bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Ribozyme‐Catalyzed Recombination and Oligonucleotide Assembly in Peptide‐RNA Condensates
Authors: Le Vay Kristian , Song Emilie Yeonwha , Ghosh Basusree , Tang T.‐Y. Dora , Mutschler Hannes
Published: September 2021

The ability of RNA to catalyze RNA ligation is critical to its central role in many prebiotic model scenarios, in particular the copying of information during self‐replication. Prebiotically plausible ribozymes formed from short oligonucleotides can catalyze reversible RNA cleavage and ligation reactions, but harsh conditions or unusual scenarios are often required to promote folding and drive the reaction equilibrium towards ligation. Here, we demonstrate that ribozyme activity is greatly enhanced by charge‐mediated phase separation with poly‐L‐lysine, which shifts the reaction equilibrium from cleavage in solution to ligation in peptide‐RNA coaggregates and coacervates. This compartmentalization enables robust isothermal RNA assembly over a broad range of conditions, which can be leveraged to assemble long and complex RNAs from short fragments under mild conditions in the absence of exogenous activation chemistry, bridging the gap between pools of short oligomers and functional RNAs.
NMR Spectroscopy of the Main Protease of SARS‐CoV‐2 and Fragment‐Based Screening Identify Three Protein Hotspots and an Antiviral Fragment
Authors: Cantrelle François‐Xavier , Boll Emmanuelle , Brier Lucile , Moschidi Danai , Belouzard Sandrine , Landry Valérie , Leroux Florence , Dewitte Frédérique , Landrieu Isabelle , Dubuisson Jean , Deprez Benoit , Charton Julie , Hanoulle Xavier
Published: September 2021

The main protease (3CLp) of the SARS‐CoV‐2, the causative agent for the COVID‐19 pandemic, is one of the main targets for drug development. To be active, 3CLp relies on a complex interplay between dimerization, active site flexibility, and allosteric regulation. The deciphering of these mechanisms is a crucial step to enable the search for inhibitors. In this context, using NMR spectroscopy, we studied the conformation of dimeric 3CLp from the SARS‐CoV‐2 and monitored ligand binding, based on NMR signal assignments. We performed a fragment‐based screening that led to the identification of 38 fragment hits. Their binding sites showed three hotspots on 3CLp, two in the substrate binding pocket and one at the dimer interface. F01 is a non‐covalent inhibitor of the 3CLp and has antiviral activity in SARS‐CoV‐2 infected cells. This study sheds light on the complex structure‐function relationships of 3CLp and constitutes a strong basis to assist in developing potent 3CLp inhibitors.
Digitalisierung der Versuchsplanung im Ingenieurbau – Planung von Messprojekten mit MR‐Brillen, 3‐D‐Druck und QR‐Codes für Monitoring und datengestützte Bestandsbewertung
Authors: Haslbeck Matthias , Friedrich Sebastian , Hindersmann Iris , Bednorz Jennifer , Braml Thomas
Published: September 2021

Die Digitalisierung und der Einsatz der BIM‐Technologie werden für die Baubranche immer wichtiger. Doch nicht nur für die Planung und den Bau von Neubauten, sondern auch für die Umsetzung und den Betrieb von Messeinrichtungen an bestehenden Hoch‐ und Ingenieurbauten können die BIM‐Methode und die visuelle Darstellung des Objekts in den physikalischen und virtuellen Modellen hilfreiche Werkzeuge sein. Am Beispiel eines Projekts zur datengestützten Bewertung einer Bestandsbrücke wird gezeigt, wie BIM, 3‐D‐Druck, QR‐Codes und Mixed‐Reality‐Brillen die Planung von Messeinrichtungen unterstützen. Die einsetzende digitale Transformation im Bauwesen und der wachsende Bedarf an datenbasierten Nachweiskonzepten für alternde Verkehrsinfrastrukturobjekte eröffnen dabei ein enormes Potenzial für die Digitalisierung. Anhand einer geplanten Versuchskampagne zur Anpassung von statischen Modellen an gemessene Daten durch Bayeśsches Updating wird gezeigt, wie dieses Potenzial genutzt werden kann, um die Planung und Ausführung von Messprojekten an Bauwerken zu unterstützen und eine Steigerung der Qualität und der Effizienz zu erreichen. Durch die Erzeugung und Visualisierung von dreidimensionalen Bauwerksmodellen und die Bereitstellung von technischen Spezifikationen der Messeinrichtungen durch QR‐Codes kann sowohl der Installationsprozess als auch die spätere Betreuung der Messtechnik unterstützt werden.
Processed pseudogenes: A substrate for evolutionary innovation
Authors: Troskie Robin‐Lee , Faulkner Geoffrey J. , Cheetham Seth W.
Published: September 2021

Processed pseudogenes may serve as a genetic reservoir for evolutionary innovation. Here, we argue that through the activity of long interspersed element‐1 retrotransposons, processed pseudogenes disperse coding and noncoding sequences rich with regulatory potential throughout the human genome. While these sequences may appear to be non‐functional, a lack of contemporary function does not prohibit future development of biological activity. Here, we discuss the dynamic evolution of certain processed pseudogenes into coding and noncoding genes and regulatory elements, and their implication in wide‐ranging biological and pathological processes. Also see the video abstract here: https://youtu.be/iUY_mteVoPI
Spruce Hard Carbon Anodes for Lithium‐Ion Batteries
Authors: Drews Mathias , Büttner Jan , Bauer Manuel , Ahmed Junaid , Sahu Rajib , Scheu Christina , Vierrath Severin , Fischer Anna , Biro Daniel
Published: September 2021

