bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPCT-18. A TWO-PART, PHASE 1 STUDY OF RHENIUM-186 NANOLIPOSOME (186RNL) DELIVERED BY CONVECTION ENHANCED DELIVERY FOR RECURRENT, REFRACTORY, OR PROGRESSIVE EPENDYMOMA AND HIGH-GRADE GLIOMA (HGG) AND NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: Plant Ashley , Goldman Stewart , Lam Sandi , DeCuypere Michael , Stein Gregory , Brenner Andrew 
Published: June 2021

Abstract

Ependymoma, HGG, and DIPG are gliomas that are often difficult to treat, frequently aggressive, and often carry an extremely poor prognosis. While external beam radiation therapy (EBRT) remains a central component of the management of pediatric gliomas, it is limited by tolerance of the surrounding normal brain tissue. Rhenium-186 NanoLiposome (186RNL) permits the selective delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. In a Phase 1 trial in adults with recurrent glioblastoma (NCT01906385), the mean absorbed dose to the tumor when coverage was 75% or greater (n=10) was 392 Gy (CI 306 – 478). Thus far, the therapy has been well tolerated, no dose-limiting toxicity has been observed, and no treatment-related serious adverse events have occurred despite markedly higher absorbed doses than typically delivered by EBRT (n=18).

Methods
This is a two-part, Phase 1 dose-finding study followed by an expansion cohort to explore efficacy. Part 1 will enroll up to 18 subjects to determine the maximum feasible dose (MFD) of 186RNL administered by convection enhanced delivery (CED). Tumor size will be limited to a diameter of 4 cm in the longest axis and a volume of 34 mL. The dose limiting toxicity period (DLT) is 28 days post infusion. Part 2 will independently evaluate 186RNL in 3 different cohorts: Cohort A: up to 12 subjects with a diagnosis of recurrent, refractory, or progressive ependymoma; Cohort B: up to 12 subjects with a diagnosis of recurrent, refractory, or progressive HGG; Cohort C: up to 15 subjects with newly diagnosed DIPG. The primary endpoint is overall response rate (ORR) by Radiographic Assessment in Pediatric Neuro-Oncology (RAPNO) criteria. Secondary endpoints are PFS-24 and OS-24 in Cohort A and PFS-12 and OS-12 in Cohorts B and C. Planned enrollment will begin in H2 2021.
EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS
Authors: Miller Alexandra , Szalontay Luca , Bouvier Nancy , Ahmed Hamza , Hill Katherine , Rafailov Johnathan , Lee Alex , Rodriguez-Sanchez Irene , Yildirim Onur , Patel Arti , Bale Tejus , Benayed Ryma , Arcila Maria , Donzelli Maria , Dunkel Ira , Gilheeney Stephen , Khakoo Yasmin , Kramer Kim , Sait Sameer F , Greenfield Jeffrey , Souweidane Mark , Haque Sofia , Mauguen Audrey , Berger Michael , Mellinghoff Ingo , Karajannis Matthias 
Published: June 2021

Abstract

Purpose
Pediatric central nervous system tumors remain a leading cause of cancer-related death in children and adolescents. Safe sampling of tumor tissue for diagnostic purposes may be challenging. Subclinical detection of disease prior to clinical or imaging progression may provide opportunity for earlier intervention and ultimately improve overall survival. Additionally, our understanding of molecular evolution in response to therapy remains limited, given the rarity of serial sampling of tumor tissue.

Methods
We report our experience with minimally invasive molecular diagnostics using a validated next generation sequencing assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) obtained at the time of surgery, by intraventricular catheter or lumbar puncture. All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families.

Results
We analyzed 64 CSF samples from 45 pediatric and adolescent and young adult (AYA) patients (pediatric=25; AYA=20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n=10), medulloblastoma (n=10), pineoblastoma (n=5), low grade glioma (n=4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n=4), metastatic retinoblastoma (n=4), ependymoma (n=3), and other (n=5). Somatic alterations were detected in 28/64 samples (44.4%) and in at least one sample per unique patient in 22/45 patients (48.8%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (86.3%). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient’s disease course.

