bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward Zero Harm: Mackenzie Health’s Journey Toward Becoming a High Reliability Organization and Eliminating Avoidable Harm
Authors: Wilson Mary-Agnes , Sinno Maya , Hacker Teper Matthew , Courtney Karoline , Nuseir Deema , Schonewille Aidan , Rauchwerger David , Taher Ahmed
Published: February 2022

Objectives

In response to an organizational survey revealing low safety culture scores, we implemented a “zero harm” approach to eliminate preventable harm across a wide variety of clinical areas. We aimed to achieve this objective within 3 years.

Methods

We developed a 5-part strategy for cultural and process redesign that included (1) engaging leadership; (2) developing an organization-specific patient safety framework; (3) monitoring specific quality aims based on high-risk, high-volume, high-cost, and problem-prone areas; (4) standardizing a 3-part review process that includes a root cause analysis for moderate and critical patient safety incidents; and (5) communicating progress to staff in real time via unit-specific electronic dashboards.

Results

In less than 1 year, we increased patient safety incident reporting by 37% while simultaneously decreasing falls with injury by 39%, pressure injury rates by 37%, and central line–associated blood stream infections by 34%. We also improved medication reconciliation rate by 3.3% and decreased our irretrievable specimen rate to 0. Finally, we noted increased awareness around patient safety within clinical teams, with open discussions about patient safety becoming a routine part of patient care.

Conclusions

This study describes an initiative that sought to introduce system-wide changes to practice and patient safety culture in a rapid time frame. Results suggest that our 5-step approach to transformation may confer substantial gains in patient safety for peer institutions. Next steps include continuing to expand and monitor quality aims as we progress through our journey to eliminating preventable patient harm in our healthcare system.
Impact of Extended Duty Hours on Perceptions of Care and Objective Patient Outcomes
Authors: Salgado Sanjay M. , Katz Joel T. , Pelletier Stephen R. , Goodberlet Melanie , Kelly Julie , Duperreault Megan , Ali Nadaa B. , Shields Helen M.
Published: February 2022

Objective

In 2017, interns were permitted to work continuously for up to 28 hours at a time, a reversal from the previously mandated 16-hour limit. Our objective was to evaluate perceptions of care and patient outcomes on an extended (28-hour) compared with a limited (16-hour) duty-hour system on identical interdisciplinary teams.

Methods

Sixty-two interns, 27 residents, 28 attendings, and 449 patients participated. Patients completed surveys assessing their satisfaction. Anonymous weekly surveys were obtained from interns, residents, and attendings evaluating perceptions of intern tiredness, overall satisfaction, and performance. Nursing surveys evaluated intern and medical team performance. Objective outcome measures, including intensive care unit transfers, length of stay, readmissions, mortality, and complications, were assessed through a retrospective, blinded chart review.

Results

Patients reported similar satisfaction in care. Extended duty-hour interns reported significantly decreased familiarity with their patients, decreased ability to conduct physical exams on new patients, increased tiredness, and decreased overall satisfaction. Residents overseeing extended-duty interns reported significantly decreased quality in intern presentations and overall quality of teaching, and increased perception of intern tiredness and increased incorrect orders. Attending physicians reported significantly improved quality of new patient presentations by extended duty-hour interns. No significant differences in patient objective outcome measures were noted.

Conclusions

Extended intern duty hours do not affect patient’s satisfaction with their care. Although interns in the extended duty-hour system reported significantly increased fatigue and decreased overall satisfaction and residents’ perceived increases in incorrect intern orders in the extended duty-hour system, there were no detrimental effects on patient safety.
Celeribacter litoreus sp. nov., isolated from intertidal sediment
Authors: Li Yi , Ding Yun-Yun , Dang Yan-Ru , Bai Yun , Guan Li , Liu Ning-Hua , Wang Yu-Zhu , Kang Mei-Lin , Zhang Yu-Qiang , Zhang Xi-Ying
Published: February 2022

A Gram-negative, aerobic, non-flagellated and rod-shaped bacterium, strain ASW11-22T, was isolated from an intertidal sediment collected from a coastal area of Qingdao, PR China. The strain grew at 15–40 °C (optimum, 37 °C), at pH 6.0–9.0 (optimum, pH 7.0) and with 0.5–10 % (w/v) NaCl (optimum, 1.0 %). It hydrolysed gelatin and aesculin but did not reduce nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ASW11-22T belonged to the genus

Celeribacter

, showing the highest sequence similarity to the type strains of

Celeribacter halophilus

MCCC 1A06432T (98.20 %) and

Celeribacter ethanolicus

NH195T (97.84 %). The genomic DNA G+C content was 59.1 mol%. The major cellular fatty acid (>10 %) of the strain was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and its main polar lipids were phosphatidylglycerol and one unidentified aminolipid. The sole respiratory quinone of strain ASW11-22T was ubiquinone-10. On the basis of the polyphasic evidence presented in this paper, strain ASW11-22T represents a novel

