bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volvox as a Model for Studying Cell Death and Senescence
Authors: Desnitskiy A. G. 
Published: August 2021

Abstract
The spherical green alga Volvox consists of several hundred or thousand of somatic cells that undergo terminal differentiation, senescence and death, and a small number of gonidia (asexual reproductive cells) that give rise to the next generation. In the first part of this paper, the ontogenetic diversity of the genus Volvox is briefly considered, as well as the mechanisms of differentiation into the two types of cells mentioned above, which have been thoroughly studied during recent years in Volvox carteri. Then, a detailed critical analysis of the literature and some of my own data on senescence and cell death (mainly in V. carteri and, to a lesser extent, in V. aureus) was carried out, and it was noted that this aspect of Volvox developmental biology has not been sufficiently studied. Some perspectives of further research of the processes of cell death and senescence in representatives of the genus Volvox in a comparative aspect are indicated.
Examining the interseasonal resurgence of respiratory syncytial virus in Western Australia
Authors: Foley David Anthony , Phuong Linny Kimly , Peplinski Joseph , Lim Selina Mei , Lee Wei Hao , Farhat Asifa , Minney-Smith Cara A , Martin Andrew C , Mace Ariel O , Sikazwe Chisha T , Le Huong , Levy Avram , Hoeppner Tobias , Borland Meredith L , Hazelton Briony , Moore Hannah C , Blyth Christopher , Yeoh Daniel K , Bowen Asha C 
Published: August 2021

BackgroundFollowing a relative absence in winter 2020, a large resurgence of respiratory syncytial virus (RSV) detections occurred during the 2020/2021 summer in Western Australia. This seasonal shift was linked to SARS-CoV-2 public health measures. We examine the epidemiology and RSV testing of respiratory-coded admissions, and compare clinical phenotype of RSV-positive admissions between 2019 and 2020.MethodAt a single tertiary paediatric centre, International Classification of Diseases, 10th edition Australian Modification-coded respiratory admissions longer than 12 hours were combined with laboratory data from 1 January 2019 to 31 December 2020. Data were grouped into bronchiolitis, other acute lower respiratory infection (OALRI) and wheeze, to assess RSV testing practices. For RSV-positive admissions, demographics and clinical features were compared between 2019 and 2020.ResultsRSV-positive admissions peaked in early summer 2020, following an absent winter season. Testing was higher in 2020: bronchiolitis, 94.8% vs 89.2% (p=0.01); OALRI, 88.6% vs 82.6% (p=0.02); and wheeze, 62.8% vs 25.5% (p<0.001). The 2020 peak month, December, contributed almost 75% of RSV-positive admissions, 2.5 times the 2019 peak. The median age in 2020 was twice that observed in 2019 (16.4 vs 8.1 months, p<0.001). The proportion of RSV-positive OALRI admissions was greater in 2020 (32.6% vs 24.9%, p=0.01). There were no clinically meaningful differences in length of stay or disease severity.InterpretationThe 2020 RSV season was in summer, with a larger than expected peak. There was an increase in RSV-positive non-bronchiolitis admissions, consistent with infection in older RSV-naïve children. This resurgence raises concern for regions experiencing longer and more stringent SARS-CoV-2 public health measures.
Dexamethasone intravitreal implant in treatment-naïve diabetic macular oedema: findings from the prospective, multicentre, AUSSIEDEX study
Authors: Fraser-Bell Samantha , Kang Hyong Kwon , Mitchell Paul , Arnold Jennifer J , Tainton Jodi , Simonyi Susan 
Published: August 2021

