bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPCT-12. NATIONAL MULTICENTERED RETROSPECTIVE REVIEW OF DEMOGRAPHIC, TUMOUR AND INTRAOPERATIVE FEATURES ASSOCIATED WITH THE DEVELOPMENT OF CEREBELLAR MUTISM AFTER PEDIATRIC POSTERIOR FOSSA TUMOUR RESECTION
Authors: Kameda-Smith Michelle , Elliott Cameron , Moore Hannna , Sader Nicholas , Tso Michael , Alsuwaihel Mosaab , Dakson Ayoub , Ajani Olufemi , Yarascavitch Blake , Fleming Adam , Mehta Vivek , Farrokhyar Forough , Yikilmaz Ali , Stein Nina , Singh Sheila 
Published: June 2021

Abstract

Background
Cerebellar mutism (CM) is a condition characterized by a significant lack or loss of speech in children following posterior fossa (PF) surgery. The biological origin of CM remains largely unclear and remains the subject of ongoing debate. Despite multidisciplinary rehabilitative interventions, the outcome is less favorable than initially described. Given the treatment refractory nature of CM, central to its management is prevention.

Methods
A national multi-centered retrospective review of all the children undergoing posterior fossa resection at 4 Canadian academic pediatric institutions was undertaken. Patient, tumour, surgical features suggested to be associated with the post-operative development of CM were reviewed to identify pre-operative and intra-operative factors that may predict post-operative CM occurrence.

Results
258 pediatric patients were identified after posterior fossa lesion resection. Mean age at surgery was 6.74 years (SD 4.60) and 42.2% were female. Frozen section was available in 90.3% of cases. The majority of final tumour histology was medulloblastoma (35.7%), pilocytic astrocytoma (32.6%), ependymoma (17.1%) and exophytic glioma (1.2%). Intra-operative impression of adherence to the floor of the 4th ventricle was negative in 47.7%, positive in 36.8% of cases. The extent of resection assessed intraoperatively as gross total resection was 69.8% of cases. Intra-operative abrupt changes in blood pressure and/or heart rate was identified in 19.4% and 17.8% of cases. CM was experienced in 19.5% of patients (N=50), with the majority of cases identified by post-operative day 7. The clinical resolution of CM as mainly assessed by a neurosurgeon (86%) and was complete, significantly resolved, slight improvement, no improvement or deterioration in 56.0%, 8.0%, 20.0%, 14.0%, 2.0% respectively.

Conclusion
As a devastating surgical complication, identifying and understanding the biological origin of CM is the first step to complication avoidance. Maximal safe resection irrespective of intra-operative pathology remains the goal to avoid the devastating complication of CM.
EPCT-22 SAFETY AND EFFICACY OF INTRAVENTRICULAR IMMUNOVIROTHERAPY WITH ONCOLYTIC HSV-1 G207 FOR TREATMENT OF LEPTOMENINGEAL DISEASE
Authors: Kang Kyung-Don , Bernstock Joshua , Mott Bryan , Nan Li , Li Rong , Totsch Stacie , Gary Sam , Ghajar-Rahimi Gelare , Etminan Tina , Eisemann Tanja , Wechsler-Reya Robert , Beierle Elizabeth , Gillespie George , Markert James , Friedman Gregory 
Published: June 2021