In this work, lithium‐ion battery full‐cells based on spruce‐derived hard carbon anodes and an electrochemical pre‐lithiation method are presented in combination with a detailed analysis of full‐cell operation and the lithiation state. The physical and electrochemical properties agree well with those of previous biomass‐derived hard carbon anodes. However, low initial coulombic efficiencies of 65 % represent one of the major challenges of the developed anodes with respect to full‐cell operation. To counteract the initial lithium loss, in‐situ electrochemical pre‐lithiation was conducted, allowing battery operation in the same cell setup without reassembly. Consequently, significantly increased capacities, cycle life, and first cycle coulombic efficiency were obtained in comparison to untreated anodes (195 mAh/g versus 150 mAh/g, state of health (SOH) 80 after 150 cycles versus 70 cycles, and 90 % versus 65 %). In summary, spruce‐based hard carbon has the potential to be an environmentally friendly alternative to standard graphite.
Full‐Atom Model of the Agonist LPS‐Bound Toll‐like Receptor 4 Dimer in a Membrane Environment
Authors: Matamoros‐Recio Alejandra , Franco‐Gonzalez Juan Felipe , Perez‐Regidor Lucia , Billod Jean‐Marc , Guzman‐Caldentey Joan , Martin‐Santamaria Sonsoles
Published: September 2021

The Toll‐like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD‐2) innate immunity system is a membrane receptor of paramount importance as therapeutic target. Its assembly, upon binding of Gram‐negative bacteria lipopolysaccharide (LPS), and also dependent on the membrane composition, finally triggers the immune response cascade. We have combined ab‐initio calculations, molecular docking, all‐atom molecular dynamics simulations, and thermodynamics calculations to provide the most realistic and complete 3D models of the active full TLR4 complex embedded into a realistic membrane to date. Our studies give functional and structural insights into the transmembrane domain behavior in different membrane environments, the ectodomain bouncing movement, and the dimerization patterns of the intracellular Toll/Interleukin‐1 receptor domain. Our work provides TLR4 models as reasonable 3D structures for the (TLR4/MD‐2/LPS)2 architecture accounting for the active (agonist) state of the TLR4, and pointing to a signal transduction mechanism across cell membrane. These observations unveil relevant molecular aspects involved in the TLR4 innate immune pathways and will promote the discovery of new TLR4 modulators.
Cobalt and Iron Stabilized Ketyl, Ketiminyl and Aldiminyl Radical Anions
Authors: Sieg Grégoire , Pessemesse Quentin , Reith Sascha , Yelin Stefan , Limberg Christian , Munz Dominik , Werncke C. Gunnar
Published: September 2021

Carbonyl and iminyl based radical anions are reactive intermediates in a variety of transformations in organic synthesis. Herein, the isolation of ketyl, and more importantly unprecedented ketiminyl and aldiminyl radical anions coordinated to cobalt and iron complexes is presented. Insights into the electronic structure of these unusual metal bound radical anions is provided by X‐Ray diffraction analysis, NMR, IR, UV/Vis and Mössbauer spectroscopy, solid and solution state magnetometry, as well as a by a detailed computational analysis. The metal bound radical anions are very reactive and facilitate the activation of intra‐ and intermolecular C−H bonds.
The Touchscreen‐Based Trial‐Unique, Nonmatching‐To‐Location (TUNL) Task as a Measure of Working Memory and Pattern Separation in Rats and Mice
Authors: Barnard Ilne L. , Onofrychuk Timothy J. , McElroy Dan L. , Howland John G.
Published: September 2021

The TUNL task is an automated touchscreen task used to evaluate the cognitive processes involved in working memory (WM) and spatial pattern separation in rodents. Both rats and mice can be used. To elicit working memory processes, the rodent must distinguish between a sample (familiar) light stimulus and a novel light stimulus after a delay. With a correct selection, the rodent will receive a food reward. A major benefit of TUNL compared to other similar tasks is the circumvention of spatial “mediating strategies” that the rodent may use to supplement or replace working memory processes to complete the task successfully. Each trial is ‘unique’, as the stimuli are pseudo‐randomized between trials in an array of spatial locations. The TUNL task uses a progression of six training steps to teach the rodent the associated rules necessary to complete the full task. Task performance is typically measured by trials completed and by accuracy. Task accuracy can be evaluated across various spatial separations to engage hippocampal‐dependent processes involved in spatial pattern separation. The latency between trial responses can also be evaluated, with food reward collection latency as a measure of motivation. The TUNL task can be used to assess working memory and cognitive deficits in rodent models with neurodegenerative and neurological disorders, providing a valuable tool to screen for new treatment options, in addition to assessing basic neurobiology. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Handling and habituation prior to training

Basic Protocol 2: Initial Touch Training

Basic Protocol 3: Must Touch Training

Basic Protocol 4: Must Initiate Training

Basic Protocol 5: Punish Incorrect Training

Basic Protocol 6: Initial TUNL Training

Basic Protocol 7: Full TUNL Training

Support Protocol 1: Using ABET II touch program

Support Protocol 2: Preparation of touchscreen chambers prior to training sessions
Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals
Authors: Shi Liu , Buchanan Colin R. , Cox Simon R. , Hillary Robert F. , Marioni Riccardo E. , Campbell Archie , Hayward Caroline , Stolicyn Aleks , Whalley Heather C. , Harris Mathew A. , Waymont Jennifer , Waiter Gordon , Backhouse Ellen , Wardlaw Joanna M. , Steele Douglas , Mcintosh Andrew , Lovestone Simon , Buckley Noel J. , Nevado‐Holgado Alejo J.
Published: September 2021

Introduction

This study aims to first discover plasma proteomic biomarkers relating to neurodegeneration (N) and vascular (V) damage in cognitively normal individuals and second to discover proteins mediating sex‐related difference in N and V pathology.