Celeribacter

species, for which the name Celeribacter litoreus sp. nov. is proposed. The type strain is ASW11-22T (=KCTC 82495T=MCCC 1K05584T).
Tenebrionibacter intestinalis gen. nov., sp. nov., a member of a novel genus of the family Enterobacteriaceae, isolated from the gut of the plastic-eating mealworm Tenebrio molitor L.
Authors: Hu Lin , Yang Yu
Published: February 2022

A Gram-negative, white-pigmented, motile and rod-shaped strain, BIT-L3T, was isolated from the gut of plastic-eating mealworm Tenebrio molitor L. Its taxonomic position was determined by using a polyphasic approach. A preliminary analysis based on the 16S rRNA gene sequence (1445 bp) revealed that this strain was closely related to the members within the family

Enterobacteriaceae

. Phylogenetic trees based on the concatenated partial sequences of seven housekeeping genes (atpD, gyrB, infB, rpoB, pyrG, fusA, leuS) and genome sequences further showed that strain BIT-L3T constituted a separate lineage within the family Enterobacteriaceae. In silico DNA–DNA hybridization values and average nucleotide identity values between strain BIT-L3T and its closest related species within the family

Enterobacteriaceae

were less than 21.8 and 76.7 %, respectively. The major fatty acids (>5 %) of strain BIT-L3T were C16 : 0, C14 : 0, C17 : 0 cyclo, summed feature 8 (comprising C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c and/or iso-C15 : 0 2-OH) and summed feature 2 (comprising iso-C16 : 1 I/C14 : 0 3-OH and/or C12 : 0 aldehyde and/or an unknown fatty acid of equivalent chain length 10.9525). Its genomic DNA G+C content was 53.7 mol%. Based on the results of phylogenetic, physiological and biochemical analyses, strain BIT-L3T is considered to represent a novel species of a novel genus within the family

Enterobacteriaceae

, for which the name Tenebrionibacter intestinalis gen. nov., sp. nov. is proposed. The type strain is BIT-L3T (=CCTCC AB 2020371T=LMG 32222T=TBRC 14825T).
Robust regulatory architecture of pan-neuronal gene expression
Authors: Leyva-Díaz Eduardo , Hobert Oliver
Published: February 2022

Pan-neuronally expressed genes, such as genes involved in the synaptic vesicle release cycle or in neuropeptide maturation, are critical for proper function of all neurons, but the transcriptional control mechanisms that direct such genes to all neurons of a nervous system remain poorly understood. We show here that six members of the CUT family of homeobox genes control pan-neuronal identity specification in C. elegans. Single CUT mutants show barely any effects on pan-neuronal gene expression or global nervous system function, but such effects become apparent and progressively worsen upon removal of additional CUT family members, indicating a critical role of gene dosage. Overexpression of each individual CUT gene rescued the phenotype of compound mutants, corroborating that gene dosage, rather than the activity of specific members of the gene family, is critical for CUT gene function. Genome-wide binding profiles as well as mutation of CUT binding sites by CRISPR/Cas9 genome engineering show that CUT genes directly control the expression of pan-neuronal features. Moreover, CUT genes act in conjunction with neuron-type specific transcription factors to control pan-neuronal gene expression. Our study, therefore, provides a previously missing key insight into how neuronal gene expression programs are specified and reveals a highly buffered and robust mechanism that controls the most critical functional features of all neuronal cell types.
POST-ACUTE SEQUELAE AND ADAPTIVE IMMUNE RESPONSES IN PEOPLE LIVING WITH HIV RECOVERING FROM SARS-COV-2 INFECTION
Authors: Peluso Michael J. , Spinelli Matthew A. , Deveau Tyler-Marie , Forman Carrie A. , Munter Sadie E. , Mathur Sujata , Tang Alex F. , Lu Scott , Goldberg Sarah A. , Arreguin Mireya I. , Hoh Rebecca , Tai Viva , Chen Jessica Y. , Martinez Enrique O. , Chenna Ahmed , Winslow John W. , Petropoulos Christos J. , Sette Alessandro , Weiskopf Daniella , Kumar Nitasha , Lynch Kara L. , Hunt Peter W. , Durstenfeld Matthew S. , Hsue Priscilla Y. , Kelly J. Daniel , Martin Jeffrey N. , Glidden David V. , Gandhi Monica , Deeks Steven G. , Rutishauser Rachel L. , Henrich Timothy J.
Published: February 2022

Background

Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).

Methods

We measured SARS-CoV-2 specific humoral and cellular responses in people with and without HIV recovering from COVID-19 (n=39 and n=43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing post-acute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T cell responses, as well as differences in the prevalence of PASC.

Results

Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T cell responses as compared with a well-matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2 specific memory CD8+ T cells (p=0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2 specific CD4+ T cells (p=0.007). Higher CD4/CD8 ratio was associated with lower PD-1 expression on SARS-CoV-2 specific CD8+ T cells (0.34-fold effect, p=0.02). HIV status was strongly associated with PASC (odds ratio 4.01, p=0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.

