bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Facial Paralysis Management: A National Survey Study
Authors: Benyo Sarah , Saadi Robert A. , Shokri Tom , Lighthall Jessyka G.
Published: August 2022

Introduction:

Advances in operative management, minimally invasive procedures, and physical therapy have allowed for dramatic improvements in functional and cosmetic outcomes in patients with facial paralysis. Our goal was to evaluate the current trends and practice patterns in the diagnosis and management of facial paralysis by provider demographics.

Materials and Methods:

An electronic questionnaire was distributed to members of the American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS). Practice patterns in the diagnosis and treatment were compared by level of training (fellowship-trained facial plastic and reconstructive surgeon versus non-fellowship trained), practice type (academic and private), practice length, patient volume, and presence of a dedicated facial nerve clinic. The bivariate associations of the outcome variables and the stratification factors were analyzed using 2-way contingency tables and Fisher’s exact tests.

Results:

The survey was sent to 1129 members of the AAFPRS. The response rate was 11.7% (n=132). Most respondents were fellowship-trained surgeons (79%) in the academic setting (55%), and most have been in practice for more than 10 years (53%). Practice setting and patient volume were the factors most associated with significant variations in management, including the use of facial paralysis grading scales, photography/videography, patient-reported outcome metrics, as well as differences in both noninvasive and surgical management.

Conclusion:

Based on the present study, several physician demographic factors may play a role in choosing which diagnostic and treatment options are employed for facial paralysis, with practice setting and patient volume appearing to be the 2 variables associated with the most significant differences.
Effective communication and patient safety among nurses in perioperative settings: a best practice implementation project
Authors: Nedelcu Catalin Marian , Niculiă Oana Otilia , Nedelcu Viorica , Zazu Mariana , Mazilu Doina Carmen , Klugarová Jitka , Klugar Miloslav
Published: August 2022

Objectives:

The aim of this implementation project was to promote evidence-based best practice regarding effective communication and patient safety amongst nurses in perioperative settings.

Introduction:

One of the main causes of surgical errors is inadequate communication. To address this issue, published research has shown that effective communication among healthcare professionals (HCPs) within and between all phases of perioperative care, as well as the proper transfer of all patient information at all transition points, are essential for ensuring patient safety and quality of care.

Methods:

This best practice implementation project was conducted based on the JBI implementation model and included three phases of activity: a baseline audit, a strategies implementation stage and a follow-up audit. The audit criteria used were based on a JBI evidence summary and referred to: education, interdisciplinary team, conflict resolution, team communication, transfer of patient information and safety intraoperative processes. The project was carried out in the perioperative environment of a university hospital, and the sample included 52 nurses.

Results:

Eleven audit criteria were used in the baseline audit. For four of these criteria (on education and information transfer) the compliance was zero, for five criteria (on intraoperative processes) the compliance had values between 31 and 66% and for two criteria (on interdisciplinary team/conflict resolution documentation and team communication monitoring), the identified compliance was maximum (100%). Following the identification of four barriers to compliance and the implementation of targeted strategies, the follow-up audit showed complete compliance (100%) for all criteria except three, for which the identified compliance values were 96, 95 and 25%.

Conclusion:

The implementation of appropriate strategies in this project has led to a significant improvement in nurses’ compliance with all audit criteria except one, regarding the verbal transfer of patient information. However, future audits and strategies are needed not only to support the improvements obtained but also to significantly increase the compliance rate for the audit criterion for which only a slight increase in compliance was recorded.
Genetic determinants of antimicrobial resistance in three multi-drug resistant strains of Cutibacterium acnes isolated from patients with acne: a predictive in silico study
Authors: Beirne Catriona , McCann Emily , McDowell Andrew , Miliotis Georgios
Published: August 2022

Objectives. Using available whole genome data, the objective of this in silico study was to identify genetic mechanisms that could explain the antimicrobial resistance profile of three multi-drug resistant (MDR) strains (CA17, CA51, CA39) of the skin bacterium

Cutibacterium acnes

previously recovered from patients with acne. In particular, we were interested in detecting novel genetic determinants associated with resistance to fluoroquinolone and macrolide antibiotics that could then be confirmed experimentally.

Methods. A range of open source bioinformatics tools were used to ‘mine’ genetic determinants of antimicrobial resistance and plasmid borne contigs, and to characterise the phylogenetic diversity of the MDR strains.

Results. As probable mechanisms of resistance to fluoroquinolones, we identified a previously described resistance associated allelic variant of the gyrA gene with a ‘deleterious' S101L mutation in type IA1 strains CA51 (ST1) and CA39 (ST1), as well as a novel E761R ‘deleterious’ mutation in the type II strain CA17 (ST153). A distinct genomic sequence of the efflux protein YfmO which is potentially associated with resistance to MLSB antibiotics was also present in CA17; homologues in CA51, CA39, and other strains of

Cutibacterium acnes

, were also found but differed in amino acid content. Strikingly, in CA17 we also identified a circular 2.7 kb non-conjugative plasmid (designated pCA17) that closely resembled a 4.8 kb plasmid (pYU39) from the MDR

Salmonella enterica

strain YU39.