Methods

Five thousand and thirty‐two plasma proteins were measured in 1061 cognitively normal individuals (628 females and 433 males), nearly 90% of whom had magnetic resonance imaging measures of hippocampal volume (as N) and white matter hyperintensities (as V).

Results

Differential protein expression analysis and co‐expression network analysis revealed different proteins and modules associated with N and V, respectively. Furthermore, causal mediation analysis revealed four proteins mediated sex‐related difference in N and one protein mediated such difference in V damage.

Discussion

Once validated, the identified proteins could help to select cognitively normal individuals with N and V pathology for Alzheimer's disease clinical trials and provide targets for further mechanistic studies on brain sex differences, leading to sex‐specific therapeutic strategies.
Phonological working memory and central executive function differ in children with typical development and dyslexia
Authors: Alt Mary , Fox Annie , Levy Roy , Hogan Tiffany P. , Cowan Nelson , Gray Shelley
Published: September 2021

The primary purpose of this study was to compare the working memory performance of monolingual English‐speaking second‐grade children with dyslexia (N = 82) to second‐grade children with typical development (N = 167). Prior to making group comparisons, it is important to demonstrate invariance between working memory models in both groups or between‐group comparisons would not be valid. Thus, we completed invariance testing using a model of working memory that had been validated for children with typical development (Gray et al., 2017) to see if it was valid for children with dyslexia. We tested three types of invariance: configural (does the model test the same constructs?), metric (are the factor loadings equivalent?), and scalar (are the item intercepts the same?). Group comparisons favoured the children with typical development across all three working memory factors. However, differences in the Focus‐of‐Attention/Visuospatial factor could be explained by group differences in non‐verbal intelligence and language skills. In contrast, differences in the Phonological and Central Executive working memory factors remained, even after accounting for non‐verbal intelligence and language. Results highlight the need for researchers and educators to attend not only to the phonological aspects of working memory in children with dyslexia, but also to central executive function.
Probabilistic early warning signals
Authors: Laitinen Ville , Dakos Vasilis , Lahti Leo
Published: September 2021

Ecological communities and other complex systems can undergo abrupt and long‐lasting reorganization, a regime shift, when deterministic or stochastic factors bring them to the vicinity of a tipping point between alternative states. Such changes can be large and often arise unexpectedly. However, theoretical and experimental analyses have shown that changes in correlation structure, variance, and other standard indicators of biomass, abundance, or other descriptive variables are often observed prior to a state shift, providing early warnings of an anticipated transition. Natural systems manifest unknown mixtures of ecological and environmental processes, hampered by noise and limited observations. As data quality often cannot be improved, it is important to choose the best modeling tools available for the analysis.

We investigate three autoregressive models and analyze their theoretical differences and practical performance. We formulate a novel probabilistic method for early warning signal detection and demonstrate performance improvements compared to nonprobabilistic alternatives based on simulation and publicly available experimental time series.

The probabilistic formulation provides a novel approach to early warning signal detection and analysis, with enhanced robustness and treatment of uncertainties. In real experimental time series, the new probabilistic method produces results that are consistent with previously reported findings.

Robustness to uncertainties is instrumental in the common scenario where mechanistic understanding of the complex system dynamics is not available. The probabilistic approach provides a new family of robust methods for early warning signal detection that can be naturally extended to incorporate variable modeling assumptions and prior knowledge.
Contributions of wild and provisioned foods to the diets of domestic cats that depredate wild animals
Authors: Cecchetti Martina , Crowley Sarah L. , Goodwin Cecily E. D. , Cole Holly , McDonald Jennifer , Bearhop Stuart , McDonald Robbie A.
Published: September 2021

