bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation based glioblastoma subclassification is related to tumoral T-cell infiltration and patient survival
Authors: Dejaegher Joost , Solie Lien , Hunin Zoé , Sciot Raf , Capper David , Siewert Christin , Van Cauter Sofie , Wilms Guido , van Loon Johan , Ectors Nadine , Fieuws Steffen , Pfister Stefan M , Van Gool Stefaan W , De Vleeschouwer Steven 
Published: October 2020

Abstract

Background
Histologically classified glioblastomas (GBM) can have different clinical behavior and response to therapy, for which molecular subclassifications have been proposed. We evaluated the relationship of epigenetic GBM subgroups with immune cell infiltrations, systemic immune changes during radiochemotherapy, and clinical outcome.

Methods
450K genome-wide DNA methylation was assessed on tumor tissue from 93 patients with newly diagnosed GBM, treated with standard radiochemotherapy and experimental immunotherapy. Tumor infiltration of T cells, myeloid cells, and Programmed cell death protein 1 (PD-1) expression were evaluated. Circulating immune cell populations and selected cytokines were assessed on blood samples taken before and after radiochemotherapy.

Results
Forty-two tumors had a mesenchymal, 27 a receptor tyrosine kinase (RTK) II, 17 RTK I, and 7 an isocitrate dehydrogenase (IDH) DNA methylation pattern. Mesenchymal tumors had the highest amount of tumor-infiltrating CD3+ and CD8+ T cells and IDH tumors the lowest. There were no significant differences for CD68+ cells, FoxP3+ cells, and PD-1 expression between groups. Systemically, there was a relative increase of CD8+ T cells and CD8+ PD-1 expression and a relative decrease of CD4+ T cells after radiochemotherapy in all subgroups except IDH tumors. Overall survival was the longest in the IDH group (median 36 mo), intermediate in RTK II tumors (27 mo), and significantly lower in mesenchymal and RTK I groups (15.5 and 16 mo, respectively).

Conclusions
Methylation based stratification of GBM is related to T-cell infiltration and survival, with IDH and mesenchymal tumors representing both ends of a spectrum. DNA methylation profiles could be useful in stratifying patients for immunotherapy trials.
Host- and Pathogen-Related Factors for Acute Cardiac Events in Pneumococcal Pneumonia
Authors: Rombauts Alexander , Abelenda-Alonso Gabriela , Càmara Jordi , Lorenzo-Esteller Laia , González-Díaz Aida , Sastre-Escolà Enric , Gudiol Carlota , Dorca Jordi , Tebé Cristian , Pallarès Natàlia , Ardanuy Carmen , Carratalà Jordi 
Published: October 2020

Abstract

Background
Acute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce.

Methods
A retrospective study was conducted of a prospective cohort of patients hospitalized for CAP between 1996 and 2019. Logistic regression and funnel plot analyses were performed to determine host- and pathogen-related factors for ACEs.

Results
Of 1739 episodes of pneumococcal CAP, 1 or more ACEs occurred in 304 (17.5%) patients, the most frequent being arrhythmia (n = 207), heart failure (n = 135), and myocardial infarction (n = 23). The majority of ACEs (73.4%) occurred within 48 hours of admission. Factors independently associated with ACEs were older age, preexisting heart conditions, pneumococcal bacteremia, septic shock at admission, and high-risk pneumonia. Among 983 pneumococcal isolates, 872 (88.7%) were serotyped and 742 (75.5%) genotyped. The funnel plot analyses did not find any statistically significant association between serotypes or clonal complexes with ACEs. Nevertheless, there was a trend toward an association between CC230 and these complications. ACEs were independently associated with 30-day mortality (adjusted odds ratio, 1.88; 95% CI, 1.11–3.13).

Conclusions
ACEs are frequent in pneumococcal pneumonia and are associated with increased mortality. The risk factors defined in this study may help identify patients who must undergo close follow-up, including heart rhythm monitoring, and special care to avoid fluid overload, particularly during the first 48 hours of admission. These high-risk patients should be the target for preventive intervention strategies.
CHARACTERIZATION OF A LANTHANUM BROMIDE DETECTOR FOR EYE LENS DOSIMETRY AT THE CANDU NUCLEAR POWER PLANTS BASED ON DIRECT MEASUREMENTS OF THE GAMMA-RAY SPECTRA
Authors: Laranjeiro A S , Bohra F , Byun S H , Atanackovic J , Hanu A R 
Published: October 2020