Conclusions

We identified potentially important differences in SARS-CoV-2 specific CD4+ and CD8+ T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.
FiNN: A toolbox for neurophysiological network analysis
Authors: Scherer Maximilian , Wang Tianlu , Guggenberger Robert , Milosevic Luka , Gharabaghi Alireza
Published: February 2022

Recently, neuroscience has seen a shift from localist approaches to network-wide investigations of brain function. Neurophysiological signals across different spatial and temporal scales provide insight into neural communication. However, additional methodological considerations arise when investigating network-wide brain dynamics rather than local effects. Specifically, larger amounts of data, investigated across a higher dimensional space, are necessary.

Here, we present FiNN (Find Neurophysiological Networks), a novel toolbox for the analysis of neurophysiological data with a focus on functional and effective connectivity. FiNN provides a wide range of data processing methods, and statistical and visualization tools to facilitate inspection of connectivity estimates and the resulting metrics of brain dynamics. The Python toolbox (https://github.com/neurophysiological-analysis/FiNN) and its documentation (https://neurophysiological-analysis.github.io/FiNN/) are freely available.

We evaluated FiNN against a number of established frameworks on both a conceptual and an implementation level. We found FiNN to require much less processing time and memory than other toolboxes. In addition, FiNN adheres to a design philosophy of easy access and modifiability, while providing efficient data processing implementations. Since the investigation of network-level neural dynamics is experiencing increasing interest, we place FiNN at the disposal of the neuroscientific community as open-source software.
Locomotion-induced gain of visual responses cannot explain visuomotor mismatch responses in layer 2/3 of primary visual cortex
Authors: Vasilevskaya Anna , Widmer Felix C. , Keller Georg B. , Jordan Rebecca
Published: February 2022

The aim of this work is to provide a comment on a recent paper by Muzzu and Saleem (2021). In brief, our concern is that the authors claim that visuomotor mismatch responses in mouse visual cortex can be explained by a locomotion-induced gain of visual halt responses, without directly comparing these responses to mismatch responses. Without a direct comparison, the claim that one response can explain the other appears difficult to uphold, more so because previous work finds that a uniform locomotion-induced gain cannot explain mismatch responses. To support these arguments, we analyzed a series of layer 2/3 calcium imaging datasets and show that coupling between visual flow and locomotion greatly enhances mismatch responses in an experience dependent manner compared to halts in non-coupled visual flow. This is consistent with mismatch responses representing visuomotor prediction errors. Thus, we conclude that feature selectivity cannot explain mismatch responses in mouse visual cortex.
Learning vs. minding: How subjective costs can mask motor learning
Authors: Healy Chadwick M. , Berniker Max , Ahmed Alaa A.
Published: February 2022

When learning new movements some people make larger kinematic errors than others, interpreted as a reduction in motor-learning ability. Consider a learning task where error-cancelling strategies incur higher effort costs, specifically where subjects reach to targets in a force field. Concluding that those with greater error have learned less has a critical assumption: everyone uses the same error-canceling strategy. Alternatively, it could be that those with greater error may be choosing to sacrifice error reduction in favor of a lower effort movement. Here, we test this hypothesis in a dataset that includes both younger and older adults, where older adults exhibited greater kinematic errors. Utilizing the framework of optimal control theory, we infer subjective costs (i.e., strategies) and internal model accuracy (i.e., proportion of the novel dynamics learned) by fitting a model to each population’s trajectory data. Our results demonstrate trajectories are defined by a combination of the amount learned and strategic differences represented by relative cost weights. Based on the model fits, younger adults could have learned between 65-90% of the novel dynamics. Critically, older adults could have learned between 60-85%. Each model fit produces trajectories that match the experimentally observed data, where a lower proportion learned in the model is compensated for by increasing costs on kinematic errors relative to effort. This suggests older and younger adults could be learning to the same extent, but older adults have a higher relative cost on effort compared to younger adults. These results call into question the proposition that older adults learn less than younger adults and provide a potential explanation for the equivocal findings in the literature. Importantly, our findings suggest that the metrics commonly used to probe motor learning paint an incomplete picture, and that to accurately quantify the learning process the subjective costs of movements should be considered.

Author Summary

Here we show that how a person values effort versus error in their movements has an impact on their overall strategy for performing those movements and adapting to a novel environment. When error alone is considered as a measure of learning, it appears that certain populations such as older adults are significantly worse at learning new motor tasks. However, using an optimal control framework, we are able to parse out differences in how much a population or person has learned, as well as how they subjectively value factors such as effort and error. In the case of older adults, we show that they could be learning as much as younger adults but exhibit larger errors because they care more about expending extra effort to reduce them.
Scalable sequence database search using Partitioned Aggregated Bloom Comb-Trees
Authors: Marchet Camille , Limasset Antoine
Published: February 2022