Predation of wildlife by domestic cats Felis catus presents a threat to biodiversity conservation in some ecological contexts. The proportions of wild prey captured and eaten by domestic cats and thus the contributions of wild prey to cat diets are hard to quantify. This limits the understanding of any impacts of cats may have on wild animal populations and confounds analyses of the effects of interventions aimed at reducing wildlife killing. We used stable isotope analyses to quantify the relative contributions of wild and provisioned foods to the diets of domestic cats kept as companion animals and which frequently captured wild prey. We tested the effects of treatments aimed at reducing killing upon stable isotope ratios of cat whiskers and, where treatments had significant effects, we estimated variation in the contributions of wild prey to cats’ diets before and during treatment. We evaluated bells, Birdsbesafe collar covers, provision of food in a “puzzle feeder,” provision of food in which meat was the principal source of protein, object play, and a control group. As expected, cat diets consisted primarily of provisioned foods, though the contribution of wild animals to the diets of these cats, all of which regularly caught wild animals, was low (cat food ˜96%, wild animals ˜3–4%). Compared to the pre‐treatment period and control group, cats with a Birdsbesafe collar cover exhibited a significant reduction in nitrogen stable isotope ratios in their whiskers and consumed less wild prey, most likely attributable to effective inhibition of hunting, particularly for birds. Fitting cats with a Birdsbesafe collar cover, therefore, reduced both returns of wild birds and consumption of wild prey. While multiple interventions can significantly affect the numbers of wild animals that cats capture and return home, the remarkably small dietary contributions made by wild animal prey mean dietary change is harder to discern. Domestic cats rely almost exclusively on food provided by people, even when they frequently kill wild animals. This suggests that the hunting behavior of domestic cats may be driven by behavioral motivations, or by a need to address micronutrient requirements, but is unlikely to alter macronutrient intake.
Salt marsh establishment in poorly consolidated muddy systems: effects of surface drainage, elevation, and plant age
Authors: Cao Haobing , Zhu Zhenchang , van Belzen Jim , Gourgue Olivier , van de Koppel Johan , Temmerman O. Stijn , Herman Peter M. J. , Zhang Liquan , Yuan Lin , Bouma Tjeerd J.
Published: September 2021

Conservation and restoration of salt marsh ecosystems are becoming increasingly important because of the many ecosystem services they provide. However, the processes controlling salt marsh establishment and persistence, especially on bare tidal flats in muddy areas, remain unclear. As muddy sediments typically experience a restriction of soil drainage, we expect that a surface drainage relief due to a heterogeneity topography, as might occur on the edge of tidal channels, can facilitate the establishment of salt marsh vegetation on muddy tidal flats. By means of a manipulative field experiment, using “Mega‐Marsh Organ” mesocosms, we investigated the impact of surface drainage and elevation relative to mean sea level on (1) the survival of Spartina anglica seedlings from three different age classes: 1‐yr, 3‐month, and 1‐week; and (2) the growth performance of mature S. anglica marsh tussocks. S. anglica seedling survival, especially in the establishment phase, was positively affected by better surface drainage, increases of seedling age, and higher elevation relative to mean sea level. That is, the survival rate of S. anglica seedlings at the end of 6th week increased from 0% (at surface water undrained, 1‐week, 0 cm elevation) to 94.44% (at surface water drained, 1‐yr, 90 cm elevation). In contrast, surface drainage did not affect the performance of large S. anglica marsh tussocks, as only increased elevation relative to mean sea level was shown to affect S. anglica tussock growth in terms of plant height, shoot numbers, and dry biomass. Based on our findings, we proposed a conceptual model to understand how surface drainage‐driven feedbacks in a heterogeneous topography may be reinforced to induce salt marsh establishment in muddy systems. Further testing of present hypothesized model would be beneficial for insights into salt marsh establishment on tidal mudflats.
Estimates of losses and recovery of ecosystem services for oiled beaches lack clarity and ecological realism
Authors: Fegley Stephen R. , Michel Jacqueline
Published: September 2021

Assessing environmental injury requires accurate, timely information of damage responses and realistic translation of that information into estimates of services lost to the public. The accuracy of both steps improves with the extent of ecological understanding of the impacted habitat; more accurate assessments produce more effective rehabilitation efforts and equitable compensation decisions. Exposed, sandy beaches are one of our most familiar and highly valued coastal areas, yet, when oiled, providing uncontested environmental assessments for beaches challenges both responsible parties and natural resource trustees. The dynamic, physical nature of exposed beaches has limited experimental inquiry preventing the development of widely accepted ecological models describing beach function. The same dynamic nature confounds sampling beaches efficiently in the aftermath of an oil spill. To constrain oiled beach impact assessments in the future and to encourage investigation of topics relevant to beach environmental assessment, we provide a summary of beach ecosystem services, re‐examine the results of the limited number of relevant oiled beach studies, define ecological criteria that would improve extrapolating injury assessments drawn from cognate literature, and identify research topics for investigation.
Influence of interlaminar flux between cores on iron loss in three‐legged wound transformer core
Authors: Inoue Hirotaka , Omura Takeshi , Yamaguchi Hiroi , Senda Kunihiro
Published: September 2021

A three‐legged wound transformer core is composed of two inner cores and one outer core, and the interlaminar flux occurs between inner and outer cores in three‐phase excitations. Past analyses of magnetic properties of three‐legged wound transformer cores were based on the model of independent magnetic paths in the individual core, and did not factor the influence of interlaminar flux in the calculations. This paper shows experimental results of interlaminar flux between cores and iron loss increase caused by that. Results show that the interlaminar flux between the inner and outer core increases the local iron loss in the boundary region of the inner and outer core.
NICE diagnostic heart failure pathway: screening referrals identifies patients better served by community‐based management
Authors: Morton Geraint , Bolam Helena , Hirmiz Zaid , Chahal Raj , Guha Kaushik , Kalra Paul R.
Published: September 2021

Aims

Evaluate whether UK National Institute for Health & Care Excellence (NICE) chronic heart failure (HF) guidelines can be safely and effectively refined through specialist referral management.

