bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial fibrillation risk prediction from the 12-lead electrocardiogram using digital biomarkers and deep representation learning
Authors: Biton Shany , Gendelman Sheina , Ribeiro Antônio H , Miana Gabriela , Moreira Carla , Ribeiro Antonio Luiz P , Behar Joachim A
Published: August 2021

Aims

This study aims to assess whether information derived from the raw 12-lead electrocardiogram (ECG) combined with clinical information is predictive of atrial fibrillation (AF) development.

Methods and results

We use a subset of the Telehealth Network of Minas Gerais (TNMG) database consisting of patients that had repeated 12-lead ECG measurements between 2010 and 2017 that is 1 130 404 recordings from 415 389 unique patients. Median and interquartile of age for the recordings were 58 (46–69) and 38% of the patients were males. Recordings were assigned to train-validation and test sets in an 80:20% split which was stratified by class, age and gender. A random forest classifier was trained to predict, for a given recording, the risk of AF development within 5 years. We use features obtained from different modalities, namely demographics, clinical information, engineered features, and features from deep representation learning. The best model performance on the test set was obtained for the model combining features from all modalities with an area under the receiver operating characteristic curve (AUROC) = 0.909 against the best single modality model which had an AUROC = 0.839.

Conclusion

Our study has important clinical implications for AF management. It is the first study integrating feature engineering, deep learning, and Electronic medical record system (EMR) metadata to create a risk prediction tool for the management of patients at risk of AF. The best model that includes features from all modalities demonstrates that human knowledge in electrophysiology combined with deep learning outperforms any single modality approach. The high performance obtained suggest that structural changes in the 12-lead ECG are associated with existing or impending AF.
Automated external defibrillators delivered by drones to patients with suspected out-of-hospital cardiac arrest
Authors: Schierbeck Sofia , Hollenberg Jacob , Nord Anette , Svensson Leif , Nordberg Per , Ringh Mattias , Forsberg Sune , Lundgren Peter , Axelsson Christer , Claesson Andreas
Published: August 2021

Aims

Early defibrillation is critical for the chance of survival in out-of-hospital cardiac arrest (OHCA). Drones, used to deliver automated external defibrillators (AEDs), may shorten time to defibrillation, but this has never been evaluated in real-life emergencies. The aim of this study was to investigate the feasibility of AED delivery by drones in real-life cases of OHCA.

Methods and results

In this prospective clinical trial, three AED-equipped drones were placed within controlled airspace in Sweden, covering approximately 80 000 inhabitants (125 km2). Drones were integrated in the emergency medical services for automated deployment in beyond-visual-line-of-sight flights: (i) test flights from 1 June to 30 September 2020 and (ii) consecutive real-life suspected OHCAs. Primary outcome was the proportion of successful AED deliveries when drones were dispatched in cases of suspected OHCA. Among secondary outcomes was the proportion of cases where AED drones arrived prior to ambulance and time benefit vs. ambulance. Totally, 14 cases were eligible for dispatch during the study period in which AED drones took off in 12 alerts to suspected OHCA, with a median distance to location of 3.1 km [interquartile range (IQR) 2.8–3.4). AED delivery was feasible within 9 m (IQR 7.5–10.5) from the location and successful in 11 alerts (92%). AED drones arrived prior to ambulances in 64%, with a median time benefit of 01:52 min (IQR 01:35–04:54) when drone arrived first. In an additional 61 test flights, the AED delivery success rate was 90% (55/61).

Conclusion

In this pilot study, we have shown that AEDs can be carried by drones to real-life cases of OHCA with a successful AED delivery rate of 92%. There was a time benefit as compared to emergency medical services in cases where the drone arrived first. However, further improvements are needed to increase dispatch rate and time benefits.

Trial registration number

ClinicalTrials.gov Identifier: NCT04415398.
Towards a Taxonomic Classification of Humus Forms
Authors: Green R. N. , Trowbridge R. L. , Klinka K.
Published: August 2021

A two-category taxonomic classification and a methodology for field description are proposed to aid in consistent identification and interpretation of humus forms for ecosystem research, surveys, and management. The classification uses the nomenclature principles of the U.S. soil taxonomy and the master organic horizon designations of the Canadian system of soil classification. It includes humus form taxa that have been recognized in Europe and North America. Recognized taxa are defined on the basis of observable and easily measurable morphological properties. Three taxa, Mor, Moder, and Mull, are recognized at the order level and are differentiated according to the type of F horizon and the relative prominence of organic-enriched A horizons. These reflect principal differences in the nature and rate of decomposition processes. Names of the 16 taxa at the lower, group level are created by adding formative elements to the name of the order. For example, groups of the Mor order are differentiated according to the relative thickness of F and H horizons (Hemimors and Humimors); degree of humification in the H horizon (Resimors); content of decaying wood (Lignomors); and moisture regime (Hydromors, Fibrimors, and Mesimors). Phases can be formed for any taxon to recognize important morphological properties that deviate from the taxonomic differentiae. Keys to the recognized taxa and descriptions of representative humus form profiles for each group are provided to assist in identification. Methods for describing, sampling, and surveying humus forms are presented to facilitate field examinations and subsequent studies.
Genome and transcriptome assemblies of the kuruma shrimp,Marsupenaeus japonicus
Authors: Kawato Satoshi , Nishitsuji Koki , Arimoto Asuka , Hisata Kanako , Kawamitsu Mayumi , Nozaki Reiko , Kondo Hidehiro , Shinzato Chuya , Ohira Tsuyoshi , Satoh Noriyuki , Shoguchi Eiichi , Hirono Ikuo
Published: August 2021

