bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of COPD Patients with Flame Burn and Inhalation Injuries at a Single Institution
Authors: Nam Jason , Sljivic Sanja , Matthews Robert , Pak Joyce , Agala Chris B , Nizamani Rabia , King Booker , Williams Felicia N 
Published: October 2022

Abstract
The presence of any comorbid condition may lead to worse outcomes after burn injury. Chronic obstructive pulmonary disease (COPD) is a condition with significant morbidity and mortality. In 2018, about 16 million adults in the United States reported a diagnosis of COPD based on data from the American Lung Association. The objective of this study was to explore the outcomes of patients with COPD admitted to our Burn Center with flame burns and/or inhalation injury. Patients were identified using our Institutional Burn Center registry and linked to the clinical and administrative data. All adult flame-injured and/or inhalation injury-only patients admitted to our burn center between July 1, 2011 and June 30, 2020 were included. Demographics, length of stay, burn, and patient characteristics and outcomes, including mortality, were evaluated. Four thousand three hundred ninety-seven patients were included in the study. Patients were divided into two populations, those with COPD (n = 515) and those without a diagnosis of COPD (n = 3882). Patients with COPD were older, more likely to be white and male, and had smaller sized burns, p &lt; .001. Patients with COPD were more likely to be smokers and have comorbid conditions. There was no statistically significant difference between the incidence of inhalation injury, lengths of stay, or number of ventilator days. Burn size and inhalation injury increased mortality risk regardless of COPD severity, as did age among those not on home oxygen. More studies are needed to determine the genomic or proteomic changes in patients with COPD that lead to worse outcomes after flame injury, and/or inhalation injury alone.
Azithromycin concentration in rabbits’ plasma and posterior segment of the eyes following oral drug administration: a dose-finding study for the application in ocular toxoplasmosis
Authors: Daniel Hisar , Louisa Melva , Edwar Lukman 
Published: October 2022

Abstract

Introduction
Azithromycin has been used as an ocular toxoplasmosis alternative treatment due to its pharmacokinetic profiles. However, sufficient concentrations to promote toxoplasmosis eradication is still unknown. This study was aimed to evaluate azithromycin levels in rabbits after three regimens equivalent to human doses for ocular toxoplasmosis.

Methods
Three groups of New Zealand albino rabbits were given one of the following: azithromycin at 26 mg/kg BW daily (Group 1), 26 mg/kg BW every two days (Group 2), and 50 mg/kg BW once weekly (Group 3) for 14 days. Plasma and ocular azithromycin concentrations were examined.

Results
Following 14 days, median ratio of plasma maximum azithromycin concentration to the minimum inhibitory concentration for Toxoplasma gondii (C-max/MIC) for Group 1, and 2 were 51.29, 5.33, while Group 3 was undetected. The median azithromycin concentration in the retina-choroid was higher than the MIC in Group 1 (1356.0 ng/ml) and Group 2 (189.0 ng/ml), but not in Group 3.

Conclusion
Azithromycin administered orally at the dose of 26 mg/kg BW daily or 26 mg/kg BW every two days resulted a sufficient criteria of C-max/MIC as well as retina-choroid concentration needed for its parasiticidal activity. However, well-conducted clinical trial is warranted to support its therapeutic potential in ocular toxoplasmosis.
Primary cavernous hemangioma of the thyroid mimicking an ectopic cervical thymoma
Authors: Díaz-García Alberto , Caballero-Rodríguez Eugenia , García-Martínez Rubén , Balanzá Julio Jordán , Gómez Manuel Ángel Barrera 
Published: October 2022

Abstract
Hemangiomas are one of the most common soft tissue tumors, most of which are located in the skin and subcutaneous tissue. However, a primary thyroid hemangioma is extremely infrequent, so there are only a few cases described in the current literature. As the clinical presentation and characteristics in the imaging tests are non-specific, it is difficult to obtain a preoperative diagnosis. In most cases, the definitive diagnosis is achieved by the histological examination. Due to the rarity of this tumor, we described the case of a 51-year-old female patient affected by thyroid cavernous hemangioma, the differential diagnosis that we considered and a review of the current literature.
Visual binary stars with known orbits in Gaia EDR3
Authors: Chulkov Dmitry , Malkov Oleg 
Published: October 2022