Conclusion
We identified four general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: 1) diagnosis; 2) identification of actionable alterations; 3) track response to therapy; and 4) monitoring tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population that may improve care.
Plasma IL-8 and ICOSLG as prognostic biomarkers in glioblastoma
Authors: Holst Camilla Bjørnbak , Christensen Ib Jarle , Vitting-Seerup Kristoffer , Skjøth-Rasmussen Jane , Hamerlik Petra , Poulsen Hans Skovgaard , Johansen Julia Sidenius 
Published: June 2021

Abstract

Background
CNS immune privilege has been challenged in recent years. Glioblastoma (GBM) immune dysfunction includes complex interactions with the immune system outside the CNS. The aim of this study was to determine diagnostic and prognostic potential of immune-related proteins in plasma in GBM and interrogate biomarker presence in the brain tumor microenvironment (TME).

Methods
One hundred and fifty-eight patients with glioma WHO grade II–IV were included. Plasma collected at surgery was screened for 92 proteins using proximity extension assay technology and related to clinical outcome. Secretion and expression of candidate prognostic biomarkers were subsequently analyzed in 8 GBM cell lines and public RNAseq data.

Results
Plasma levels of 20 out of 92 screened proteins were significantly different in patients with GBM compared to patients with astrocytoma WHO grade II–III. High plasma interleukin-8 (IL-8) (hazard ratio [HR] = 1.52; P = .0077) and low CD244 (HR = 0.36; P = .0004) were associated with short progression-free survival and high plasma IL-8 (HR = 1.40; P = .044) and low ICOS ligand (ICOSLG) (HR = 0.17; P = .0003) were associated with short overall survival (OS) in newly diagnosed patients with GBM. A similar trend was found for ICOSLG (HR = 0.34; P = .053) in recurrent GBM. IL-8 was mostly secreted and expressed by mesenchymal GBM cell lines and expressed by vascular cells and immune cells in the TME. This was also the case for ICOSLG, although less consistent, and with additional expression in tumor-associated oligodendrocytes.

Conclusions
High plasma IL-8 and low ICOSLG at surgery are associated with short OS in newly diagnosed GBM. Source of plasma ICOSLG may be found outside the TME.
Waterpipe Tobacco Warnings: An Experimental Study Among a Nationally Representative Sample of US Young Adults
Authors: Sutfin Erin L , Lazard Allison J , Cornacchione Ross Jennifer , Noar Seth M , Reboussin Beth A 
Published: June 2021

Abstract

Background
Waterpipe tobacco (WT) smoking by young adults remains high and misperceptions are common. Product warnings can increase knowledge of harms and reduce use. The goal of this study was to test warning statements, including the FDA-required nicotine warning (prior to implementation), on young adults’ thinking about harms of and discouragement from WT smoking.

Methods
We conducted a between-subjects experiment in a nationally representative telephone survey of 1152 young adults aged 18–29. Participants were randomly assigned to hear one of five warning statements and reported how much, on a 4-point scale, the warning made them think about the harms and discouraged them from WT smoking.

Results
The sample was 36.8% female, 57.8% white, 20.2% Black, 24.1% Hispanic, with a mean age of 23.2 (SE = 0.25). Under half (43.5%) had ever smoked WT. There were significant differences among the statements on both thinking about harms (p &lt; .0001) and discouragement (p &lt; .0001). The FDA-required “nicotine” warning led to the lowest thinking about harms (M = 2.85, SE = 0.08) and was the least discouraging (M = 2.86, SE = 0.08), while the “100 cigarettes” warning resulted in the greatest thinking about harms (M = 3.62, SE = 0.05) and was the most discouraging (M = 3.56, SE = 0.06).

Conclusions
The nicotine warning resulted in the lowest levels of thinking about harms and discouragement from WT smoking, suggesting limited impact. However, a warning focused on comparing smoke inhalation from WT smoking to cigarettes seems promising. Warnings should cover a broad range of WT health effects, and possibly comparisons to cigarettes. Findings also have implications for the content of international waterpipe warnings.