AimTo evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME).MethodsThe open-label, prospective, phase 4, real-world study included pseudophakic eyes and phakic eyes scheduled for cataract surgery that were treatment-naïve or non-responsive to antivascular endothelial growth factors. No eyes were excluded based on baseline best-corrected visual acuity (BCVA) or central subfield retinal thickness (CRT). After the initial DEX injection at the baseline visit, reinjection was permitted at ≥16-week intervals. Week-16 and week-52 visits were mandatory. Primary endpoints were changes in mean BCVA and CRT from baseline to 52 weeks.ResultsOf 200 eyes enrolled in the AUSSIEDEX study, 57 were treatment-naïve. Baseline mean BCVA was 58.8 letters and baseline mean CRT was 418.6 µm; changes in mean BCVA and CRT from baseline to 52 weeks in this subgroup were 3.4 letters (p=0.042) and –89.6 µm (p<0.001), respectively, with a mean 2.5 injections. The change in mean CRT from baseline was –55.8 µm at week 16 (p<0.001). The most common adverse event was increased intraocular pressure (IOP), with 20.0% of eyes requiring IOP-lowering medication. One patient was discontinued due to increased IOP. No eyes required filtration surgery. No serious, treatment-related ocular adverse events were reported.ConclusionIn this largest prospective, real-world study of DEX monotherapy for DME to date, DEX significantly improved CRT and BCVA at 52 weeks in treatment-naïve eyes, without new safety concerns, supporting DEX use in treatment-naïve DME.Trial registration numberNCT02731911.
Protocol for a scoping review on the methods for engaging long-term care residents with dementia in research and guideline development
Authors: McArthur Caitlin , Quigley Adria , Affoo Rebecca , Earl Marie , Moody Elaine 
Published: August 2021

IntroductionPatient engagement is important when developing health guidelines to ensure high-quality and patient-centred recommendations. However, patient engagement in research and guideline development remains suboptimal, particularly for vulnerable populations, including residents with dementia living in long-term care (LTC) who are often not included in research and guideline development because of perceived and actual challenges with their health, memory, concentration and communication. Optimal strategies and methods for engaging LTC residents with dementia in research and guideline development remain unknown.Methods and analysisWe will conduct a scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension to answer the research questions: (1) What methods have been used to engage LTC residents with dementia in research and guideline development? (2) What are the outcomes of resident engagement? (3) What are the barriers and facilitators to resident engagement? Systematic searches for peer-reviewed articles will be conducted in: Academic Search Premier (EBSCO), APA PsycINFO (EBSCO), CINAHL (EBSCO), Medline (OVID), Embase (Elsevier), Web of Science, and Cochrane Database and in grey literature. Two team members will screen articles and extract data. Results will be presented according to the research question they address. We will engage stakeholders including residents, family members, healthcare providers and representatives from relevant organisations throughout the study.Ethics and disseminationThe scoping review will synthesise what is known about resident engagement in research and guideline development. It may identify gaps in the literature about the optimal methods to engage residents in performing research and developing guidelines and reveal opportunities for new methods. The results will be helpful for researchers and policy-makers seeking to develop guidelines and researchers engaging in topics that reflect the priorities and experiences of people with dementia. Results of the scoping review will be disseminated via publication in a peer-reviewed journal and conference presentations, and a one-page lay summary will be shared with our engaged stakeholders.
Emergency medicine patient wait time multivariable prediction models: a multicentre derivation and validation study
Authors: Walker Katie , Jiarpakdee Jirayus , Loupis Anne , Tantithamthavorn Chakkrit , Joe Keith , Ben-Meir Michael , Akhlaghi Hamed , Hutton Jennie , Wang Wei , Stephenson Michael , Blecher Gabriel , Paul Buntine , Sweeny Amy , Turhan Burak 
Published: August 2021

ObjectivePatients, families and community members would like emergency department wait time visibility. This would improve patient journeys through emergency medicine. The study objective was to derive, internally and externally validate machine learning models to predict emergency patient wait times that are applicable to a wide variety of emergency departments.MethodsTwelve emergency departments provided 3 years of retrospective administrative data from Australia (2017–2019). Descriptive and exploratory analyses were undertaken on the datasets. Statistical and machine learning models were developed to predict wait times at each site and were internally and externally validated. Model performance was tested on COVID-19 period data (January to June 2020).ResultsThere were 1 930 609 patient episodes analysed and median site wait times varied from 24 to 54 min. Individual site model prediction median absolute errors varied from±22.6 min (95% CI 22.4 to 22.9) to ±44.0 min (95% CI 43.4 to 44.4). Global model prediction median absolute errors varied from ±33.9 min (95% CI 33.4 to 34.0) to ±43.8 min (95% CI 43.7 to 43.9). Random forest and linear regression models performed the best, rolling average models underestimated wait times. Important variables were triage category, last-k patient average wait time and arrival time. Wait time prediction models are not transferable across hospitals. Models performed well during the COVID-19 lockdown period.ConclusionsElectronic emergency demographic and flow information can be used to approximate emergency patient wait times. A general model is less accurate if applied without site-specific factors.
Acute fetal response to high-intensity interval training in the second and third trimesters of pregnancy
Authors: Anderson Julie , Pudwell Jessica , McAuslan Colin , Barr Logan , Kehoe Jessica , Davies Gregory A. 
Published: August 2021

