bluuebunny/crossref_metadata_2025_split huggingface dataset:
Musical experience partially counteracts temporal speech processing deficits in putative mild cognitive impairment
Authors: Price Caitlin N. , Bidelman Gavin M. 
Published: June 2022

AbstractMild cognitive impairment (MCI) commonly results in more rapid cognitive and behavioral declines than typical aging. Individuals with MCI can exhibit impaired receptive speech abilities that may reflect neurophysiological changes in auditory‐sensory processing prior to usual cognitive deficits. Benefits from current interventions targeting communication difficulties in MCI are limited. Yet, neuroplasticity associated with musical experience has been implicated in improving neural representations of speech and offsetting age‐related declines in perception. Here, we asked whether these experience‐dependent effects of musical experience might extend to aberrant aging and offer some degree of cognitive protection against MCI. During a vowel categorization task, we recorded single‐channel electroencephalograms (EEGs) in older adults with putative MCI to evaluate speech encoding across subcortical and cortical levels of the auditory system. Critically, listeners varied in their duration of formal musical experience (0–21 years). Musical experience sharpened temporal precision in auditory cortical responses, suggesting that musical experience produces more efficient processing of acoustic features by counteracting age‐related neural delays. Additionally, robustness of brainstem responses predicted the severity of cognitive decline, suggesting that early speech representations are sensitive to preclinical stages of cognitive impairment. Our results extend prior studies by demonstrating positive benefits of musical experience in older adults with emergent cognitive impairments.
Spectrum of paired‐like homeobox 2b immunoexpression in pediatric brain tumors with embryonal morphology
Authors: Alturkustani Murad , Walker Adam D. , Tran Ivy , Snuderl Matija , Cotter Jennifer A. 
Published: June 2022

AbstractPaired‐like homeobox 2b (PHOX2B) is an established immunomarker for peripheral neuroblastoma and autonomic nervous system cells. We aimed to evaluate the utility of PHOX2B immunostaining in central nervous system (CNS) tumors with embryonal morphology. Fifty‐one tumors were stained with PHOX2B and submitted for whole slide image analysis: 35 CNS tumors with embryonal morphology (31 CNS embryonal tumors and four gliomas); and 16 peripheral neuroblastomas were included for comparison. Diffuse nuclear immunopositivity was observed in all (16/16) neuroblastomas (primary and metastatic). Among CNS embryonal tumors, focal immunoreactivity for PHOX2B was observed in most (5/7) embryonal tumors with multilayered rosettes (ETMR) and a single high‐grade neuroepithelial tumor (HGNET) with PLAGL2 amplification; the remaining 27 CNS tumors were essentially immunonegative (<0.05% positive). Among ETMR, PHOX2B expression was observed in a small overall proportion (0.04%–4.94%) of neoplastic cells but focally reached up to 39% in 1 mm ‘hot spot’ areas. In the PLAGL2‐amplified case, 0.09% of the total neoplastic population was immunoreactive, with 0.53% in the ‘hot spot’ area. Care should be taken in interpreting PHOX2B immunopositivity in a differential diagnosis that includes metastatic neuroblastoma and CNS tumors; focal or patchy expression should not be considered definitively diagnostic of metastatic peripheral neuroblastoma.
Sincerity in bulk
Authors: Paterson Grace 
Published: June 2022

AbstractThis paper is concerned with situations in which a speaker issues many speech acts at the same time. A common example is the publication of a large text such as a book containing many distinct assertions. It is argued that these cases present a challenge for speech act theory related to how we are to understand sincerity. With reference to the well known paradox of the preface, it is argued that sincerity of such bulk speech cannot be understood as a simple conjunction of the sincerity of the encoded acts. A proposal is given according to which sincere bulk speech requires the speaker explicitly and as precisely as possible mark any subsets of her communication about which she has doubts.
Simulated RBC antibody identification training panels created using SARS‐CoV‐2 kodecytes and immune plasma
Authors: Perry Holly , Henry Stephen M. 
Published: June 2022