Abstract
Leptomeningeal metastatic disease (LMD) occurs in 30–50% of newly diagnosed and recurrent pediatric malignant cerebellar tumors and 20–45% of malignant supratentorial tumors. Radiation and chemotherapy often cause substantial long-term neurotoxicity and outcomes remain poor for patients with LMD. At recurrence, LMD is generally minimally responsive to conventional therapies. Immunovirotherapy with engineered oncolytic HSV-1 G207 has emerged as a promising treatment for children with high-grade brain tumors. G207 infects and kills tumor cells while sparing normal cells and stimulates a robust anti-tumor immune response. Intratumoral G207 inoculation demonstrated safety and preliminary efficacy in a pediatric Phase 1 trial in recurrent/progressive high-grade glioma (NCT02457845), and a Phase 2 trial (NCT04482933) is forthcoming. Additionally, a Phase 1 trial of intratumoral G207 in recurrent/progressive malignant pediatric cerebellar tumors is ongoing (NCT03911388). While intratumoral inoculation delivers G207 directly to a primary tumor, it requires neurosurgical procedures thereby limiting repeat doses. Thus, we sought to establish the safety and efficacy of intraventricular G207. Utilizing an immunocompetent, HSV-sensitive murine strain, we determined that a standard 1x107 plaque-forming units (PFU) dose of G207 resulted in damage to the ependymal lining. However, interferon induction with an intraventricular low-dose (1x104 PFU) of G207 or polyinosinic-polycytidylic acid (poly I:C), a toll-like receptor 3 agonist, three days prior to standard treatment dose protected the ependymal lining. This approach enabled safe delivery of multiple subsequent doses. Importantly, with these protective measures, G207 significantly prolonged survival in pediatric patient-derived xenograft models and an immunocompetent murine LMD model of group 3 medulloblastoma, the most aggressive and fatal subtype. Collectively, these data indicate that toxicity from intraventricular G207 can be safely mitigated prior to a therapeutic dose, and that intraventricular G207 effectively targets group 3 medulloblastoma including LMD. These findings provide support for clinical translation of intraventricular G207.
Cotton Textiles and the Industrial Revolution in a Global Context
Authors: Riello Giorgio 
Published: June 2021

Abstract
In recent decades, economic historians have revisited the Industrial Revolution in a global context. Their interpretations rely mostly on comparative methods. This article shows instead that there is a profound and significant relationship between industrialization and global exchange, and that consumption of cotton textiles was central to such a relationship. Yet, historians should not consider global trade in the context of separate world regions. The history of cotton textiles reveals the extent to which the worldwide integration of different spaces of commerce and consumption, most especially those of the Atlantic and the Indian oceans, brought advantages to European traders and manufacturers. Taking this view, the article argues that the demand and consumption of textiles were important in determining the scale as well as the shape and specialisms of European textile production. This was not only the demand generated by European consumers — as supported by much of the European ‘consumer revolution’ literature — but also the demand of a wider group of users in the Atlantic region. The reshaping of trade and consumption in turn had important consequences for the production of cotton textiles both in India and in Europe.
Quantitative Proteome and PTMome Analysis of Arabidopsis thaliana Root Responses to Persistent Osmotic and Salinity Stress
Authors: Rodriguez Maria C , Mehta Devang , Tan Maryalle , Uhrig Richard G 
Published: June 2021

Abstract
Abiotic stresses such as drought result in large annual economic losses around the world. As sessile organisms, plants cannot escape the environmental stresses they encounter but instead must adapt to survive. Studies investigating plant responses to osmotic and/or salt stress have largely focused on short-term systemic responses, leaving our understanding of intermediate to longer-term adaptation (24 h to d) lacking. In addition to protein abundance and phosphorylation changes, evidence suggests reversible lysine acetylation may also be important for abiotic stress responses. Therefore, to characterize the protein-level effects of osmotic and salt stress, we undertook a label-free proteomic analysis of Arabidopsis thaliana roots exposed to 300 mM mannitol and 150 mM NaCl for 24 h. We assessed protein phosphorylation, lysine acetylation and changes in protein abundance, detecting significant changes in 245, 35 and 107 total proteins, respectively. Comparison with available transcriptome data indicates that transcriptome- and proteome-level changes occur in parallel, while post-translational modifications (PTMs) do not. Further, we find significant changes in PTMs, and protein abundance involve different proteins from the same networks, indicating a multifaceted regulatory approach to prolonged osmotic and salt stress. In particular, we find extensive protein-level changes involving sulfur metabolism under both osmotic and salt conditions as well as changes in protein kinases and transcription factors that may represent new targets for drought stress signaling. Collectively, we find that protein-level changes continue to occur in plant roots 24 h from the onset of osmotic and salt stress and that these changes differ across multiple proteome levels.
Pectin Modification in Seed Coat Mucilage by In Vivo Expression of Rhamnogalacturonan-I- and Homogalacturonan-Degrading Enzymes
Authors: McGee Robert , Dean Gillian H , Wu Di , Zhang Yuelin , Mansfield Shawn D , Haughn George W 
Published: June 2021

