bluuebunny/crossref_metadata_2025 huggingface dataset:
Progressive involvement of cardiac conduction system in paediatric patients with Kearns–Sayre syndrome: how to predict occurrence of complete heart block and sudden cardiac death?
Authors: Di Mambro Corrado , Tamborrino Pietro Paolo , Silvetti Massimo Stefano , Yammine Marie Laure , Marcolin Cecilia , Righi Daniela , Baban Anwar , Martinelli Diego , Dionisi Vici Carlo , Drago Fabrizio
Published: October 2020

Aims

The aims of this study are to evaluate the progressive involvement of the cardiac conduction system in the Kearn–Sayre syndrome (KSS) and to establish criteria for the prevention of episodes of syncope or sudden cardiac death.

Methods and results

This is a prospective monocentric study including KSS patients, with diagnosis based on clinical manifestations, muscle biopsy, and genetic tests, before the age of 18. All patients underwent cardiac screening examination with 12-lead electrocardiogram (ECG), 24-h Holter monitoring, and pacemaker (PM) interrogation twice a year. Fifteen patients (nine males, mean age 16.6 ± 3.9 years) with a sporadic KSS were recruited. All subjects manifested at least one of the intraventricular conduction defects (IVDs): 1 right bundle branch block (RBBB), 2 left anterior fascicular block (LAFB), 11 a bi-fascicular block (RBBB + LAFB), and 1 left posterior fascicular block. Most children with bi-fascicular block developed LAFB before the RBBB (P = 0.0049). In six patients, IVD degenerated into atrioventricular block (AVB). Endocavitary PM was implanted in 11 patients (6 with AVB and 5 with a bi-fascicular block), while an implantable cardioverter-defibrillator only in one patient with a non-sustained ventricular tachycardia. Four died at mean age of 14.7 ± 2.6 years, but none of them suddenly.

Conclusion

Even a ‘simple’ ECG can predict the arrhythmic risk and the occurrence of catastrophic events in young patients with KSS. Left anterior fascicular block precedes RBBB in determining the bi-fascicular block and this can predict an inexorable progression of the conduction defects even in a short time. Pacemaker implantation may be indicated in these patients since the first bi-fascicular block manifestation.
Comparison of SARS-CoV-2 RT-PCR on a high-throughput molecular diagnostic platform and the cobas SARS-CoV-2 test for the diagnostic of COVID-19 on various clinical samples
Authors: Opota Onya , Brouillet René , Greub Gilbert , Jaton Katia
Published: October 2020

Objectives:In order to cope with the rapid spread of the COVID-19 pandemic, we introduced on our in-house high-throughput molecular diagnostic platform (MDx Platform) a real-time reverse transcriptase PCR (RT-PCR) to detect the SARS-CoV-2 from any clinical specimens. The aim of this study was to compare the RT-PCR results obtain with the MDx Platform and the commercial assay cobas SARS-CoV-2 (Roche) on nasopharyngeal swab and other clinical specimens including sputum, bronchial aspirate, bronchoalveolar lavage and anal swabs. Methods: Samples received in our laboratory from patients suspected of COVID-19 (n = 262) were tested in parallel with our MDx platform SARS-CoV-2 PCR and with the cobas SARS-CoV-2 test. Results: The overall agreement between the two tests for all samples tested was 99.24% (260/262), which corresponded to agreements of 100% (178/178) on nasopharyngeal swabs, 95.45% (42/44) on lower respiratory tract specimen with discordant resultS obtained for very high cycle threshold (Ct) value and 100% (40/40) on anorectal swabs. The Ct values for nasopharyngeal swabs displayed an excellent correlation (R2 > 96%) between both tests. Conclusions: The high agreements between the cobas SARS-CoV-2 test and the MDx platform supports the use of both methods for the diagnostic of COVID-19 on various clinical samples. Very few discrepant results may occur at very low viral load.
Integration
à tout prix
: Islam, Islamism, and the Hijab in Yamina Benguigui’s
Aïcha
Authors: Bouamer Siham
Published: October 2020

This study examines the depiction of Islam in
Aïcha
, Yamina Benguigui’s series of
téléfilms
released between 2009 and 2012 on the French public television channel, France 2
.
While this specific cultural production offers promising possibilities for the renewal of the representation of Maghrebi-French young people in mainstream media, the study argues that Benguigui fails to differentiate Islam from radical Islamism in her discussion of a successful model of integration. Specifically, it aims to unpack the representation of the politics of the hijab through the heroine, Aïcha. It demonstrates that she serves as an agent who cultivates the conflation of religion with fundamentalism, which ultimately nurtures a fear of the presence of Muslims in France.
Internal structure of the San Jacinto fault zone at the Ramona Reservation, north of Anza, California, from dense array seismic data
Authors: Qin Lei , Share Pieter-Ewald , Qiu Hongrui , Allam Amir A , Vernon Frank L , Ben-Zion Yehuda
Published: October 2020

