bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demographic and Glycemic Factors Linked With Diabetes Distress in Teens With Type 1 Diabetes
Authors: Inverso Hailey , LeStourgeon Lauren M , Parmar Angie , Bhangui Isha , Hughes Bailey , Straton Emma , Alford Madeleine , Streisand Randi , Jaser Sarah S 
Published: June 2022

AbstractObjectiveDiabetes distress (DD) is a negative emotional response related to the burdens of living with type 1 diabetes (T1D) and is linked with diabetes outcomes, such as hemoglobin A1c (A1c). Yet, less is known about how other glycemic indicators, average blood glucose and time in range, relate to DD, and which demographic characteristics are associated with higher DD.MethodsIn total, 369 teens (Mage 15.6 ± 1.4, 51% female, MT1D duration 6.7 ± 3.8 years) screened for DD using The Problem Areas in Diabetes—Teen Version to determine eligibility for an ongoing multi-site behavioral trial. The associations of DD, demographic factors, and glycemic indicators (A1c, average blood glucose, and time in range) were analyzed.ResultsTwenty-nine percent of teens (n = 95) scored above the clinical cutoff (≥44) for DD. Females scored significantly higher on average than males. Black/African American, non-Hispanic youth screened significantly higher compared to youth from other racial/ethnic groups. Higher DD scores were related to higher A1c and average blood glucose, and lower time in range. Logistic regression models revealed that females were significantly more likely to report clinically elevated DD than males, and teens with higher A1c were 1.3 times more likely to report DD. Age and diabetes duration were not significantly associated with clinically elevated DD scores.ConclusionsResults demonstrated that DD is most prevalent in Black, non-Hispanic and female teens, and DD is associated with higher average blood glucose and lower time in range. Further investigation into these disparities is warranted to promote optimal health outcomes for teens with T1D.
Symptoms and Central Sensory Integration in People With Chronic mTBI: Clinical Implications
Authors: Martini Douglas N , Gera Geetanjali , Brumbach Barbara H , Campbell Kody R , Parrington Lucy , Chesnutt James , King Laurie A 
Published: June 2022

ABSTRACT

Introduction
Balance deficits in people with chronic mild traumatic brain injury (mTBI; ≥3 months post-mTBI), thought to relate to central sensory integration deficits, are subtle and often difficult to detect. The purpose of this study was to determine the sensitivity of the instrumented modified clinical test of sensory integration for balance (mCTSIB) in identifying such balance deficits in people with symptomatic, chronic mTBI and to establish the associations between balance and mTBI symptom scores in the chronic mTBI group.

Methods
The Institutional Review Board approved these study methods. Forty-one people with chronic mTBI and balance complaints and 53 healthy controls performed the mCTSIB (eyes open/closed on firm/foam surfaces; EoFi, EcFi, EoFo, and EcFo) with a wearable sensor on their waist to quantify sway area (m2/s4). Sensory reweighting variables were calculated for the firm and foam stance conditions. A stopwatch provided the clinical outcome for the mCTSIB (time). Each participant completed the Neurobehavioral Symptom Inventory (NSI), which quantifies mTBI-related symptoms and provides a total score, as well as sub-scores on affective, cognitive, somatic, and vestibular domains.

Results
The mTBI group reported significantly higher symptom scores across each NSI sub-score (all Ps &lt; .001). The mTBI group had a significantly larger sway area than the control group across all mCTSIB conditions and the mTBI group had significantly higher sensory reweighting scores compared to the control group on both the firm (P = .01) and foam (P = .04) surfaces. Within the mTBI group, the NSI vestibular score significantly related to the mCTSIB sway area EcFi (r = 0.38; P = .02), sway area EcFo (r = 0.43; P = .006), sensory reweighting firm (r = 0.33; P = .04), and sensory reweighting foam (r = 0.38; P = .02). The average sway area across the 4 mCTSIB conditions was significantly (area under the curve: 0.77; P &lt; .001) better at differentiating groups than the mCTSIB clinical total score. The average sway area across the 4 mCTSIB conditions had a sensitivity of 73% and a specificity of 71%. The clinical mCTSIB outcome scores were not different between groups.