The kuruma shrimp Marsupenaeus japonicus (order Decapoda, family Penaeidae) is an economically important crustacean that occurs in shallow, warm seas across the Indo-Pacific. Here, using a combination of Illumina and Oxford Nanopore Technologies platforms, we produced a draft genome assembly of M. japonicus (1.70 Gbp; 18,210 scaffolds; scaffold N50 = 234.9 kbp; 34.38% GC, 93.4% BUSCO completeness) and a complete mitochondrial genome sequence (15,969 bp). As with other penaeid shrimp genomes, the M. japonicus genome is extremely rich in simple repeats, which occupies 27.4% of the assembly. A total of 26,381 protein-coding gene models (94.7% BUSCO completeness) were predicted, of which 18,005 genes (68.2%) were assigned functional description by at least one method. We also produced an Illumina-based transcriptome shotgun assembly (40,991 entries; 93.0% BUSCO completeness) and a PacBio Iso-Seq transcriptome assembly (25,415 entries; 67.5% BUSCO completeness). We envision that the M. japonicus genome and transcriptome assemblies will serve as useful resources for the basic research, fisheries management, and breeding programs of M. japonicus.
Thermodynamically consistent model for poroelastic rocks towards tectonic and volcanic processes and earthquakes
Authors: Roubíček T
Published: August 2021

A general-purpose model combining concepts from rational continuum mechanics, fracture and damage mechanics, plasticity, and poromechanics is devised in Eulerian coordinates, involving objective time derivatives. The model complies with mass, momentum, and energy conservation as well as entropy inequality and objectivity. It is devised to cover many diverse phenomena, specifically rupture of existing lithospheric faults, tectonic earthquakes, generation and propagation of seismic waves, birth of new tectonic faults, or volcanic activity, aseismic creep, folding of rocks, aging of rocks, long-distance saturated water transport and flow in poroelastic rocks, melting of rocks and formation of magma chambers, or solidification of magma.
Messi vs. Massi, Prior Right vs. Reputation: The Decision of the Court of Justice of the European Union and Its Assessment with Regard to the Turkish Trademark Law
Authors: Özkan ÇiĞdem YataĞan
Published: August 2021

The Messi case,1 which originated with the decision of the European Union Intellectual Property Office (EUIPO) in 2011 and was finalized in 2020, surprised the IP world/practitioners with the remarks of the first instance court and the Court of Justice of the European Union (CJEU) as their findings were contrary to the established case law regarding the implementation of the relative grounds of refusal. Lionel Messi was a party to the court case as the applicant of the later application for the same classes of goods; the first instance court overruled the appeal of the owner of the earlier trademark based on relative grounds, given Lionel Messi’s reputation as a famous football player and thus the reputation of his surname ‘Messi’, even though the two trademarks were considered visually and phonetically similar. It was reiterated in the court decision that the reputation of the owner of the later trademark application neutralized the likelihood of confusion with the earlier trademark. Moreover, the judgment (dated 17 September 2020) of the Tenth Chamber of the CJEU went beyond the ordinary scope of trademark law. In this study we will discuss, in the context of the Messi decision, the influence of the reputation of a later trademark on conceptual differentiation and the possible results of not adducing evidence proving the reputation of a trademark.
Projection-free nonconvex stochastic optimization on Riemannian manifolds
Authors: Weber Melanie , Sra Suvrit
Published: August 2021

We study stochastic projection-free methods for constrained optimization of smooth functions on Riemannian manifolds, i.e., with additional constraints beyond the parameter domain being a manifold. Specifically, we introduce stochastic Riemannian Frank–Wolfe (Fw) methods for nonconvex and geodesically convex problems. We present algorithms for both purely stochastic optimization and finite-sum problems. For the latter, we develop variance-reduced methods, including a Riemannian adaptation of the recently proposed Spider technique. For all settings, we recover convergence rates that are comparable to the best-known rates for their Euclidean counterparts. Finally, we discuss applications to two classic tasks: the computation of the Karcher mean of positive definite matrices and Wasserstein barycenters for multivariate normal distributions. For both tasks, stochastic Fw methods yield state-of-the-art empirical performance.
Testing the inferred transcription rates of a dynamic, gene network model in absolute units
Authors: Urquiza-García Uriel , Millar Andrew J
Published: August 2021