We image the internal structure of the San Jacinto fault zone (SJFZ) near Anza, California, with seismic data recorded by two dense arrays (RA and RR) from ∼42 000 local and ∼180 teleseismic events occurring between 2012 and 2017. The RA linear array has short aperture (∼470 m long with 12 strong motion sensors) and recorded for the entire analysed time window, whereas the RR is a large three-component nodal array (97 geophones across a ∼2.4 km × 1.4 km area) that operated for about a month in September–October 2016. The SJFZ at the site contains three near-parallel surface traces F1, F2 and F3 from SW to NE that have accommodated several Mw > 6 earthquakes in the past 15 000 yr. Waveform changes in the fault normal direction indicate structural discontinuities that are consistent with the three fault surface traces. Relative slowness from local events and delay time analysis of teleseismic arrivals in the fault normal direction suggest a slower SW side than the NE with a core damage zone between F1 and F2. This core damage zone causes ∼0.05 s delay at stations RR26–31 in the teleseismic P arrivals compared with the SW-most station, and generates both P- and S-type fault zone trapped waves. Inversion of S trapped waves indicates the core damaged structure is ∼100 m wide, ∼4 km deep with a Q value of ∼20 and 40 per cent S-wave velocity reduction compared with bounding rocks. Fault zone head waves observed at stations SW of F3 indicate a local bimaterial interface that separates the locally faster NE block from the broad damage zone in the SW at shallow depth and merges with a deep interface that separates the regionally faster NE block from rocks to the SW with slower velocities at greater depth. The multiscale structural components observed at the site are related to the geological and earthquake rupture history at the site, and provide important information on the preferred NW propagation of earthquake ruptures on the San Jacinto fault.
Antisemitism in the “Jewish NKVD” in Soviet Ukraine on the Eve of World War II
Authors: Viola Lynne
Published: October 2020

Following the German invasion of the USSR on June 22, 1941, murderous violence against local Jews broke out in many localities of the territories it had occupied in the wake of the 1939 Soviet-German Non-Aggression Pact. In particular, organizers demanded revenge for the recent Stalinist repressions and deportations. Participants claimed that the “Jewish Soviet state,” the “Jewish NKVD,” or local Jews had been responsible for those crimes. Even now, the legend of prewar Jewish responsibility figures in the dubious “double genocide” thesis animating nationalistic historiographies in Eastern Europe and its international diasporas. The following study counters that mythology, addressing the story of actual Jews in the NKVD at the end of the 1930s. It draws on the archives of the Ukrainian security services, especially records that document Stalin’s effort to divert blame for the recent Great Terror onto senior and mid-level officials. Stalin’s green light to criticize the bosses gave other NKVD officers the opportunity to address many issues, including that of antisemitism among NKVD cadres. These sources suggest that antisemitism was in fact a potent force within the NKVD in Ukraine and elsewhere.
“For the Eradication of Polish and Jewish-Muscovite Rule in Ukraine”: An Examination of the Crimes of the Ukrainian Legion of Self-Defense
Authors: Radchenko Yuri , Usach Andrii
Published: October 2020

This study examines the German-sponsored Ukrainian Legion of Self-Defense (Ukrains’kyi Legion Samooborony, ULS), both its rank and file and its Ukrainian and German officers. Drawing upon sources in German, Ukrainian, American, and Israeli archives, the authors analyze the Legion’s command structure, its relationship to the Third Reich, and its relationship to the Organization of Ukrainian Nationalists branch led by Andriy Atansovich Mel’nyk. The presentation of the political and military careers of lower-, mid-, and upper-level Legionnaires reveals their participation in killings of Jews, Poles, and other Ukrainians. The authors also identify the motivations of many of the actors. A close analysis of one case of German and Ukrainian “cooperation” in the Holocaust and other mass murders, this article relates to the debate over whether Holocaust perpetrators were “Ordinary Men.”
Operation Reinhard in District Galicia: Three Levels of Narrative about the Holocaust
Authors: Wylegała Anna
Published: October 2020

Utilizing a variety of evidentiary sources, this article identifies and applies three different levels of narrative of the history of Operation Reinhard in the District of Galicia, revealing the potential benefits and limitations to each approach. Level one applies a macro-historical narrative that looks to broader statistical and data-driven trends. The second level identifies common shared experiences and general conclusions derived from individual experiences, and level three explores the microhistories of particular towns, families, and individuals. The author suggests a better way to comprehend the range of victim, bystander, and perpetrator experiences, and to more fully depict the scope of a major genocidal operation.
Cayley Graphs Without a Bounded Eigenbasis
Authors: Sah Ashwin , Sawhney Mehtaab , Zhao Yufei
Published: October 2020

Does every $n$-vertex Cayley graph have an orthonormal eigenbasis all of whose coordinates are $O(1/\sqrt{n})$? While the answer is yes for abelian groups, we show that it is no in general. On the other hand, we show that every $n$-vertex Cayley graph (and more generally, vertex-transitive graph) has an orthonormal basis whose coordinates are all $O(\sqrt{\log n / n})$, and that this bound is nearly best possible. Our investigation is motivated by a question of Assaf Naor, who proved that random abelian Cayley graphs are small-set expanders, extending a classic result of Alon–Roichman. His proof relies on the existence of a bounded eigenbasis for abelian Cayley graphs, which we now know cannot hold for general groups. On the other hand, we navigate around this obstruction and extend Naor’s result to nonabelian groups.
Bounds for Elimination of Unknowns in Systems of Differential-Algebraic Equations
Authors: Ovchinnikov Alexey , Pogudin Gleb , Vo Thieu N
Published: October 2020