Conclusion
People with chronic mTBI appear to have central sensory integration deficits detectable by instrumented measures of postural assessment. These findings suggest that central sensory integration should be targeted in rehabilitation for people with chronic mTBI.
Stellar populations of the globular cluster NGC 5053 investigated using AstroSat-Ultra Violet Imaging Telescope
Authors: Nikitha K J , Vig S , Ghosh S K 
Published: June 2022

ABSTRACT
Globular clusters (GCs), being old and densely packed, serve as ideal laboratories to test stellar evolution theories. Although there is enormous literature on GCs in optical bands, studies in the ultraviolet (UV) regime are sparse. In this work, we study the stellar populations of a metal-poor and a rather dispersed GC, NGC 5053, using the UV instrument of AstroSat, namely the Ultra Violet Imaging Telescope in three far-UV (F154W, F169M, F172M) and three near-UV (N219M, N245M, N263M) filters. Photometry was carried out on these images to construct a catalogue of UV stars, of which the cluster members were identified using Gaia EDR3 catalogue. UV and optical colour–magnitude diagrams (CMDs) help us locate known stellar populations such as blue horizontal branch stars, RR-Lyrae stars, red horizontal branch stars, blue straggler stars (BSSs), SX-Phe, red giant branch, and AGB stars. Based on their locations in the CMDs, we have identified eight new BSS candidates, six probable eBSSs, and an extreme horizontal branch candidate. Their nature has been confirmed by fitting their spectral energy distributions (SEDs) with stellar atmospheric models. We believe the BSS population of this cluster is likely to have a collisional origin based on our analyses of their radial distribution and SEDs. BaSTI-IAC isochrones were generated to characterize the cluster properties, and we find that the observed brightness and colours of cluster members are best fit with a model that is α-enhanced with Y =0.247, [Fe/H] = −1.9, and age =12.5 ± 2.0 Gyr.
Exploring the outskirts of the EAGLE disc galaxies
Authors: Varela-Lavin Silvio , Tissera Patricia B , Gómez Facundo A , Bignone Lucas A , Lagos Claudia del P 
Published: June 2022

ABSTRACT
Observations show that the surface brightness of disc galaxies can be well-described by a single exponential (TI), up-bending (TIII), or down-bending (TII) profiles in the outskirts. Here we characterize the mass surface densities of simulated late-type galaxies from the eagle project according to their distribution of mono-age stellar populations, the star formation activity, and angular momentum content. We find a clear correlation between the inner scale lengths and the stellar spin parameter, λ, for all three disc types with λ &gt; 0.35. The outer scale lengths of TII and TIII discs show a positive trend with λ, albeit weaker for the latter. TII discs prefer fast rotating galaxies. With regards to the stellar age distribution, negative and U-shape age profiles are the most common for all disc types. Positive age profiles are determined by a more significant contribution of young stars in the central regions, which decrease rapidly in the outer parts. TII discs prefer relative higher contributions of old stars compared to other mono-age populations across the discs whereas TIII discs become progressively more dominated by intermediate age (2–6 Gyr) stars for increasing radius. The change in slope of the age profiles is located after the break of the mass surface density. We find evidence of larger flaring for the old stellar populations in TIII systems compared to TI and TII, which could indicate the action of other processes. Overall, the relative distributions of mono-age stellar populations and the dependence of the star formation activity on radius are found to shape the different disc types and age profiles.
Rhenium(I) conjugates as tools for tracking cholesterol in cells
Authors: Lazniewska Joanna , Bader Christie , Hickey Shane M , Selemidis Stavros , O'Leary John , Simpson Peter V , Stagni Stefano , Plush Sally E , Massi Massimiliano , Brooks Doug 
Published: June 2022