AbstractBackgroundTraining is essential to develop and maintain skills required to be a competent serologist, yet samples required to achieve this are often difficult to obtain. We evaluated the feasibility of SARS‐CoV‐2 peptide modified RBCs (1144‐kodecytes) to develop simulated antibody screening and identification panels of reagent RBCs suitable for practical training, recognition, and grading of serologic reactions.Study Design and MethodsRBCs from a single donor were modified into kodecytes using Kode Technology function‐spacer‐lipid constructs bearing a short SARS‐CoV‐2 peptide. Kodecytes and unmodified cells were then arranged in patterns representative of RBC antibody profiles as simulated antibody screening and identification reagent cell panels (SASID), and then tested against immune donor plasma samples containing SARS‐CoV‐2 antibodies. Manual tube and two different gel card serologic platforms were evaluated by routine techniques. SASID exemplars were created for antibodies including D, Cw, f (ce), Jka (strong, weak, dosing), mixtures of D + E, Jka + K, Fya + E, high and low frequency antibodies and a warm IgG autoantibody.ResultsKodecytes (positive reactions) and unmodified cells (negative) when arranged and tested in appropriate patterns in SASID panels were able to mimic IgG antibody reactions, and were capable of measuring both accuracy and precision in reaction grading.ConclusionsKodecytes can be used to rapidly create in‐house simulated yet realistic antibody screening and identification panels suitable for large scale training in the recognition and grading of serologic reactions.
Cannabis use and risks of respiratory and all-cause morbidity and mortality: a population-based, data-linkage, cohort study
Authors: Vozoris Nicholas T , Zhu Jingqin , Ryan Clodagh M , Chow Chung-Wai , To Teresa 
Published: June 2022

IntroductionAlthough cannabis is frequently used worldwide, its impact on respiratory health is characterised by controversy.ObjectiveTo evaluate the association between cannabis use and respiratory-related emergency room (ER) visits and hospitalisations.MethodsA retrospective, population-based, cohort study was carried out, linking health survey and health administrative data for residents of Ontario, Canada, aged 12–65 years, between January 2009 and December 2015. Individuals self-reporting cannabis use within the past year were matched to control individuals (people who reported never using cannabis, or used cannabis only once, and more than 12 months ago) in upwards of a 1:3 ratio on 31 different variables, using propensity score matching methods. Respiratory-related and all-cause ER visits or hospitalisations, and all-cause mortality, were evaluated up to 12 months following the index date.ResultsWe identified 35 114 individuals who had either used cannabis in the past year or were controls, of whom 6425 (18.3%) used cannabis in the past year. From this group, 4807 (74.8%) were propensity-score matched to 10 395 control individuals. In the propensity score matched cohort, there was no significant difference in odds of respiratory-related ER visit or hospitalisation between cannabis users and the control group (OR 0.91, 95% CI 0.77 to 1.09). Compared with control individuals, cannabis users had significantly increased odds of all-cause ER visit or hospitalisation (OR 1.22, 95% CI 1.13 to 1.31) and there was no significant difference with respect to all-cause mortality (OR 0.99, 95% CI 0.49 to 2.02).ConclusionsAlthough no significant association was observed between cannabis use and respiratory-related ER visits or hospitalisations, the risk of an equally important morbidity outcome, all-cause ER visit or hospitalisation, was significantly greater among cannabis users than among control individuals. Therefore, cannabis use is associated with increased risk for serious adverse health events and its recreational consumption is not benign.
Brane cosmology with variable tension
Authors: Belinchón José Antonio , Dib Sami 
Published: June 2022

We study brane-world models and demonstrate that such models do not admit self-similar solutions through the matter collineation approach. By introducing the hypothesis of variable brane tension, λ, we outline the new effective field equation (EFE) in the most simple case (symmetric embedding) under the assumption that the fundamental constants in five dimensions (5D) are constants. In this case, we find the exact form that each physical quantity may take in order that the EFE become invariant under scale transformations. By taking into account such assumptions, we find that in four dimensions the gravitational constant κ2 ∼  λ, while the cosmological constant Λ ∼  λ2 is always decreasing. These results are quite general and valid for any homogeneous self-similar metric. Nevetheless, the study of the EFE under scale symmetries suggests that ρ ∼  λ (as a functional relationship). This allows us to get a growing κ2 but, in this case, the fundamental constants in 5D must vary as well. We outline a toy model allowing such a possibility.
Study on Analysis of Several Molecular Identification Methods for Ciliates of Colpodea (Protista, Ciliophora)
Authors: Song Yumeng , Hao Tingting , Li Bailin , Zheng Weibin , Liu Lihui , Wang Li , Chen Ying , Pan Xuming 
Published: June 2022