The circadian clock coordinates plant physiology and development. Mathematical clock models have provided a rigorous framework to understand how the observed rhythms emerge from disparate, molecular processes. However, models of the plant clock have largely been built and tested against RNA time-series data in arbitrary, relative units. This limits model transferability, refinement from biochemical data and applications in synthetic biology. Here, we incorporate absolute mass units into a detailed model of the clock gene network in Arabidopsis thaliana. We re-interpret the established P2011 model, highlighting a transcriptional activator that overlaps the function of REVEILLE 8/LHY-CCA1-LIKE 5. The new U2020 model incorporates the repressive regulation of PRR genes, a key feature of the most detailed clock model KF2014, without greatly increasing model complexity. We tested the experimental error distributions of qRT–PCR data calibrated for units of RNA transcripts per cell and of circadian period estimates, in order to link the models to data more appropriately. U2019 and U2020 models were constrained using these data types, recreating previously described circadian behaviours with RNA metabolic processes in absolute units. To test their inferred rates, we estimated a distribution of observed, transcriptome-wide transcription rates (Plant Empirical Transcription Rates, PETR) in units of transcripts per cell per hour. The PETR distribution and the equivalent degradation rates indicated that the models’ predicted rates are biologically plausible, with individual exceptions. In addition to updated clock models, FAIR (Findable, Accessible, Interoperable, Re-usable) data resources and a software environment in Docker, this validation process represents an advance in biochemical realism for models of plant gene regulation.
Awareness, perception and the practice of COVID-19 prevention among residents of a state in the South-South region of Nigeria: implications for public health control efforts
Authors: Owhonda Golden , Maduka Omosivie , Nwadiuto Ifeoma , Tobin-West Charles , Azi Esther , Ojimah Chibianotu , Alasia Datonye , Olofinuka Ayo-Maria , Agala Vetty , Paul John Nwolim , Nria Doris , Okafor Chinenye , Ndekwu Ifeoma , Opara Chikezie , Newsom Chris
Published: August 2021

Background

As with any epidemic, coronavirus disease 2019 (COVID-19) has evoked panic, fear and misconceptions. The risk communication pillar of the Public Health Emergency Operations Centre is responding to the pandemic by facilitating correct and consistent information to enable the adoption of behaviours to prevent and control COVID-19. This study explored awareness, perception and practice of COVID-19 prevention among residents in Rivers State, Nigeria, during the early stages of the COVID-19 pandemic response.

Methods

This was a descriptive cross-sectional survey among 1294 adult residents across all districts of the state. It employed an interviewer-administered questionnaire. Knowledge was graded as excellent for scores of ≥80%, good for scores of 50–79% and poor for scores of <50%. Respondents who washed all critical parts of their hands were categorised as adopting correct handwashing practice. Regression modelling was employed to determine predictors of knowledge and practice of COVID-19 prevention with p=0.05.

Results

The respondents were aged 18–80 y with an average age of 39.6 (SD=11.9) y. A total of 710 (54.9%) were male, 476 (36.8%) were unemployed with 685 (52.9%) having secondary education. The most common sources of information about COVID-19 were radio jingles (1102; 86.7%) and television adverts (940; 74.0%). Overall, 608 (47.0%) of the respondents had a poor knowledge of COVID-19. About 443 (34.9%) respondents believed they were unlikely to contract the virus. Only 505 (39.0%) of respondents washed all the critical parts of their hands correctly. Occupation (adjusted OR [AOR]=1.39, 95% CI 1.07 to 1.82, p=0.01), level of education (AOR=4.71, 95% CI 1.90 to 11.68, p<0.001) and location (AOR=1.75, 95% CI 1.29 to 2.38; p<0.001) significantly predicted respondents’ knowledge about COVID-19. The significant predictors of practice of COVID-19 were age (AOR=0.60, 95% CI 0.42 to 0.84, p=0.003), occupation (AOR=1.93, 95% CI 1.41 to 2.63, p<0.001), location (AOR=2.35, 95% CI 1.65 to 3.34, p<0.001) and knowledge about COVID-19 (AOR=7.75, 95% CI 5.94 to 10.11, p<0.001).

Conclusions

Broadcast media has a pivotal role to play in risk communication for behavioural change for the control of current and future epidemics in this population.
Characterization of Enterobacter cloacae and Citrobacter freundii species complex isolates with decreased susceptibility to cephalosporins from United States hospitals and activity of ceftazidime/avibactam and comparator agents
Authors: Sader Helio S , Mendes Rodrigo E , Doyle Timothy B , Davis Andrew P , Castanheira Mariana
Published: August 2021

Objectives

To evaluate the antimicrobial susceptibility and resistance mechanisms to β-lactams among Enterobacter cloacae and Citrobacter freundii from United States medical centres.

Methods

2571 E. cloacae and 1008 C. freundii species complex isolates were consecutively collected from 77 medical centres and susceptibility tested by broth microdilution method. Isolates displaying MIC values ≥16 mg/L for ceftazidime or ≥2 mg/L for cefepime (n = 914) were tested for β-lactamase-encoding genes using whole genome sequencing.

Results

Overall susceptibility to ceftazidime and cefepime were 73.9% and 91.2% among E. cloacae and 74.2% and 93.5% among C. freundii, respectively. Sixty-three isolates harboured a carbapenemase gene, including 56 blaKPC, 2 blaNMC-A, and 5 metallo-β-lactamase genes. Among non-carbapenemase producers, 121 isolates had at least one ESBL-encoding gene, mainly blaSHV (81) or blaCTX-M (61), and 15 had a transferable AmpC gene, mainly blaDHA-1 (8) or blaFOX-5 (6). Carbapenemase, ESBL, or transferable AmpC-encoding genes were not identified among 718 of 914 (78.6%) isolates sequenced. The most active agents against isolates with a decreased susceptibility to ceftazidime and/or cefepime were ceftazidime/avibactam (MIC50/90, 0.5/1 mg/L; 99.3% susceptible), amikacin (MIC50/90, 1/4 mg/L; 99.5% susceptible), and meropenem (MIC50/90, 0.06/0.5 mg/L; 92.9% susceptible). The isolates resistant to ceftazidime/avibactam were the five MBL producers and one E. cloacae isolate with a reduced expression of OmpF and overexpression of AcrAB-TolC.