Abstract
The cell wall is essential for plant survival. Determining the relationship between cell wall structure and function using mutant analysis or overexpressing cell wall–modifying enzymes has been challenging due to the complexity of the cell wall and the appearance of secondary, compensatory effects when individual polymers are modified. In addition, viability of the plants can be severely impacted by wall modification. A useful model system for studying structure–function relationships among extracellular matrix components is the seed coat epidermal cells of Arabidopsis thaliana. These cells synthesize relatively simple, easily accessible, pectin-rich mucilage that is not essential for plant viability. In this study, we expressed enzymes predicted to modify polysaccharide components of mucilage in the apoplast of seed coat epidermal cells and explored their impacts on mucilage. The seed coat epidermal-specific promoter TESTA ABUNDANT2 (TBA2) was used to drive expression of these enzymes to avoid adverse effects in other parts of the plant. Mature transgenic seeds expressing Rhamnogalacturonate lyase A (RglA) or Rhamnogalacturonate lyase B (RglB) that degrade the pectin rhamnogalacturonan-I (RG-I), a major component of mucilage, had greatly reduced mucilage capsules surrounding the seeds and concomitant decreases in the monosaccharides that comprise the RG-I backbone. Degradation of the minor mucilage component homogalacturonan (HG) using the HG-degrading enzymes Pectin lyase A (PLA) or ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE2 (ADPG2) resulted in developing seed coat epidermal cells with disrupted cell–cell adhesion and signs of early cell death. These results demonstrate the feasibility of manipulating the seed coat epidermal cell extracellular matrix using a targeted genetic engineering approach.
Effects of ad libitum food intake, insufficient sleep and weekend recovery sleep on energy balance
Authors: Depner Christopher M , Melanson Edward L , Eckel Robert H , Higgins Janine A , Bergman Bryan C , Perreault Leigh , Knauer Oliver A , Birks Brian R , Wright Kenneth P 
Published: June 2021

AbstractStudy ObjectivesInsufficient sleep is believed to promote positive energy balance (EB) and weight gain. Increasing weekend sleep duration to “recover” from weekday sleep loss is common, yet little is known regarding how weekend recovery sleep influences EB. We conducted a randomized controlled trial to assess how: (1) 2 days and 8 days of insufficient sleep and (2) ad libitum weekend recovery sleep impact EB (energy intake [EI] – energy expenditure [EE]).MethodsFollowing ten baseline days with 9 h per night sleep opportunities, participants completed one of three 10-day experimental protocols with ad libitum EI: control (9 h sleep opportunities; n = 8; 23 ± 5 years [mean ± SD]); sleep restriction (SR; 5 h sleep opportunities; n = 14; 25 ± 5 years); sleep restriction with weekend recovery sleep (SR + WR; 5 days insufficient sleep, 2 days ad libitum weekend recovery sleep, 3 days recurrent insufficient sleep; n = 14; 27 ± 4 years).ResultsTwenty-four hour EB increased (p &lt; 0.001; main effect) by an average of 797.7 ± 96.7 (±SEM) kcal during the 10-day experimental protocol versus baseline with no significant differences between groups. Percent change from baseline in 24 h-EE was higher (p &lt; 0.05) on day 2 of insufficient sleep (SR and SR + WR groups; 10 ± 1%) versus adequate sleep (control group; 4 ± 3%).ConclusionsIn this between-group study, the effects of adequate sleep and insufficient sleep, with or without or weekend recovery sleep, on 24 h-EB were similar. Examining EB and body weight changes using within-subject cross-over designs and “free-living” conditions outside the laboratory (e.g. sleep extension) are needed to advance our understanding of the links between insufficient sleep, weekend recovery sleep and weight-gain.
A Model Template Approach for Rapid Evaluation and Application of Physiologically Based Pharmacokinetic Models for Use in Human Health Risk Assessments: A Case Study on Per- and Polyfluoroalkyl Substances
Authors: Bernstein Amanda S , Kapraun Dustin F , Schlosser Paul M 
Published: June 2021

Abstract
Physiologically based pharmacokinetic (PBPK) models are commonly used in risk assessments to perform inter- and intraspecies extrapolations as well as to extrapolate between different dosing scenarios; however, they must first undergo quality assurance review, which can be a time-consuming process, especially when model code is not readily available. We developed and implemented (using R and MCSim) a PBPK model template capable of replicating published model results for several chemical-specific PBPK models. This model template allows for faster quality assurance review because the general model equations only need to be reviewed once, and application to a specific chemical then only requires reviewing input parameters. The model template can implement PBPK models with oral and intravenous exposure routes, varying numbers of tissue compartments, renal reabsorption, and multiple elimination pathways, including fecal, urinary, and biliary. Using the model template, we reproduced published model simulation results for perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluorooctanoate, and perflouorooctane sulfonate. We also show that the template can be a useful tool for identifying potential model errors. Thus, the model template allows for faster evaluation and review of published PBPK models and provides a proof of concept for using this approach with broader classes of chemical-specific PBPK models.
Update on cardiovascular risk in nonalcoholic fatty liver disease
Authors: Johnston Michael P. , Patel Janisha , Byrne Christopher D. 
Published: June 2021