Conclusions. This study has provided a detailed explanation of potential genetic determinants for MDR in the

Cutibacterium acnes

strains CA17, CA39 and CA51. Further laboratory investigations will be required to validate these in silico results, especially in relation to pCA17.
Flavobacterium litorale sp. nov., isolated from red alga
Authors: Muhammad Neak , Le Han Ho , Lee Yong-Jae , Ko Jaeho , Nguyen Tra T. H. , Kim Song-Gun
Published: August 2022

A Gram-stain-negative and rod-shaped bacterial strain (WSW3-B6T) was isolated from red alga collected from the West Sea, Republic of Korea. Cells of strain WSW3-B6T were non-motile, aerobic and produced slightly yellow and mucoid colonies on marine agar. The strain grew optimally at 23–30 °C, with 0.5–4 % NaCl (w/v) and at pH 6.5–8.5. A phylogenetic analysis of the 16S rRNA gene revealed that strain WSW3-B6T belongs to the genus

Flavobacterium

within the family

Flavobacteriaceae

, having the highest sequence similarity to

Flavobacterium arcticum

SM1502T (96.7%), followed by

Flavobacterium salilacus

subsp.

altitudinum

LaA7.5T (96.2%) and

Flavobacterium salilacus

subsp.

salilacus

SaA2.12T (96.2%). The complete sequence of a circular chromosome of strain WSW3-B6T determined by combination of Oxford Nanopore and Illumina platforms comprised a total 2 725 095 bp with G+C content of 37.1 mol%. A comparative analysis based on the whole genome also showed the distinctiveness of strain WSW3-B6T. The average nucleotide identity (ANI) values between strain WSW3-B6T and the closest strains

F. arcticum

SM1502T,

F. salilacus

subsp.

altitudinum

LaA7.5T and

F. salilacus

subsp.

salilacus

SaA2.12T were 78.3, 77.8 and 77.7 %, respectively, while the digital DNA–DNA hybridization (dDDH) values between strain WSW3-B6T and the above closely related strains were 21.0, 20.4 and 20.3 %, respectively. Both the ANI and dDDH values supported the creation of a new species in the genus

Flavobacterium

. The major fatty acids (>10 %) were iso-C15 : 0 (19.3 %), C16 : 0 (14.0 %), iso-C17 : 0 3-OH (13.1 %) and C18 : 0 (10.7 %). The polar lipids of strain WSW3-B6T included phosphatidylethanolamine, three unidentified aminolipids and three unidentified lipids. Moreover, MK-6 was the only respiratory quinone. A comparison of the phylogenetic distinctiveness and the unique phenotypic and chemotaxonomic characteristics among strain WSW3-B6T and closely related type strains supported that strain WSW3-B6T (=KCTC 82708T=GDMCC 1.2627T) represents a novel species of the genus

Flavobacterium

, for which the name Flavobacterium litorale sp. nov. is proposed.
JMM Profile: Fosfomycin: a potential antibiotic for multi- and extensively resistant bacteria
Authors: Wangchinda Walaiporn , Rattanaumpawan Pinyo
Published: August 2022

Fosfomycin (FOF) is the first antimicrobial of the epoxide class. It is commercially available in oral and parenteral formulations. Oral FOF is widely used to treat uncomplicated cystitis in women, while parenteral FOF is extensively utilized for upper urinary tract infections. FOF has a broad-spectrum bactericidal activity with a low risk of cross-resistance to other antimicrobial classes. Therefore, parenteral FOF is increasingly prescribed adjunctive therapy to treat extra-urinary tract infections caused by multidrug-resistant, Gram-negative bacteria.
Resting-state aperiodic neural activity as a novel objective marker of daytime somnolence
Authors: Cross Zachariah R. , Kang Teng Yuan , Lushington Kurt , Sarkar Paroma , Singh Parmjit , Johnston Sonya , Yeo Aeneas , Chatburn Alex
Published: August 2022

Study Objectives

Current assessment of excessive daytime somnolence (EDS) requires subjective measurements such as the Epworth Sleepiness Scale (ESS), and/or resource intensive sleep laboratory investigations. Recent work 1,2 has called for more non-performance-based measures of EDS. One promising non-performance-based measure of EDS is the aperiodic component of electroencephalography (EEG). Aperiodic (non-oscillatory) activity reflects excitation/inhibition ratios of neural populations and is altered in various states of consciousness, and thus may be a potential biomarker of hypersomnolence.

Methods

We retrospectively analysed EEG data from patients who underwent a Multiple Sleep Latency Test (MSLT) and determined whether aperiodic neural activity is predictive of EDS. Participants having undergone laboratory polysomnogram and next day MSLT were grouped into MSLT+ (n = 26) and MSLT– (n = 33) groups (mean sleep latency of < 8min and > 10min, respectively) and compared against a non-clinical (Control) group of participants (n = 26).

Results

While the MSLT+ and MSLT– groups did not differ in their aperiodic activity, the Control group had a significantly flatter slope and larger offset compared to both MSLT+ and MSLT– groups. Logistic regression machine learning predicted group status (i.e., symptomatic, non-symptomatic) with 90% accuracy based on the aperiodic slope while controlling for age. Slow oscillation-spindle coupling was also significantly stronger in the Control group relative to MSLT+ and MSLT– groups.