Methods and results

All referrals to a UK centre 1/3/2019–30/5/2019 and 1/6/2020–31/7/2020 were reviewed by HF specialists. Patients were triaged to specialist assessment in HF clinic, according to the NICE HF diagnostic pathway [urgency based on N‐terminal pro brain natriuretic peptide (NTproBNP) levels], or the referrer given remote Advice & Guidance (A&G), to aid primary care management. Standardized triage criteria for recommending primary care management were (i) presentation inconsistent with HF, (ii) competing comorbidity/frailty meant specialist assessment in clinic not in patient's best interests, (iii) recent assessment for same condition, or (iv) patient had known HF. Following triage patients managed in the primary care were categorized as low or high risk of adverse outcomes. Outcome measures were 90 day all‐cause and HF hospital admission and mortality rates. Four hundred and eighty‐six patients had the median age of 80 (74–86) years, and 253 (52%) were male. Two hundred and six (42%) had NTproBNP > 2000 pg/mL. Primary care management was recommended for 128 patients (26%): 105 (22%) A&G alone and 23 input from community HF nurse specialists. Primary care management was recommended due to the following: presentation inconsistent with HF 53 (42%), more important competing comorbidity/frailty 35 (27%), recent assessment 17 (13%), and known HF 23 (18%). Patients managed in primary care had higher rates of all‐cause hospitalization (30% vs. 19%; P = 0.018) and death (7% vs. 2%; P = 0.0054) than those seen in HF clinic. Of those managed in primary care, 50 (39%) were determined to be at low risk and 78 (61%) at high risk. High‐risk patients were older (87 vs. 80 years; P = 0.0026), had much higher NTproBNP (2666 vs. 697 pg/mL; P < 0.0001), and were managed in the primary care due to severe comorbidity (45%) or known HF (31%). They had extremely high rates of adverse outcomes: 35 all‐cause hospitalization (45%), 12 HF hospitalization (15%), and 9 deaths (12%). Low‐risk patients were usually felt not to have HF (86%) and confirmed to have low rates of adverse outcomes: three all‐cause hospitalizations (6%; P < 0.0001 compared with high risk) and zero HF hospitalization (P = 0.0033) or death (P = <0.012).

Conclusions

Incorporating specialist referral management into NICE HF diagnostic pathway reduces the demand on HF clinics and may improve the patient experience by facilitating community care. However, many of the patients identified for primary care management are at very high risk of adverse outcomes in the short term and are frequently hospitalized. Urgent implementation of alternative pathways and community‐based care packages in parallel for these high‐risk patients is extremely important.
Characteristics and outcomes of heart failure with recovered left ventricular ejection fraction
Authors: Zhang Xinxin , Sun Yuxi , Zhang Yanli , Chen Feifei , Dai Mengyuan , Si Jinping , Yang Jing , Li Xiao , Li Jiaxin , Xia Yunlong , Tse Gary , Liu Ying
Published: September 2021

Aims

There is an emerging interest in elucidating the natural history and prognosis for patients with heart failure with reduced ejection fraction (HFrEF) in whom left ventricular ejection fraction (LVEF) subsequently improves. The characteristics and outcomes were compared between heart failure with recovered ejection fraction (HFrecEF) and persistent HFrEF.

Methods and results

This is a retrospective study of adults who underwent at least two echocardiograms 3 months apart between 1 November 2015 and 31 October 2019 with an initial diagnosis of HFrEF. The subjects were divided into HFrecEF group (second LVEF > 40%, ≥10% absolute improvement in LVEF) and persistent HFrEF group (<10% absolute improvement in LVEF) according to the second LVEF. To further study the characteristics of HFrecEF patients, the cohort was further divided into LVEF improvement of 10–20% and >20% subgroups. The primary outcomes were all‐cause mortality and rehospitalization. A total of 1160 HFrEF patients were included [70.2% male, mean (standard deviation) age: 62 ± 13 years]. On the second echocardiogram, 284 patients (24.5%) showed HFrecEF and 876 patients (75.5%) showed persistent HFrEF. All‐cause mortality was identified in 23 (8.10%) HFrecEF and 165 (18.84%) persistent HFrEF, whilst 76 (26.76%) and 426 (48.63%) showed rehospitalizations, respectively. Survival analysis showed that the persistent HFrEF subgroup experienced a significantly higher mortality at 12 and 24 months and a higher hospitalization at 12, 24, 48, and more than 48 months following discharge. Multivariate Cox regression showed that persistent HFrEF had a higher risk of all‐cause mortality [hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.49–3.56, P = 0.000] and rehospitalization (HR 1.85, 95% CI 1.45–2.36, P = 0.000) than the HFrecEF group. Subgroup analysis showed that the LVEF ≥ 20% improvement subgroup had lower rates of adverse outcomes compared with those with less improvement of 10–20%.