Elimination of unknowns in systems of equations, starting with Gaussian elimination, is a problem of general interest. The problem of finding an a priori upper bound for the number of differentiations in elimination of unknowns in a system of differential-algebraic equations (DAEs) is an important challenge, going back to Ritt (1932). The first characterization of this via an asymptotic analysis is due to Grigoriev’s result (1989) on quantifier elimination in differential fields, but the challenge still remained. In this paper, we present a new bound, which is a major improvement over the previously known results. We also present a new lower bound, which shows asymptotic tightness of our upper bound in low dimensions, which are frequently occurring in applications. Finally, we discuss applications of our results to designing new algorithms for elimination of unknowns in systems of DAEs.
Risk factors associated with medication ordering errors
Authors: Abraham Joanna , Galanter William L , Touchette Daniel , Xia Yinglin , Holzer Katherine J , Leung Vania , Kannampallil Thomas
Published: October 2020

Objective

We utilized a computerized order entry system–integrated function referred to as “void” to identify erroneous orders (ie, a “void” order). Using voided orders, we aimed to (1) identify the nature and characteristics of medication ordering errors, (2) investigate the risk factors associated with medication ordering errors, and (3) explore potential strategies to mitigate these risk factors.

Materials and Methods

We collected data on voided orders using clinician interviews and surveys within 24 hours of the voided order and using chart reviews. Interviews were informed by the human factors–based SEIPS (Systems Engineering Initiative for Patient Safety) model to characterize the work systems–based risk factors contributing to ordering errors; chart reviews were used to establish whether a voided order was a true medication ordering error and ascertain its impact on patient safety.

Results

During the 16-month study period (August 25, 2017, to December 31, 2018), 1074 medication orders were voided; 842 voided orders were true medication errors (positive predictive value = 78.3 ± 1.2%). A total of 22% (n = 190) of the medication ordering errors reached the patient, with at least a single administration, without causing patient harm. Interviews were conducted on 355 voided orders (33% response). Errors were not uniquely associated with a single risk factor, but the causal contributors of medication ordering errors were multifactorial, arising from a combination of technological-, cognitive-, environmental-, social-, and organizational-level factors.

Conclusions

The void function offers a practical, standardized method to create a rich database of medication ordering errors. We highlight implications for utilizing the void function for future research, practice and learning opportunities.
Development and Validation of an Analytical Method for Volatiles with Endogenous Production in Putrefaction and Submersion Situations
Authors: Pinto Mélanie , Eusébio Ermelinda , Monteiro Carla
Published: October 2020

A group of 16 volatile substances (ethyl acetate, 2-propanol, 1-propanol, methanol, acetone, ethanol, acetaldehyde, diethyl ether, methyl ethyl ketone, 1-butanol, 2-butanol, t-butanol, isobutanol, 2-methyl-1-butanol, 3-methyl-1-butanol and 1-pentanol) were qualitatively and quantitatively analyzed through a method developed for volatiles with endogenous production in putrefaction and submersion situations. The method was validated for blood, urine and vitreous humor, using a gas chromatograph (Varian 450-GC) with a flame ionization detector coupled to a headspace injector (HS-GC–FID). The vials were prepared by diluting 100 µL of the sample of interest in 1 mL of internal standard (acetonitrile 100 mg/L), using two capillary columns (VF-624ms and VF-5ms) with different polarities to ensure that all test compounds would be properly identified and undoubtedly distinguished from the rest. All volatiles were studied in a range of 50 to 2,000 mg/L in terms of selectivity/specificity, detection and quantification limits, linearity and calibration model, precision, accuracy, bias, robustness and stability according to the Scientific Working Group for Forensic Toxicology. Detection and quantification limits were between 1 to 8 mg/L and 4 to 24 mg/L, respectively, with coefficient of variation values under 10% in bias studies and in intermediate precision studies for most substances. The developed method was applied to real cases to test the method.
Giant otter diet differs between habitats and from fisheries offtake in a large Neotropical floodplain
Authors: Leuchtenberger Caroline , Rheingantz Marcelo L , Zucco Carlos A , Catella Agostinho C , Magnusson William E , Mourão Guilherme
Published: October 2020

Giant otters Pteronura brasiliensis are semiaquatic mammals that mainly eat fish, the abundance of which is affected by seasonal flooding and habitat structure. The piscivorous habits of giant otters lead to negative human perception and conflicts with fisheries. We compared giant otter feeding habits between seasons and habitats in the Southern Pantanal, Brazil, by analyzing feces collected between September 2008 and June 2011.We investigated whether habitat and season affected P. brasiliensis diet composition and prey size. We calculated the frequency of occurrence, relative frequency, and overlap of fish species eaten by giant otters and caught by fishermen. The giant otters had a more diverse assemblage of fish prey than the offtake in the fisheries. We did not find strong seasonality in otter diets, but diet composition and prey size differed between rivers and lakes. The giant otter diet had higher overlap with the offtake of sport than with professional fishermen. Although the otters’ piscivorous diet often leads to negative perceptions by humans, the low overlap between otter diet and species taken in local fisheries suggests that otters have little effect on the commercial fishery. These results indicate that educational programs could be used to reduce perceived conflict between giant otters and fishermen.
Triple P for Parents of Children with Phenylketonuria: A Nonrandomized Trial
Authors: Mitchell Amy E , Morawska Alina , Kirby Grace , McGill James , Coman David , Inwood Anita
Published: October 2020

Objective

Families of children with phenylketonuria (PKU) report child emotional and behavioral problems, parenting stress, and parenting difficulties, which are associated with worse health-related quality of life. This study aimed to examine acceptability and feasibility of a brief, group-based parenting program (Healthy Living Triple P) for families of children with PKU.