The Sequence Read Archive public database has reached 45 Peta-bytes of raw sequences and doubles its nucleotide content every two years. Although BLAST-like methods can routinely search for a sequence in a small collection of genomes, making searchable immense public resources accessible is beyond the reach of alignment-based strategies. In recent years, abundant literature tackled the task of finding a sequence in extensive sequence collections usingk-mer-based strategies. At present, the most scalable methods are approximate membership query data structures that combine the ability to query small signatures or variants while being scalable to collections up to 10,000 eukaryotic samples. Here, we present PAC, a novel approximate membership query data structure for querying collections of sequence datasets. PAC index construction works in a streaming fashion without any disk footprint besides the index itself. It shows a 3 to 6 fold improvement in construction time compared to other compressed methods for comparable index size. A PAC query can need single random access and be performed in constant time in favorable instances. Using limited computation resources, we built PAC for very large collections. They include 32,000 human RNA-seq samples in five days, the entire Genbank bacterial genome collection in a single day for an index size of 3.5TB. The latter is, to our knowledge, the largest sequence collection ever indexed using an approximate membership query structure. We also showed that PAC’s ability to query 500,000 transcript sequences in less than an hour. PAC’s open-source software is available athttps://github.com/Malfoy/PAC.
Positional Context of Myonuclear Transcription during Injury-induced Muscle Regeneration
Authors: Buckley Kole H. , Nestor-Kalinoski Andrea L. , Pizza Francis X.
Published: February 2022

Fundamental aspects underlying skeletal muscle regeneration after injury are poorly understood. This investigation begins to address deficiencies in knowledge by examining the kinetics of myonuclear accretion, positioning, and global transcription during injury-induced muscle regeneration in mice. We demonstrate that myonuclear accretion plateaus within 7 d of an injury and that the majority (~70%) of myonuclei are centrally aligned in linear arrays (nuclear chains) throughout the course of regeneration. Relatively few myonuclei were found in a peripheral position (~20%) or clustered (~10%) together during regeneration. Importantly, transcriptional activity of individual myonuclei in nuclear chains was high, and greater than that of peripheral or clustered myonuclei. Transcription occurring primarily in nuclear chains elevated the collective transcriptional activity of regenerating myofibers during the later stage of regeneration. Importantly, the number of myonuclei in chains and their transcriptional activity were statistically correlated with an increase in myofiber size during regeneration. Our findings demonstrate the positional context of transcription during regeneration and highlight the importance of centralized nuclear chains in facilitating hypertrophy of regenerating myofibers after injury.
Shisa7-dependent regulation of GABAA receptor single-channel gating kinetics
Authors: Castellano David , Wu Kunwei , Keramidas Angelo , Lu Wei
Published: February 2022

GABAA receptors (GABAARs) mediate the majority of fast inhibitory transmission throughout the brain. Although it is widely known that pore-forming subunits critically determine receptor function, it is unclear whether their single-channel properties are modulated by GABAAR-associated transmembrane proteins. We previously identified Shisa7 as a GABAAR auxiliary subunit that modulates the trafficking, pharmacology, and kinetic properties of these receptors. In particular, Shisa7 accelerates receptor deactivation; however, the underlying mechanisms by which Shisa7 controls GABAAR kinetics have yet to be determined. Here we have performed single-channel recordings and find that while Shisa7 does not change channel slope conductance, it reduces the frequency of openings. Importantly, Shisa7 modulates GABAAR gating by decreasing the duration and open probability (Po) within bursts. Kinetic analysis of dwell times, activation modeling, and macroscopic simulations indicate that Shisa7 accelerates GABAAR deactivation by governing the time spent between close and open states during gating. Together, our data provide a mechanistic basis for how Shisa7 controls GABAAR gating kinetics and reveal for the first time that GABAAR single-channel properties can be modulated by an auxiliary subunit. These findings shed light on processes that shape the temporal dynamics of GABAergic transmission.
Cross-modality Synthesis of EM Time Series and Live Fluorescence Imaging
Authors: Santella Anthony , Kolotuev Irina , Kizilyaprak Caroline , Bao Zhirong
Published: February 2022

Analyses across imaging modalities allow the integration of complementary spatiotemporal information about brain development, structure and function. However, systematic atlasing across modalities is limited by challenges to effective image alignment. We combine highly spatially resolved electron microscopy (EM) and highly temporally resolved time-lapse fluorescence microscopy (FM) to examine the emergence of a complex nervous system in C. elegans embryogenesis. We generate an EM pseudo time series at four classic developmental stages and create a landmark-based co-optimization algorithm for cross-modality image alignment, which handles developmental heterochrony among datasets to achieve accurate single-cell level alignment. Synthesis based on the EM series and time-lapse FM series carrying different cell-specific markers reveals critical dynamic behaviors across scales of identifiable individual cells in the emergence of the primary neuropil, the nerve ring, as well as a major sensory organ, the amphid. Our study paves the way for systematic cross-modality analysis in C. elegans and demonstrates a powerful approach that may be applied broadly.