Conclusions

Our results provide first evidence that aperiodic neural dynamics and sleep-based cross-frequency coupling is predictive of EDS, thereby providing a novel avenue for basic and applied research in the study of sleepiness.
VEGF subtype A and B Gene Expression, Clues to a Temporal Signature in Kawasaki Disease, Implications for Coronary Pathogenesis through a Secondary analysis of Clinical Datasets
Authors: Rashid Asrar , Toufiq M. , Khilnani Praveen , Malik Zainab A. , Sharief Javed , Kadwa Raziya , Brusletto Berit S. , Sarpal Amrita , Chaussabel Damien , Malik Rayaz , Quraishi Nasir , Benakatti Govind , Zaki Syed A. , Ogrodzki Pauline , Zaher Walid , Zouhbi Mouhamad Al , Saleh Husam , Khayer Ahmad Al , Nadeem M. Rashid , Shaikh Guftar , Hussain Shazia , Tariq Mishal , Al-Dubai Ahmed , Hussain Amir
Published: August 2022

Background and Aim

An essential issue for Kawasaki Disease (KD) is the development of coronary artery disease. We decided to investigate (VEGF) subtype gene expression in KD due to the proangiogenic nature of Vasoactive Endothelial Growth Factor A (VEGF). VEGF-A is a known angiogenic molecule with pro-inflammatory effects, whereas the role of VEGFB has been less defined.

Method

KD Microarray and RNA-seq datasets were selected using a comprehensive search strategy of the NCBI GEO Dataset, which resulted in eight studies from whole blood. This included three extensive studies in KD (KD1-KD3). Further, one study dataset from coronary artery tissue, the Coronary Artery Dataset (CAD), was also included to appreciate end-stage KD.

Results

In CAD, cases of KD versus controls, VEGF-B was up-regulated (p = 4.932e-02). KD1, KD Acute versus convalescent samples, VEGF-A is up-regulated (p=1.258e-07) and VEGF-B was down-regulated (p=1.42e-28). Similar up regulation of VEGF-A and down regulation of VEGF-B was seen in KD2 (p=1.140e-04; p=1.746e-02) and KD3 (p=1.140e-04; p=1.746e-02), both are KD Versus Controls. VEGF-A up-regulated (p=1.140e-04), VEGF-B down-regulated (p=1.746e-02).KD3, KD versus Control; VEGF-A up-regulated (p=1.140e-04), VEGF-B down regulated (p=1.746e-02).

Conclusions

In acute KD VEGF-A up-regulation, with VEGFB being down-regulated, the reverse being true of the convalescent situation. This suggests a temporal inverse relationship between VEGF-A and VEGF-B may have biomarker implications. Moreover, a dual therapeutic strategy, enhancing VEGFB while minimizing VEGFA effects, could be a possible advancement over current KD related-therapies. Further work defining the relationship of VEGF-A to VEGF-B in KD-related angiogenesis is suggested.
CONNECTOR, fitting and clustering of longitudinal data to reveal a new risk stratification system
Authors: Pernice Simone , Sirovich Roberta , Grassi Elena , Viviani Marco , Ferri Martina , Sassi Francesco , Alessandrì Luca , Tortarolo Dora , Calogero Raffaele A. , Trusolino Livio , Bertotti Andrea , Beccuti Marco , Olivero Martina , Cordero Francesca
Published: August 2022

The transition from the evaluation of a single time point to the examination of the entire dynamic evolution of a system is possible only in the presence of the proper framework. The strong variability of dynamic evolution makes the definition of an explanatory procedure for data fitting and data clustering challenging. Here we present CONNECTOR, a data-driven framework able to analyze and inspect longitudinal data in a straightforward and revealing way. When used to analyze tumor growth kinetics over time in 1599 patient-derived xenograft (PDX) growth curves from ovarian and colorectal cancers, CONNECTOR allowed the aggregation of time-series data through an unsupervised approach in informative clusters. Through the lens of a new perspective of mechanism interpretation, CONNECTOR shed light onto novel model aggregations and identified unanticipated molecular associations with response to clinically approved therapies.
Uremic toxin indoxyl sulfate induces trained immunityviathe AhR-dependent arachidonic acid pathway in end-stage renal disease (ESRD)
Authors: Kim Hee Young , Kang Yeon Jun , Kim Dong Hyun , Jang Jiyeon , Lee Su Jeong , Kim Gwanghun , Koh Hee Byung , Ko Ye Eun , Shin Hyun Mu , Lee Hajeong , Yoo Tae-Hyun , Lee Won-Woo
Published: August 2022

Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytesviaepigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as Arachidonate 5-Lipoxygenase (ALOX5) and ALOX5 Activating Protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6-day training, they exhibit enhanced TNF-α and IL-6 production to LPS. Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α afterin vivoandex vivoLPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.
Spiking burstiness and working memory in the human medial temporal lobe
Authors: Cocina Francesco , Vitalis Andreas , Caflisch Amedeo
Published: August 2022