Methods

An uncontrolled nonrandomized trial design was used. Families of children aged 2–12 years (N = 17) completed questionnaire measures assessing child behavior and impact of PKU on quality of life (primary outcomes), and parenting behavior, self-efficacy and stress, and children’s behavioral and emotional adjustment (secondary outcomes). Routinely collected blood phenylalanine (Phe) levels were obtained from the treating team. Parents selected two child behaviors as targets for change. The intervention comprised two, 2-hr group sessions delivered face-to-face or online. Assessment was repeated at 4-week postintervention (T2) and 4-month follow-up (T3).

Results

Attrition was low and parent satisfaction with the intervention (face-to-face and online) was high. All families achieved success with one or both child behavior goals, and 75% of families achieved 100% success with both behavior goals by T3; however, there was no change in health-related quality of life. There were moderate improvements in parent-reported ineffective parenting (total score, d = 0.87, 95% CI −1.01 to 2.75) and laxness (d = 0.59, 95% CI −1.27 to 2.46), but no effects on parenting stress or children’s adjustment. Phe levels improved by 6month post-intervention for children with elevated preintervention levels.

Conclusions

Results support intervention acceptability and feasibility. A randomized controlled trial is warranted to establish intervention efficacy.
Nitric oxide affects seed oil accumulation and fatty acid composition through proteinS-nitrosation
Authors: Liu Jing , Zhu Xiao-Yi , Deng Lin-Bin , Liu Hong-Fang , Li Jun , Zhou Xue-Rong , Wang Han-Zhong , Hua Wei
Published: October 2020

Nitric oxide (NO) is a key signaling molecule regulating several plant developmental and stress responses. Here, we report that NO plays an important role in seed oil content and fatty acid composition. RNAi silencing of Arabidopsis S-nitrosoglutathione reductase 1 (GSNOR1) led to reduced seed oil content. In contrast, nitrate reductase double mutant nia1nia2 had increased seed oil content, compared with wild-type plants. Moreover, the concentrations of palmitic acid (C16:0), linoleic acid (C18:2), and linolenic acid (C18:3) were higher, whereas those of stearic acid (C18:0), oleic acid (C18:1), and arachidonic acid (C20:1) were lower, in seeds of GSNOR1 RNAi lines. Similar results were obtained with rapeseed embryos cultured in vitro with the NO donor sodium nitroprusside (SNP), and the NO inhibitor NG-Nitro-L-arginine Methyl Ester (L-NAME). Compared with non-treated embryos, the oil content decreased in SNP-treated embryos, and increased in L-NAME-treated embryos. Relative concentrations of C16:0, C18:2 and C18:3 were higher, whereas C18:1 concentration decreased in rapeseed embryos treated with SNP. Proteomics and transcriptome analysis revealed that three S-nitrosated proteins and some key genes involved in oil synthesis, were differentially regulated in SNP-treated embryos. Therefore, regulating NO content could be a novel approach to increasing seed oil content in cultivated oil crops.
How accurately can we detect the splashback radius of dark matter haloes and its correlation with accretion rate?
Authors: Xhakaj Enia , Diemer Benedikt , Leauthaud Alexie , Wasserman Asher , Huang Song , Luo Yifei , Adhikari Susmita , Singh Sukhdeep
Published: October 2020

The splashback radius (Rsp) of dark matter haloes has recently been detected using weak gravitational lensing and cross-correlations with galaxies. However, different methods have been used to measure Rsp and to assess the significance of its detection. In this paper, we use simulations to study the precision and accuracy to which we can detect the splashback radius with 3D density, 3D subhalo, and weak lensing profiles. We study how well various methods and tracers recover Rsp by comparing it with the value measured directly from particle dynamics. We show that estimates of Rsp from density and subhalo profiles correspond to different percentiles of the underlying Rsp distribution of particle orbits. At low accretion rates, a second caustic appears and can bias results. Finally, we show that upcoming lensing surveys may be able to constrain the Rsp–Γdyn relation directly.
Deblending galaxies with variational autoencoders: A joint multiband, multi-instrument approach
Authors: Arcelin Bastien , Doux Cyrille , Aubourg Eric , Roucelle Cécile ,   (The LSST Dark Energy Science Collaboration)
Published: October 2020