Abstract
Gamma-ray spectra were measured using a LaBr$_{3}$(Ce) spectrometer during the outage periods, aiming at quantifying the gamma source term of radiation workers’ exposure, at the CANDU nuclear power reactors, for the purposes of eye lens dosimetry. The spectra were measured inside the boiler rooms, of the Bruce Power and Ontario Power Generation (OPG) CANDU nuclear power plants, where workers are exposed to relatively high dose rates radiation fields during the maintenance work. Prior to measurements at the CANDU reactors, the pulse shaping parameters of the gamma spectrometer were optimised for high rates gamma fields, up to an input rates of 120 kcps, in order to accomplish a high output rate with a reasonable energy resolution. In parallel, the response of the LaBr$_{3}$(Ce) detector was characterized by experiments and Monte Carlo simulations. The gamma spectra measured at the CANDU reactors were reported in terms of the gamma-ray fluence rate spectrum. In all measured data, $^{60}$Co and $^{95}$Nb were main contributors of the gamma fields. The measured spectra have been used to calculate the dosimetric quantities of interest: personal dose equivalents H$_{p}$(10) and H$_{p}$(0.07) and eye lens absorbed dose.
Brain Perfusion Mediates the Relationship Between miRNA Levels and Postural Control
Authors: Chen Yufen , Herrold Amy A , Martinovich Zoran , Bari Sumra , Vike Nicole L , Blood Anne J , Walter Alexa E , Harezlak Jaroslaw , Seidenberg Peter H , Bhomia Manish , Knollmann-Ritschel Barbara , Stetsiv Khrystyna , Reilly James L , Nauman Eric A , Talavage Thomas M , Papa Linda , Slobounov Semyon , Breiter Hans C ,   for the Concussion Neuroimaging Consortium
Published: October 2020

AbstractTranscriptomics, regional cerebral blood flow (rCBF), and a virtual reality-based spatial motor task were integrated using mediation analysis in a novel demonstration of “imaging omics.” Data collected in National Collegiate Athletic Association (NCAA) Division I football athletes cleared for play before in-season training showed significant relationships in 1) elevated levels of miR-30d and miR-92a to elevated putamen rCBF, 2) elevated putamen rCBF to compromised Balance scores, and 3) compromised Balance scores to elevated microRNA (miRNA) levels. rCBF acted as a consistent mediator variable (Sobel’s test P &lt; 0.05) between abnormal miRNA levels and compromised Balance scores. Given the involvement of these miRNAs in inflammation and immune function and that vascular perfusion is a component of the inflammatory response, these findings support a chronic inflammatory model in these athletes with 11 years of average football exposure. rCBF, a systems biology measure, was necessary for miRNA to affect behavior.
Oral mucosa changes associated with chronic oral and inhalation exposure to 2,4-dichlorophenoxiacetic acid (2,4-D) in Wistar rats
Authors: Parizi José Luiz Santos , de Mello Odorizzi Gisele Aparecida Sales , Sato Grace Mitiko Rosati Hori , Patrão Isabela Bocardi , Nai Gisele Alborghetti 
Published: October 2020

Abstract
The respiratory tract and the oral mucosa are the first areas contaminated by pesticides. The herbicide dichlorophenoxyacetic acid (2,4-D) is a widely used pesticide across the world for both crops and gardens. The aim of this study was to evaluate oral mucosal damage after an experimental simulation of chronic oral and inhalational environmental exposure to 2,4-D formulation. Eighty male Wistar rats were exposed to three distinct concentrations of 2,4-D formulation (low—187.17 mg/m3; medium—313.31 mg/m3; and high—467.93 mg/m3). Oral exposure (through contaminated feed) or inhalation exposure lasted 6 months. Rat tongues were collected for cyto- and histopathology. There was a difference between exposure groups in the intensity of tissue congestion. Most rats exposed to 2,4-D presented mucosal inflammation at both cytology and histology (P &lt; 0.05). Hyperkeratosis only occurred in rats exposed orally at the high concentration. There was an increase in the number of nucleoli-organizing regions in the dorsal epithelium as the 2,4-D concentration increased (P &lt; 0.001). The inhalation route was more associated with increased mitosis figures and nucleoli-organizing region count (P &lt; 0.05). Chronic oral and inhalation exposure to high concentrations of 2,4-D formulation caused an increase in the proliferation rate and thickness of the tongue epithelium and stimulated the inflammatory response in the tissue.
Putative Effector Genes Distinguish Two Pathogenicity Groups ofFusarium oxysporumf. sp.spinaciae
Authors: Batson Alexander M. , Fokkens Like , Rep Martijn , du Toit Lindsey J. 
Published: October 2020