Persistent activity has commonly been considered to be a hallmark of working memory (WM). Recent evidence indicates that neuronal discharges in the medial temporal lobe (MTL) are compatible with WM neural patterns observed in cortical areas. However, the characterization of this activity rarely consists of measurements other than firing rates of single neurons. Moreover, a varied repertoire of firing dynamics has been reported in the MTL regions, which motivate the more detailed examination of the relationships between WM processes and discharge patterns undertaken here. Specifically, we investigate at different resolution levels firing irregularities in electrode recordings from the hippocampus, amygdala, and the entorhinal cortex of epileptic patients during a WM task. We show that some types of (ir)regularities predict response times of the patients depending on the trial periods under consideration. Prominent burst activity at the population level is observed in the amygdala and entorhinal cortex during memory retrieval. In general, regular and bursty neurons contribute to the decoding of the memory load, yet they display important differences across the three anatomical areas. Our results suggest that non-random (non-Poisson) patterns are relevant for WM, which calls for the development and use of statistics complementary to mere spike counts.
Defining the separation landscape of topological domains for decoding consensus domain organization of 3D genome
Authors: Dang Dachang , Zhang Shao-Wu , Duan Ran , Zhang Shihua
Published: August 2022

Topologically associating domains (TADs) have emerged as basic structural and functional units of genome organization, and have been determined by many computational methods from Hi-C contact maps. However, the TADs obtained by different methods vary greatly, which makes the accurate determination of TADs a challenging issue and hinders subsequent biological analyses about their organization and functions. Obvious inconsistencies among the TADs identified by different methods indeed make the statistical and biological properties of TADs overly depend on the method we chose rather than on the data. To this end, we employ the consensus structural information captured by these methods to define the TAD separation landscape for decoding consensus domain organization of the 3D genome. We demonstrate that the TAD separation landscape could be used to compare domain boundaries across multiple cell types for discovering conserved and divergent topological structures, decipher three types of boundary regions with diverse biological features, and identify Consensus Topological Associating Domains (ConsTADs). We illustrate that these analyses could deepen our understanding of the relationships between the topological domains and chromatin states, gene expression, and DNA replication timing. In short, we provide an alternative solution to deal with the serious inconsistencies of TADs obtained via different methods by defining the TAD separation landscape and ConsTAD.
Isotope effects on radical pair performance in cryptochrome: a new hypothesis for the evolution of animal migration
Authors: Galván Ismael , Hassasfar Abbas , Adams Betony , Petruccione Francesco
Published: August 2022

Mechanisms occurring at the atomic level are now known to drive processes essential for life, as revealed by quantum effects on biochemical reactions. Some macroscopic characteristics of organisms may thus show an atomic imprint, which may be transferred across organisms and affect their evolution. This possibility is considered here for the first time, with the aim of elucidating the appearance of an animal innovation with an unclear evolutionary origin: migratory behaviour. This trait may be mediated by a radical pair (RP) mechanism in the retinal flavoprotein cryptochrome, providing essential magnetic orientation for migration. Isotopes may affect the performance of quantum processes through their nuclear spin. Here, we consider a simple model and then apply the standard open quantum system approach to the spin dynamics of cryptochrome RP. We changed the spin quantum number (I) and g-factor of hydrogen and nitrogen isotopes to investigate their effect on RP’s yield and magnetic sensitivity. Strong differences arose between isotopes withI=1 andI=1/2 in their contribution to cryptochrome magnetic sensitivity, particularly regarding Earth’s magnetic field strengths (25-65 µT). In most cases, isotopic substitution improved RP’s magnetic sensitivity. Migratory behaviour may thus have been favoured in animals with certain isotopic compositions of cryptochrome.
Taking shortcuts: Great for travel, but not for reproducible methods sections
Authors: Standvoss Kai , Kazezian Vartan , Lewke Britta R. , Bastian Kathleen , Chidambaram Shambhavi , Arafat Subhi , Alsharif Ubai , Herrera-Melendez Ana , Knipper Anna-Delia , Seco Bruna M. S. , Soto Nina Nitzan , Rakitzis Orestis , Steinecker Isa , Till Philipp van Kronenberg , Zarebidaki Fereshteh , Weissgerber Tracey L.
Published: August 2022

Methods sections are often missing critical details needed to reproduce an experiment. Methodological shortcut citations, in which authors cite previous papers instead of describing the method in detail, may contribute to this problem. This meta-research study used three approaches to systematically examine the use of shortcut citations in neuroscience, biology and psychiatry. First, we examined papers to determine why authors use citations in the methods section and to assess how often shortcut citations were used. Common reasons for using citations in the methods section included explaining how something was done by citing a previous resource that used the method (methodological shortcut citation), giving credit or specifying what was used (who or what citation), and providing context or a justification (why citation). Next, we reviewed 15 papers to determine what can happen when readers follow shortcut citations to find methodological details. While shortcut citations can be used effectively, problems encountered included difficulty identifying or accessing the cited materials, missing or insufficient descriptions of the cited method, and chains of shortcut citations. Third, we examined journal policies. Fewer than one quarter of journals had policies describing how authors should report methods that have been described previously or asking authors to explain modifications of previously described methods. We propose that methodological shortcut citations should meet three criteria; cited resources should describe a method very similar to the authors’ method, provide enough detail to allow others to implement the method, and be open access. We outline actions that authors and journals can take to use shortcut citations responsibly, while fostering a culture of open and reproducible methods reporting.
Loss of EED in the oocyte causes initial fetal growth restriction followed by placental hyperplasia and offspring overgrowth
Authors: Oberin Ruby , Petautschnig Sigrid , Tsai Tesha , Jarred Ellen G. , Qu Zhipeng , Youngson Neil A. , Bildsoe Heidi , Truong Thi T. , Fernando Dilini , van den Buuse Maarten , Gardner David K. , Sims Natalie A. , Adelson David L. , Western Patrick S.
Published: August 2022