Highlights

An EM time series to examine the emergence of an entire nervous system

A landmark-based co-optimization algorithm for cross modality image alignment in the presence of developmental heterochrony

Integration of EM and fluorescence series reveals cell behaviors at high spatial and temporal resolution

Systematic single-cell annotation of EM data enables efficient navigation and targeted re-imaging
Differential adaptive potential and vulnerability to climate-driven habitat loss in Brazilian mangroves
Authors: de Deus Vidal João , Mori Gustavo Maruyama , Cruz Mariana Vargas , da Silva Michele Fernandes , de Moura Yohans Alves , de Souza Anete Pereira
Published: February 2022

Geographic and environmental differences have been identified as factors influencing Brazilian mangrove trees’ genetic diversity. Geographically, distinct species have convergent spatial genetic structures, indicating a limited gene flow between northern and southern populations. Environmentally, genomic studies and common garden experiments have found evidence of local adaptations along the latitudinal gradient of the Brazilian coast. However, little is known about how such adaptive heterogeneity could be affected by a rapidly changing climate in the coming decades, and the combination of deforestation and climate-induced habitat loss may affect these forests and their genetic diversity. Here, we applied two genomic-environmental association methods to model the turnover of potentially adaptive alleles for two dominant mangrove trees: Avicennia germinans and A. schaueriana. We analyzed a total of 134 individuals from six populations of A. germinans and ten populations of A. schaueriana spanning the Brazilian coast from 1 °S to 28 °S. Gradient forest models identified temperature-related variables as the most important predictors for A. germinans outlier loci, whereas both temperature and precipitation were important for A. schaueriana. We modeled allele frequencies and projected them for future climatic scenarios to estimate adaptively driven vulnerability. We assessed climate-driven habitat loss through climate-only distribution models and calculated annual deforestation rates for each sampled region. Finally, to assess the vulnerability of individual populations, we combined the environmental suitability, deforestation data, and adaptive vulnerability projections. For both species, subtropical populations presented a higher vulnerability than equatorial populations to climate-driven habitat loss. We also identified deforestation rates at the sampled sites that were alarmingly higher than the global average mangrove deforestation rate. Our results provide improved estimates of the impacts of ongoing climate change and human-caused habitat loss on the distribution of mangroves and highlight the importance of site-based conservation strategies that consider individual subtropical and equatorial mangrove forests.
Unpacking COVID-19 and Conspiracy Theories in the UK Black Community
Authors: Vandrevala Tushna , Hendy Jane , Hanson Kristin , Alidu Lailah , Ala Aftab
Published: February 2022

Objectives

Conspiracy theories are associated with significant COVID-19 health consequences including lower engagement with protective behaviours. This study uses sensemaking theory, a process of constructing meanings through interpersonal exchanges that enable people to interpret their world to explain the theoretical process underlying the development of conspiratorial beliefs around COVID-19 within Black African and Caribbean communities in the UK.

Design

Qualitative, in-depth interviews were used.

Methods

Twenty-eight members of the communities were recruited; semi-structured interviews were analysed using grounded theory.

Results

Our findings provide an explanation of how an environment of crisis combined with current and historical mistrust, perceived injustice and inequality provided a context in which alternative conspiracy narratives could thrive. The nature of these conspiratorial beliefs made more sense to many of our respondent’s than institutional sources (such as the UK Government). Critically, these alternative beliefs helped respondents shape their decision-making, leading to non-engagement with COVID protective behaviours.

Conclusions

We conclude that the uncertainty of the pandemic, combined with historical and contemporary perceived injustice and mistrust, and a lack of specific identity-aligned messaging, created a perfect environment for conspiratorial sense-making to thrive. This alternative sensemaking was inconsistent with the health-protection messaging espoused by Government. To ensure all groups in society are protected, and for health promotion messages to take purchase, the experiences of different target audiences must be taken into account, with sensemaking anchored in lived experience.
Why FIT and bHLH Ib interdependently regulate Fe-uptake
Authors: Cai Yuerong , Yang Yujie , Ping Huaqian , Lu Chengkai , Lei Rihua , Li Yang , Liang Gang
Published: February 2022

FIT (FER-LIKE IRON DEFICIENCY- INDUCED TRANSCRIPTION FACTOR) and four bHLH Ib transcription factors (TFs) bHLH38, bHLH39, bHLH100 and bHLH101, are the master regulators of Fe uptake genes, and they interact with each other to activate the Fe uptake systems. However, it remains unclear why FIT and bHLH Ib depend on each other to regulate the Fe deficiency response. By analyzing Fe deficiency phenotypes and Fe uptake genes, we found that the quadruplebhlh4xmutants (bhlh38 bhlh39 bhlh100 bhlh101) mimic thefitmutant. Subcellular localization analyses indicate that bHLH38 and bHLH39 are preferentially expressed in the cytoplasm whereas bHLH100 and bHLH101 in the nucleus. Transcriptome data show that the genes involved in Fe signaling pathway show the same expression trends inbhlh4xandfit. Genetic analyses suggest that FIT and bHLH Ib depend each other to regulate the Fe deficiency response. Further biochemical assays indicate that bHLH Ib TFs possess the DNA binding ability and FIT has the transcription activation ability. This work concludes that FIT and bHLH Ib form a functional transcription complex in which bHLH Ib is responsible for target recognition and FIT for transcription activation, explaining why FIT and bHLH Ib interdependently regulate Fe uptake.
DILIC: An AI based classifier to search for Drug-Induced Liver Injury literature
Authors: Rathee Sanjay , MacMahon Meabh , Liu Anika , Katritsis Nicholas , Youssef Gehad , Hwang Woochang , Wollman Lilly , Han Namshik
Published: February 2022