The application of molecular techniques to accurately identify protozoan species can correct previous misidentifications based on traditional morphological identification. Colpodea ciliates have many toxicological and cytological applications, but their subtle morphological differences and small body size hinder species delineation. Herein, we used Cox I and β-tubulin genes, alongside fluorescence in situ hybridization (FISH), to evaluate each method in delineating Colpodea species. For this analysis, Colpoda harbinensis n. sp., C. reniformis, two populations of C. inflata, Colpoda compare grandis, and five populations of Paracolpoda steinii, from the soil in northeastern China, were used. We determined that (1) the Cox I gene was more suitable than the β-tubulin gene as a molecular marker for defining intra- and interspecific level relationships of Colpoda. (2) FISH probes designed for Colpoda sp., C. inflata, Colpoda compare grandis, and Paracolpoda steinii, provided rapid interspecific differentiation of Colpodea species. (3) Colpoda harbinensis n. sp. was established and mainly characterized by its size in vivo (approximately

80
×
60

μ
m

), a reniform body in outline, one macronucleus, its spherical shape, a sometimes nonexistent micronucleus, 11–15 somatic kineties, and five or six postoral kineties. In conclusion, combining oligonucleotide probes, DNA barcoding, and morphology for the first time, we have greatly improved the delineation of Colpodea and confirmed that Cox I gene was a promising DNA barcoding marker for species of Colpodea, and FISH could provide useful morphological information as complementing traditional techniques such as silver carbonate.
Analysis of the p-11B Fusion Scenario with Compensation of the Transfer of Kinetic Energy of Protons and Alpha Particles to the Gas Medium by the Electric Field
Authors: Shmatov Mikhail L. , Batani Dimitri 
Published: June 2022

The energy balance of the p-11B fusion scenario with compensation of the transfer of kinetic energy of protons and alpha particles to the gas medium by the electric field is considered. It is shown that such scenario cannot provide the use of p-11B fusion reaction for power production due to the very low ratio of the energy release of the fusion reaction to the energy necessary for compensation. The upper boundary of this ratio is about2×10−3.
Reengineering Ponatinib to Minimize Cardiovascular Toxicity
Authors: Hnatiuk Anna P. , Bruyneel Arne A.N. , Tailor Dhanir , Pandrala Mallesh , Dheeraj Arpit , Li Wenqi , Serrano Ricardo , Feyen Dries A.M. , Vu Michelle M. , Amatya Prashila , Gupta Saloni , Nakauchi Yusuke , Morgado Isabel , Wiebking Volker , Liao Ronglih , Porteus Matthew H. , Majeti Ravindra , Malhotra Sanjay V. , Mercola Mark 
Published: June 2022

Abstract

Small molecule tyrosine kinase inhibitors (TKI) have revolutionized cancer treatment and greatly improved patient survival. However, life-threatening cardiotoxicity of many TKIs has become a major concern. Ponatinib (ICLUSIG) was developed as an inhibitor of the BCR-ABL oncogene and is among the most cardiotoxic of TKIs. Consequently, use of ponatinib is restricted to the treatment of tumors carrying T315I-mutated BCR-ABL, which occurs in chronic myeloid leukemia (CML) and confers resistance to first- and second-generation inhibitors such as imatinib and nilotinib. Through parallel screening of cardiovascular toxicity and antitumor efficacy assays, we engineered safer analogs of ponatinib that retained potency against T315I BCR-ABL kinase activity and suppressed T315I mutant CML tumor growth. The new compounds were substantially less toxic in human cardiac vasculogenesis and cardiomyocyte contractility assays in vitro. The compounds showed a larger therapeutic window in vivo, leading to regression of human T315I mutant CML xenografts without cardiotoxicity. Comparison of the kinase inhibition profiles of ponatinib and the new compounds suggested that ponatinib cardiotoxicity is mediated by a few kinases, some of which were previously unassociated with cardiovascular disease. Overall, the study develops an approach using complex phenotypic assays to reduce the high risk of cardiovascular toxicity that is prevalent among small molecule oncology therapeutics.

Significance:
Newly developed ponatinib analogs retain antitumor efficacy but elicit significantly decreased cardiotoxicity, representing a therapeutic opportunity for safer CML treatment.
Extracellular Vesicles May Predict Response to Radioembolization and Sorafenib Treatment in Advanced Hepatocellular Carcinoma: An Exploratory Analysis from the SORAMIC Trial
Authors: Shuen Timothy Wai Ho , Alunni-Fabbroni Marianna , Öcal Elif , Malfertheiner Peter , Wildgruber Moritz , Schinner Regina , Pech Maciej , Benckert Julia , Sangro Bruno , Kuhl Christiane , Gasbarrini Antonio , Chow Pierce Kah Hoe , Toh Han Chong , Ricke Jens 
Published: June 2022

Abstract

Purpose:
SORAMIC is a randomized controlled trial in patients with advanced hepatocellular carcinoma (HCC) undergoing sorafenib ± selective internal radiation therapy (SIRT). We investigated the value of extracellular vesicle (EV)-based proteomics for treatment response prediction.