Fusarium wilt of spinach, caused by Fusarium oxysporum f. sp. spinaciae, is an important disease during warm conditions in production regions with acid soils, yet little is known about what confers pathogenicity to spinach in F. oxysporum f. sp. spinaciae genetically. To identify candidate fungal genes that contribute to spinach Fusarium wilt, each of 69 geographically diverse F. oxysporum isolates was tested for pathogenicity on each of three spinach inbreds. Thirty-nine isolates identified as F. oxysporum f. sp. spinaciae caused quantitative differences in disease severity among the inbreds that revealed two distinct pathogenicity groups of F. oxysporum f. sp. spinaciae. Putative effector gene profiles, predicted from whole-genome sequences generated for nine F. oxysporum f. sp. spinaciae isolates and five nonpathogenic, spinach-associated F. oxysporum (NPS) isolates, distinguished the F. oxysporum f. sp. spinaciae isolates from the NPS isolates, and separated the F. oxysporum f. sp. spinaciae isolates into two groups. Five of the putative effector genes appeared to be unique to F. oxysporum f. sp. spinaciae, as they were not found in 222 other publicly available genome assemblies of F. oxysporum, implicating potential involvement of these genes in pathogenicity to spinach. In addition, two combinations of the 14 known Secreted in Xylem (SIX) genes that have been affiliated with host pathogenicity in other formae speciales of F. oxysporum were identified in genome assemblies of the nine F. oxysporum f. sp. spinaciae isolates, either SIX8 and SIX9 or SIX4, SIX8, and SIX14. Characterization of these putative effector genes should aid in understanding mechanisms of pathogenicity in F. oxysporum f. sp. spinaciae, developing molecular tools for rapid detection and quantification of F. oxysporum f. sp. spinaciae, and breeding for resistance to Fusarium wilt in spinach.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Escape the Pharmacy: An Active Learning Strategy for the Nursing Pharmacology Classroom
Authors: Hadenfeldt Cindy J. , Naylor Heather M. , Aufdenkamp Marilee A. 
Published: October 2020

Abstract
Escape the Pharmacy is a fast-moving collaborative challenge for students in nursing and other health professions programs requiring coursework in pharmacology. Teams of students compete to solve a series of puzzles that reinforce knowledge of safe analgesic administration. Information regarding maximum dosing and adverse effects of opioids, nonsteroidal anti-inflammatories, and acetaminophen is included, as well as content on types of pain receptors. Recognition of opioid toxicity and symptoms of oversedation are all part of the challenge of escaping the pharmacy.
Relationship Between Second-to-Fourth Digit Ratio (as a Biomarker) and Tramadol Dependence
Authors: Khalifa Fatma N. , Shaheen Somaya H. , Magdi Mai M. , Basyoni Hoda A. 
Published: October 2020

Objectives:
Digit ratio (2D:4D ratio), the ratio between the length of the second and fourth fingers, is considered a putative biomarker of prenatal testosterone exposure relative to estrogen exposure, consequently it has been linked to several behaviors within the personality such as academic performance, nicotine and alcohol misuse, and also with other behaviors. Our aim is to investigate any possible association between 2D:4D ratios and tramadol dependence.

Participants and Methods:
A group of 99 male patients with tramadol dependence [diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)] were interviewed and their digital ratios were (2D:4D ratios) measured, then the findings were compared with 99 healthy males.

Results:
Patients with tramadol dependence had lower 2D:4D ratios of their right and left hands when compared with those without tramadol use disorder. There was no significant correlation between 2D:4D ratio and age of patients, age of onset, duration, and amount of tramadol use.

Conclusion:
These findings suggest that high prenatal exposure to testosterone levels could be associated with tramadol dependence as detected by a lower 2D:4D ratio.
Palliative Irradiation of Sacral Metastases
Authors: Soyfer Viacheslav , Gez Elihau , Novikov Ilya , Brautbar Oded , Corn Benjamin W. 
Published: October 2020

Background and Purpose:
The sacrum as radiation target, raises a conceptual question: should the structure be regarded as a single unit or 5 distinct bones. If the entire sacrum must be irradiated there is a higher risk of rectal morbidity.