Germline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to placental hyperplasia in mammalian offspring generated by somatic cell nuclear transfer (SCNT). In this study, we show that offspring from mouse oocytes lacking the Polycomb protein Embryonic Ectoderm Development (EED) were initially growth restricted, characterised by low blastocyst cell counts and substantial mid-gestational developmental delay. This initial developmental delay was followed by striking late-gestational placental hyperplasia, fetal catch-up growth and extended gestational length that culminated in offspring overgrowth. This involved remodelling of the placenta, including expansion of fetal and maternal tissues and conspicuous expansion of the glycogen enriched cell population in the junctional zone that was associated with a delay in parturition. Despite this remodelling and offspring catchup growth, fetal/placental weight ratio and fetal blood glucose levels were low indicating low placental efficiency. Genome-wide analyses identified extensive transcriptional dysregulation in affected placentas, including a range of imprinted and non-imprinted genes and increased expression of the H3K27me3-imprinted geneSlc38a4,which regulates transport of essential amino acids in the placenta. Our data provide an explanation for apparently opposing observations of growth restriction and overgrowth of offspring derived fromEed-nulloocytes and demonstrate that PRC2-dependent programming in the oocyte regulates fetal and placental growth and developmental outcomes.
Exploring the adaptability and robustness of the central carbon metabolism of Mycoplasma pneumoniae
Authors: Zondervan Niels A. , Yus Eva , Sévin Daniel C. , Martinez Sira , Gallo Carolina , Schaap Peter J. , Lluch-Senar Maria , Serrano Luis , Martins dos Santos Vitor A. P. , Suarez-Diez Maria
Published: August 2022

In this study we explored the adaptability and robustness of glycolysis and pyruvate metabolism of Mycoplasma pneumoniae (MPN). We used a dual approach, we analysed metabolomics data collected for a large number of OE and KO mutants and perturbation samples. Furthermore, we trained a dynamic model of central carbon metabolism and tested the model’s capacity to predict these mutants and perturbation samples as well as identify key controlling factors in central carbon metabolism. Our analysis of metabolite data as well as our model analysis indicate MPN metabolism is inherently robust against perturbations due to its network structure. Two key control hubs of central carbon metabolism were identified.
WITCH-NG: Efficient and Accurate Alignment of Datasets with Sequence Length Heterogeneity
Authors: Liu Baqiao , Warnow Tandy
Published: August 2022

Multiple sequence alignment (MSA) is a basic part of many bioinformatics pipelines, including in phylogeny estimation, prediction of structure for both RNAs and proteins, and metagenomic sequence analysis. Yet many sequence datasets exhibit substantial sequence length heterogeneity, both because of large insertions and deletions (indels) in the evolutionary history of the sequences and the inclusion of sequencing reads or incompletely assembled sequences in the input. A few methods have been developed that can be highly accurate in aligning datasets with sequence length heterogeneity, with UPP (Nguyen et al., 2015) one of the first methods to achieve good accuracy, and WITCH (Shen et al., Bioinformatics 2021) an improvement on UPP for accuracy, In this paper, we show how we can speed up WITCH. Our improvement includes replacing a critical step in WITCH (currently performed using a heuristic search) by a polynomial time exact algorithm using Smith-Waterman. Our new method, WITCH-NG (i.e., “next generation WITCH”, pronounced “witching”) achieves the same accuracy but is substantially faster. WITCH-NG is available in open source form at https://github.com/RuneBlaze/WITCH-NG.
Counting is Almost All You Need
Authors: Akerman Ofek , Isakov Haim , Levi Reut , Psevkin Vladimir , Louzoun Yoram
Published: August 2022

The immune memory repertoire encodes the history of present and past infections and immunological attributes of the individual. As such, multiple methods were proposed to use T-cell receptor (TCR) repertoires to detect disease history. We here show that the counting method outperforms all existing algorithms. We then show that the counting can be further improved using a novel attention model to weight the different TCRs. The attention model is based on the projection of TCRs using a Variational AutoEncoder (VAE). Both counting and attention algorithms predict better than any current algorithm whether the host had CMV and its HLA alleles. As an intermediate solution between the complex attention model and the very simple counting model, we propose a new Graph Convolutional Network approach that obtains the accuracy of the attention model and the simplicity of the counting model. The code for the models used in the paper are provided in:https://github.com/louzounlab/CountingIsAlmostAllYouNeed
Phosphorylation at Ser65 modulates ubiquitin conformational dynamics
Authors: Yovanno Remy A. , Yu Alvin , Wied Tyler J. , Lau Albert Y.
Published: August 2022