Purpose of review
To summarize recent evidence demonstrating increased cardiovascular disease (CVD) risk, and how CVD risk may be reduced, in patients with nonalcoholic fatty liver disease (NAFLD).

Recent findings
NAFLD is a multisystem disease, defined by a spectrum of liver fat-associated conditions extending from simple steatosis, to inflammation, fibrosis and cirrhosis. NAFLD not only increases the risk of liver morbidity and mortality but also increases the risk of CVD morbidity and mortality and is associated with recognized CVD risk factors such as hypertension, atherogenic dyslipidaemia, type 2 diabetes mellitus and chronic kidney disease. Evidence suggests that the liver fibrosis stage may be a strong CVD risk factor. Lifestyle measures (e.g. weight loss and increased physical activity) are effective in improving CVD risk factors. Hypoglycaemic agents, such as the peroxisome proliferator-activated receptor gamma agonist pioglitazone and the glucagon-like peptide-1 receptor agonist liraglutide, reduce cardiovascular risk and may improve liver histology. Statin and antihypertensive treatments are well tolerated and currently it is unclear whether novel antifibrotic drugs will reduce CVD risk.

Summary
Assessment and treatment of increased cardiovascular risk is important in patients with NAFLD. If not contra-indicated, pioglitazone or a glucagon-like peptide 1 agonist should be considered and may benefit both CVD risk and early liver disease.
Is it Noise? Factors Linked With Sleep Interruption in Hospitalized Patients
Authors: Mori Candace , Boss Karrie , Indermuhle Patty , Stahl Erica , Chiu Sheau-Huey , Shanks Linda 
Published: June 2021

Purpose/Aim
The aim of this study was to explore the perceived quality of sleep and sleep disturbances in hospitalized patients.

Design
A prospective descriptive, exploratory, cross-sectional study was conducted at a 172-bed community hospital in Northeast Ohio. A convenient sample of 100 hospitalized patients was recruited from medical/surgical, progressive care, and intensive care units.

Methods
Participants used the Richards-Campbell Sleep Questionnaire to report sleep. A quality of sleep assessment survey was used to collect information regarding 17 factors leading to decreased quality of sleep.

Results
Mean sleep score was 47.92 for each question regarding sleep depth, latency, awakenings, time spent awake, and overall sleep quality. Pearson's correlation showed a significantly positive correlation between measure of noise and sleep score. Five environmental factors were identified as most disruptive to sleep: pain, laboratory draws, staff, blood pressure checks, and intravenous alarms.

Conclusion
The positive correlation between sleeping well and higher noise levels is noteworthy. Raising awareness about the importance of sleep in the hospital setting and introducing interventions to promote a quiet environment and minimize sleep-disturbing factors may increase patient satisfaction scores and improve healing.
College Students’ COVID-19 Vaccine Beliefs and Intentions: Implications for interventions
Authors: Small Meg L. , Lennon Robert P. , Dziak John J. , Smith Rachel A. , Sommerville Gillian , Bharti Nita 
Published: June 2021

AbstractOn college campuses, effective management of vaccine-preventable transmissible pathogens requires understanding student vaccination intentions. This is necessary for developing and tailoring health messaging to maximize uptake of health information and vaccines. The current study explored students’ beliefs and attitudes about vaccines in general, and the new COVID-19 vaccines specifically. This study provides insights into effective health messaging needed to rapidly increase COVID-19 vaccination on college campuses—information that will continue to be informative in future academic years across a broad scope of pathogens. Data were collected via an online cohort survey of college students aged 18 years and older residing on or near the campus of a large public university during fall 2020. Overall, we found COVID-19 vaccine hesitancy in college students correlated strongly with some concerns about vaccines in general as well as with concerns specific to COVID-19 vaccines. Taken together, these results provide further insight for message development and delivery, and can inform more effective interventions to advance critical public health outcomes on college campuses beyond the current pandemic.
IgG index and not serum 25-hydroxyvitamin D is associated with age at onset of multiple sclerosis
Authors: Stridh Pernilla , Kockum Ingrid , Huang Jesse 
Published: June 2021