Conclusions

Hyperproduction of chromosomal AmpC appears to be the most common mechanism of resistance to ceftazidime and/or cefepime in E. cloacae and C. freundii. Ceftazidime/avibactam remained highly active against most isolates showing decreased susceptibility to ceftazidime and/or cefepime.
Methane emissions and δ13C composition from beef steers consuming increasing proportions of sericea lespedeza hay on bermudagrass hay diets
Authors: van Cleef Flavia O S , Dubeux José C B , Naumann Harley D , Santos Erick R S , Sollenberger Lynn E , Vendramini João M B , Ruiz-Moreno Martin , Ciriaco Francine M , DiLorenzo Nicolas
Published: August 2021

An experiment was conducted to evaluate the effects of different proportions of ‘Au Grazer’ sericea lespedeza [SL, Lespedeza cuneata (Dum. Cours.) G. Don], a legume rich in condensed tannins (CT), on nutrient intake and digestibility, and to estimate methane (CH4) emissions and 13C isotopic composition (δ13CCH4) from beef steers consuming a forage-based diet. Twenty-five Angus-crossbred steers were distributed in a randomized complete block design (344 ± 48 kg initial BW), and randomly assigned to one of five treatments: 0SL, 25SL, 50SL, 75SL, and 100SL, diets containing 0%, 25%, 50%, 75%, and 100% of SL hay, respectively, mixed with ‘Tifton-85’ bermudagrass hay (Cynodon spp.). The study was carried out for two experimental periods of 21-d each. The statistical model included the fixed effect of treatment and random effects of block, experimental period, and their interaction. Apparent total tract digestibility of crude protein, neutral detergent fiber, and acid detergent fiber was linearly decreased (P < 0.001) by the inclusion of SL. No effects were observed for total CH4 emissions per day, nor for CH4 relative to organic matter intake or digestible organic matter with the inclusion of SL. However, emission of CH4 in relation to intake of CT was affected by treatment (P < 0.001). A linear (P < 0.001) decrease and a quadratic effect (P < 0.001) were observed for δ13C of diets and gas, respectively, in which diets and enteric CH4 with greater inclusion of SL were more depleted in 13C. Moreover, the difference in δ13C between diets and gas (Δδ13C) had a linear decrease (P = 0.001) with the inclusion of SL. The model developed to predict the C3 proportions in the enteric CH4 fitted to predicted values (P < 0.0001). Therefore, greater proportions of SL resulted in lesser CH4 emission when CT intake was considered and the isotopic composition from enteric CH4 was able to predict the contribution of SL in the emissions.
Autophagy in sexual plant reproduction: new insights
Authors: Zhou Xuemei , Zhao Peng , Sun Meng-Xiang
Published: August 2021

Autophagy is a mechanism by which damaged or unwanted cells are degraded and their constituents recycled. Over the past decades, research focused on autophagy has expanded from yeast to mammals and plants, and the core machinery regulating autophagy appears to be conserved. In plants, autophagy has essential roles in responses to stressful conditions and also contributes to normal development, especially in the context of reproduction. Here, based on recent efforts to understand the roles and molecular mechanisms underlying autophagy, we highlight the specific roles of autophagy in plant reproduction and provide new insights for further studies.
The Role of Israel in American Haredi Life
Authors: Krakowski Moshe , Rand Elana Riback , Brooks Suzanne
Published: August 2021

This article examines the role of Israel in the daily lives of American haredim in both Yeshivish and Hasidic communities. Evidence drawn from over 25 interviews with yeshivish and hasidic lay leaders, school administrators, magazine publishers, and community members presents a nuanced portrait of attitudes toward, and ideologies regarding, the State of Israel. Although historically and sociologically Zionism has been seen as a key issue distinguishing modern and haredi Jewish communities, this distinction may lie more at the level of ideological affirmation, rather than actual behavior, knowledge, or belief.
WALLABY pre-pilot survey: H i content of the Eridanus supergroup
Authors: For B-Q , Wang J , Westmeier T , Wong O I , Murugeshan C , Staveley-Smith L , Courtois H M , Pomarède D , Spekkens K , Catinella B , McQuinn K B W , Elagali A , Koribalski B S , Lee-Waddell K , Madrid J P , Popping A , Reynolds T N , Rhee J , Bekki K , Dènes H , Kamphuis P , Verdes-Montenegro L
Published: August 2021

We present observations of the Eridanus supergroup obtained with the Australian Square Kilometre Array Pathfinder (ASKAP) as part of the pre-pilot survey for the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY). The total number of detected H i sources is 55, of which 12 are background galaxies not associated with the Eridanus supergroup. Two massive H i clouds are identified and large H i debris fields are seen in the NGC 1359 interacting galaxy pair, and the face-on spiral galaxy NGC 1385. We describe the data products from the source finding algorithm and present the basic parameters. The presence of distorted H i morphology in all detected galaxies suggests ongoing tidal interactions within the subgroups. The Eridanus group has a large fraction of H i-deficient galaxies as compared to previously studied galaxy groups. These H i-deficient galaxies are not found at the centre of the group. We find that galaxies in the Eridanus supergroup do not follow the general trend of the atomic gas fraction versus stellar mass scaling relation, which indicates that the scaling relation changes with environmental density. In general, the majority of these galaxies are actively forming stars.
Plasma properties, switchback patches, and low α-particle abundance in slow Alfvénic coronal hole wind at 0.13 au
Authors: Woolley Thomas , Matteini Lorenzo , McManus Michael D , Berčič Laura , Badman Samuel T , Woodham Lloyd D , Horbury Timothy S , Bale Stuart D , Laker Ronan , Stawarz Julia E , Larson Davin E
Published: August 2021