Phosphorylation of ubiquitin at Ser65 increases the population of a rare C-terminally retracted (CR) conformation. Transition between the CR and the Major ubiquitin conformations is critical for promoting mitochondrial degradation. The mechanisms by which the Major and CR conformations of Ser65-phosphorylated (pSer65) ubiquitin interconvert, however, have not yet been revealed. Here, we perform all-atom molecular dynamics simulations using the string method with swarms of trajectories to calculate the lowest free-energy path between these two conformers. Our analysis reveals the existence of a Bent intermediate in which the C-terminal residues of the β5 strand shift to resemble the CR conformation, while pSer65 retains contacts resembling the Major conformation. This stable intermediate was reproduced in well-tempered metadynamics calculations, with the exception of a Gln2Ala mutant that disrupts contacts with pSer65. Lastly, dynamical network modelling reveals that the transition from the Major to CR conformations involves a decoupling of residues near pSer65 from the adjacent β1 strand.
A Shape Sensing Mechanism driven by Arp2/3 and cPLA2licenses Dendritic Cells for Migration to Lymph Nodes in Homeostasis
Authors: Alraies Zahraa , Rivera Claudia A. , Delgado Maria-Graciela , Sanséau Doriane , Maurin Mathieu , Amadio Roberto , Piperno Giulia Maria , Dunsmore Garett , Yatim Aline , Mariano Livia Lacerda , Sáez Pablo J. , Gratia Matthieu , Lamiable Olivier , Moreau Aurélie , Williart Alice , Albaud Benoit , Legoix Patricia , Nakano Hideki , Cook Donald N , Lawrence Toby , Manel Nicolas , Benvenuti Federica , Ginhoux Florent , Moreau Hélène D. , Nader Guilherme P.F. , Piel Matthieu , Lennon-Duménil Ana-Maria
Published: August 2022

Motile cells such as immune and cancer cells experience large deformation events that result from the physical constraints they encounter while migrating within tissues or circulating between organs. It has become increasingly clear that these cells can survive and adapt to these changes in cell shape using dedicated shape sensing pathways. However, how shape sensing impacts their function and fate remains largely unknown. Here we identify a shape sensing mechanism that couples cell motility to expression of CCR7, the chemokine receptor that guides immune cells to lymph nodes. We found that this mechanism is controlled by the lipid metabolism enzyme cPLA2, requires an intact nuclear envelop and exhibits an exquisitely sensitive activation threshold tuned by ARP2/3 and its inhibitor Arpin. We further show that shape sensing through the ARP2/3-cPLA2axis controls Ikkβ-NFκB-dependent transcriptional reprogramming of dendritic cells, which instructs them to migrate to lymph nodes in an immunoregulatory state compatible with their homeostatic tolerogenic function. These results highlight that the cell shape changes experienced by motile cells evolving within the complex environment of tissues can dictate their behavior and fate.
Comparison and benchmark of long-read based structural variant detection strategies
Authors: Lin Jiadong , Jia Peng , Wang Songbo , Ye Kai
Published: August 2022

Background

Recent advances in long-read callers and assembly methods have greatly facilitated structural variants (SV) detection via read-based and assembly-based detection strategies. However, the lack of comparison studies, especially for SVs at complex genomic regions, complicates the selection of proper detection strategy for ever-increasing demand of SV analysis.

Results

In this study, we compared the two most widely-used strategies with six long-read datasets of HG002 genome and benchmarked them with well curated SVs at genomic regions of different complexity. First of all, our results suggest that SVs detected by assembly-based strategy are slightly affected by assemblers on HiFi datasets, especially for its breakpoint identity. Comparably, though read-based strategy is more versatile to different sequencing settings, aligners greatly affect SV breakpoints and type. Furthermore, our comparison reveals that 70% of the assembly-based calls are also detectable by read-based strategy and it even reaches 90% for SVs at high confident regions. While 60% of the assembly-based calls that are totally missed by read-based callers is largely due to the challenges of clustering ambiguous SV signature reads. Lastly, benchmarking with SVs at complex genomic regions, our results show that assembly-based approach outperforms read-based calling with at least 20X coverage, while read-based strategy could achieve 90% recall even with 5X coverage.

Conclusions

Taken together, with sufficient sequencing coverage, assembly-based strategy is able to detect SVs more consistently than read-based strategy under different settings. However, read-based strategy could detect SVs at complex regions with high sensitivity and specificity but low coverage, thereby suggesting its great potential in clinical application.
Recovery of Metagenomic Data from theAedes aegyptiMicrobiome using a Reproducible Snakemake Pipeline: MINUUR
Authors: Foo Aidan , Cerdeira Louise , Hughes Grant L. , Heinz Eva
Published: August 2022

Background

Ongoing research of the mosquito microbiome aims to uncover novel strategies to reduce pathogen transmission. Sequencing costs, especially for metagenomics, are however still significant. A resource that is increasingly used to gain insights into host-associated microbiomes is the large amount of publicly available genomic data based on whole organisms like mosquitoes, which includes sequencing reads of the host-associated microbes and provides the opportunity to gain additional value of these initially host-focused sequencing projects.