Conclusions

Heart failure with recovered ejection fraction is a distinct HF phenotype with better clinical outcomes compared with those with persistent HFrEF. HFrecEF patients have a relatively better short‐term mortality at 24 months but not thereafter.
Guanidine improves DEAE anion exchange‐based analytical separation of plasmid DNA
Authors: Černigoj Urh , Vidič Jana , Ferjančič Ana , Sinur Urša , Božič Klemen , Mencin Nina , Martinčič Celjar Anže , Gagnon Pete , Štrancar Aleš
Published: September 2021

Elution of strong and weak anion exchangers with sodium chloride gradients is commonly employed for analysis of sample mixtures containing different isomers of plasmid DNA. Gradient elution of a weak anion exchanger (diethylaminoethyl) in the presence of guanidine hydrochloride (Gdn) roughly doubles resolution between open‐circular (oc) and supercoiled (sc) isomers. It also improves resolution among sc, linear, and multimeric/aggregated forms. Sharper elution peaks with less tailing increase sensitivity about 30%. However, elution with an exclusively Gdn gradient to 900 mM causes more than 10% loss of plasmid. Elution with a sodium chloride gradient while maintaining Gdn at a level concentration of 300 mM achieves close to 100% recovery of sc plasmid while maintaining the separation improvements achieved by exclusively Gdn elution. Corresponding improvements in separation performance are not observed on a strong (quaternary amine) anion exchanger. Other chaotropic salts do not produce a favorable result on either exchanger, nor does the inclusion of surfactants or EDTA. Selectivity of the diethylaminoethyl‐Gdn method is orthogonal to electrophoresis, but with better quantification than agarose electrophoresis, better quantitative accuracy than CE, and resolution approaching CE.
Evaluation of machine learning algorithms to classify and map landforms in Antarctica
Authors: Siqueira Rafael G. , Veloso Gustavo V. , Fernandes‐Filho Elpídio I. , Francelino Márcio R. , Schaefer Carlos Ernesto G. R. , Corrêa Guilherme R.
Published: September 2021

The detailed geomorphology of ice‐free landscapes of Antarctica is key to understanding how their highly fragile environments respond to climate change, at different temporal and spatial scales. Despite the recent advances in geomorphological studies of ice‐free areas, machine learning applications to produce landform maps are still scarce on the Antarctic continent. In this study, we evaluated the predictive performance of different supervised machine learning algorithms to produce digital geomorphological maps in Vega Island—Antarctic Peninsula region. We tested six different models: average artificial neural networks, C5.0 decision tree, random forest, support vector machine, supervised self‐organizing map and weighted k‐nearest neighbours. We used an initial set of 54 geomorphometric and spectral predictors, from which redundant variables with Pearson correlation coefficient >|0.95| were removed, and only the most important predictors for each model were selected using recursive feature elimination. For training, we ran each model 100 times and predictions were assessed by the kappa and global accuracy values. The best predictors were the Red Edge 6 and SWIR 11 bands, roughness concentration index, elevation and drainage density. The decision trees C5.0 and random forest had the best performance, with average validation kappa of 0.85 ± 0.03 and 0.84 ± 0.03, respectively, evidencing excellent prediction. Despite the similar performance, random forest showed greater uncertainty degree and accuracy when classifying complex landforms, attesting to its great robustness. From sensitivity and specificity values, we observed that the glaciers and talus showed higher accuracy, whereas cryoplanated platforms and scree slopes had the worst classification. The presented methodology optimized the classification by selecting the most important predictors, assessing accuracy and evaluating uncertainty. The results indicated that machine learning methods have great potential to produce geomorphological mappings in the Antarctic ice‐free areas, as a promising tool to provide detailed information on remote, harsh polar environments.
Data sets for the Upper Penticton Creek watershed experiment: A paired‐catchment study to support investigations of watershed response to forest dynamics and climatic variability in an inland snow‐dominated region
Authors: Moore R. Dan , Allen Diana , MacKenzie Lucy , Spittlehouse David , Winkler Rita
Published: September 2021

The Upper Penticton Creek watershed experiment is one of a handful of forestry‐focused paired catchment experiments in the snow‐dominated zone of western North America. The study involves an undisturbed control catchment and two treatment catchments. Streamflow has been monitored at weirs on all three streams since 1985. Following a pre‐harvest monitoring period, the treatment catchments were subject to clearcut harvesting in multiple passes that cumulatively covered ~50% of the catchments. In addition to streamflow, available hydrometeorological data sets include weather observations, snowpack water equivalent, rainfall interception, soil water content and water table levels in soil piezometers and bedrock wells. The data archive also includes digital elevation models, a Lidar‐derived image of tree heights in 2016, and vector data associated with lakes and reservoirs, the stream network, clearcut boundaries, a soil map and the logging road network. Together, these data sets provide a basis for empirical analyses of hydrological response to forest dynamics and climatic variability, and for calibration and testing hydrological models using internal variables. They should also provide useful data sets for educational purposes.

Novelty Statement

Upper Penticton Creek is the only long‐term, snowmelt‐dominated, experimental paired catchment study in western Canada and one of only a few in western North America. Four decades of environmental monitoring and research at this site provide an important data set to support analysis and modelling of hydrologica response to forest disturbance and climatic variability.
Retinoic acid and taurine enhance differentiation of the human bone marrow stem cells into cone photoreceptor cells and retinal ganglion cells
Authors: Forouzanfar Fatemeh , Soleimannejad Mostafa , Soltani Amin , Sadat Mirsafaee Parisa , Asgharzade Samira
Published: September 2021