Implications
This study indicates that the nicotine warning is the least effective at making young adults think about the harms of and discouraging WT smoking. The FDA and other countries should consider requiring warnings to cover a broader range of health harms, misperceptions, and possibly comparisons to cigarettes.
Microsatellite Markers fromPeronospora tabacina, the Cause of Blue Mold of Tobacco, Reveal Species Origin, Population Structure, and High Gene Flow
Authors: Nowicki Marcin , Hadziabdic Denita , Trigiano Robert N. , Runge Fabian , Thines Marco , Boggess Sarah L. , Ristaino Jean , Spring Otmar 
Published: June 2021

Peronospora tabacina is an obligate parasite that causes blue mold of tobacco. The pathogen reproduces primarily by sporangia, whereas the sexual oospores are rarely observed. A collection of 122 isolates of P. tabacina was genotyped using nine microsatellites to assess the population structure of individuals from subpopulations collected from central, southern, and western Europe; the Middle East; Central America; North America; and Australia. Genetic variations among the six subpopulations accounted for ∼8% of the total variation, including moderate levels of genetic differentiation, high gene flow among these subpopulations, and a positive correlation between geographic and genetic distance (r = 0.225; P < 0.001). Evidence of linkage disequilibrium (P < 0.001) showed that populations contained partially clonal subpopulations but that subpopulations from Australia and Mediterranean Europe did not. High genetic variation and population structure among samples could be explained by continuous gene flow across continents via infected transplant exchange and/or long-distance dispersal of sporangia via wind currents. This study analyzed the most numerous P. tabacina collection and allowed conclusions regarding the migration, mutation, and evolutionary history of this obligate biotrophic oomycete. The evidence pointed to the species origin in Australia and identified intracontinental and intercontinental migration patterns of this important pathogen.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Health expenditure among the outpatient of type-2 diabetes in selected hospital of Kathmandu district: A cross sectional study
Authors: Shrestha Rasmita , Shakya Aditya 
Published: June 2021

AbstractIntroductionOut of Pocket (OOP) expenditure is the dominant financing mechanism in the low and middle-income countries. In these countries the prevalence of diabetes has been rising more rapidly which can lead to various micro-vascular complications thus increasing the risk of dying prematurely.MethodsA cross-sectional - comparative and hospital-based study was carried out in which OOP expenditure of diabetic patient treating in public and private hospital was compared. A total of 154 diabetic patients i.e.77 in each type of hospitals were selected purposively in consultation with attending physician and staffs. Face to face interview was done to diabetic patient with a minimum of one year of illness using structured questionnaire. Lorentz curve and concentration curve were prepared using income and expenditure of the patients.ResultAmong154 patients, 97.4% patients had paid out of pocket for the treatment of diabetes. Mean direct cost per month was NRs. 7312.17 in public and NRs. 10125.31 in private hospital. Direct medical cost had higher share in total direct cost i.e. 60.5% in public and 69.3 % in private hospital. Medicine cost had higher percentage share (50.9%) in public hospital and laboratory cost had higher percentage share (68%) in private hospital.ConclusionDirect medical cost was higher in private hospital as compared to public hospital. All the income groups have to pay similar amount of money for the treatment i.e. economic burden for the treatment of disease was found higher for the poor people as there was not any financial protection mechanism.
Policy and Effectiveness of Covid-19 Response
Authors: Dolgikh Serge 
Published: June 2021

AbstractA comparative analysis of selected national jurisdictions with respect to Covid-19 policy response indicated that factors such as effective communications and effective targeted intervention in the environments of higher epidemiological risk can be the key factors in the overall effectiveness of the epidemiological response minimizing both the impact of the epidemics and disruptions in the life of the society.
Impact of vaccination and undetected cases on the COVID-19 pandemic dynamics in Qatar in 2021
Authors: Nesteruk Igor 
Published: June 2021