Drug-Induced Liver Injury (DILI) is a class of Adverse Drug Reactions (ADR) which causes problems in both clinical and research settings. It is the most frequent cause of acute liver failure in the majority of western countries and is a major cause of attrition of novel drug candidates. Manual trawling of literature for is the main route of deriving information on DILI from research studies. This makes it an inefficient process prone to human error. Therefore, an automatized AI model capable of retrieving DILI-related papers from the huge ocean of literature could be invaluable for the drug discovery community. In this project, we built an artificial intelligence (AI) model combining the power of Natural Language Processing (NLP) and Machine Learning (ML) to address this problem. This model uses NLP to filter out meaningless text (e.g. stopwords) and uses customized functions to extract relevant keywords as singleton, pair, triplet and so on. These keywords are processed by apriori pattern mining algorithm to extract relevant patterns which are used to estimate initial weightings for a ML classifier. Along with pattern importance and frequency, an FDA-approved drug list mentioning DILI adds extra confidence in classification. The combined power of these methods build a DILI classifier (DILIC) with 94.91% cross-validation and 94.14% external validation accuracy. To make DILIC as accessible as possible, including to researchers without coding experience, an R Shiny App capable of classifing single or multiple entries for DILI is developed to enhance ease of user experience and made available at https://researchmind.co.uk/diliclassifier/).
Sequence-based Functional Metagenomics Reveals Novel Natural Diversity of Functioning CopA in Environmental Microbiomes
Authors: Li Wenjun , Wang Likun , Li Xiaofang , Zheng Xin , Cohen Michael F. , Liu Yong-Xin
Published: February 2022

Exploring natural diversity of functional genes/proteins from environmental DNA (eDNA) in a high-throughput fashion remains challenging. In this study, we developed a sequence-based functional metagenomics procedure for mining the diversity of copper resistance genecopAin global microbiomes, by combining the metagenomic assembly technology, local BLAST, evolutionary trace analysis (ETA), chemical synthesis, and conventional functional genomics. In total, 88 metagenomes were collected from a public database and subjected tocopAdetection, resulting in 93,899 hits. Manual curation of 1214 hits of high-confidence led to the retrieval of 517 unique CopA candidates, which were further subjected to ETA. Eventually 175 novelcopAsequences of high-quality were discovered. Phylogenetic analysis showed that almost all of these putative CopA proteins are distantly related to known CopA proteins, with 55 sequences from totally unknown species. Ten novel and three knowncopAgenes were chemically synthesized for further functional genomic tests using the Cu-sensitiveEscherichia coli(ΔcopA). Growth test and Cu uptake determination showed that five novel clones had positive effects on host Cu resistance and uptake. One recombinant harboringcopA-like 15 (copAL15) successfully restored Cu resistance of host with a substantially enhanced Cu uptake. Two novelcopAgenes were fused with thegfpgene and expressed inE. colifor microscopic observation. Imaging results showed that they were successfully expressed and their proteins were localized to the membrane. The results here greatly expand the diversity of known CopA proteins, and the sequence-based procedure developed overcomes biases in length, screening methods, and abundance of conventional functional metagenomics.
The sialidase NEU3 promotes pulmonary fibrosis in mice
Authors: Pilling Darrell , Sahlberg Kyle , Karhadkar Tejas R. , Chen Wensheng , Gomer Richard H.
Published: February 2022

Sialic acid is often the distal sugar on glycoconjugates, and sialidases are enzymes that remove this sugar. In fibrotic lesions in human and mouse lungs, there is extensive desialylation of glycoconjugates, and upregulation of sialidases including the extracellular sialidase NEU3. In the bleomycin model of pulmonary fibrosis, mice lacking NEU3 (Neu3-/-) showed strongly attenuated bleomycin-induced weight loss, lung damage, inflammation, upregulation of TGF-β1, and fibrosis. This indicates that NEU3 is necessary for the full spectrum of bleomycin-induced pulmonary fibrosis. To determine if NEU3 is sufficient for fibrosis, mice not treated with bleomycin were treated with recombinant murine NEU3 or inactive NEU3. Aspiration of NEU3 caused inflammation and fibrosis in the lungs, while inactive NEU3 caused inflammation but not fibrosis. Mice were also treated with NEU3 starting 10 days after bleomycin. In male but not female mice, NEU3 increased inflammation and fibrosis. Inactive NEU3 did not enhance bleomycin-induced lung fibrosis. These results suggest that NEU3 is sufficient to induce fibrosis in the lungs, and that this effect is mediated by NEU3’s enzymic activity.
Predatory mites, a green pesticide, and an Entomopathogenic compound: A proposed IPM tactic based on pest species diversity indices and population dynamics
Authors: Zidan Islam Mohammad , El-Saiedy Elsayed Mohamed Ahmed K. , Abou-Elella Gomaa Mohamed , Hassan Mourad Fahmy
Published: February 2022