Degeneration and apoptotic death of the photoreceptor cell‐layer of retina are a major cause of irreversible blindness in the development era. The stem cell replacement therapy is one of the strategies for the retinal repairing. In addition, exogenous signals critically contribute to the direction of lineage decisions that causes the fate‐restricted photoreceptor progenitors from stem cell progeny in culture. It has been found that epidermal growth factor (EGF), taurine, and retinoic acid (RA) initially act in the instructive as well as lineage‐restricted way in the progenitor lineage for producing neuroretinal cells or photoreceptor like cells from stem cell. The study aims to investigate the effect of RA and taurine in differentiation of the human bone marrow stem cell into cone photoreceptors cells and retinal ganglion cells. Mesenchymal stem cell was derived from human bone marrow of the term delivery. Therefore, the cultured cells have been treated with Dulbecco's modified Eagle's medium (DMEM)/high glucose (H+). After the four‐cell passage, basal medium was replaced with DMEM/F12 complemented with 50 μmol/L taurine, RA (1 µM) and EGF (1 µg/ml). Subsequently cellular change morphology was detected following 7 and 14 days. Then, gene expression of neuroretinal and photoreceptor cell biomarkers (CRX, OTX2, PKC‐α, recoverin, and Rho) were examined by quantitative polymerase chain reaction (Q‐PCR). Also, cells were cultured, fixed, and then immunocytochemical analyzed. Primary antibodies included CRX and Rho. Cellular morphology demonstrated spindle elongated morphology. Taurine alone and combination of RA upregulate neuroretinal and photoreceptor cell biomarkers in messenger RNA and protein levels but along with EGF have not significant effect. Our data showed that taurine combination with RA can differentiate bone marrow mesenchymal stem cells into neuroretinal or photoreceptor like cells in vitro that can offer an attractive treatment ground for transplantation in the cell‐replacement therapy for some forms of the retinal degeneration.
Ocean acidification alters the diversity and structure of oyster associated microbial communities
Authors: Unzueta‐Martínez Andrea , Downey‐Wall Alan M. , Cameron Louise P. , Ries Justin B. , Lotterhos Katie E. , Bowen Jennifer L.
Published: September 2021

Host‐associated microbial communities are fundamental to host physiology, yet it is unclear how these communities will respond to environmental disturbances. Here, we disentangle the environment‐linked and host‐linked effects of ocean acidification on oyster‐associated microbial communities. We exposed adult oysters (Crassostrea virginica) to CO2‐induced ocean acidification (400 vs. 2800 ppm) for 80 d. We measured the oyster extrapallial fluid pH and sampled the gills for microbial analysis at six time points. We found that different subsets of microbes were linked to acidification (n = 34 amplicon sequence variants [ASVs]) and to host response (n = 20 ASVs) with little overlap (n = 8 ASVs), suggesting that some members of the oyster microbiome were more responsive to environmental conditions while others were more tightly linked to host condition. Our results provide insight into which members of the oyster microbiome may contribute to the health and resistance of their host, and which members are the most vulnerable to changing environmental conditions.
The intrinsic phenomena of concentration and cavitation on the Riemann solutions for the perturbed macroscopic production model
Authors: Zhang Yunfeng , Sun Meina
Published: September 2021

The exact solutions of the Riemann problems for the two different perturbed macroscopic production models are considered and constructed, respectively, for all the possible cases. It is found that the asymptotic limits of solutions to the Riemann problem for the first kind of perturbed macroscopic production model do not converge to those of the pressureless gas dynamics model, because the delta shock wave in the limiting situation has different propagation speed and strength from those for the pressureless gas dynamics model. In order to remedy it, the second kind of perturbed macroscopic production model is proposed, whose asymptotic limits of Riemann solutions are identical with those of the pressureless gas dynamics model.
Oscillation of nonlinear even order differential equations with mixed neutral terms
Authors: Grace Said R. , Abbas Syed , Sajid Mohammad
Published: September 2021

This paper discusses the oscillation of nonlinear even‐order differential equations with mixed nonlinear neutral terms. We establish new oscillation criteria, which extend, improve, and simplify existing criteria given in the literature. For illustration, some examples are provided.
Understanding the experiences of patients with cancers in hospitals during COVID‐19 pandemic in China: A qualitative research study
Authors: Chen Xing , Deng Wenyu , Zhou Wenjuan , Liu Ying , Chen Jinfeng , Gao Yuan , Xiao Kuirong , Man Lin , Qu Wanting , Zeng Hongjuan , Ye Sha
Published: September 2021

Aim

To explore the experiences of patients with cancers in hospitals during the COVID‐19 pandemic.

Design

A qualitative research study.

Methods

Using a phenomenological approach, we enrolled 22 patients with cancers in the Hunan Cancer Hospital from 20 February 2020 to 10 April 2020. The interviews were conducted face‐to‐face and were analysed by Colaizzi's 7‐step method. This study aligns with the COREQ checklist.

Results

The experiences of patients with cancers in hospitals during the COVID‐19 pandemic can be categorized into four major themes: (1) emotional changes; (2) delays in visiting hospital; (3) barriers to accessing medical care services, and (4) inconvenience related to logistics services.
Psychometric validation of the Chinese version of the PROMIS Social Relationships Short Forms
Authors: Cai Tingting , Huang Qingmei , Wu Fulei , Xia Haozhi , Yuan Changrong
Published: September 2021

Aim

This study aimed to culturally adapt and psychometrically validate the PROMIS Social Relationships Short Forms (PROMIS‐SR) among Chinese patients with breast cancer.

Design

A cross‐sectional study.