Abstract
Cholesterol is vital to control membrane integrity and fluidity, but is also a precursor to produce steroid hormones, bile acids, and vitamin D. Consequently, altered cholesterol biology has been linked to many diseases, including metabolic syndromes and cancer. Defining the intracellular pools of cholesterol and its trafficking within cells is essential to understand both normal cell physiology and mechanisms of pathogenesis. We have synthesized a new cholesterol mimic (ReTEGCholestanol), comprising a luminescent rhenium metal complex and a cholestanol targeting unit, linked using a tetraethylene glycol (TEG) spacer. ReTEGCholestanol demonstrated favourable imaging properties and improved water solubility when compared to a cholesterol derivative, and structurally related probes lacking the TEG linker. A non-malignant and three malignant prostate cell lines were used to characterize the uptake and intracellular distribution of ReTEGCholestanol. The ReTEGCholestanol complex was effectively internalized and mainly localized to late endosomes/lysosomes in non-malignant PNT1a cells, while in prostate cancer cells it also accumulated in early endosomes and multivesicular bodies, suggesting disturbed cholesterol biology in the malignant cells. The ReTEGCholestanol is a novel imaging agent for visualizing endosomal uptake and trafficking, which may be used to define cholesterol related biology including membrane integration and altered lipid trafficking/processing.
Systematic evaluation of parameters in RNA bisulfite sequencing data generation and analysis
Authors: Johnson Zachary , Xu Xiguang , Pacholec Christina , Xie Hehuang 
Published: June 2022

Abstract
The presence of 5-methylcytosine (m5C) in RNA molecules has been known for decades and its importance in regulating RNA metabolism has gradually become appreciated. Despite recent advances made in the functional and mechanistic understanding of RNA m5C modifications, the detection and quantification of methylated RNA remains a challenge. In this study, we compared four library construction procedures for RNA bisulfite sequencing and implemented an analytical pipeline to assess the key parameters in the process of m5C calling. We found that RNA fragmentation after bisulfite conversion increased the yield significantly, and an additional high temperature treatment improved bisulfite conversion efficiency especially for sequence reads mapped to the mitochondrial transcriptome. Using Unique Molecular Identifiers (UMIs), we observed that PCR favors the amplification of unmethylated templates. The low sequencing quality of bisulfite-converted bases is a major contributor to the methylation artifacts. In addition, we found that mitochondrial transcripts are frequently resistant to bisulfite conversion and no p-m5C sites with high confidence could be identified on mitochondrial mRNAs. Taken together, this study reveals the various sources of artifacts in RNA bisulfite sequencing data and provides an improved experimental procedure together with analytical methodology.
ATRT-01. Reconstitution of cGAS/ STING pathway via epigenetic reprogramming leads to anti-viral inflammatory signaling in Atypical teratoid rhabdoid tumors (ATRTs)
Authors: Mangoli Avani , Hariharan Seetha , Ashley David , Fuller Rebecca , Bowie Michelle , Briley Aaron , Brown Michael , Hostettler Janell 
Published: June 2022

Abstract
BACKGROUND: Atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive brain tumors that affect young children characterized by biallelic inactivation of the SMARCB1 gene. Though patients benefit from multimodal therapy, there is no improvement in overall survival which necessitates the exploration of alternative approaches. Innate-based immune and epigenetic therapies have shown benefits in several cancers. The role of innate immune signaling has not been investigated in ATRTs. Our previous data from several ATRT cell lines showed loss of expression of key innate signaling components, like cGAS and STING that are needed for sensing extracellular dsDNA. Additionally, ATRT cell lines do not respond to STING agonists, like cGAMP or ISD. RESULTS: Co-treatment of ATRT cell lines, BT-12 and BT-16 with two epigenetic modulators, panobinostat and decitabine, leads to re-expression of cGAS and STING in a time-dependent manner. Furthermore, treatment with decitabine alone leads to demethylation of several CpG sites on the STING promoter and increased expression of STING mRNA. Panobinostat and decitabine co-treatment reconstitute STING-mediated innate signaling, as measured by IRF-3 and STAT1 phosphorylation and production of ISG-15 and IFIT-1 after treatment with cGAMP, a STING agonist. Co-treatment with panobinostat and decitabine also induced expression of antiviral pro-inflammatory chemokines/cytokines in ATRT cell lines, including type III IFN, IL-6, IL-8, IL-28, and IL-29. CONCLUSION: Our data suggest that ATRT cell lines are unresponsive to innate agonists possibly due to the loss of expression of key innate immune components. However, the cGAS/STING pathway is reactivated by epigenetic drugs, specifically the combination of panobinostat and decitabine. This is further potentiated by treating with STING agonists like cGAMP. Combination treatment of ATRT cell lines with panobinostat and decitabine also induced antiviral inflammatory signaling. This response could be a potential treatment modality to inhibit tumor growth and/or mediate cancer immunotherapy in these aggressive tumors.
ATRT-17. A phase II study of continuous low dose panobinostat in paediatric patients with malignant rhabdoid tumours and atypical teratoid rhabdoid tumours.
Authors: Wood Paul , Desai Jayesh , Waldeck Kelly , Cain Jason , Gottardo Nicholas , Strong Robyn , Kinross Kathryn , Carr Michelle , Jones Janelle , Wong Lily , Ziegler David , Hansford Jordan , Michael Michael , Ashley David 
Published: June 2022