ABSTRACTThe third COVID-19 pandemic wave in Qatar was simulated with the use of the generalized SIR-model and the accumulated number of cases reported by Johns Hopkins University for the period: April 25 - May 8, 2021. Comparison with the SIR-curves calculated before for the second wave showed that the effect of mass vaccination is not evident during 4 months after its onset in December 2020. Additional simulations have demonstrated that many COVID-19 cases are not detected. The real accumulated number of cases can exceed the laboratory-confirmed one more than 5 times. This fact drastically increases the probability of meeting an infectious person and the epidemic duration.
Development of a Deep Learning Model for Early Alzheimer’s Disease Detection from Structural MRIs and External Validation on an Independent Cohort
Authors: Liu Sheng , Masurkar Arjun V. , Rusinek Henry , Chen Jingyun , Zhang Ben , Zhu Weicheng , Fernandez-Granda Carlos , Razavian Narges ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2021

AbstractEarly diagnosis of Alzheimer’s disease plays a pivotal role in patient care and clinical trials. In this study, we have developed a new approach based on 3D deep convolutional neural networks to accurately differentiate mild Alzheimer’s disease dementia from mild cognitive impairment and cognitively normal individuals using structural MRIs. For comparison, we have built a reference model based on the volumes and thickness of previously reported brain regions that are known to be implicated in disease progression. We validate both models on an internal held-out cohort from The Alzheimer’s Disease Neuroimaging Initiative (ADNI) and on an external independent cohort from The National Alzheimer’s Coordinating Center (NACC). The deep-learning model is more accurate and significantly faster than the volume/thickness model. The model can also be used to forecast progression: subjects with mild cognitive impairment misclassified as having mild Alzheimer’s disease dementia by the model were faster to progress to dementia over time. An analysis of the features learned by the proposed model shows that it relies on a wide range of regions associated with Alzheimer’s disease. These findings suggest that deep neural networks can automatically learn to identify imaging biomarkers that are predictive of Alzheimer’s disease, and leverage them to achieve accurate early detection of the disease.
A meta-analysis of polygenic risk scores for mood disorders, neuroticism, and schizophrenia in antidepressant response
Authors: Fanelli Giuseppe , Domschke Katharina , Minelli Alessandra , Gennarelli Massimo , Martini Paolo , Bortolomasi Marco , Maron Eduard , Squassina Alessio , Kasper Siegfried , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Forloni Gianluigi , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Ronchi Diana De ,   European College of Neuropsychopharmacology (ECNP) Pharmacogenomics & Transcriptomics Thematic Working Group, Baune Bernhard T , Serretti Alessandro , Fabbri Chiara 
Published: June 2021

AbstractAbout two-thirds of patients with major depressive disorder (MDD) fail to achieve symptom remission after the initial antidepressant treatment. Despite a role of genetic factors was proven, the specific underpinnings are not fully understood yet. Polygenic risk scores (PRSs), which summarise the additive effect of multiple risk variants across the genome, might provide insights into the underlying genetics. This study aims to investigate the possible association of PRSs for bipolar disorder, MDD, neuroticism, and schizophrenia (SCZ) with antidepressant non-response or non-remission in patients with MDD. PRSs were calculated at eight genome-wide P-thresholds based on publicly available summary statistics of the largest genome-wide association studies. Logistic regressions were performed between PRSs and non-response or non-remission in six European clinical samples, adjusting for age, sex, baseline symptom severity, recruitment sites, and population stratification. Results were meta-analysed across samples, including up to 3,637 individuals. Bonferroni correction was applied. In the meta-analysis, no result was significant after Bonferroni correction. The top result was found for MDD-PRS and non-remission (p=0.004), with patients in the highest vs. lowest PRS quintile being more likely not to achieve remission (OR=1.5, 95% CI=1.11-1.98, p=0.007). Nominal associations were also found between MDD-PRS and non-response (p=0.013), as well as between SCZ-PRS and non-remission (p=0.035). Although PRSs are still not able to predict non-response or non-remission, our results are in line with previous works; methodological improvements in PRSs calculation may improve their predictive performance and have a meaningful role in precision psychiatry.
High concordance of 70-gene recurrence risk signature and 80-gene molecular subtyping signature between core needle biopsy and surgical resection specimens in early-stage breast cancer
Authors: Crozier Jennifer A. , Barone Julie , Whitworth Pat , Cheong Abraham , Maganini Robert , Falk Jeffrey , Wei Jia-Perng , Mee Sammy , Ruby Jake , Yang Suoyi , Huynh Yen , Witteveen Anke , Finn Christine , Corcoran Kate , Dreezen Christa , Dauer Patricia , Menicucci Andrea , Wang Shiyu , Tran Annie , Yoder Erin , van der Baan Bastiaan , Audeh William , Glas Annuska ,   FLEX Investigators Group
Published: June 2021