The majority of women do not meet the recommended levels of exercise during their pregnancies, frequently due to a lack of time. High-intensity interval training offers a potential solution, providing an effective, time-efficient exercise modality. This exercise modality has not been studied in pregnancy therefore, the objective of this study was to evaluate fetal response to a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy. Fourteen active, healthy women with uncomplicated, singleton pregnancies participated in a high-intensity interval training resistance circuit between 28 + 0/7 and 32 + 0/7 weeks. A Borg rating of perceived exertion of 15–17/20 and an estimated heart rate of 80%–90% of maternal heart-rate maximum was targeted. Fetal well-being was evaluated continuously with fetal heart-rate tracings and umbilical artery Doppler velocimetry conducted pre-and post-exercise. Fetal heart rate tracings were normal throughout the exercise circuit. Post-exercise, umbilical artery end-diastolic flow was normal and significant decreases were observed in the mean systolic/diastolic ratios, pulsatility indexes and resistance indexes. Therefore, in a small cohort of active pregnant women, a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy appears to be a safe exercise modality with no acute, adverse fetal effects but further study is required. Novelty: High-intensity interval training, at an intensity in excess of current recommendations, does not appear to be associated with any adverse fetal effects in previously active pregnant women. High-intensity interval training is an enjoyable and effective exercise modality in previously active pregnant women.
Marine record of late-glacial readvance and last recession of Laurentide ice, inner Frobisher Bay, Baffin Island, Arctic Canada
Authors: Deering Robert , Bell Trevor , Forbes Donald L. 
Published: August 2021

The Cockburn Substage readvance marks the last major late-glacial advance of the northeast sector of the Laurentide Ice Sheet on Baffin Island. The causes of this abrupt, late reversal of retreat are still unclear, but greater chronological control may provide some insight. To date, the literature has focused on the large terminal moraines in the region, providing a date of readvance (circa 9.5–8.5 ka cal BP). In Frobisher Bay, the Cockburn Substage readvance and recession onshore are marked by a series of moraines spread over ∼20 km along the inner bay. Acoustic marine mapping reveals five distinct transverse ridges, morphologically suggestive of grounding-zone wedges, and two later fields of DeGeer moraines on the floor of the inner bay. These indicate that the style of ice retreat (beginning no later than 8.5 ka cal BP) changed over time from punctuated recession of a floating ice front (20 km over >680 years, with four pauses) to more regular tidewater ice-front retreat, reaching the head of the bay 900 years or more after withdrawal from the outer Cockburn limit. The established chronology for final recession in the region is based largely on radiocarbon dating of bulk shell samples and single shells of deposit-feeding molluscs, notably Portlandia arctica, affected by old carbon from carbonate-rich sediments. Sedimentary analysis and judicious sampling for 14C dating of glaciomarine and marine facies in seabed sediment cores enables development of a late- and post-glacial lithostratigraphy that indicates final withdrawal of ice from the drainage basin by 7 ka cal BP.
Theoretical investigation on tautomerism and NLO properties of salicylideneaniline derivatives
Authors: Daho N. , Benhalima N. , Khelfaoui F. , Sadouki O. , Elkeurti M. , Akil Z. 
Published: August 2021