Methods

To analyse non-host reads from existing genomic data, we developed a snakemake workflow called MINUUR (MicrobialINsightsUsingUnmappedReads). Within MINUUR, reads derived from the host-associated microbiome were extracted and characterised using taxonomic classifications and metagenome assembly followed by binning and quality assessment. We applied this pipeline to five publicly availableAedes aegyptigenomic datasets, consisting of 62 samples with a broad range of sequencing depths.

Results

We demonstrate that MINUUR recovers previously identified phyla and genera and is able to extract bacterial metagenome assembled genomes (MAGs) associated to the microbiome. Of these MAGS, 42 are high-quality representatives with >90% completeness and <5% contamination. These MAGs improve the genomic representation of the mosquito microbiome and can be used to facilitate genomic investigation of key genes of interest. Furthermore, we show that samples with a high number of KRAKEN2 assigned reads produce more MAGs.

Conclusions

Our metagenomics workflow, MINUUR, was applied to a range ofAedes aegyptigenomic samples to characterise microbiome-associated reads. We confirm the presence of key mosquito-associated symbionts that have previously been identified in other studies and recovered high-quality bacterial MAGs. In addition, MINUUR and its associated documentation are freely available on GitHub (https://github.com/aidanfoo96/MINUUR) and provide researchers with a convenient workflow to investigate microbiome data included in the sequencing data for any applicable host genome of interest.
Single-cell phylogenies reveal deviations from clock-like, neutral evolution in cancer and healthy tissues
Authors: Borgsmüller Nico , Valecha Monica , Kuipers Jack , Beerenwinkel Niko , Posada David
Published: August 2022

How tumors evolve affects cancer progression, therapy response, and relapse. However, whether tumor evolution is driven primarily by selectively advantageous or neutral mutations remains under debate. Resolving this controversy has so far been limited by the use of bulk sequencing data. Here, we leverage the high resolution of single-cell DNA sequencing (scDNA-seq) to test for clock-like, neutral evolution. Under neutrality, different cell lineages evolve at a similar rate, accumulating mutations according to a molecular clock. We developed and benchmarked a test of the somatic clock based on single-cell phylogenies and applied it to 22 scDNA-seq datasets. We rejected the clock in 10/13 cancer and 5/9 healthy datasets. The clock rejection in seven cancer datasets could be related to known driver mutations. Our findings demonstrate the power of scDNA-seq for studying somatic evolution and suggest that some cancer and healthy cell populations are driven by selection while others seem to evolve under neutrality.
Mathematical model of the fast phase of the chlorophyll fluorescence induction curve
Authors: Lavrentyev V.M.
Published: August 2022

In natural conditions, plants are affected by various adverse environmental factors that can disrupt the photosynthetic apparatus, which can reduce the productivity of plants and ultimately reduce their yield. Measurement of the chlorophyll fluorescence induction (CFI) curve is a simple, non-destructive, inexpensive, and fast tool that can be used to analyze photosynthetic reactions and plant conditions. Mathematical modeling of the chlorophyll fluorescence induction curve is important not only for understanding the complex processes of photosynthesis but also can have practical applications in predicting ways to increase plant productivity. Currently, there are a sufficient number of models of varying complexity and detail that describe the processes of photosynthesis, however, no final agreement has been reached. A new model of reactions occurring in the process of the fast phase of the CFI curve, i.e. in the process of electron transport in the electron transport chain (ETC), is presented here. In the ETC model, it is considered as a system of elements in which electrons are sequentially transferred from one element of the system to another, according to the properties of the elements themselves and the connections between them. In addition, the mathematical model is based on the idea of dividing the entire flow of electrons, which moves through the ETC, into a sequence of individual flows. The proposed mathematical model differs in that each stage of electron transfer along the ETC is described separately and sequentially with the help of connection functions. This makes it possible to write the equations for the real OJIP curve and, as a result of their solution, to obtain the parameters of the entire electron transfer process.
On a mathematical connection between single-elimination sports tournaments and evolutionary trees
Authors: King Matthew C. , Rosenberg Noah A.
Published: August 2022

How many ways are there to arrange the sequence of games in a single-elimination sports tournament? We consider the connection between this enumeration problem and the enumeration of “labeled histories,” or sequences of asynchronous branching events, in mathematical phylogenetics. The possibility of playing multiple games simultaneously in different arenas suggests an extension of the enumeration of labeled histories to scenarios in which multiple branching events occur simultaneously. We provide a recursive result enumerating game sequences and labeled histories in which simultaneity is allowed. For a March Madness basketball tournament of 68 labeled teams, the number of possible sequences of games is ~ 1.91 × 1078if arbitrarily many arenas are available, but only ~ 3.60 × 1068if all games must be played sequentially on the same arena.
Theoretical and practical refinements of sans spike-in quantitative ChIP-seq with application to p300/CBP inhibition
Authors: Dickson Bradley M. , Kupai Ariana , Vaughan Robert M. , Rothbart Scott B.
Published: August 2022