Blending of galaxies has a major contribution in the systematic error budget of weak-lensing studies, affecting photometric and shape measurements, particularly for ground-based, deep, photometric galaxy surveys, such as the Rubin Observatory Legacy Survey of Space and Time (LSST). Existing deblenders mostly rely on analytic modelling of galaxy profiles and suffer from the lack of flexible yet accurate models. We propose to use generative models based on deep neural networks, namely variational autoencoders (VAE), to learn probabilistic models directly from data. We train a VAE on images of centred, isolated galaxies, which we reuse, as a prior, in a second VAE-like neural network in charge of deblending galaxies. We train our networks on simulated images including six LSST bandpass filters and the visible and near-infrared bands of the Euclid satellite, as our method naturally generalizes to multiple bands and can incorporate data from multiple instruments. We obtain median reconstruction errors on ellipticities and r-band magnitude between ±0.01 and ±0.05, respectively, in most cases, and ellipticity multiplicative bias of 1.6 per cent for blended objects in the optimal configuration. We also study the impact of decentring and prove the method to be robust. This method only requires the approximate centre of each target galaxy, but no assumptions about the number of surrounding objects, pointing to an iterative detection/deblending procedure we leave for future work. Finally, we discuss future challenges about training on real data and obtain encouraging results when applying transfer learning.
Pfam: The protein families database in 2021
Authors: Mistry Jaina , Chuguransky Sara , Williams Lowri , Qureshi Matloob , Salazar Gustavo A , Sonnhammer Erik L L , Tosatto Silvio C E , Paladin Lisanna , Raj Shriya , Richardson Lorna J , Finn Robert D , Bateman Alex
Published: October 2020

The Pfam database is a widely used resource for classifying protein sequences into families and domains. Since Pfam was last described in this journal, over 350 new families have been added in Pfam 33.1 and numerous improvements have been made to existing entries. To facilitate research on COVID-19, we have revised the Pfam entries that cover the SARS-CoV-2 proteome, and built new entries for regions that were not covered by Pfam. We have reintroduced Pfam-B which provides an automatically generated supplement to Pfam and contains 136 730 novel clusters of sequences that are not yet matched by a Pfam family. The new Pfam-B is based on a clustering by the MMseqs2 software. We have compared all of the regions in the RepeatsDB to those in Pfam and have started to use the results to build and refine Pfam repeat families. Pfam is freely available for browsing and download at http://pfam.xfam.org/.
RNAcentral 2021: secondary structure integration, improved sequence search and new member databases
Authors:   RNAcentral Consortium, Sweeney Blake A , Petrov Anton I , Ribas Carlos E , Finn Robert D , Bateman Alex , Szymanski Maciej , Karlowski Wojciech M , Seemann Stefan E , Gorodkin Jan , Cannone Jamie J , Gutell Robin R , Kay Simon , Marygold Steven , dos Santos Gil , Frankish Adam , Mudge Jonathan M , Barshir Ruth , Fishilevich Simon , Chan Patricia P , Lowe Todd M , Seal Ruth , Bruford Elspeth , Panni Simona , Porras Pablo , Karagkouni Dimitra , Hatzigeorgiou Artemis G , Ma Lina , Zhang Zhang , Volders Pieter-Jan , Mestdagh Pieter , Griffiths-Jones Sam , Fromm Bastian , Peterson Kevin J , Kalvari Ioanna , Nawrocki Eric P , Petrov Anton S , Weng Shuai , Bouchard-Bourelle Philia , Scott Michelle , Lui Lauren M , Hoksza David , Lovering Ruth C , Kramarz Barbara , Mani Prita , Ramachandran Sridhar , Weinberg Zasha
Published: October 2020

RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences that provides a single access point to 44 RNA resources and >18 million ncRNA sequences from a wide range of organisms and RNA types. RNAcentral now also includes secondary (2D) structure information for >13 million sequences, making RNAcentral the world’s largest RNA 2D structure database. The 2D diagrams are displayed using R2DT, a new 2D structure visualization method that uses consistent, reproducible and recognizable layouts for related RNAs. The sequence similarity search has been updated with a faster interface featuring facets for filtering search results by RNA type, organism, source database or any keyword. This sequence search tool is available as a reusable web component, and has been integrated into several RNAcentral member databases, including Rfam, miRBase and snoDB. To allow for a more fine-grained assignment of RNA types and subtypes, all RNAcentral sequences have been annotated with Sequence Ontology terms. The RNAcentral database continues to grow and provide a central data resource for the RNA community. RNAcentral is freely available at https://rnacentral.org.
Determinants of correlated expression of transcription factors and their target genes
Authors: Zaborowski Adam B , Walther Dirk
Published: October 2020

While transcription factors (TFs) are known to regulate the expression of their target genes (TGs), only a weak correlation of expression between TFs and their TGs has generally been observed. As lack of correlation could be caused by additional layers of regulation, the overall correlation distribution may hide the presence of a subset of regulatory TF–TG pairs with tight expression coupling. Using reported regulatory pairs in the plant Arabidopsis thaliana along with comprehensive gene expression information and testing a wide array of molecular features, we aimed to discern the molecular determinants of high expression correlation of TFs and their TGs. TF-family assignment, stress-response process involvement, short genomic distances of the TF-binding sites to the transcription start site of their TGs, few required protein-protein-interaction connections to establish physical interactions between the TF and polymerase-II, unambiguous TF-binding motifs, increased numbers of miRNA target-sites in TF-mRNAs, and a young evolutionary age of TGs were found particularly indicative of high TF–TG correlation. The modulating roles of post-transcriptional, post-translational processes, and epigenetic factors have been characterized as well. Our study reveals that regulatory pairs with high expression coupling are associated with specific molecular determinants.
Benchmarking and integrating genome-wide CRISPR off-target detection and prediction
Authors: Yan Jifang , Xue Dongyu , Chuai Guohui , Gao Yuli , Zhang Gongchen , Liu Qi
Published: October 2020