Abstract
BACKGROUND: Panobinostat treatment has been shown to terminally differentiate malignant rhabdoid tumours (MRT) and atypical teratoid rhabdoid tumours (ATRT) in pre-clinical models. We report results of the open label, phase II study of oral panobinostat in patients with newly diagnosed or relapsed MRT/ATRT. AIMS: To assess the anti-tumour activity of low dose, continuous oral panobinostat as well as its associated toxicities. To assess the biological activity of low dose panobinostat by measuring histone H4 acetylation status in peripheral mononuclear cells (PMNC), and differentiation markers. METHODS: Following primary institutional standard of care induction and consolidation chemotherapy and/or radiation treatment, patients were enrolled and commenced on panobinostat as a continuous daily oral dose starting at 10mg/m2/day, with a three-week wash out period between therapies. Real-time acetylation status, measuring acetylated H4 on PMNC, was performed to determine the pharmacodynamics of panobinostat at different dosing levels. Patients were monitored for toxicity; dose reductions were in decrements of 2mg/m2/day. RESULTS: A total of 13 patients with newly diagnosed ATRT/MRT and one patient with relapsed MRT have been enrolled. The average age at enrollment was 3.6 years (range 0.8-6.8 years). The mean treatment duration was 206 days (13-344 days). Currently, six patients (42.9%) remain on study with a mean study duration of 531 days (range 13-895 days). 6/14 patients (42.9%) were removed due to disease progression at a mean study duration of 245 days (44-560 days). 2/14 patients (14.3%) withdrew due to toxicity. 12/14 patients (85.7%) required dose reductions. The main toxicities were thrombocytopaenia and leukopaenia (Grade III-IV). Real-time pharmacodynamic assessment of panobinostat, at a dose as low as 6mg/m2/day resulted in significant acetylation of histone H4 in PMNC. CONCLUSIONS: Treatment with low dose panobinostat is well tolerated in infants and children with MRT/ATRT, with significant acetylation of histone H4 in PMNC.
RARE-32. Phase 0 and feasibility single-institution clinical trial of intravenous tocilizumab for adamantinomatous craniopharyngioma
Authors: Dorris Kathleen , Mettetal Ashley , Dahl Nathan , Hemenway Molly , Winzent-Oonk Shelby , Prince Eric , Vijmasi Trinka , McWilliams Jennifer , Jordan Kimberly , Mirsky David , Hoffman Lindsey , Hankinson Todd 
Published: June 2022