In this work, a comprehensive investigation of the salicylideneaniline derivatives is carried out using density functional theory to determine their linear and nonlinear optical (NLO) properties. Geometry optimizations, for gas and solvent phases, of the tautomers (enol and keto forms) are calculated using B3LYP levels with 6-31G(d,p) basis set. An intramolecular proton transfer, for 1SA-E and 2SA-E, is performed by a PES scan process at the B3LYP/6-31G(d,p) level. The optical properties are determined and show that they have extremely high NLO properties. In addition, the RDG analysis, molecular electrostatic potential (MEP), and gap energy are calculated. The low energy gap value indicates the possibility of intramolecular charge transfer. The frontier molecular orbital calculations clearly show the inverse relationship of HOMO–LUMO gap with the first-order hyperpolarizability (β = 59.6471 × 10–30 esu), confirming that the salicylideneaniline derivatives can be used as attractive future NLO materials. Therefore, the reactive sites are predicted using MEP and the visible absorption maxima are analyzed using a theoretical UV–Vis spectrum. Natural bond orbitals are used to investigate the stability, charge delocalization, and intramolecular hydrogen bond.
Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma
Authors: Boudreau C. Elizabeth , Najem Hinda , Ott Martina , Horbinski Craig , Fang Dexing , DeRay Chase M. , Levine Jonathan M. , Curran Michael A. , Heimberger Amy B. 
Published: August 2021

Abstract

Purpose:
Activation of STING (stimulator of interferon genes) can trigger a robust, innate antitumor immune response in immunologically “cold” tumors such as glioblastoma.

Patients and Methods:
A small-molecule STING agonist, IACS-8779, was stereotactically administered using intraoperative navigation intratumorally in dogs with spontaneously arising glioblastoma. The phase I trial used an escalating dose design, ascending through four dose levels (5–20 μg). Treatment was repeated every 4–6 weeks for a minimum of two cycles. Radiographic response to treatment was determined by response assessment in neuro-oncology (RANO) criteria applied to isovoxel postcontrast T1-weighted MR images obtained on a single 3T magnet.

Results:
Six dogs were enrolled and completed ≥1 cycle of treatment. One dog was determined to have an abscess and was removed from further analysis. One procedure-related fatality was observed. Radiographic responses were dose dependent after the first cycle. The first subject had progressive disease, whereas there was 25% volumetric reduction in one subject and greater than 50% in the remaining surviving subjects. The median progression-free survival time was 14 weeks (range: 0–22 weeks), and the median overall survival time was 32 weeks (range: 11–39 weeks).

Conclusions:
Intratumoral STING agonist (IACS-8779) administration was well tolerated in dogs with glioblastoma to a dose of 15 μg. Higher doses of IACS-8779 were associated with radiographic responses.
Phase I/II Trial of Vemurafenib in Dogs with Naturally Occurring, BRAF-mutated Urothelial Carcinoma
Authors: Rossman Paul , Zabka Tanja S. , Ruple Audrey , Tuerck Dietrich , Ramos-Vara José A. , Liu Liling , Mohallem Rodrigo , Merchant Mark , Franco Jackeline , Fulkerson Christopher M. , Bhide Ketaki P. , Breen Matthew , Aryal Uma K. , Murray Elaine , Dybdal Noel , Utturkar Sagar M. , Fourez Lindsey M. , Enstrom Alexander W. , Dhawan Deepika , Knapp Deborah W. 
Published: August 2021

Abstract
BRAF-targeted therapies including vemurafenib (Zelboraf) induce dramatic cancer remission; however, drug resistance commonly emerges. The purpose was to characterize a naturally occurring canine cancer model harboring complex features of human cancer, to complement experimental models to improve BRAF-targeted therapy. A phase I/II clinical trial of vemurafenib was performed in pet dogs with naturally occurring invasive urothelial carcinoma (InvUC) harboring the canine homologue of human BRAFV600E. The safety, MTD, pharmacokinetics, and antitumor activity were determined. Changes in signaling and immune gene expression were assessed by RNA sequencing and phosphoproteomic analyses of cystoscopic biopsies obtained before and during treatment, and at progression. The vemurafenib MTD was 37.5 mg/kg twice daily. Anorexia was the most common adverse event. At the MTD, partial remission occurred in 9 of 24 dogs (38%), with a median progression-free interval of 181 days (range, 53–608 days). In 18% of the dogs, new cutaneous squamous cell carcinoma and papillomas occurred, a known pharmacodynamic effect of vemurafenib in humans. Upregulation of genes in the classical and alternative MAPK-related pathways occurred in subsets of dogs at cancer progression. The most consistent transcriptomic changes were the increase in patterns of T lymphocyte infiltration during the first month of vemurafenib, and of immune failure accompanying cancer progression. In conclusion, the safety, antitumor activity, and cutaneous pharmacodynamic effects of vemurafenib, and the development of drug resistance in dogs closely mimic those reported in humans. This suggests BRAF-mutated canine InvUC offers an important complementary animal model to improve BRAF-targeted therapies in humans.
CD8+ T–cell Immune Surveillance against a Tumor Antigen Encoded by the Oncogenic Long Noncoding RNA PVT1
Authors: Kikuchi Yasuhiro , Tokita Serina , Hirama Tomomi , Kochin Vitaly , Nakatsugawa Munehide , Shinkawa Tomoyo , Hirohashi Yoshihiko , Tsukahara Tomohide , Hata Fumitake , Takemasa Ichiro , Sato Noriyuki , Kanaseki Takayuki , Torigoe Toshihiko 
Published: August 2021