Systematic evaluation of genome-wide Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) off-target profiles is a fundamental step for the successful application of the CRISPR system to clinical therapies. Many experimental techniques and in silico tools have been proposed for detecting and predicting genome-wide CRISPR off-target profiles. These techniques and tools, however, have not been systematically benchmarked. A comprehensive benchmark study and an integrated strategy that takes advantage of the currently available tools to improve predictions of genome-wide CRISPR off-target profiles are needed. We focused on the specificity of the traditional CRISPR SpCas9 system for gene knockout. First, we benchmarked 10 available genome-wide off-target cleavage site (OTS) detection techniques with the published OTS detection datasets. Second, taking the datasets generated from OTS detection techniques as the benchmark datasets, we benchmarked 17 available in silico genome-wide OTS prediction tools to evaluate their genome-wide CRISPR off-target prediction performances. Finally, we present the first one-stop integrated Genome-Wide Off-target cleavage Search platform (iGWOS) that was specifically designed for the optimal genome-wide OTS prediction by integrating the available OTS prediction algorithms with an AdaBoost ensemble framework.
DescribePROT: database of amino acid-level protein structure and function predictions
Authors: Zhao Bi , Katuwawala Akila , Oldfield Christopher J , Dunker A Keith , Faraggi Eshel , Gsponer Jörg , Kloczkowski Andrzej , Malhis Nawar , Mirdita Milot , Obradovic Zoran , Söding Johannes , Steinegger Martin , Zhou Yaoqi , Kurgan Lukasz
Published: October 2020

We present DescribePROT, the database of predicted amino acid-level descriptors of structure and function of proteins. DescribePROT delivers a comprehensive collection of 13 complementary descriptors predicted using 10 popular and accurate algorithms for 83 complete proteomes that cover key model organisms. The current version includes 7.8 billion predictions for close to 600 million amino acids in 1.4 million proteins. The descriptors encompass sequence conservation, position specific scoring matrix, secondary structure, solvent accessibility, intrinsic disorder, disordered linkers, signal peptides, MoRFs and interactions with proteins, DNA and RNAs. Users can search DescribePROT by the amino acid sequence and the UniProt accession number and entry name. The pre-computed results are made available instantaneously. The predictions can be accesses via an interactive graphical interface that allows simultaneous analysis of multiple descriptors and can be also downloaded in structured formats at the protein, proteome and whole database scale. The putative annotations included by DescriPROT are useful for a broad range of studies, including: investigations of protein function, applied projects focusing on therapeutics and diseases, and in the development of predictors for other protein sequence descriptors. Future releases will expand the coverage of DescribePROT. DescribePROT can be accessed at http://biomine.cs.vcu.edu/servers/DESCRIBEPROT/.
Revisiting the organization of Polycomb-repressed domains: 3D chromatin models from Hi-C compared with super-resolution imaging
Authors: Liu Lei , Hyeon Changbong
Published: October 2020

The accessibility of target gene, a factor critical for gene regulation, is controlled by epigenetic fine-tuning of chromatin organization. While there are multiple experimental techniques to study change of chromatin architecture with its epigenetic state, measurements from them are not always complementary. A qualitative discrepancy is noted between recent super-resolution imaging studies, particularly on Polycomb-group protein repressed domains in Drosophila cell. One of the studies shows that Polycomb-repressed domains are more compact than inactive domains and are segregated from neighboring active domains, whereas Hi-C and chromatin accessibility assay as well as the other super-resolution imaging studies paint a different picture. To examine this issue in detail, we analyzed Hi-C libraries of Drosophila chromosomes as well as distance constraints from one of the imaging studies, and modeled different epigenetic domains by employing a polymer-based approach. According to our chromosome models, both Polycomb-repressed and inactive domains are featured with a similar degree of intra-domain packaging and significant intermixing with adjacent active domains. The epigenetic domains explicitly visualized by our polymer model call for extra attention to the discrepancy of the super-resolution imaging with other measurements, although its precise physicochemical origin still remains to be elucidated.
The Cigarette Smoking Initiation and Continuation in Adolescents Undergoing a Long-Term Behavioral Intervention
Authors: Masihay-Akbar Hasti , Amiri Parisa , Cheraghi Leila , Momenan Amir Abbas , Azizi Fereidoun
Published: October 2020

Introduction

Targeting adolescents’ smoking reduces its burden on health systems. We investigated the effects of the first multidisciplinary community-based lifestyle intervention in the Eastern Mediterranean region, on smoking initiation, continuation, and risk of current smoking in Iranian adolescents.

Methods

The current analyses were conducted on 945 nonsmoker adolescents (12–18 years) who participated in Phase II of Tehran Lipid and Glucose Study (TLGS) and were examined four times in 12 years. The lifestyle intervention including school-based and public programs was implemented, focusing on all components of healthy lifestyle. Using a two-step cluster analysis, families were classified as high and low risk, based on parental risk factors of adolescents’ smoking. Participants who failed to complete all the follow-ups (n = 99) and those with missing smoking data were excluded. Subsequently, 872 adolescents (538 control, 334 intervention) were included in the Cox model on smoking initiation, and 674 adolescents (414 control, 260 intervention) were included in the logistic regression on smoking status.

