bluuebunny/crossref_metadata_2025_split huggingface dataset:
The 28-Day Mortality Outcome of the Complete Hour-1 Sepsis Bundle in the Emergency Department
Authors: Prachanukool Thidathit , Sanguanwit Pitsucha , Thodamrong Fuangsiri , Suttapanit Karn 
Published: November 2021

ABSTRACT

Introduction:
The Surviving Sepsis Campaign published the Hour-1 Sepsis Bundle in 2018. The first-hour management of patients with sepsis in the emergency department (ED) is important, as suggested in the Hour-1 Sepsis Bundle. The objectives of the present study were to evaluate 28-day mortality and delayed septic shock with use of a complete and incomplete Hour-1 Sepsis Bundle in the ED.

Methods:
This prospective cohort study included adult patients with sepsis from March to July 2019. We followed the sepsis protocol used in the ED of a tertiary care hospital.

Results:
We enrolled 593 patients, with 55.9% in the complete Hour-1 Sepsis Bundle group. The 28-day mortality was 3.9% overall and no significant difference between the complete and incomplete Hour-1 Sepsis Bundle groups (3.6% vs. 4.2%, P = 0.707). Complete Hour-1 Sepsis Bundle treatment was not associated with 28-day mortality (adjusted OR = 2.04, 95% confidence interval [CI] = 0.72–5.74, P = 0.176) or delayed septic shock (adjusted OR = 0.74, 95% CI = 0.30–1.78, P = 0.499). Completion of each bundle did not affect outcomes of 28-day mortality and delayed septic shock.

Conclusions:
The complete Hour-1 Sepsis Bundle treatment in the ED was not significantly associated with 28-day mortality and delayed septic shock.

Trial registration:
The trial was registered in the Thai Clinical Trial Registry, TCTR 20200526013.
Limited impact of contact tracing in a University setting for COVID-19 due to asymptomatic transmission and social distancing
Authors: Stocks Daniel , Nixon Emily , Trickey Adam , Homer Martin , Brooks-Pollock Ellen 
Published: November 2021

AbstractContact tracing is an important tool for controlling the spread of infectious diseases, including COVID-19. Here, we investigate the spread of COVID-19 and the effectiveness of contact tracing in a university population, using a data-driven ego-centric network model constructed with social contact data collected during 2020 and similar data collected in 2010. We find that during 2020, university staff and students consistently reported fewer social contacts than in 2010, however those contacts occurred more frequently and were of longer duration. We find that contact tracing in the presence of social distancing is less impactful than without social distancing. By combining multiple data sources, we show that University-aged populations are likely to develop asymptomatic COVID-19 infections. We find that asymptomatic index cases cannot be reliably back-traced through contact tracing and consequently transmission in their social network is not significantly reduced through contact tracing. In summary, social distancing restrictions had a large impact on limiting COVID-19 outbreaks in universities; to reduce transmission further contact tracing should be used in conjunction with alternative interventions.
Large-scale algorithmic search identifies stiff and sloppy dimensions in synaptic architectures consistent with murine neocortical wiring
Authors: Jabri Tarek , MacLean Jason N. 
Published: November 2021

AbstractComplex systems can be defined by “sloppy” dimensions, meaning that their behavior is unmodified by large changes to specific parameter combinations, and “stiff” dimensions whose change results in considerable behavioral modification. In the neocortex, sloppiness in synaptic architectures would be crucial to allow for the maintenance of asynchronous irregular spiking dynamics with low firing rates despite a diversity of inputs, states, and both short- and long-term plasticity. Using simulations on neural networks with first-order spiking statistics matched to firing in murine visual cortex while varying connectivity parameters, we determined the stiff and sloppy parameters of synaptic architectures across three classes of input (brief, continuous, and cyclical). Algorithmically-generated connectivity parameter values drawn from a large portion of the parameter space reveal that specific combinations of excitatory and inhibitory connectivity are stiff and that all other architectural details are sloppy. Stiff dimensions are consistent across input classes with self-sustaining synaptic architectures following brief input occupying a smaller subspace as compared to the other input classes. Experimentally estimated connectivity probabilities from mouse visual cortex are consistent with the connectivity correlations found and fall in the same region of the parameter space as architectures identified algorithmically. This suggests that simple statistical descriptions of spiking dynamics are a sufficient and parsimonious description of neocortical activity when examining structure-function relationships at the mesoscopic scale. Additionally, coarse graining cell types does not prevent the generation of accurate, informative, and interpretable models underlying simple spiking activity. This unbiased investigation provides further evidence of the importance of the interrelationship of excitatory and inhibitory connectivity to establish and maintain stable spiking dynamical regimes in the neocortex.Author SummaryConnections between neurons are continuously changing to allow learning and adaptation to new stimuli. However, the ability of neural networks to vary these connections while avoiding excessively high- or low-activity states is still not well understood. We tackled this question by studying how changes in the parameters of connectivity within and between different neuronal populations impacted network activity in computational models. We identified specific combinations of parameters, deemed “stiff”, that must be maintained to observe activity consistent with recordings from murine visual cortex, while the rest of the parameters can be varied freely with minimal effects on activity. Our results agree with experimentally measured connectivity statistics demonstrating the importance of balancing opposing forces to maintain activity in a natural regime.
Fluorescent and bioluminescent calcium indicators with tuneable colors and affinities
Authors: Mertes Nicole , Busch Marvin , Huppertz Magnus-Carsten , Hacker Christina Nicole , Gürth Clara-Marie , Kühn Stefanie , Hiblot Julien , Koch Birgit , Johnsson Kai 
Published: November 2021