The study was aimed to conduct the population dynamics and diversity indices for three major pest species in order to design an IPM protocol in two experimental sites (Om Saber, Beheira Governorate 30°29’50.6”N, 30°46’18.8”E), and (Kom Oshim, Fayoum Governorate 29°34’40.9”N, 30°55’38.3”E). The resulted data showed statistically significant fluctuation, population dynamics, abundance, distribution, and diversity indices of the two-spotted spider mite (TSSM)Tetranychus urticaeKoch (Acari: Tetranychidae), the silver leaf whiteflyBemisia tabaciGenn. (Hemiptera: Aleyrodidae), and the onion thripsThrips tabaciLindman (Thysanoptera: Thripidae) which recorded on four plant species belonging to Brassicaceae (Siberian (Russian) kaleBrassica napus var. pabulariaL. and Italian (Tuscan) kaleBrassica oleracea var. palmifolia), and Lamiaceae (SpearmintMentha spicataL. and Saudi MintMentha longifoliaL.). The proposed IPM program consisted of predatory mites;Phytoseiulus persimilisAthias-Henriot,Amblyseius swirskiiAthias-Henriot, andCydnoseius negevi(Swirski & Amitai) (Acari: Phytoseiidae), a green pesticide, and an entomopathogenic compound. It was concluded that abiotic and biotic factors together help in explaining why various pest species build their communities rapidly and increase their parameters that become above the EIL. Such factors are hypothesized to affect the plant-arthropod, predator-herbivore, predator-predator, and tri-trophic interactions. And it recommends the application of such protocol should consider the timing of tacking an action and merging tactics together to get the maximum efficiency.
Semaphorin 3G exacerbates joint inflammation through the accumulation and proliferation of macrophages in the synovium
Authors: Shoda Jumpei , Tanaka Shigeru , Etori Keishi , Hattori Koto , Kasuya Tadamichi , Ikeda Kei , Maezawa Yuko , Suto Akira , Suzuki Kotaro , Nakamura Junichi , Maezawa Yoshiro , Takemoto Minoru , Betsholtz Christer , Yokote Koutaro , Ohtori Seiji , Nakajima Hiroshi
Published: February 2022

Objective

Methotrexate (MTX) is an anchor drug for rheumatoid arthritis (RA) treatment; however, the exact mechanisms by which MTX improves RA activity are still debatable. This study aimed to understand the roles of molecules whose expression is affected by MTX in RA patients and find novel therapeutic targets.

Methods

CD4+ T cells from 28 treatment naïve RA patients before and 3 months after the initiation of MTX treatment were subjected to DNA microarray analyses. The expression of Semaphorin 3G (Sema3G), as one of the differentially-expressed genes, and its receptor, Neuropilin-2 (Nrp2), was evaluated in RA synovium and collagen-induced arthritis (CIA) synovium. CIA and collagen antibody-induced arthritis (CAIA) were induced in Sema3G-deficient (Sema3G-/-) mice and control mice, and the clinical score, histological score, and serum cytokines were assessed. The migration and proliferation of Sema3G-stimulated bone marrow-derived macrophages (BMMs) were analyzed in vitro. The effect of local Sema3G administration during CAIA on the clinical score and the quantity of infiltrating macrophages was evaluated.

Results

The expression of Sema3G in CD4+ T cells was downregulated by MTX treatment in RA patients. Sema3G was expressed in RA but not osteoarthritis synovium, and its receptor Nrp2 was mainly expressed on activated macrophages. Sema3G deficiency ameliorated CIA and CAIA. Sema3G stimulation enhanced the migration and proliferation of BMMs. The local administration of Sema3G deteriorated CAIA and increased infiltrating macrophages.

Conclusions

Upregulation of Sema3G in RA synovium is a novel mechanism to deteriorate joint inflammation through the accumulation of macrophages.

Key messages

Semaphorin 3G is expressed in the inflamed synovium in human and mice.

The receptor of Semaphorin 3G is mainly expressed on M1 macrophages.

Semaphorin 3G deteriorates inflammatory arthritis through macrophage proliferation and migration.
Distinctiveness and continuity in transcriptome and connectivity in the anterior-posterior axis of the paraventricular nucleus of thalamus
Authors: Shima Yasuyuki , Skibbe Henrik , Sasagawa Yohei , Fujimori Noriko , Nikaido Itoshi , Hattori Nobutaka , Kato Tadafumi
Published: February 2022

The paraventricular nucleus of the thalamus (PVT) projects axons to multiple areas and mediates a wide range of behaviors. Heterogeneity of functions and axonal projections in PVT have been reported, but what cell types exist in PVT and how different they are have not been addressed. We applied single-cell RNA sequencing to depict transcriptomic characteristics of mouse PVT neurons. The transcriptome of PVT neurons had a continuous distribution with the largest variance corresponding to the anterior-posterior axis. Although the single-cell transcriptome classified PVT neurons into four types, transcriptomic and histological analyses showed their continuity. Similarly, anterior and posterior subpopulations had nearly non-overlapping axon projection patterns, while another population showed intermediate patterns. In addition, they responded differently to appetite-related neuropeptides, and their chemogenetic activation showed opposing effects in food consumption. Our studies showed contrasts and continuity of PVT neurons underlying their function as a behavior-modulating hub.
The relationship of balanced scorecard perspectives and government organization performance measurement
Authors: Rahayu Sri , Yudi Yudi , Rahayu Rahayu , Luthfi Musthafa
Published: February 2022

Purpose

This research aimed to analyze the causality between the four perspectives in the balanced scorecard (BSC) performance and to analyze the different performance of the four perspectives for the two group schools studied.