Materials and Methods:
Images of 53 patients with sacral metastases were reviewed. The extent of sacral involvement was documented. The location of the rectum was recorded relative to the individual sacral bones.

Results:
In 37.7% only S1 and S2 were involved by metastatic disease. In 41.5% there was metastatic involvement of S1-S3. In 1 patient there was involvement of S5 only. In 10 cases the entire sacrum was infested by metastatic disease. The rectum never extended to the height of S1. In 38% the upper pole of the rectum reached the S3 level. In toto, there were 64.2% where the inferior extension of sacral metastatic involvement did not overlap the upper pole of the rectum. Palliation of pain was achieved in 19/20 patients treated with partial sacral irradiation.

Conclusions:
The distal part of the sacrum is rarely involved in the metastatic process. Avoidance of radiation therapy to the lower sacrum simultaneously enables effective palliation and sparing of the adjacent rectum.
Osocimab: A Novel Agent in Preventing Venous Thromboembolism
Authors: Beavers Craig J. , Wayne Nathaniel B. 
Published: October 2020

Abstract:
The nature of orthopedic surgery, and specifically total knee arthroplasty, lends itself to the development of venous thromboembolism given endothelial injury from the surgical procedure, promotion of an acute hypercoagulable state, and the prolonged period of immobilization after surgery promoting stasis; all factors of Virchow's triad. Current guidelines recommend the direct acting oral anticoagulants, enoxaparin, fondaparinux, and warfarin as options for venous thromboembolism prevention. However, these agents may still be prone to unacceptable bleeding risk, given they mostly target the extrinsic pathway of the clotting cascade, and have other characteristics which can be problematic for use. Investigators have determined patients with factor XI deficiency seem to be protected for thrombotic risk and seem to be devoid of bleeding sequelae. This has led to the development of osocimab, a fully humanized monoclonal G1 antibody designed specifically to functionally neutralize factor XIa. Phase 1 clinical trials have demonstrated an agent with a long half-life (∼30 days) with minimal requirement of renal elimination and hepatic metabolism. Phase 2 trials have identified that an optimal dose range, 0.6–1.2 mg/kg, as a 1-time dose preoperatively or postoperatively is effective in preventing thrombotic complications with minimal bleeding risk compared with standard of care for elective total knee arthroplasty patients. Future clinical development will be able to clearly outline the role this agent will play in the future.
Cardiopulmonary Rehabilitation in Pediatric Patients With Congenital and Acquired Heart Disease
Authors: McBride Michael G. , Burstein Danielle S. , Edelson Jonathan B. , Paridon Stephen M. 
Published: October 2020

Background:
Heart disease in children and adolescents is common, approaching 1.0% of the population. In those patients with complex physiology and severe cardiac dysfunction, the inability to participate in physical activity results in significant obstacles to normal acts of daily living and significantly diminished quality of life. Attempts to study the practicality and benefits of cardiopulmonary rehabilitation (CR) programs in this population have been hampered by the heterogeneity of lesions, lack of facilities, and trained personnel to supervise these types of programs. Although there are numerous articles on CR in children with cardiac disease, all suffer from the same basic problems of small sample size, short duration of study, and heterogeneous study populations.

Purpose:
The purpose of this review was to first evaluate the current rehabilitation literature on both congenital cardiac defects and acquired abnormalities—in this latter group placing a significant emphasis on cardiomyopathies, as well as the special populations in the peri-transplant period and/or mechanical circulatory support. Second, we discussed what is known about practical approaches to CR for the various types of pediatric-specific cardiac conditions. This limited data will be supplemented by the current approach of our institution to CR in these populations with the understanding that this is by no means a consensus approach to these patients. Finally, we summarized research goals for this growing group of patients.

Conclusion:
Cardiopulmonary rehabilitation in pediatric congenital and acquired heart disease is currently a field in its infancy. Significant strides have been made for complex heart disease and impaired myocardial function. Current research holds the promise for the development of programs that are practical, scalable, and can be implemented in most clinical sites within the foreseeable future.
CHORIOCAPILLARIS VASCULAR PARAMETERS IN NORMAL EYES AND THOSE WITH PACHYCHOROID WITH AND WITHOUT DISEASE
Authors: Spaide Richard F. , Ledesma-Gil Gerardo 
Published: October 2020

Purpose:
To evaluate the vascular characteristics of the choriocapillaris in eyes with pachychoroid as compared with normal controls.