AbstractWe introduce a family of bright, rhodamine-based calcium indicators with tuneable affinities and colors. The indicators can be specifically localized to different cellular compartments and are compatible with both fluorescence and bioluminescence readouts through conjugation to HaloTag fusion proteins. Importantly, their increase in fluorescence upon localization enables no-wash live-cell imaging, which greatly facilitates their use in biological assays. Applications as fluorescent indicators in rat hippocampal neurons include the detection of single action potentials and of calcium fluxes in the endoplasmic reticulum (ER). Applications as bioluminescent indicators include the recording of the pharmacological modulation of nuclear calcium in high-throughput-compatible assays. The versatility and remarkable ease of use of these indicators make them powerful tools for bioimaging and bioassays.Graphical abstract
Semaphorin signaling restricts neuronal regeneration in C. elegans
Authors: Harreguy MB , Tanvir Z , Shah E , Simprevil B , Tran TS , Haspel G 
Published: November 2021

AbstractExtracellular signaling proteins serve as neuronal growth cone guidance molecules during development and are well positioned to be involved in neuronal regeneration and recovery from injury. Semaphorins and their receptors, the plexins, are a family of conserved proteins involved in development that, in the nervous system, are axonal guidance cues mediating axon pathfinding and synapse formation. The Caenorhabditis elegans genome encodes for three semaphorins and two plexin receptors: the transmembrane semaphorins, SMP-1 and SMP-2, signal through their receptor, PLX-1, while the secreted semaphorin, MAB-20, signals through PLX-2. Here, we evaluate the locomotion behavior of knockout animals missing each of the semaphorins and plexins and the neuronal morphology of plexin knockout animals; we described the cellular expression pattern of the promoters of all plexins in the nervous system of C. elegans; and we evaluated their effect on the regrowth and reconnection of motoneuron neurites and the recovery of locomotion behavior following precise laser microsurgery. Regrowth and reconnection were more prevalent in the absence of each plexin, while recovery of locomotion surpassed regeneration in all genotypes.
Initiation of organ maturation and fruit ripening in grapevine is controlled by the CARPO-NAC transcription factor
Authors: D’Incà Erica , Foresti Chiara , Orduña Luis , Amato Alessandra , Vandelle Elodie , Santiago Antonio , Botton Alessandro , Cazzaniga Stefano , Bertini Edoardo , Pezzotti Mario , Giovannoni James , Vrebalov Julia , Matus José Tomás , Tornielli Giovanni Battista , Zenoni Sara 
Published: November 2021

ABSTRACTGrapevine is a woody temperate perennial plant and one of the most important fruit crops with global relevance in both the fresh fruit and winemaking industries. Unfortunately, global warming is affecting viticulture by altering developmental transitions and fruit maturation processes. In this context, uncovering the molecular mechanisms controlling the onset and progression of ripening could prove essential to maintain high-quality grapes and wines. Through a deep inspection of previously published transcriptomic data we identified the NAC family member VviCARPO (Controlled Adjustment of Ripening and maturation of Plant Organs) as a key regulator of grapevine maturation whose induction precedes the expression of well-known ripening associated genes. We explored VviCARPO binding landscapes through DAP-seq and overlapped its bound genes with transcriptomics datasets from stable and transient VviCARPO overexpressing grapevine plants to define a set of high-confidence targets. Among these, we identified key molecular ripening markers. Physiological, metabolic and promoter activation analyses showed that VviCARPO induces chlorophyll degradation and anthocyanin accumulation through the up-regulation of VviSGR1 and VviMYBA1, respectively, with the latter being up-regulated through a VviCARPO-VviNAC03 regulatory complex. Despite showing a closer phylogenetic relationship to senescent-related AtNAP homologues, VviCARPO complemented the nor mutant phenotype in tomato, suggesting it may have acquired a dual role as an orchestrator of both ripening- and senescence-related processes. Our data supports CARPO as a master regulator of the grapevine vegetative-to-mature phase organ transition and therefore an essential target for insuring fruit quality and environmental resilience.SIGNIFICANT STATEMENTCARPO is a grape NAC transcription factor central to fruit ripening and tissue senescence. This regulator influences multiple biological pathways common to both processes including cell wall metabolism, chlorophyll degradation, pigment production and hormone synthesis/signaling through regulation of their key genes. As various external stresses and changing climatic conditions influence vegetative growth and berry ripening, CARPO could prove a useful genetic and breeding target towards maintaining necessary crop performance and fruit-quality characteristics.
Automated Parallel Pattern Search Optimisation of Microfluidic Geometry for Extracellular Vesicle Liquid Biopsies
Authors: Hisey Colin L. , Lim Arvin , Tyler A.J. , Chamley Larry W. , Blenkiron Cherie , Clarke Richard J. 
Published: November 2021