The Parker Solar Probe (PSP) mission presents a unique opportunity to study the near-Sun solar wind closer than any previous spacecraft. During its fourth and fifth solar encounters, PSP had the same orbital trajectory, meaning that solar wind was measured at the same latitudes and radial distances. We identify two streams measured at the same heliocentric distance (∼0.13 au) and latitude (∼–$3{_{.}^{\circ}}5$) across these encounters to reduce spatial evolution effects. By comparing the plasma of each stream, we confirm that they are not dominated by variable transient events, despite PSP’s proximity to the heliospheric current sheet. Both streams are consistent with a previous slow Alfvénic solar wind study once radial effects are considered, and appear to originate at the Southern polar coronal hole boundary. We also show that the switchback properties are not distinctly different between these two streams. Low α-particle abundance (∼0.6  per cent) is observed in the encounter 5 stream, suggesting that some physical mechanism must act on coronal hole boundary wind to cause α-particle depletion. Possible explanations for our observations are discussed, but it remains unclear whether the depletion occurs during the release or the acceleration of the wind. Using a flux tube argument, we note that an α-particle abundance of ∼0.6  per cent in this low-velocity wind could correspond to an abundance of ∼0.9  per cent at 1 au. Finally, as the two streams roughly correspond to the spatial extent of a switchback patch, we suggest that patches are distinct features of coronal hole wind.
AtHDA6 functions as an H3K18ac eraser to maintain pericentromeric CHG methylation inArabidopsis thaliana
Authors: Wang Qianwen , Bao Xiucong , Chen Shengjie , Zhong Huan , Liu Yaqin , Zhang Li , Xia Yiji , Kragler Friedrich , Luo Ming , Li Xiang David , Lam Hon-Ming , Zhang Shoudong
Published: August 2021

Pericentromeric DNA, consisting of high-copy-number tandem repeats and transposable elements, is normally silenced through DNA methylation and histone modifications to maintain chromosomal integrity and stability. Although histone deacetylase 6 (HDA6) has been known to participate in pericentromeric silencing, the mechanism is still yet unclear. Here, using whole genome bisulfite sequencing (WGBS) and chromatin immunoprecipitation-sequencing (ChIP-Seq), we mapped the genome-wide patterns of differential DNA methylation and histone H3 lysine 18 acetylation (H3K18ac) in wild-type and hda6 mutant strains. Results show pericentromeric CHG hypomethylation in hda6 mutants was mediated by DNA demethylases, not by DNA methyltransferases as previously thought. DNA demethylases can recognize H3K18ac mark and then be recruited to the chromatin. Using biochemical assays, we found that HDA6 could function as an ‘eraser’ enzyme for H3K18ac mark to prevent DNA demethylation. Oxford Nanopore Technology Direct RNA Sequencing (ONT DRS) also revealed that hda6 mutants with H3K18ac accumulation and CHG hypomethylation were shown to have transcriptionally active pericentromeric DNA.
ARG-SHINE: improve antibiotic resistance class prediction by integrating sequence homology, functional information and deep convolutional neural network
Authors: Wang Ziye , Li Shuo , You Ronghui , Zhu Shanfeng , Zhou Xianghong Jasmine , Sun Fengzhu
Published: August 2021

Antibiotic resistance in bacteria limits the effect of corresponding antibiotics, and the classification of antibiotic resistance genes (ARGs) is important for the treatment of bacterial infections and for understanding the dynamics of microbial communities. Although several methods have been developed to classify ARGs, none of them work well when the ARGs diverge from those in the reference ARG databases. We develop a novel method, ARG-SHINE, for ARG classification. ARG-SHINE utilizes state-of-the-art learning to rank machine learning approach to ensemble three component methods with different features, including sequence homology, protein domain/family/motif and raw amino acid sequences for the deep convolutional neural network. Compared with other methods, ARG-SHINE achieves better performance on two benchmark datasets in terms of accuracy, macro-average f1-score and weighted-average f1-score. ARG-SHINE is used to classify newly discovered ARGs through functional screening and achieves high prediction accuracy. ARG-SHINE is freely available at https://github.com/ziyewang/ARG_SHINE.
CONSULT: accurate contamination removal using locality-sensitive hashing
Authors: Rachtman Eleonora , Bafna Vineet , Mirarab Siavash
Published: August 2021

A fundamental question appears in many bioinformatics applications: Does a sequencing read belong to a large dataset of genomes from some broad taxonomic group, even when the closest match in the set is evolutionarily divergent from the query? For example, low-coverage genome sequencing (skimming) projects either assemble the organelle genome or compute genomic distances directly from unassembled reads. Using unassembled reads needs contamination detection because samples often include reads from unintended groups of species. Similarly, assembling the organelle genome needs distinguishing organelle and nuclear reads. While k-mer-based methods have shown promise in read-matching, prior studies have shown that existing methods are insufficiently sensitive for contamination detection. Here, we introduce a new read-matching tool called CONSULT that tests whether k-mers from a query fall within a user-specified distance of the reference dataset using locality-sensitive hashing. Taking advantage of large memory machines available nowadays, CONSULT libraries accommodate tens of thousands of microbial species. Our results show that CONSULT has higher true-positive and lower false-positive rates of contamination detection than leading methods such as Kraken-II and improves distance calculation from genome skims. We also demonstrate that CONSULT can distinguish organelle reads from nuclear reads, leading to dramatic improvements in skim-based mitochondrial assemblies.
Formalizing falsification for theories of consciousness across computational hierarchies
Authors: Hanson Jake R , Walker Sara I
Published: August 2021