AbstractIntroductionWith an increase in neoadjuvant therapy recommendations for most early-stage breast cancer patients due to the COVID-19 pandemic, it has become increasingly imperative to ensure that molecular diagnostic assays provide reliable results from preoperative core needle biopsies. Therefore, the objective of this study was to determine the concordance of MammaPrint results (70-gene signature) and BluePrint results (80-gene signature) between core needle biopsies (CNB) and surgical resection (SR) specimens using prospectively collected matched tissues from patients enrolled in the FLEX trial (NCT03053193).MethodsWe analyzed 113 matched CNB and SR tumor specimens from women with early-stage breast cancer enrolled in the FLEX trial. Each patient enrolled in the trial receives a MammaPrint recurrence risk classification test with or without BluePrint molecular subtyping. Concordance of MammaPrint is reported using overall percentage agreement, positive predictive value (PPV, High Risk), negative predictive value (NPV, Low Risk), and Cohen’s kappa coefficient. Additionally, correlations between sample types are reported using Pearson correlation coefficient.ResultsWe found good concordance for MammaPrint results between CNB and SR tumor samples (90.3%, κ = 0.803), with a 95.1% NPV and 84.6% PPV. There was also a strong correlation of MammaPrint indices between CNB and SR specimens (r = 0.94). In addition to our primary objective, we determined the concordance of BluePrint subtyping in the matched tumor samples, and found excellent concordance (98.2%) and strong correlation of BluePrint scores within each subtype.ConclusionCNB samples demonstrated overall high concordance with paired SR samples for MammaPrint risk classification, ensuring that physicians are provided with accurate prognostic information for therapy decisions based on testing of core biopsy tissue. Further, BluePrint molecular subtyping also had good concordance between the sample types, outperforming concordance rates based on traditional IHC based classification. Overall, with an increase in neoadjuvant therapy, physicans and patients can be assured that MammaPrint and BluePrint provide reliable results that guide timely and appropriate therapies using preoperative CNB specimens.
Variation in the reporting of elective surgeries and its influence on patient safety indicators
Authors: Locey Kenneth J. , Webb Thomas A. , Farooqui Sana , Hota Bala 
Published: June 2021

AbstractBackgroundUS hospital safety is routinely measured via patient safety indicators (PSIs). Receiving a score for most PSIs requires a minimum number of qualifying cases, which are partly determined by whether the associated diagnosis-related group (DRG) was surgical and whether the surgery was elective. While these criteria can exempt hospitals from PSIs, it remains to be seen whether exemption is driven by low volume, small numbers of DRGs, or perhaps, policies that determine how procedures are classified as elective.MethodsUsing Medicare inpatient claims data from 4,069 hospitals between 2015 and 2017, we examined how percentages of elective procedures relate to numbers of surgical claims and surgical DRGs. We used a combination of quantile regression and machine learning based anomaly detection to characterize these relationships and identify outliers. We then used a set of machine learning algorithms to test whether outliers were explained by the DRGs they reported.ResultsAverage percentages of elective procedures generally decreased from 100% to 60% in relation to the number of surgical claims and the number of DRGs among them. Some providers with high volumes of claims had anomalously low percentages of elective procedures (5% – 40%). These low elective outliers were not explained by the particular surgical DRGs among their claims. However, among hospitals exempted from PSIs, those with the greatest volume of claims were always low elective outliers.ConclusionSome hospitals with relatively high numbers of surgical claims may have classified procedures as non-elective in a way that ultimately exempted them from certain PSIs.