Results

Mean age of adolescents was 15.08 ± 1.94 years at baseline. The hazard of the smoking initiation was significantly lower in the intervention (hazard ratio = 0.71, 95% confidence interval: 0.51–0.99; p = .044) compared with control group. At the end of the fourth follow-up, intervention reduced the odds of current cigarette smoking by 29%. Within the intervention group, the high-risk cluster was at a 35% lower risk of initiating smoking and had 37% lower odds of becoming a current smoker. However, the intervention could not make a difference in preventing those who initiated smoking from maintaining it during the follow-ups.

Conclusions

Our results demonstrate that lifestyle modification programs targeting at-risk populations could reduce risk of smoking initiation and current smoking in adolescents in long term.

Implications

Experiencing cigarette smoking at the critical period of adolescence could result in adulthood habitual smoking. Therefore, identifying adolescents who are more at risk of smoking initiation and implementing targeted interventions are of great importance in public health. Our findings highlight the long-term effectiveness of a multidisciplinary community-based behavioral intervention on forming smoking behaviors in adolescents. The current intervention was successful in reducing smoking uptake in adolescents living in high-risk families.
Fear of Pain Across the Adult Life Span
Authors: Wright Casey D , McNeil Daniel W
Published: October 2020

Background

Pain continues to be an important public health concern, especially given the opioid crisis in industrialized countries. It is important to understand the association between emotions such as fear and anxiety and the experience of pain as both a physiological and affective experience. Fear or anxiety about pain is in fact a well-known predictor of and close associate of pain. Nociception and pain history differ depending on age, yet little empirical evidence exists on how fear of pain varies over the life span. The purpose of this study was to provide a cross-sectional examination of the relations between age and fear of pain across the adult life span.

Methods

Using cross-sectional data from 4,122 participants who completed the Fear of Pain Questionnaire-9, structural equation modeling and regression techniques were used to examine the association between fear of pain and age.

Results

A positive linear association was discovered between age and fear of severe or minor pain, and a negative association was discovered between age and fear of medical or dental pain. Quadratic and cubic relations were also significant for fear of severe pain, fear of medical and dental pain, and overall fear of pain, but not for fear of minor pain.

Conclusions

Unique trajectories for different components of pain-related fear exist across the adult life span and may be affected by increased exposure to medical and dental experiences over time and by the awareness of a greater likelihood of experiencing pain later in the life span.
Policing Reform in the Context of Plural Policing: The South African Case
Authors: Berg Julie
Published: October 2020

Using South African examples, this article explores how legitimacy is constituted amongst state and non-state actors in a highly pluralized context of limited statehood and the implications that this has for policing reform. In particular, it explores the means by which the legitimacy of the state and non-state is relational, co-produced, and co-dependent by focusing on two components of legitimacy: effectiveness and accountability. Given the contextual realities of policing legitimation in pluralized contexts, the article provides a critical appraisal of the challenges for policing reform.
Stochastic Revealed Preferences with Measurement Error
Authors: Aguiar Victor H , Kashaev Nail
Published: October 2020

A long-standing question about consumer behaviour is whether individuals’ observed purchase decisions satisfy the revealed preference (RP) axioms of the utility maximization theory (UMT). Researchers using survey or experimental panel data sets on prices and consumption to answer this question face the well-known problem of measurement error. We show that ignoring measurement error in the RP approach may lead to overrejection of the UMT. To solve this problem, we propose a new statistical RP framework for consumption panel data sets that allows for testing the UMT in the presence of measurement error. Our test is applicable to all consumer models that can be characterized by their first-order conditions. Our approach is non-parametric, allows for unrestricted heterogeneity in preferences and requires only a centring condition on measurement error. We develop two applications that provide new evidence about the UMT. First, we find support in a survey data set for the dynamic and time-consistent UMT in single-individual households, in the presence of nonclassical measurement error in consumption. In the second application, we cannot reject the static UMT in a widely used experimental data set in which measurement error in prices is assumed to be the result of price misperception due to the experimental design. The first finding stands in contrast to the conclusions drawn from the deterministic RP test of Browning (1989, International Economic Review, 979–992). The second finding reverses the conclusions drawn from the deterministic RP test of Afriat (1967, International Economic Review, 8, 6–77) and Varian (1982, Econometrica, 945–973).
Epidemiology of systemic sclerosis in the UK: an analysis of the Clinical Practice Research Datalink
Authors: Pauling John D , McGrogan Anita , Snowball Julia , McHugh Neil J
Published: October 2020

Objectives

We developed and tested a robust case ascertainment strategy within the Clinical Practice Research Datalink (CPRD), with the aim of assessing the incidence, prevalence, mortality and delay in diagnosis of SSc in the UK.

Methods

A two-stage case ascertainment strategy was devised and tested to establish a valid cohort of SSc cases within the CPRD. Incidence, prevalence and mortality statistics were analysed, alongside evaluation of the relationship between primary care codes for RP and SSc to examine diagnostic delay.

Results

SSc Read codes were identified in 3123 patients (from a study cohort of >10.1 million individuals). Of these, 1757 cases of SSc were identified using our case ascertainment approach. The overall incidence rate of SSc over the period between 1999 and 2017 was 10.7/million/year (95% CI: 9.9–11.4), being higher in females [17.69/million/year (95% CI: 16.32–19.07)] than in males [3.59/million/year (95% CI: 2.97–4.21)]. The overall prevalence of SSc in adults was 235.5/million (95% CI: 207.2–245.7). The mean rate of mortality was 32/1000 person-years, with an overall standardized mortality ratio of 3.51 (95% CI: 3.19–3.84). Of those with an initial code of RP prior to a Read code of SSc, 191/854 (22.4%) had a lag period of >10 years.