ABSTRACT
A total of 3350 objects from the Sixth Catalog of Orbits of Visual Binary Stars (ORB6) are investigated to validate Gaia Early Data Release 3 (EDR3) parallaxes and provide mass estimates for the systems. We show that two-thirds of binaries with a separation of 0.2–0.5 arcsec are left without a parallax solution in EDR3. Special attention is paid to 521 pairs with the parallax known separately for each component. We find 16 entries that are deemed to be chance alignments of unrelated stars. First we show examples of high-confidence binary systems with significant differences in the reported parallaxes of their components. Next we conclude that the reported Gaia EDR3 parallax errors are underestimated, by at least a factor of 3, for sources with a large renormalized unit-weight error (RUWE). Parallaxes are needed to estimate stellar masses. Because nearly 30 per cent of ORB6 entries lack a 5- or 6-parameter solution in EDR3, we attempt to enrich the astrometric data. Distant companions of ORB6 entries are revealed in EDR3 by the analysis of stellar proper motions and Hipparcos parallaxes. Notably, in 28 cases, intrinsic EDR3 parallaxes of the binary components appear to be less reliable than the parallax of the outer companions. Gaia DR2, The Tycho-Gaia Astrometric Solution (TGAS) and Hipparcos parallaxes are used when EDR3 data are unavailable. A synthetic mass–luminosity relationship in the G band for main-sequence stars is obtained to provide mass estimates along with dynamical masses calculated via Kepler’s third law.
sstar: A Python Package for Detecting Archaic Introgression from Population Genetic Data with S*
Authors: Huang Xin , Kruisz Patricia , Kuhlwilm Martin 
Published: October 2022

Abstract
S* is a widely used statistic for detecting archaic admixture from population genetic data. Previous studies used freezing-archer to apply S*, which is only directly applicable to the specific case of Neanderthal and Denisovan introgression in Papuans. Here, we implemented sstar for a more general purpose. Compared with several tools, including SPrime, SkovHMM, and ArchaicSeeker2.0, for detecting introgressed fragments with simulations, our results suggest that sstar is robust to differences in demographic models, including ghost introgression and two-source introgression. We believe sstar will be a useful tool for detecting introgressed fragments in various scenarios and in non-human species.
Pro-drug Nanoparticle Loaded Supramolecular Hydrogels for Drug Delivery to IDH1 Wild-Type Glioblastoma
Authors: Cavanagh Robert , Baquain Saif , Alexander Cameron , Scherman Oren , Rahman Ruman 
Published: October 2022

Abstract

AIMS
A hyaluronic acid-based hydrogel with mechanical properties comparable to human brain tissue is being investigated as an implantable drug-delivery vehicle for post-surgical treatment of IDH1 wild-type glioblastoma (GBM). Hydrogels are to be loaded with polymeric pro-drug nanoparticles to enable controlled drug release and increased drug penetration through brain parenchyma for enhanced treatment of residual disease within and beyond the invasive margin.

METHOD
A panel of patient-derived glioblastoma cell lines resected from tumour core and invasive margin, have been used to generate tumour spheroids. Chemotherapeutic drug screening has been performed to select lead compounds for formulation and gel loading. Synergies of drug combinations have been studied for potential combination loading. Upcoming work will investigate nanoparticle internalisation, spheroid penetration and prodrug nanoparticle potency. Nanoparticle loaded hydrogels are then to be studied for validation of effective in vitro application.

RESULTS
Current results demonstrate that patient-derived cell lines can generate robust, reproducible tumour spheroids with diameters approx. 350-400 µm. Patient-to-patient differences in drug potencies were observed, with differences also noted between counterpart core and marginal cells from the same patients, illustrating the importance of using patient-derived cells and distinct regional cells to study heterogenous disease such as GBM. Drug combination experiments indicated synergy of topoisomerase I inhibitor (Irinotecan) with PARP inhibitor (Ola-parib). Interestingly, combination of PARP inhibition with topoisomerase II inhibitors (Doxorubicin, Etoposide) was found not synergistic.