Methods:
Eyes with pachychoroid disease were defined as those with a history of central serous chorioretinopathy or peripapillary pachychoroid syndrome. Pachychoroid without disease was defined as eyes with no history of disease with a subfoveal choroidal thickness ≥ the age-adjusted 95th percentile thickness. Frame-averaged optical coherence tomography angiography images of the choriocapillaris obtained with a Zeiss Plex Elite were binarized, skeletonized, and evaluated for vascular branching parameters.

Results:
There were 7 normal control subjects, 10 subjects with pachychoroid without disease, and 17 pachychoroid disease subjects. Mean choriocapillaris vessel segment length was 12.19 µm in eyes with pachychoroid disease as compared with 11.48 µm in normal controls and 11.62 µm in pachychoroid without disease (P = 0.003 and P = 0.006, respectively). The branches per square millimeter were fewer in pachychoroid disease (1,215), as compared with normal controls (1,471) or pachychoroid without disease (1,384; P < 0.001, and P = 0.002, respectively). The choriocapillaris vessel diameter was larger, but the fractal dimension was smaller in pachychoroid disease eyes as compared with normal eyes or pachychoroid without disease eyes. There was no statistically significant difference between normal controls and pachychoroid without disease for any measured vascular parameter of the choriocapillaris.

Conclusion:
Choriocapillaris vascular parameters suggest that pachychoroid is not necessarily pathologic. It is possible that choroidal thickening is an epiphenomenon, and there are more significant vascular parameters that are related to disease. These concepts may help guide future prospective studies.
NONPERFUSION ASSESSMENT IN RETINAL VEIN OCCLUSION
Authors: Glacet-Bernard Agnès , Miere Alexandra , Houmane Badreddine , Tilleul Julien , Souied Eric 
Published: October 2020

Purpose:
To compare widefield optical coherence tomography angiography (OCTA) to ultra-widefield fluorescein angiography (UWFA) in the assessment of nonperfusion in retinal vein occlusion (RVO).

Methods:
A cross-sectional study of 43 eyes of 43 patients with RVO examined using both widefield OCTA (PLEX Elite, Carl Zeiss Meditec, Dublin, CA) with a panoramic montage of five 12 × 12-mm images and UWFA (Optos, 200°). Qualitative analysis was performed according to nonperfusion areas (cutoff: three disk areas) on widefield OCTA. The quantitative analysis assessed the vascular density on the widefield OCTA and ischemic index on UWFA.

Results:
The ischemic index on UWFA and vascular density in the superficial and deep plexus correlated significantly (P = 0.019, r = 0.357 and P < 0.013, r = 0.375, respectively). The qualitative classification on widefield OCTA and ischemic index on UWFA correlated significantly (P < 0.001, r = 0.618). For the detection of marked nonperfusion (ischemic index ≥ 25%), widefield OCTA had a sensitivity of 100% and a specificity of 64.9%.

Conclusion:
The presence of nonperfusion on UWFA correlated with widefield OCTA. Optical coherence tomography angiography could help to identify high-risk RVO patients who might benefit from a further evaluation using fluorescein angiography.
Per- and Polyfluoroalkyl Substance and Cardio Metabolic Markers in Firefighters
Authors: Khalil Naila , Ducatman Alan M. , Sinari Shripad , Billheimer Dean , Hu Chengcheng , Littau Sally , Burgess Jefferey L. 
Published: October 2020

Objective:
To evaluate if serum polyfluoroalkyl substances (PFAS) were associated with cardiometabolic markers.

Methods:
Serum PFAS were evaluated in 38 Arizona firefighters and 49 participants from the 2009 to 2010 National Health and Nutrition Examination Survey (NHANES). Cardiometabolic markers including carotid intima-medial thickness (CIMT) were measured in the firefighters.

Results:
Firefighters had elevated perfluorohexane sulfonic acid (PFHxS) and lower perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) compared to NHANES participants; for nine of the other 12 PFAS the values were not significantly different. There were significant negative associations among firefighters between perfluorodecanoic acid (PFDeA) and total cholesterol and PFUA and interleukin-6. PFAS concentrations were not associated with CIMT.

Conclusion:
PFHxS levels were elevated in firefighters compared to NHANES subjects. Serum PFAS concentrations were not associated with increased cardiometabolic risk measures in this population of firefighters.