Experimental Design:
The analysis population comprised 25 patients receiving SIRT+sorafenib and 20 patients receiving sorafenib alone. Patients were classified as responders or nonresponders based on changes in AFP and imaging or overall survival. Proteomic analysis was performed on plasma EVs by LC/MS, followed by bioinformatics analysis. Clinical relevance of candidate EV proteins was validated by survival and receiver-operating characteristic analysis with bootstrap internal sampling validation. Origin of circulating EV was explored by IHC staining of liver and tumor tissues and transcriptomics of blood cells.

Results:
Proteomic analysis identified 56 and 27 EV proteins that were differentially expressed in plasma EVs between responders and nonresponders receiving SIRT+sorafenib and sorafenib alone, respectively. High EV-GPX3/ACTR3 and low EV-ARHGAP1 were identified as candidate biomarkers at baseline from the 13 responders to SIRT+sorafenib with statistically significant AUC = 1 for all and bootstrap P values 2.23 × 10−5, 2.22 × 10−5, and 2.23 × 10−5, respectively. These patients showed reduced abundance of EV-VPS13A and EV-KALRN 6 to 9 weeks after combined treatment with significant AUC and bootstrap P values. In reverse, low GPX3 and high ARHGAP1 demonstrated better response to sorafenib monotherapy with AUC = 0.9697 and 0.9192 as well as bootstrap P values 8.34 × 10−5 and 7.98 × 10−4, respectively. HCC tumor was the likely origin of circulating EVs.

Conclusions:
In this exploratory study, EV-based proteomics predicted response to SIRT+sorafenib and sorafenib-only treatment in patients with advanced HCC of metabolic origin.
Nivolumab Retreatment in Non–Small Cell Lung Cancer Patients Who Responded to Prior Immune Checkpoint Inhibitors and Had ICI-Free Intervals (WJOG9616L)
Authors: Akamatsu Hiroaki , Teraoka Shunsuke , Takamori Shinkichi , Miura Satoru , Hayashi Hidetoshi , Hata Akito , Toi Yukihiro , Shiraishi Yoshimasa , Mamesaya Nobuaki , Sato Yuki , Furuya Naoki , Oyanagi Jun , Koh Yasuhiro , Misumi Toshihiro , Yamamoto Nobuyuki , Nakagawa Kazuhiko 
Published: June 2022

Abstract

Purpose:
To explore the efficacy of retreatment with immune checkpoint inhibitors (ICI) in patients with advanced non–small cell lung cancer (NSCLC) who responded to prior ICI and had adequate ICI-free interval.

Patients and Methods:
Patients with advanced NSCLC who had achieved complete response (CR), partial response (PR), or stable disease for ≥6 months with prior ICI therapy preceding progression were prospectively enrolled. All patients should have had ICI-free interval ≥60 days before registration. Patients were treated with nivolumab (240 mg) every 2 weeks until progression. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival, and safety (Trial Identifier, UMIN000028561).

Results:
Sixty-one patients were enrolled during October 2017 to February 2020, with 59 analyzed for efficacy. Regarding prior ICI, 41 patients had CR or PR. Median treatment on ICI and median ICI-free intervals were 8.1 months and 9.2 months, respectively. Twenty patients experienced immune-related adverse events (irAE) that required discontinuation of prior ICI. Nivolumab retreatment demonstrated ORR of 8.5% [95% confidence interval (CI), 2.8–18.7%] and median PFS of 2.6 months (95% CI, 1.6–2.8 months) while 5 responders had 11.1 months of median PFS. In the multivariate analysis, ICI-free interval was the only predictive factor of PFS (HR, 2.02; P = 0.02), while prior efficacy or history of irAE was not. Common adverse events were skin disorders (23%), malaise (20%), and hypoalbuminemia (15%).

Conclusions:
Even in patients who initially responded to prior ICI and had ICI-free interval, once resistance occurred, retreatment with nivolumab had limited efficacy.
Survival Probability and Survival Benefit Associated With Primary Prevention Implantable Cardioverter‐Defibrillator Generator Changes
Authors: Bilchick Kenneth C. , Wang Yongfei , Curtis Jeptha P. , Shadman Ramin , Dardas Todd F. , Anand Inder , Lund Lars H. , Dahlström Ulf , Sartipy Ulrik , Levy Wayne C. 
Published: June 2022

Background
As patients derive variable benefit from generator changes (GCs) of implantable cardioverter‐defibrillators (ICDs) with an original primary prevention (PP) indication, better predictors of outcomes are needed.