CONCLUSION
Together, data gathered on single drug and drug-drug combinations will inform upcoming formulation and in vitro application of hydrogels planned, with eventual translation to pre-clinical in vivo models.
Modelling SHH-Medulloblastoma Using Cerebellar Organoids
Authors: van Essen Max , Kilfeather Peter , Cowley Sally , Jacob John , Becker Esther 
Published: October 2022

Abstract

AIMS
Medulloblastoma (MB) comprises four main groups (SHH, WNT, group 3 and group 4), with distinct molecular, clinical and demographic features. These differences suggest opportunities for tailored and improved treatment. Despite its promise, translation into targeted therapy has been slow, limited by the lack of laboratory models that recapitulate patient tumours. Sporadic and inherited forms of SHH-MB are frequently due to mutations in the tumour suppressor gene PTCH1. Here, we aim to exploit human induced pluripotent stem cells (hiPSC) and CRISPR/Cas9 gene editing, to target PTCH1 in a clinically relevant context, thereby establishing an innovative model of MB.

METHOD
CRISPR/Cas9 mutation of PTCH1 in hiPSCs was followed by their differentiation into cerebellar organoids. Mutant organoids were studied for early consequences on cerebellar development and tumorigenesis.

RESULTS
PTCH1-mutation resulted in enhanced SHH-pathway activity in cerebellar organoids. Homozygous PTCH1-mutation prevented the formation of cerebellar progenitor cells, closely mimicking the effects of high SHH- signalling on neuronal progenitors in early embryonal development. Heterozygous PTCH1-mutant hiPSCs could be differentiated into cerebellar organoids, displayed increased growth rate and expressed oncogenes specific to SHH-MB, resembling preneoplasia and MB stem cells.

CONCLUSION
These results show that cerebellar organoids are a promising new model to study early oncogenic events in MB. Our model presents opportunities for the discovery of new targets which could benefit patients with a genetic predisposition to MB in particular. Refined knowledge of early drivers will be invaluable to guide drug selection and improve prospects for clinical translation.
Hippocampal Dosimetry and Neurocognitive Function in Patients Undergoing Stereotactic Radiosurgery for Brain Metastases
Authors: Iqbal Sahar , Williams Maeve , Smalley Michelle , Daisley-Devoy Tara , Wise Richard , Staffurth John , Maclean Jillian , Tilsley Owen , Powell James 
Published: October 2022

Abstract

AIMS
To measure neurocognitive function (NCF) and correlate with hippocampus dose in patients undergoing stereotactic radiosurgery (SRS) for 1-3 brain metastases.

METHOD
We conducted a prospective observational study measuring NCF before and after SRS in patients with 1-3 brain metastases and correlated changes with hippocampal dosimetry Patients underwent NCF testing at baseline, 1 month, 3 months and 6 months post SRS and quality of life was measured at each time point. NCF tests included Hopkin’s Verbal learning test, controlled oral word association test and trail making tests. Hippocampus was outlined in line with RTOG guidance and dose was collected from the treatment planning system.

RESULTS
36 patients were recruited. Mean age was 64 years, median WHO performance status 1 (range 0-2). At baseline, 65% of patients displayed NCF impairment in at least 1 NCF domain and 33% didn’t exhibit any neurological symptoms. Asymptomatic patients has underlying diagnosis of non-small cell lung cancer or melanoma. NCF impairment was evident at 1, 3 and 6 months for 50%, 66% and 40% patients respectively. Decline at 1 month was associated with higher median dose to 0.1cc of hippocampus (5 Gy vs 2.35 Gy). Association with hippocampal dose and NCF impairment at 3 and 6 months was not observed.

CONCLUSION
A significant proportion of patients exhibited impaired NCF at baseline with greatest NCF decline seen at 1 months and subsequent recovery of NCF evident at 6 months. Dose to hippocampus 0.1cc may be associated with acute NCF toxicity. Main limitations of this study was small number of patients.
Glioma Cell Invasion Is Dependent Upon the DNA Damage Response Kinase ATR
Authors: Birch Joanna , Strathdee Karen , Derby Sarah , Koessinger Anna , Chalmers Anthony , Norman Jim , Carruthers Ross 
Published: October 2022

Abstract

AIMS
Gliomas have high levels of DNA replication stress and clinical trials of inhibitors of the key replication stress response protein ATR (ataxia telangiectasia and rad 3 related protein) as radiosensitisers are planned. We aimed to investigate the effect of ATR inhibition on the ability of glioma cells to infiltrate and invade the brain.