Abstract
BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. ACP lacks medical antitumor therapies. Current standard therapy with surgery and radiation is associated with poor quality of life. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control. METHODS: Children aged 2–21 years with newly diagnosed or previously treated ACP with measurable disease are eligible for the Phase 0/feasibility single-institution clinical trial (NCT03970226) of intravenous (IV) tocilizumab at Children’s Hospital Colorado. The phase I stratum involves IV tocilizumab prior to a standard-of-care surgical resection. The feasibility portion of the trial involves IV tocilizumab every two weeks for up to 13 28-day cycles. Tocilizumab is administered at the established weight-based pediatric dosage of 8 mg/kg for patients who weigh ≥30kg or 12 mg/kg for patients who weigh &lt;30kg. RESULTS: To date, three patients have been enrolled on the Phase 0 component of the trial. These patients demonstrated clinically relevant levels of tocilizumab (≥ 4µg/mL) in serum, cyst fluid, and/or tumor tissue, compared to undetectable levels in control samples. Two patients (1 male and 1 female; median age 10.5 years) have enrolled on the feasibility stratum; one patient had best response of minor response but met definition of progressive disease at cycle 11. One patient with extensive disease required dose reduction for myelosuppression. CONCLUSION: Systemic delivery of tocilizumab at the established pediatric dosage is promising for treatment of ACP based on preclinical work and its demonstrated penetration into cystic and solid portions of ACP tumors. The therapy to date has been well tolerated overall. Further study is planned through a CONNECT consortium international Phase II trial.
DIPG-07. Preclinical and case study results underpinning the phase II clinical trial testing the combination of ONC201 and paxalisib for the treatment of patients with diffuse midline glioma (NCT05009992)
Authors: Dun Matthew D , Jackson Evangeline R , Duchatel Ryan J , Persson Mika L , Mannan Abdul , Yadavilli Sridevi , Parackal Sarah , Game Shaye , Chong Wai Chin , Jayasekara Samantha , Le Grand Marion , Kearney Padraic S , Douglas Alicia M , Findlay Izac J , Staudt Dilana , Germon Zacary P , Skerrett-Byrne David A , Nixon Brett , Smith Nathan D , Hulleman Esther , Day Bryan , McCowage Geoff B , Alvaro Frank , Waszak Sebastian M , Larsen Martin R , Colino-Sanguino Yolanda , Valdes-Mora Fatima , Rakotomalala Andria , Meignan Samuel , Pasquier Eddy , Vitanza Nicholas A , Nazarian Javad , Koschmann Carl , Cain Jason , Mueller Sabine 
Published: June 2022

Abstract
Diffuse midline gliomas (DMG), including those of the brainstem (diffuse intrinsic pontine glioma - DIPG), are pediatric CNS tumors recognized as the most lethal of all children’s cancers. Palliative radiotherapy is the only approved treatment, with survival just 9-11–months post-diagnosis. ONC201 shows preclinical and emerging clinical efficacy in early-stage clinical trials, extending survival of DIPG patients by ~9-11–months compared to historic controls. However, patients invariably develop resistance, with some patients completely refractory to treatment. Using a multi-omics approach, including pharmacology, proteomics, genomics, epigenetics, in vitro and in vivo modeling, across ten international laboratories, we have uncovered the inherent mechanisms of resistance to ONC201. We find ONC201 elicits antagonism of the Dopamine receptor D2 (DRD2), whilst also causing mitochondrial degradation through potent agonism of the Mitochondrial protease CLPP, that drives proteolysis of the electron transport chain (ETC) protein Succinate dehydrogenase A (SDHA) and degradation of critical mitochondrial tricarboxylic acid (TCA) cycle regulator Isocitrate dehydrogenase 3B (IDH3B). Loss mitochondrial respiration increased hypoxia and reduced α-ketoglutarate, inhibiting lysine demethylation, increasing methylation of H3K4me3 and H3K27me3, thus altering the epigenome of primary DIPG cells. Loss of SDHA caused oxidation of succinate forming superoxide driving redox regulated PI3K/AKT signaling, counteracted using the PI3K/AKT inhibitor paxalisib. The combination of ONC201 and paxalisib synergically extended survival of two aggressive DIPG PDX models (SU-SIPG-VI vehicle=73 vs. combination=100-days, p=0.0027; SF8626 vehicle=36 vs. combination=43-days, p=0.0002). Compassionate access to this combination (n=2 patients; immediately post-RT and following re-RT) resulted in reductions in tumor volume and complete resolution of disease symptoms, extending overall survival (e.g., diagnosis patient MR axial scan=1554 mm2 , following eight months on the combination, current tumor volume=464 mm2 (&lt;70%), patient remains on treatment). Our findings harness the powerful anti-DMG/DIPG pharmacokinetic/dynamic properties of ONC201 and paxalisib, a combination that is currently in clinical trials (NCT05009992).