Method

The PROMIS‐SR was translated into simplified Chinese by strictly adhering to the Functional Assessment of Chronic Illness Therapy translation method and was subsequently tested among patients with breast cancer (N = 965). Eligible patients filled out the demographic information questionnaire, the PROMIS‐SR, and the Functional Assessment of Cancer Therapy‐Breast.

Results

Confirmatory factor analysis (CFA) provided support for the original structure of the PROMIS‐SR. All instruments reported strong known‐group, cross‐cultural and convergent validity, as hypothesized. Correlation coefficients ranged from 0.67 to 0.85, and Cronbach's α of all items were high (0.90–0.94).
Childhood acute lymphoblastic leukemia treatment in an academic hospital in Kenya: Treatment outcomes and health‐care providers’ perspectives
Authors: Olbara Gilbert , van der Wijk Thyra , Njuguna Festus , Langat Sandra , Mwangi Henry , Skiles Jodi , Vik Terrry A. , Kaspers Gertjan J.L. , Mostert Saskia
Published: September 2021

Background

Early deaths and treatment nonadherence are major reasons for low childhood acute lymphoblastic leukemia (ALL) survival in low‐ and middle‐income countries. This study assessed treatment outcomes of children presenting with ALL and evaluated perspectives of health‐care providers (HCP) on ALL treatment at a Kenyan academic hospital.

Methods

This was a combined retrospective medical records and cross‐sectional questionnaire study. Treatment outcomes of 136 children diagnosed with ALL between 2010 and 2016 were collected. Questionnaires were completed by 245 HCP (response rate, 86%) between September and October 2016.

Results

Childhood ALL treatment outcomes were death (30%), progressive or relapsed disease (26%), abandonment (24%), and event‐free survival (20%). Of all deaths, 80% were early deaths (prior or during induction), whereas 20% occurred in remission. Probability of event‐free survival at three years was 18%. Only 57% of HCP believed childhood ALL can be cured, with more doctors (96%) than other HCP (45%) believing in curability of ALL (P < 0.001). The majority of HCP (96%) thought that experienced doctors should put more time and effort into making parents understand the diagnosis and necessity to complete treatment. According to HCP, reasons for protocol nonadherence included parental financial difficulties (94%) and use of alternative treatment (79%).

Conclusions

Event‐free survival for ALL in Kenya is low. The primary reason for treatment failure is early death from treatment‐related complications. More efforts should be directed toward improving supportive care strategies. In the opinion of HCPs, improved communication with parents and supervision of junior staff will improve ALL treatment outcomes.
Numerical and experimental investigations on the low‐velocity impact properties of hybrid Kevlar fiber/basalt fiber reinforced epoxy composites: Effects of impactor nose shape and fiber stacking sequences
Authors: Karamooz Mohammad Reza , Rahmani Hossein , Khosravi Hamed
Published: September 2021

In the present work, the effect of impactor nose shape and fiber stacking sequences on the low‐velocity impact properties of hybrid Kevlar/basalt fiber reinforced epoxy composites was investigated. The composite specimens were prepared using hand lay‐up method with six types of fiber stacking sequences including sandwich hybrid, intercalated hybrid and not‐hybrid. The impact tests were conducted using three types of impactor nose shapes (hemispherical, conical, and flat) at two impact energies of 40 and 60 J. Some characteristics of the composites like maximum force, absorbed energy, and damage area were evaluated. Also, the impact behavior of the composites was simulated in Abacus finite element software and the obtained results were compared with the experimental values. The results indicated the hybridization of Kevlar by basalt fibers (intercalated hybrid) considerably improved the impact properties of the specimen. Besides, when the conical impactor was employed, the highest absorbed energy and damaged area were obtained.
Cell‐free DNA screening for fetal aneuploidy using the rolling circle method: A step towards non invasive prenatal testing simplification
Authors: Pavanello Enza , Sciarrone Andrea , Guaraldo Varvara , Muccinelli Elisabetta , Ciuffreda Valentina Pia , Sauro Pina , Bondielli Giulia , Mirante Sandra , Mengozzi Giulio , Viora Elsa , Cuckle Howard , Pasini Barbara
Published: September 2021

Objective

To assess the efficacy of cell‐free (cf)DNA screening for aneuploidy using the automated system based on rolling circle replication.

Methods

A prospective study among women referred for invasive prenatal diagnosis between July 2018 and December 2019. The plasma fraction was extracted within 5 days from blood collection, stored at −20°C and cfDNA measured between January and December 2019.

Results

A total of 805 women were recruited; 778 with singleton pregnancies and 27 twins. There were 48 Down syndrome, 25 Edwards syndrome and 3 Patau syndrome cases. Overall, the no‐call rate was 2.6% (95% confidence interval 1.6%–3.9%) which reduced from 4.7% to 1.1% after relocation of the system (p < 0.002) to ensure a constant ambient temperature below 25°C. In singletons the Down syndrome detection rate (DR) was 100% (93%–100%) and false‐positive rate (FPR) 0.14% (0.00%–0.79%). The Edwards syndrome DR was 96% (80%–100%) and FPR 0.78% (0.29%–1.7%). One false‐positive had a confined placental trisomy 18 and the remaining five a z‐score requiring sample repetition; all the false‐positives occurred before system relocation (p < 0.005). Patau syndrome DR and FPR were 67% (9.4%–99%) and 0.26% (0.03%–0.95%).

Conclusion

The cfDNA rolling circle method yields similar results to other methods provided that room temperature is adequately controlled.