METHOD
Live cell imaging in a panel of primary glioma cultures following siRNA or pharmacological inhibition of ATR. Invasion following treatment of murine orthotopic gliomas was determined by immunohistochemistry. Intravital imaging of GFP expressing murine orthotopic xenografts via an intracranial window model of glioma was undertaken.

RESULTS
Invading margins of human glioma samples demonstrated increased pATR expression relative to core. Live cell imaging demonstrated reduced cell velocity following ATR inhibition (Berzosertib/BAY1895344) or siRNA. Cytoplasmic vacuolation occurred following ATRi or siRNA which were single walled structures which engulf high molecular weight dextran, compatible with blockade of macropinosome processing. Live cell imaging with GFP-integrin α5 and integrin recycling assays showed sequestration of integrins within macropinosomes and reduced integrin cycling. Intravital in vivo imaging of murine xenograft tumours confirmed vacuolation and dextran uptake following ATRi, whilst a further in vivo study demonstrated a reduction in invading tumour cells.

CONCLUSION
We demonstrate a novel role for ATR in facilitating macropinocytic vesicle trafficking and integrin recycling in GBM cells which results in a profound motility defect in vitro and in vivo. ATR inhibitors are entering early phase trials as radiation sensitisers and we propose that therapeutic benefit will extend beyond DNA damage potentiation.
Core outcomes in Brain Tumour Trials – The COBra Study Review of Glioma Trial Registration Data
Authors: Retzer Ameeta , Baddeley Elin , Sivell Stephanie , Seddon Kathy , Bulbeck Helen , Nelson Annmarie , Calvert Melanie , Grant Robin , Adams Richard , Watts Colin , Aiyegbusi Olalekan Lee , Rivera Samantha Cruz , Kearns Pamela , Dirven Linda , Byrne Anthony 
Published: October 2022

Abstract

AIMS
Trial registration supports unbiased reporting of research studies. Despite inconsistent use globally and sub-optimal completeness, registration is associated with publication of the same outcomes as defined in trial protocols, though these are not necessarily reported in published results. In the core outcomes in brain tumour trials (COBra) study a registry review was undertaken, alongside a systematic review of qualitative literature and semi-structured interviews, to develop a core outcome set (COS) outcome longlist. The study aims to identify all outcomes reported across all glioma trial registration data.

METHOD
Phase 3 interventional glioma trials involving patients aged 18 and over, registered on clinicaltrials.gov or the ISRCTN registry were included. Two researchers independently searched the databases and registered data and available protocols were retrieved. Two reviewers independently extracted basic trial data including primary and secondary outcomes. Outcomes were categorised according to an ontology developed through literature review.

RESULTS
91 trials were identified. Primary outcome categories reported were survival (84%), disease activity (14%), symptoms (4%), adverse events (3%) and resource use (1%). Secondary outcome categories reported were survival (60%), adverse events (52%), quality of life (QoL, 41%), disease activity (30%), symptoms (20%), function (12%), resource use (7%), health status (7%), and economic (3%). The review contributed 15 unique outcomes to the final outcome longlist of 35.

CONCLUSION
Trial registries represent a pragmatic solution in COS development and enabled identification of outcomes not present in other data sources. Under half of registered glioma studies included QoL outcomes; a small minority included functional outcomes or economic evaluation.
CaPaBLE - Assessing the Patient Generated Index Methodology in High Grade Glioma Patients and Caregivers
Authors: Pakzad-Shahabi Lillie , Tallant James , Le Calvez Kerlann , Wells Mary , Williams Matt 
Published: October 2022

Abstract

AIMS
CaPaBLE tests the feasibility and acceptability of assessing quality of life (QoL) using the patient-, or caregiver-generated index (PGI/CaGI) methodology in patients with HGG and their caregivers.

METHOD
CaPaBLE, (https://www.isrctn.com/ISRCTN45555598), followed patients and/or their caregivers up to 6 months. Standard measures for patients were EORTC QLQ-C30/BN20, for caregivers the CarGOQOL questionnaire. The QoL topics raised through PGI/CaGI have been coded to the most relevant domain from their respective standard measure for an initial assessment of concordance.