AbstractBackgroundVitamin D deficiency is associated with an increased risk of multiple sclerosis (MS). However, its effect on the age of disease onset remains unclear. This study examines the relationship between serum 25 hydroxyvitamin D (25(OH)D) levels and age of first symptom onset among recently diagnosed MS patients.MethodSerum 25(OH)D was measured from forty MS patients sampled near disease onset. After correcting seasonal variability, a multivariable linear regression was used to examine associations to age at onset.ResultsSerum 25(OH)D was not correlated with age at onset (P>0.5). However, CSF IgG index was lower among patients with later disease onset (β=-5.35, P=0.028). Furthermore, we observed bias resulting from non-random distribution of sampling by season, which after correcting indicates a higher 25(OH)D level among patients sampled at relapse compared to remission, instead of lower as previously reported.ConclusionIn summary, serum 25(OH)D was not associated with the age at onset.
Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19 – A double-blind, randomized placebo-controlled trial
Authors: Biber Asaf , Mandelboim Michal , Harmelin Geva , Lev Dana , Ram Li , Shaham Amit , Nemet Ital , Kliker Limor , Erster Oran , Schwartz Eli 
Published: June 2021

AbstractBackgroundIvermectin, an anti-parasitic agent, also has anti-viral properties. Our aim was to assess whether ivermectin can shorten the viral shedding in patients at an early-stage of COVID-19 infection.MethodsThe double-blinded trial compared patients receiving ivermectin 0·2 mg/kg for 3 days vs. placebo in non-hospitalized COVID-19 patients. RT-PCR from a nasopharyngeal swab was obtained at recruitment and then every two days. Primary endpoint was reduction of viral-load on the 6thday (third day after termination of treatment) as reflected by Ct level>30 (non-infectious level). The primary outcome was supported by determination of viral culture viability.ResultsEighty-nine patients were eligible (47 in ivermectin and 42 in placebo arm). Their median age was 35 years. Females accounted for 21·6%, and 16·8% were asymptomatic at recruitment. Median time from symptom onset was 4 days. There were no statistical differences in these parameters between the two groups.On day 6, 34 out of 47 (72%) patients in the ivermectin arm reached the endpoint, compared to 21/ 42 (50%) in the placebo arm (OR 2·62; 95% CI: 1·09-6·31). In a multivariable logistic-regression model, the odds of a negative test at day 6 was 2.62 time higher in the ivermectin group (95% CI: 1·06–6·45). Cultures at days 2 to 6 were positive in 3/23 (13·0%) of ivermectin samples vs. 14/29 (48·2%) in the placebo group (p=0·008).ConclusionsThere were significantly lower viral loads and viable cultures in the ivermectin group, which could lead to shortening isolation time in these patients.The study is registered atClinicalTrials.govNCT 044297411.
Revealing the host antiviral protein ZAP-S as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting
Authors: Zimmer Matthias M. , Kibe Anuja , Rand Ulfert , Pekarek Lukas , Cicin-Sain Luka , Caliskan Neva 
Published: June 2021

AbstractProgrammed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses including SARS-CoV-2, which allows production of essential structural and replicative enzymes from an alternative reading frame. Despite the importance of PRF for the viral life cycle, it is still largely unknown how and to what extent cellular factors alter mechanical properties of frameshifting RNA molecules and thereby impact virulence. This prompted us to comprehensively dissect the interplay between the host proteome and the SARS-CoV-2 frameshift element. Here, we reveal that zinc-finger antiviral protein (ZAP-S) is a direct and specific regulator of PRF in SARS-CoV-2 infected cells. ZAP-S overexpression strongly impairs frameshifting and viral replication. Using in vitro ensemble and single-molecule techniques, we further demonstrate that ZAP-S directly interacts with the SARS-CoV-2 RNA and ribosomes and interferes with the folding of the frameshift RNA. Together these data illuminate ZAP-S as de novo host-encoded specific inhibitor of SARS-CoV-2 frameshifting and expand our understanding of RNA-based gene regulation.