantifying tissue stiffness non-invasively.
We have evaluated 10 GBM patients by MRE imaging obtained prior to surgical resection. During surgery, 2–7 stereotactically navigated biopsies were collected from locations within the tumor with varying degrees of measured stiffness. Biopsies were processed to extract RNA, proteins, polar metabolites and lipids. Biomolecules were analyzed on relevant -omics platforms (RNA sequencing, MS-proteomics and lipidomics, NMR of polar metabolites).
Differential expression and gene set enrichment analysis of patient paired biopsies indicate an overall increase in macrophage infiltration and extracellular matrix re-organization associated with increased tumor stiffness. Among the most highly upregulated genes in stiff tumor tissue were lymphatic endothelial hyaluronic acid receptor 1 (LYVE-1) and macrophage receptor with collagenous structure (MARCO), both of which have been associated with immune cell infiltration and tissue stiffness.
Our preliminary findings offer novel insights into tumor morphology in GBM that can be inferred from imaging prior to surgery. This can be used to identify tumor regions with high risk of progression and infiltration, thereby informing and guiding surgical strategy and may ultimately lead to novel treatment strategies.
OTEH-8. Pathway-based approach reveals sensitivity to radiation when targeting E2F1 in Glioblastoma
Authors: Alvarado Alvaro , Tessema Kaleab , Muthukrishnan Sree , Kawaguchi Riki , Swarup Vivek , Goldman Steven , Kornblum Harley 
Published: July 2021

Abstract
The great phenotypic heterogeneity of glioblastoma (GBM) – both inter and intratumorally – has hindered therapeutic efforts. While genome-based molecular subtyping has revealed that GBMs may be parsed into several molecularly distinct categories, this insight has not translated to a significant extension of patient survival. We hypothesize that, rather than gene expression as a whole, analysis of targetable pathways could yield important insights into the development of novel classification schemes and, most importantly, to targeted therapeutics. Here, we interrogated tumor samples using a pathway-based approach to resolve tumoral heterogeneity. The Cancer Genome Atlas samples were clustered using gene set enrichment analysis and the resulting 3 clusters were informative of patient survival and only modestly overlapped with prior molecular classification. We validated our approach by generating gene lists from common elements found in the top contributing genesets for a particular cluster and testing the top targets in appropriate gliomasphere patient-derived lines. Samples enriched for cell cycle related genesets showed a decrease in sphere formation capacity, proliferation and in vivo tumor growth when E2F1, our top target, was silenced. Consistent with our theory, E2F1 knockdown had little or no effect on the growth of the non-enriched lines, despite their ability to proliferate in vitro and in vivo. We similarly analyzed single cell RNAseq datasets and correlated cell cycle and stemness signatures with the gene lists we generated, concluding that cells with stem cell signatures were depleted of E2F1 and its downstream targets. Finally, we confirmed a connection between E2F1 and cellular inhibitor of PP2A (CIP2A) in a cluster of samples. Loss of function studies reveal a diminished capacity for DNA damage regulation in E2F1 activated samples. Our studies relate inter- and intratumoral heterogeneity to critical cellular pathways dysregulated in GBM, with the ultimate goal of establishing a pipeline for patient- and tumor-specific precision medicine.
OTEH-11. Single Cell RNA Sequencing to identify cellular heterogeneity with in Pituitary Adenomas
Authors: Jain Saket , Babikir Husam , Shamardani karin , Diaz Aaron , Aghi Manish 
Published: July 2021

Abstract
Pituitary adenomas (PA) are one of the most common primary brain tumors and comprise approximately 15% of brain neoplasms. Most PA are histologically benign, but can cause significant morbidity. Previous studies utilized whole genome and exome sequencing to identify a few somatic variants, but no recurrent mutations were observed. Further studies are warranted to identify driver mutations occurring at low frequencies. We used single-cell RNA sequencing (10X Genomics) to investigate cellular heterogeneity in 12 non-functioning pituitary adenomas. Our analysis identified discrete clusters of cells associated with specific functional pathways. One of these clusters corresponded to cells expressing genes related to metabolic pathways, primarily lipid metabolism. Another cluster consistent amongst the three patients comprised cells involved in antigen presentation and processing. In addition, the copy number variation analysis highlighted distinct chromosomal alterations within our samples. Interestingly, we were able to identify clonal variations within each tumor based on chromosomal aberrations. For example, in our first patient we observed a gain of chromosome 19 and loss of chromosome 2. Our analysis showed three different clonal populations within this tumor. All three populations harbored the loss of chromosome 2, one population exhibited gain of chromosome 19, while a third population exhibited loss of chromosome 19. These early results indicate the loss of chromosome 2 as an early event in tumorigenesis and gain/loss of chromosome 19 as late events. We are currently in a process of identifying somatic variations within these tumors by variant calling. Currently we are expanding our analysis to 20 non-functional PA. Mapping the single-cell gene expression profiles with mutational phylogeny will reveal the differences in clonal evolution within the tumor subtypes. This study will help us define the molecular fingerprint of pituitary adenomas and provide insights which could be utilized in the clinic for better management of these tumors.