Abstract

CD8+ T cells recognize peptides displayed by HLA class I molecules on cell surfaces, monitoring pathologic conditions such as cancer. Advances in proteogenomic analysis of HLA ligandomes have demonstrated that cells present a subset of cryptic peptides derived from noncoding regions of the genome; however, the roles of cryptic HLA ligands in tumor immunity remain unknown. In the current study, we comprehensively and quantitatively investigated the HLA class I ligandome of a set of human colorectal cancer and matched normal tissues, showing that cryptic translation products accounted for approximately 5% of the HLA class I ligandome. We also found that a peptide encoded by the long noncoding RNA (lncRNA) PVT1 was predominantly enriched in multiple colorectal cancer tissues. The PVT1 gene is located downstream of the MYC gene in the genome and is aberrantly overexpressed across a variety of cancers, reflecting its oncogenic property. The PVT1 peptide was recognized by patient CD8+ tumor-infiltrating lymphocytes, as well as peripheral blood mononuclear cells, suggesting the presence of patient immune surveillance. Our findings show that peptides can be translated from lncRNAs and presented by HLA class I and that cancer patient T cells are capable of sensing aberrations in noncoding regions of the genome.
Race Differences in Interventions and Survival After Out‐of‐Hospital Cardiac Arrest in North Carolina, 2010 to 2014
Authors: Moeller Sidsel , Hansen Carolina M. , Kragholm Kristian , Dupre Matt E. , Sasson Comilla , Pearson David A. , Tyson Clark , Jollis James G. , Monk Lisa , Starks Monique A. , McNally Bryan , Thomas Kevin L. , Becker Lance , Torp‐Pedersen Christian , Granger Christopher B. 
Published: August 2021

Background
Following the implementation of the HeartRescue project, with interventions in the community, emergency medical services, and hospitals to improve care and outcomes for out‐of‐hospital cardiac arrests (OHCA) in North Carolina, improved bystander and first responder treatments as well as survival were observed. This study aimed to determine whether these improvements were consistent across Black versus White individuals.

Methods and Results

Using the Cardiac Arrest Registry to Enhance Survival (CARES), we identified OHCA from 16 counties in North Carolina (population 3 million) from 2010 to 2014. Temporal changes in interventions and outcomes were assessed using multilevel multivariable logistic regression, adjusted for patient and socioeconomic neighborhood‐level factors. Of 7091 patients with OHCA, 36.5% were Black and 63.5% were White. Black patients were younger, more females, had more unwitnessed arrests and non‐shockable rhythm (Black: 81.0%; White: 75.4%). From 2010 to 2014, the adjusted probabilities of bystander cardiopulmonary resuscitation (CPR) went from 38.5% to 51.2% in White,
P
<0.001; and 36.9% to 45.6% in Black,
P
=0.002, and first‐responder defibrillation went from 13.2% to 17.2% in White,
P
=0.002; and 14.7% to 17.3% in Black,
P
=0.16. From 2010 to 2014, survival to discharge only increased in White (8.0% to 11.4%,
P
=0.004; Black 8.9% to 9.5%,
P
=0.60), though, in shockable patients the probability of survival to discharge went from 24.8% to 34.6% in White,
P
=0.02; and 21.7% to 29.0% in Black,
P
=0. 10.

Conclusions
After the HeartRescue program, bystander CPR and first‐responder defibrillation increased in both patient groups; however, survival only increased significantly for White patients.