Design/methodology/approach

Quantitative data were processed using Smart PLS 0.3 and an independent sample t-test. Qualitative data collected using open questionnaires on performance achievement strategies and constraints were analyzed using the Leximancer 4.51.

Findings

Results showed that innovation and learning performance influenced financial performance and internal business performance. However, innovation and learning performance did not affect customer satisfaction performance. Internal business performance affected financial performance. However, internal business performance did not influence customer satisfaction performance. Customer satisfaction performance did not influence financial performance. Customer satisfaction performance did not mediate the relationship between innovation and learning performance and financial performance. Internal business performance mediated the relationship between innovation and learning performance and financial performance. The two school groups exhibited differing innovation and learning performance, with no difference for the other three perspectives.

Practical implications

The implication of the study is the necessity to create synergy between all parties (school and authorities) to optimize school performance. Improvement in financial performance, especially related to transparency and accountability, will help to improve stakeholders' trust in schools. The government can use the BSC to evaluate public school performance to achieve comprehensive assessment results.

Originality/value

The use of the four perspectives in the BSC performance since public schools in Indonesia have never implemented it.
Perspectives of cybersecurity for ameliorative Industry 4.0 era: a review-based framework
Authors: Haleem Abid , Javaid Mohd , Singh Ravi Pratap , Rab Shanay , Suman Rajiv
Published: February 2022

Purpose

Industry 4.0 refers to the interconnection of cyber-physical systems, which connects the physical and digital worlds by collecting digital data from physical objects/processes, and using this data to drive automation and optimisation. Digital technologies used in this revolution gather and handle massive volumes of high-velocity streams while automating field operations and supply chain activities. Cybersecurity is a complicated process that helps sort out various hacking issues of Industry 4.0. This purpose of this paper is to provide an overview on cybersecurity and its major applications for Industry 4.0.

Design/methodology/approach

The rise of Industry 4.0 technologies is changing how machines and associated information are obtained to evaluate the data contained within them. This paper undertakes a comprehensive literature-based study. Here, relevant research papers related to cybersecurity for Industry 4.0 are identified and discussed. Cybersecurity results in high-end products, with faster and better goods manufactured at a lesser cost.

Findings

Artificial intelligence, cloud computing, internet of things, robots and cybersecurity are being introduced to improve the Industry 4.0 environment. In the starting, this paper provides an overview of cybersecurity and its advantages. Then, this study discusses technologies used to enhance the cybersecurity process. Enablers, progressive features and steps for creating a cybersecurity culture for Industry 4.0 are discussed briefly. Also, the research identified the major cybersecurity applications for Industry 4.0 and discussed them. Cybersecurity is vital for better data protection in many businesses and industrial control systems. Manufacturing is getting more digitised as the sector embraces automation to a more significant level than ever before.

Originality/value

This paper states about Industry 4.0 and the safety of multiple business process systems through cybersecurity. A significant issue for Industry 4.0 devices, platforms and frameworks is undertaken by cybersecurity. Digital transformation in the Industry 4.0 era will increase industrial competitiveness and improve their capacity to make optimum decisions. Thus, this study would give an overview of the role of cybersecurity in the effective implementation of Industry 4.0.
Managing the knowledge for innovation in Eastern European firms: open or closed innovation?
Authors: Saunders Kieran , Radicic Dragana
Published: February 2022

Purpose

This study investigates the impact of cooperation with external partners on the intensity of product innovation as well as its commercial success. The focus is on firms located in the Eastern European countries that are seldom a subject of empirical innovation studies. The theoretical framework takes into account that moderate and modest innovator countries, which comprise the sample, have distinct innovation ecosystems relative to advanced economies.

Design/methodology/approach

The study uses data from the Business Environment and Enterprise Performance Survey (BEEPS) that was conducted in 2013–2014 and covering the period of the past three years. Product innovation is measured through its intensity (a number of product innovation) and through its commercial success (innovative sales). A set of hypotheses are tested using a negative binomial estimator (for the number of product innovation) and a tobit estimator (for innovative sales) estimated in Stata statistical software.

Findings

Empirical findings show that vertical cooperation has a positive effect on the intensity of innovation activities. In contrast, the authors find no evidence that horizontal cooperation or cooperation with science partners (universities and research centres) increase innovation intensity or its commercial success. Besides vertical cooperation, for a commercial success, it is equally beneficial for firms to use their own innovative ideas. These results taken together suggest that closed innovation and cooperation with customers and suppliers are critical determinants of product innovation in Eastern European firms.

Originality/value

The study contributes to expanding the research on knowledge management and open innovation in less advanced economies.