The scientific study of consciousness is currently undergoing a critical transition in the form of a rapidly evolving scientific debate regarding whether or not currently proposed theories can be assessed for their scientific validity. At the forefront of this debate is Integrated Information Theory (IIT), widely regarded as the preeminent theory of consciousness because it quantified subjective experience in a scalar mathematical measure called Φ that is in principle measurable. Epistemological issues in the form of the “unfolding argument” have provided a concrete refutation of IIT by demonstrating how it permits functionally identical systems to have differences in their predicted consciousness. The implication is that IIT and any other proposed theory based on a physical system’s causal structure may already be falsified even in the absence of experimental refutation. However, so far many of these arguments surrounding the epistemological foundations of falsification arguments, such as the unfolding argument, are too abstract to determine the full scope of their implications. Here, we make these abstract arguments concrete, by providing a simple example of functionally equivalent machines realizable with table-top electronics that take the form of isomorphic digital circuits with and without feedback. This allows us to explicitly demonstrate the different levels of abstraction at which a theory of consciousness can be assessed. Within this computational hierarchy, we show how IIT is simultaneously falsified at the finite-state automaton level and unfalsifiable at the combinatorial-state automaton level. We use this example to illustrate a more general set of falsification criteria for theories of consciousness: to avoid being already falsified, or conversely unfalsifiable, scientific theories of consciousness must be invariant with respect to changes that leave the inference procedure fixed at a particular level in a computational hierarchy.
RBP differentiation contributes to selective transmissibility of OPT3 mRNAs
Authors: Lv Xinmin , Sun Yaqiang , Hao Pengbo , Zhang Cankui , Tian Ji , Fu Mengmeng , Xu Zhen , Wang Yi , Zhang Xinzhong , Xu Xuefeng , Wu Ting , Han Zhenhai
Published: August 2021

Long-distance mobile mRNAs play key roles in gene regulatory networks that control plant development and stress tolerance. However, the mechanisms underlying species-specific delivery of mRNA still need to be elucidated. Here, the use of grafts involving highly heterozygous apple (Malus) genotypes allowed us to demonstrate that apple (Malus domestica) oligopeptide transporter3 (MdOPT3) mRNA can be transported over a long distance, from the leaf to the root, to regulate iron uptake; however, the mRNA of Arabidopsis (Arabidopsis thaliana) oligopeptide transporter 3 (AtOPT3), the MdOPT3 homolog from A. thaliana, does not move from shoot to root. Reciprocal heterologous expression of the two types of mRNAs showed that the immobile AtOPT3 became mobile and moved from the shoot to the root in two woody species, Malus and Populus, while the mobile MdOPT3 became immobile in two herbaceous species, A. thaliana and tomato (Solanum lycopersicum). Furthermore, we demonstrated that the different transmissibility of OPT3 in A. thaliana and Malus might be caused by divergence in RNA-binding proteins between herbaceous and woody plants. This study provides insights into mechanisms underlying differences in mRNA mobility and validates the important physiological functions associated with this process.
CRISPR/Cas9 mutants of tomato MICRORNA164 genes uncover their functional specialization in development
Authors: Gupta Suresh Kumar , Vishwakarma Abhaypratap , Kenea Hawi Deressa , Galsurker Ortal , Cohen Hagai , Aharoni Asaph , Arazi Tzahi
Published: August 2021

Plant MICRORNA164 (miR164) plays diverse regulatory functions by post-transcriptional repression of certain NAM/ATAF/CUC-domain transcription factors. However, the involvement of miR164 in fleshy fruit development and ripening remains poorly understood. Here, de novo prediction of tomato (Solanum lycopersicum) MIR164 genes identified four genes (SlMIR164a-d), of which SlMIR164d has an atypically long pre-miRNA. The roles of the fruit expressed SlMIR164a, b, and d were studied by analysis of their Clustered Regularly Interspaced Short Palindromic Repeats mutants. The slmir164bCR mutant plants exhibited shoot and flower abnormalities characteristic of ectopic boundary specification, whereas the shoot and flower development of slmir164aCR and slmir164dCR mutants were indistinguishable from wild-type. Strikingly, the knockout of SlMIR164a practically eliminated sly-miR164 from the developing and ripening fruit pericarp. The sly-miR164-deficient slmir164aCR fruits were smaller than the wild-type, due to reduced pericarp cell division and expansion, and displayed intense red color and matte, instead of glossy appearance, upon ripening. We found that the fruit skin phenotypes were associated with morphologically abnormal outer epidermis and thicker cuticle. Quantitation of sly-miR164 target transcripts in slmir164aCR ripening fruits demonstrated the upregulation of SlNAM3 and SlNAM2. Specific expression of their miR164-resistant versions in the pericarp resulted in the formation of extremely small fruits with abnormal epidermis, highlighting the importance of their negative regulation by sly-miR164a. Taken together, our results demonstrate that SlMIR164a and SlMIR164b play specialized roles in development: SlMIR164b is required for shoot and flower boundary specification, and SlMIR164a is required for fruit growth including the expansion of its outer epidermis, which determines the properties of the fruit skin.
Enzyme engineering and in vivo testing of a formate reduction pathway
Authors: Wang Jue , Anderson Karl , Yang Ellen , He Lian , Lidstrom Mary E
Published: August 2021