RESULTS
36 patients, 24 caregivers recruited to study; completing an average of 3 study assessment timepoints. PGI and CaGI generated 240 and 160 topics respectively. Patient concerns most frequently coded to EORTC domain of Role Functioning; Caregiver concerns mostly coded to CarGOQOL domain of Burden. Other topics frequently raised by patients such as the driving and sex life, and future planning by caregivers are not specifically raised in standard questionnaires.

CONCLUSION
Nearly all topics raised by patients and caregivers were mapped to the domains of their respective standard QoL measure. However, almost half of all topics raised by patients and caregivers mapped to a minority of the domains included in standard measures; whilst a notable number of topics are not specifically included in standard measures at all. This raises questions regarding the efficiency and relevance of such questionnaires to patient and caregivers’ daily lives.
The Anisotropic Component of the Diffusion Tensor (DTI-Q) Is Correlated to Overall Survival in Glioblastoma (GBM)
Authors: Simon Natalie , Sinha Rohit , Sravanam Sanskrithi , Mayrand Roxanne , Li Chao , Wan Yizhou , Wei Yiran , Price Stephen 
Published: October 2022

Abstract

AIMS
The aim of this study was to test if a correlation exists between the median voxel DTI-Q and overall survival in patients with GBM.

METHOD
The median voxel anisotropic (DTI-Q) values, calculated for the whole brain, the contrast-enhancing hemisphere and the contralateral hemisphere, were calculated using FSL (FMRIB Software Library, Oxford) for 33 patients with a primary diagnosis of GBM. Overall survival was calculated by subtracting the date of initial resection surgery from the date of death, for each included patient. Using R statistical software, the Pearson’s correlation coefficient was computed to establish the significance of the relationship between overall survival and whole brain median DTI-Q values, contrast-enhancing hemisphere median DTI-Q values and non-contrast-enhancing hemisphere median DTI-Q values.

RESULTS
There is a significant correlation between the median voxel DTI-Q of the whole brain and overall survival (t = -2.5362, df = 31, p-value = 0.01646), median voxel DTI-Q of the contrast-enhancing hemisphere and overall survival (t = -2.1235, df = 31, p-value = 0.0418) and the median voxel DTI-Q of the contralateral (non-contrast-enhancing) hemisphere and overall survival (t = -2.5212, df = 31, p-value = 0.01705).

CONCLUSION
The median anisotropic component of the diffusion tensor, calculated for the whole brain, contrast-enhancing and non-contrast-enhancing hemisphere, is significantly related to overall survival. This demonstrates the potential utility of DTI metrics as prognostic biomarkers that can readily be calculated in routine practice.
Low Grade Glioma - A COVID Low Surgical Priority?
Authors: White William , Rudd George , Zaki Hesham , McKevitt Fiona , Romanowski Charles , Ushewokunze Shungu 
Published: October 2022

Abstract

AIMS
During the COVID pandemic (March 2020) SBNS published guidance advising that low grade gliomas (LGG) should be categorised as “low surgical priority”, therefore surgery could be delayed by six months. Aims: (1) Examine the effect of the COVID pandemic on the time taken from neuro-oncology MDT discussion to surgery in presumed LGG. (2) Investigate the proportion of presumed LGG receiving an integrated diagnosis of high grade glioma (HGG) before and during the COVID pandemic.

METHOD
Retrospective case note analysis of patients with presumed LGG including radiological and histopathological reports. Population split into two groups – Group A pre-pandemic (March 2019-2020) and Group B mid-pandemic (March-December 2020).

RESULTS
Forty-three patients (30M, 13F) with presumed LGG were identified – 23/43 in Group A and 20/43 in Group B. Mean age was 45 years (26-77y). Twenty-two patients (Group A 12/23 (52%) & Group B 10/20 (50%)) had no radiological features of transformation. Mean number of days between discussion and surgery was 32 (2-96 days, SD=28) for group A and 98 (6-286 days, SD=92) for group B (p=.006: [95% CI: 21-110]). Fifteen patients in each group (65% v 75%) had an integrated diagnosis of HGG (p=.486). Of the patients with no radiological features of transformation 6 (50%) had a HGG in Group A and 7 (70%) in Group B (p=.342).

CONCLUSION
During the COVID pandemic patients with presumed LGG had their surgical management significantly delayed, with an increase in the proportion who were diagnosed with HGG. Presumed LGG patients should have higher surgical priority even when resources are constrained.