Conclusion

We have developed and tested a robust case ascertainment strategy to examine the incidence, prevalence, mortality and diagnostic delay of SSc using primary care records of over 10 million UK residents. A significant lag between coding of RP and SSc in many patients suggests diagnostic delay in SSc remains an important unmet need.
Exploring a Safety Signal of Antipsychotic-Associated Pneumonia: A Pharmacovigilance-Pharmacodynamic Study
Authors: Cepaityte Dainora , Siafis Spyridon , Egberts Toine , Leucht Stefan , Kouvelas Dimitrios , Papazisis Georgios
Published: October 2020

An association between antipsychotic drugs and pneumonia has been demonstrated in several studies; however, the risk for pneumonia caused by specific antipsychotics has not been extensively studied. The underlying mechanism is still unknown, and several receptor mechanisms have been proposed. Therefore, using a combined pharmacovigilance-pharmacodynamic approach, we aimed to investigate safety signals of US Food and Drug Administration (FDA)-approved antipsychotics for reporting pneumonia and the potential receptor mechanisms involved. A disproportionality analysis was performed to detect a signal for reporting “infective-pneumonia” and “pneumonia-aspiration” and antipsychotics using reports submitted between 2004 and 2019 to the FDA adverse events spontaneous reporting system (FAERS) database. Disproportionality was estimated using the crude and the adjusted reporting odds ratio (aROR) and its 95% confidence interval (CI) in a multivariable logistic regression. Linear regressions investigated the relationship between aROR and receptor occupancy, which was estimated using in vitro receptor-binding profiles. Safety signals for reporting infective-pneumonia were identified for clozapine (LL = 95% 3.4, n = 546 [aROR: 4.8]) as well as olanzapine (LL = 95% 1.5, n = 250 [aROR: 2.1]) compared with haloperidol, while aRORs were associated with higher occupancies of muscarinic receptors (beta = .125, P-value = .016), yet other anti-muscarinic drugs were not included as potential confounders. No safety signals for reporting pneumonia-aspiration were detected for individual antipsychotics. Multiple antipsychotic use was associated with both reporting infective-pneumonia (LL 95%: 1.1, n = 369 [aROR:1.2]) and pneumonia-aspiration (LL 95%: 1.7, n = 194 [aROR: 2.0]). Considering the limitations of disproportionality analysis, further pharmacovigilance data and clinical causality assessment are needed to validate this safety signal.
Unsettling the Self: the Paradoxes of Narrative Identity in Christian Testimonial Practice
Authors: Hill Graham W
Published: October 2020

Born-again conversion offers the paradoxical promise of self-transcending self-transformation, which takes narrative form when converts attempt to recount their experiences: how to tell a story of self-transformation, in which oneself is neither the author nor the agent of change? Existing scholarship suggests that conversion narratives work insofar as they resolve underlying paradoxes and stitch together a sense of coherent selfhood. This paper tacks in the opposite direction: the analysis focuses on the tendencies of conversion narratives to blur, blend and double over categorical bounds of selfhood, highlighting paradoxes rather than looking for their resolution. The paper contends, therefore, that conversion narrative practices facilitate converts’ experience of conversion, not only insofar as they resolve paradox and stitch together coherent identity, but also insofar as they cultivate ephemeral experiences and explorations of narrative paradoxes that are inherent to—though often hidden from—most any attempt to find and feel identity.
New distribution record of Anopheles rivulorum-like from Sadiola, Mali, with notes on malaria vector insecticide resistance
Authors: Wragge Sue-Ellen , Venter Nelius , Touré Dramane , Hunt Richard H , Coetzee Maureen
Published: October 2020

Background

The SEMOS gold mine in Sadiola, southwestern Mali, has been implementing a malaria vector control programme for 15 y using indoor residual house spraying and sporadic larval control. Periodic screening of the vector populations have been carried out over the years to provide information to the control programme, mainly on vector species present and their insecticide resistance status. The data from five entomological surveys, carried out in 2006, 2011, 2014, 2016 and 2018, are presented.

Methods

Adult mosquitoes were collected resting on walls inside houses and on verandas. Insecticide susceptibility assays were carried out and mosquitoes subsequently identified by species using molecular assays.

Results

The major malaria vector mosquitoes, Anopheles gambiae and Anopheles arabiensis were abundant at each sampling period with Anopheles coluzzii and Anopheles funestus being rare or absent. Anopheles rivulorum was identified in 2006 and Anopheles leesoni in 2016. The presence of Anopheles rivulorum-like, identified for the first time in 2018, was not screened for in previous surveys. Insecticide susceptibility bioassays showed resistance in both A. gambiae and A. arabiensis to pyrethroids, carbamates and dichlorodiphenyltrichloroethane over the 12 y.

Conclusions

This is the first record of A. rivulorum-like west of Côte d'Ivoire. Resistance levels to the three classes of insecticides were variable but appeared to decrease after pyrethroids were discontinued for house spraying.