Formate is an attractive feedstock for sustainable microbial production of fuels and chemicals, but its potential is limited by the lack of efficient assimilation pathways. The reduction of formate to formaldehyde would allow efficient downstream assimilation, but no efficient enzymes are known for this transformation. To develop a 2-step formate reduction pathway, we screened natural variants of acyl-CoA synthetase (ACS) and acylating aldehyde dehydrogenase (ACDH) for activity on one-carbon substrates and identified active and highly expressed homologs of both enzymes. We then performed directed evolution, increasing ACDH-specific activity by 2.5-fold and ACS lysate activity by 5-fold. To test for the in vivo activity of our pathway, we expressed it in a methylotroph which can natively assimilate formaldehyde. Although the enzymes were active in cell extracts, we could not detect formate assimilation into biomass, indicating that further improvement will be required for formatotrophy. Our work provides a foundation for further development of a versatile pathway for formate assimilation.
The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the spike protein
Authors: Resende Paola Cristina , Naveca Felipe G , Lins Roberto D , Dezordi Filipe Zimmer , Ferraz Matheus V. F , Moreira Emerson G , Coêlho Danilo F , Motta Fernando Couto , Paixão Anna Carolina Dias , Appolinario Luciana , Lopes Renata Serrano , Mendonça Ana Carolina da Fonseca , da Rocha Alice Sampaio Barreto , Nascimento Valdinete , Souza Victor , Silva George , Nascimento Fernanda , Neto Lidio Gonçalves Lima , da Silva Fabiano Vieira , Riediger Irina , Debur Maria do Carmo , Leite Anderson Brandao , Mattos Tirza , da Costa Cristiano Fernandes , Pereira Felicidade Mota , dos Santos Cliomar Alves , Rovaris Darcita Buerger , Fernandes Sandra Bianchini , Abbud Adriano , Sacchi Claudio , Khouri Ricardo , Bernardes André Felipe Leal , Delatorre Edson , Gräf Tiago , Siqueira Marilda Mendonça , Bello Gonzalo , Wallau Gabriel L
Published: August 2021

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.1 lineages bearing NTD indels ∆69-70 (which can impact several SARS-CoV-2 diagnostic protocols), ∆144 and ins214ANRN, and a new VOI N.10 derived from the B.1.1.33 lineage carrying three NTD deletions (∆141–144, ∆211, and ∆256–258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil generates new viral lineages that might be more resistant to antibody neutralization than parental variants of concern.
Relationship Between Umbilical Cord Gas Values and Neonatal Outcomes
Authors: Johnson Grace J. , Salmanian Bahram , Denning Stacie G. , Belfort Michael A. , Sundgren Nathan C. , Clark Steven L.
Published: August 2021

OBJECTIVE:

To evaluate the relationship between umbilical artery cord gas values and fetal tolerance of labor, as reflected by Apgar score. We hypothesized the existence of wide biological variability in fetal tolerance of metabolic acidemia, which, if present, would weaken one fundamental assumption underlying the use of electronic fetal heart rate (FHR) monitoring.

METHODS:

We conducted a retrospective cohort study of term, singleton, nonanomalous fetuses delivered in our institution between March 2012 and July 2020. Universally obtained umbilical cord gas values and Apgar scores were extracted. We calculated Spearman correlation coefficients and receiver operating characteristic curves for various levels of umbilical artery pH, base excess, and Apgar scores.

RESULTS:

We analyzed data from 29,787 deliveries. The statistical correlation between umbilical artery pH and base excess and both 1- and 5-minute Apgar scores was weak or nonexistent in all pH range subgroups (range 0.064–0.213). Receiver operating characteristic curve analysis suggested umbilical artery pH value of 7.22 yields the best discrimination for prediction of a severely depressed newborn (5-minute Apgar score less than 4), but sensitivity and specificity for this predictive value remains poor to moderate.

CONCLUSION:

The use of electronic FHR monitoring is predicated on a documented relationship between FHR patterns and umbilical artery pH, and an assumed correlation between pH and fetal outcomes, reflecting fetal tolerance of labor and delivery. Our data demonstrate a weak-to-absent correlation between metabolic acidemia and even short-term fetal condition, thus significantly weakening this latter assumption. No amount of future modification of FHR pattern interpretation to better predict newborn pH is likely to lead to improved newborn outcomes, given this weakness in a fundamental assumption on which FHR monitoring is based.
Patient Experiences of Telemedicine in Spine Care
Authors: Lightsey Harry M. , Yeung Caleb M. , Bernstein David N. , Sumathipala Marissa G. , Chen Antonia F. , Schoenfeld Andrew J. , Makhni Melvin C.
Published: August 2021

Study Design.

Survey-based study.

Objective.

We performed a mixed methods study involving patients using telemedicine for spine care. We sought to understand factors influencing the utilization and evaluation of this modality.