Previously, we introduced an absolute and physical quantitative scale for chromatin immunoprecipitation followed by sequencing. The scale itself was determined directly from measurements routinely made on sequencing samples without additional reagents or spike-ins. We called this approach sans spike-in quantitative ChIP, or siQ-ChIP. In this paper we extend those results in several ways. First, we simplified the calculations defining the quantitative scale. Second, we highlight the normalization constraint implied by the quantitative scale and introduce a new scheme for generating ’tracks’ for siQ-ChIP. We next introduce some whole-genome analyses that are unique to siQ-ChIP which allow us, for example, to project the IP mass onto the genome to evaluate how much of any genomic interval was captured in the IP. We apply these analyses to p300/CBP inhibition and demonstrate that response to inhibition is a function of genomic architecture. In particular, active transcription start sites are only weakly perturbed by p300/CBP inhibition while enhancers are strongly perturbed. Similar observations have been reported in the literature, but without a quantitative scale, those observations have been misinterpreted. We discuss how the siQ-ChIP approach precludes such misinterpretations, which stem from the widespread community practice of treating unquantified and unnormalized ChIP-seq tracks as though they are quantitative.
Can a short math video enhance the brain’s mathematical networks?
Authors: Amalric Marie , Roveyaz Pauline , Dehaene Stanislas
Published: August 2022

Many teaching websites, such as the Khan Academy, propose vivid videos illustrating a mathematical concept. Using fMRI, we asked whether watching such a video suffices to rapidly change the brain networks for mathematical knowledge. We capitalized on the finding that, when judging the truth of short spoken statements, distinct semantic regions activate depending on whether the statements bear on mathematical knowledge or on other domains of semantic knowledge. Here, participants answered such questions before and after watching a lively five-minute video which taught them the rudiments of a new domain. During the video, a distinct math-responsive network, comprising anterior intraparietal and inferior temporal nodes, showed inter-subject synchrony when viewing mathematics course rather than control courses in biology or law. However, this experience led to minimal subsequent changes in the activity of those domain-specific areas when answering questions on the same topics a few minutes later. All taught facts, whether mathematical or not, led to domain-general repetition enhancement, particularly prominent in the cuneus, posterior cingulate and posterior parietal cortices. We conclude that short videos do not suffice to induce a meaningful lasting change in the brain’s math-responsive network, but merely engage domain-general regions possibly involved in episodic short-term memory.

Significance Statement

Teaching mathematical concepts is difficult. To facilitate the comprehension and appeal of mathematics, several teaching websites provide vivid videos illustrating math concepts. Here, however, we show that merely watching such videos fails to improve the brain networks for mathematics. During the video itself, these networks are transiently engaged – but a few minutes later, when we ask questions about the taught concepts, performance is only minimally improved, and the participants engage generic regions thought to be involved in short-memory and language, rather than the targeted math-responsive regions. Brief video watching is therefore insufficient as a pedagogical device, probably because it misses ingredients such as teacher-pupil interactions, explicit teaching, active engagement, retrieval practice, repetition, and sleep.
Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites
Authors: Hart Melissa N. , Mohring Franziska , Donvito Sophia M. , Thomas James A. , Muller-Sienerth Nicole , Wright Gavin J. , Knuepfer Ellen , Saibil Helen R. , Moon Robert W.
Published: August 2022

Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have been studied extensively in P. falciparum and are hypothesized to have overlapping, but critical roles just prior to host cell entry. The zoonotic malaria parasite, P. knowlesi, has larger invasive merozoites and contains a smaller, less redundant, DBP and RBL repertoire than P. falciparum. One DBP (DBPα) and one RBL, normocyte binding protein Xa (NBPXa) are essential for invasion of human RBCs. Taking advantage of the unique biological features of P. knowlesi and iterative CRISPR-Cas9 genome editing, we determine the precise order of key invasion milestones and demonstrate distinct roles for each family. These distinct roles support a mechanism for phased commitment to invasion and can be targeted synergistically with invasion inhibitory antibodies.
A Genetic Variant of Fatty Acid Amide Hydrolase (FAAH) Exacerbates Hormone-Mediated Orexigenic Feeding in Mice
Authors: Balsevich Georgia , Petrie Gavin N , Heinz Daniel E , Singh Arashdeep , Aukema Robert J , Hunker Avery C , Vecchiarelli Haley A , Yau Hiulan , Sticht Martin , Thompson Roger J , Lee Francis S , Zweifel Larry S , Chelikani Prasanth K , Gassen Nils C , Hill Matthew N
Published: August 2022

Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide. A polymorphism in FAAH (FAAH C385A) reduces FAAH expression, increases anandamide levels, and increases the risk of obesity. Nevertheless, some studies have found no association between FAAH C385A and obesity. We investigated whether the environmental context governs the impact of FAAH C385A on metabolic outcomes. Using a C385A knock-in mouse model, we found that under basal conditions, there was no effect of the FAAH C385A polymorphism on body weight or composition. By contrast, FAAH A/A mice are more susceptible to glucocorticoid-induced hyperphagia, weight gain, and activation of hypothalamic AMPK. AMPK inhibition occluded the amplified hyperphagic response to glucocorticoids in FAAH A/A mice. FAAH knockdown exclusively in AgRP neurons mimicked the exaggerated feeding response of FAAH A/A mice to glucocorticoids. FAAH A/A mice likewise presented exaggerated orexigenic responses to ghrelin, while FAAH knockdown in AgRP neurons blunted leptin anorectic responses. Together, the FAAH A/A genotype amplifies orexigenic responses and decreases anorexigenic responses, providing a putative mechanism explaining the diverging human findings.