Methods and Results

In the National Cardiovascular Data Registry ICD Registry, patients undergoing GCs of initial non‐cardiac resynchronization therapy PP ICDs in 2012 to 2016, predictors of post‐GC survival and survival benefit versus control heart failure patients without ICDs were assessed. These included predicted annual mortality based on the Seattle Heart Failure Model, left ventricular ejection fraction (LVEF) >35%, and the probability that a patient's death would be arrhythmic (proportional risk of arrhythmic death [PRAD]). In 40 933 patients undergoing GCs of initial noncardiac resynchronization therapy PP ICDs (age 67.7±12.0 years, 24.5% women, 34.1% with LVEF >35%), Seattle Heart Failure Model–predicted annual mortality had the greatest effect size for decreased post‐GC survival (
P
<0.0001). Patients undergoing GCs of initial noncardiac resynchronization therapy PP ICDs with LVEF >35% had a lower Seattle Heart Failure Model–adjusted survival versus 23 472 control heart failure patients without ICDs (model interaction hazard ratio, 1.21 [95% CI, 1.11–1.31]). In patients undergoing GCs of initial noncardiac resynchonization therapy PP ICDs with LVEF ≤35%, the model indicated worse survival versus controls in the 21% of patients with a PRAD <43% and improved survival in the 10% with PRAD >65%. The association of the PRAD with survival benefit or harm was similar in patients with or without pre‐GC ICD therapies.

Conclusions
Patients who received replacement of an ICD originally implanted for primary prevention and had at the time of GC either LVEF >35% alone or both LVEF ≤35% and PRAD <43% had worse survival versus controls without ICDs.
Novel Risk Prediction Model to Determine Adverse Heart Failure Outcomes in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Chen Shi , Chen Liang , Saguner Ardan M. , Chen Kai , Akdis Deniz , Gasperetti Alessio , Brunckhorst Corinna , Tang Hanwei , Guo Guangran , Rao Man , Li Xiangjie , Song Jiangping , Duru Firat , Hu Shengshou 
Published: June 2022

Background
Patients with arrhythmogenic right ventricular cardiomyopathy are at risk for life‐threatening ventricular tachyarrhythmias, but progressive heart failure (HF) may occur in later stages of disease. This study aimed to characterize potential risk predictors and develop a model for individualized assessment of adverse HF outcomes in arrhythmogenic right ventricular cardiomyopathy.

Methods and Results
Longitudinal and observational cohorts with 290 patients with arrhythmogenic right ventricular cardiomyopathy from the Fuwai Hospital in Beijing, China, and 99 patients from the University Heart Center in Zurich, Switzerland, with follow‐up data were studied. The primary end point of the study was heart transplantation or death attributable to HF. The model was developed by Cox regression analysis for predicting risk and was internally validated. During 4.92±3.03 years of follow‐up, 48 patients reached the primary end point. The determinants of the risk prediction model were left ventricular ejection fraction, serum creatinine levels, moderate‐to‐severe tricuspid regurgitation, and atrial fibrillation. Implantable cardioverter‐defibrillators did not reduce the occurrence of adverse HF outcomes.

Conclusions
A novel risk prediction model for arrhythmogenic right ventricular cardiomyopathy has been developed using 2 large and well‐established cohorts, incorporating common clinical parameters such as left ventricular ejection fraction, serum creatinine levels, tricuspid regurgitation, and atrial fibrillation, which can identify patients who are at risk for terminal HF events, and may guide physicians to assess individualized HF risk and to optimize management strategies.
Family Resemblances in Action
Authors: van Dijk Rijk , Kirsch Thomas G. , Duarte dos Santos Franziska 
Published: June 2022

Abstract
The introduction to this special issue argues that in many countries in southern Africa a new phase in the entanglement between the religious and the political has set in. Increasingly, activists in political fields are borrowing from religious registers of discourse and practice, while conversely, activists in the religious domain are adopting discourses and practices originating in the political domain. We suggest that this religiopolitical activism is simultaneously the product of a climate of profound social change and an important transformative force within it. In order to do justice to the complex dynamics of southern African religiopolitical activism in its manifold manifestations, we draw on the concept of ‘family resemblances’. This allows us to examine how the boundaries between religious and political registers are made the object of situated social negotiations. The family resemblances explored in this special issue range from religiopolitical activists’ habitus and their communication strategies via religious leaders’ self-positionings in relation to the political, to the creation of specific religiopolitical spaces.