Summary of Background Data.

Telemedicine has been integrated into routine spine care; its long-term viability will depend not only on optimizing its safety, efficiency, and cost-effectiveness, but also on understanding patient valuation of its benefits and limitations.

Methods.

We used a clinical registry to identify spine patients seen virtually by providers at our tertiary academic medical center between March and September of 2020. We distributed an online survey that queried patients’ experiences with telemedicine. We performed statistical analyses of Likert-scale questions and a thematic analysis of free-form responses. Sociodemographic data were abstracted and analyzed.

Results.

Overall, we evaluated 139 patient surveys. High levels of patient-rated care and patient-rated experience were observed for both in-person and telemedicine visits; however, in-person visits were rated significantly higher in both respects (9.3/10 vs. 8.7/10 for patient-rated care, P < 0.001; 9.0/10 vs. 8.4/10 for patient-rated experience, P = 0.006). A preference for in-person first-time visits was observed which was not maintained for follow up appointments. Both patient and clinical factors influenced perceptions of telemedicine. Thematic analysis of free-form responses provided by 113 patients (81%) generated favorable, unfavorable, and reflective themes, each further contextualized by subthemes. Responders were not significantly different from nonresponders across sociodemographic characteristics.

Conclusion.

Our quantitative and qualitative findings yield insight into the patient experience of telemedicine in spine care. A preference for in-person visits was notable, particularly for new patient evaluations. This preference was not maintained for follow-up care. Patients acknowledged the benefits of telemedicine and reflected on its effective integration with in-person care. These results may guide best practices to improve access and patient satisfaction in the future.

Level of Evidence: 4
What management for epidermal growth factor receptor-mutated non–small-cell lung cancer, with squamous cell transformation and T790M-acquired resistance mechanisms? A Case report and review of literature
Authors: Helissey Carole , Favre Loetitia , Nguyen Anh Tuan , Mamou Elodie , Lamboley Jean-Laurent
Published: August 2021

Histological transformation into squamous cell carcinoma (SCC) is a rare mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Its pathophysiology remains unclear and its management is particularly challenging. We report on tumor progression with SCC histological transformation associated with the T790M mutation in a patient with stage IV bronchial adenocarcinoma with an L858R mutation of the EGFR gene and treated with gefitinib. We will discuss the importance of liquid and tumor biopsy in the diagnostic management of resistance mechanisms as well as therapeutic management options.
HBsAg Loss Due to Tenofovir Treatment for HBV Reactivation Following DAAs Therapy in One Patient with HBV-HCV Coinfection
Authors: He Dan-Dan , Li Wei-Zhe , Huang Shuo , Zhang Li-Ping , Li Jing-Jing , Zeng Zhao-Hai , Yu Zu-Jiang , Zeng Qing-Lei
Published: August 2021

Hepatitis B virus (HBV) reactivation induced by administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported in previous studies, the subsequent clinical outcomes varied from no symptom to liver failure or death, however, the timing of anti-HBV treatment is controversial. We report the clinical HBV reactivation in a 51 years old female fibrotic patient with chronic HBV-HCV infection during the paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) therapy. Her baseline HCV RNA, HBV DNA, alanine aminotransferase (ALT), and liver stiffness measurement levels were 5,560,000 IU/mL, <15 IU/mL, 48 U/L, and 11.8 kPa, respectively. At 8 weeks of PrOD treatment, her HCV RNA, HBV DNA, and ALT levels were <15 IU/mL, 2,880,000 IU/mL, and 837 U/L, respectively, and clinical reactivation was diagnosed. Meanwhile, tenofovir was immediately used for anti-HBV treatment. Fortunately, HBV DNA and ALT were undetectable and normalized after 16 weeks of anti-HBV therapy, and unexpectedly, hepatitis B surface antigen loss occurred at 80 weeks of anti-HBV treatment. This study may extend our understanding of the timing of anti-HBV therapy to prevent potential HBV reactivation during DAAs treatment in HBV-HCV coinfected patients, and proper initiation timing may lead to functional cure of chronic HBV infection.
Infantile ATP7B-Related End-Stage Liver Disease: An Exceptional Wilson Disease Phenotype From Consecutive Generations
Authors: Nicastro Emanuele , Iascone Maria , Di Giorgio Angelo , Brecelj Jernej , Petruzzelli Raffaella , Polishchuk Roman S. , Deheragoda Maesha , Wagner Bart E. , Sonzogni Aurelio , Bonanomi Ezio , D’Antiga Lorenzo
Published: August 2021

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism typically presenting after 3 years of age. We describe a girl presenting with neonatal cholestasis rapidly progressing to end-stage liver disease. She presented hepatosplenomegaly, neurological impairment, Coombs-negative hemolytic anemia, central hypothyroidism. A patient-parents whole exome sequencing identified a homozygous state for ATP7B mutations causing WD in the proband (p.Gln7fs/p.His1069Gln) and her mother (p.His1069Gln/p.His1069Gln), who was then confirmed to have cirrhotic WD. A causative role of copper toxicity due to ATP7B loss of function was indicated by the presence of extrahepatic features of WD, consistent tests of copper metabolism—including a 7-fold increase in liver copper—and similarity of patient’s liver gene expression profile and ultrastructure with that of WD models. This exceptionally early presentation could result from the combination of the ATP7B impairment and the intrauterine copper overload due to maternal undiagnosed WD.