AbstractMicrofluidic liquid biopsies using affinity-based capture of extracellular vesicles (EVs) have demonstrated great potential for providing rapid disease diagnosis and monitoring. However, little effort has been devoted to optimising the geometry of the microfluidic channels for maximum EV capture due to the inherent challenges of physically testing many geometric designs. To address this, we developed an automated parallel pattern search (PPS) optimiser by combining a Python optimiser, COMSOL Multiphysics, and high performance computing. This unique approach was applied to a triangular micropillar array geometry by parameterising repeating unit cells, making several assumptions, and optimising for maximum particle capture efficiency. We successfully optimised the triangular pillar arrays and surprisingly found that simply maximising the total number of pillars and effective surface area did not result in maximum EV capture, as devices with slightly larger pillars and more spacing between pillars allowed contact with slower moving EVs that followed the pillar contours more closely. We then experimentally validated this finding using bioreactor-produced EVs in the best and worst channel designs that were functionalised with an antibody against CD63. Captured EVs were quantified using a fluorescent plate reader, followed by an established elution method and nanoparticle tracking analysis. These results demonstrate the power of automated microfluidic geometry optimisations for EV liquid biopsies and will support further development of this rapidly growing field.
Contrastive learning on protein embeddings enlightens midnight zone
Authors: Heinzinger Michael , Littmann Maria , Sillitoe Ian , Bordin Nicola , Orengo Christine , Rost Burkhard 
Published: November 2021

AbstractExperimental structures are leveraged through multiple sequence alignments, or more generally through homology-based inference (HBI), facilitating the transfer of information from a protein with known annotation to a query without any annotation. A recent alternative expands the concept of HBI from sequence-distance lookup to embedding-based annotation transfer (EAT). These embeddings are derived from protein Language Models (pLMs). Here, we introduce using single protein representations from pLMs for contrastive learning. This learning procedure creates a new set of embeddings that optimizes constraints captured by hierarchical classifications of protein 3D structures defined by the CATH resource. The approach, dubbedProtTucker, has an improved ability to recognize distant homologous relationships than more traditional techniques such as threading or fold recognition. Thus, these embeddings have allowed sequence comparison to step into the “midnight zone” of protein similarity, i.e., the region in which distantly related sequences have a seemingly random pairwise sequence similarity. The novelty of this work is in the particular combination of tools and sampling techniques that ascertained good performance comparable or better to existing state-of-the-art sequence comparison methods. Additionally, since this method does not need to generate alignments it is also orders of magnitudes faster. The code is available athttps://github.com/Rostlab/EAT.
Reconstruction of sound driven, actively amplified and spontaneous motions within the tree cricket auditory organ
Authors: Mhatre Natasha , Dewey James B. , Quiñones Patricia M. , Mason Andrew , Applegate Brian E. , Oghalai John S. 
Published: November 2021

AbstractHearing consists of a delicate chain of events. Sound is first captured by an eardrum or similar organ which is set into vibrations, these vibrations must then be transmitted to sensory cells in a manner that opens mechanosensory channels generating an electrical signal. Studying this process is challenging. Auditory vibrations are in the nano- to picometer-scale and occur at fast temporal scales of milli to microseconds. Finally, most of this process occurs within the body of the animal where it is inaccessible to conventional measurement techniques. For instance, even in crickets, a century-old auditory model system, it is unclear how sound evoked vibrations are transmitted to sensory neurons. Here, we use optical coherence tomography (OCT) to measure how vibrations travel within the auditory organ of the western tree cricket (Oecanthus californicus). We also measure the reversal of this process as mechanosensory cells generate spontaneous oscillations and amplify sound-evoked vibrations. Most importantly, we found that while the mechanosensory neurons were not attached to the peripheral sound collecting structures, they were mechanically well-coupled through acoustic trachea. Thus, the acoustic trachea are not merely conduits for sound but also perform a mechanical function. Our results generate several insights into the similarities between insect and vertebrate hearing, and into the evolutionary history of auditory amplification.
Reassembling a cannon in the DNA defense arsenal: genetics of StySA, a BREX phage exclusion system in Salmonella lab strains
Authors: Zaworski Julie , Dagva Oyut , Brandt Julius , Baum Chloé , Ettwiller Laurence , Fomenkov Alexey , Raleigh Elisabeth A. 
Published: November 2021

AbstractUnderstanding mechanisms that shape horizontal exchange in prokaryotes is a key problem in biology. A major limit on DNA entry is imposed by restriction-modification (RM) processes that depend on the pattern of DNA modification at host-specified sites. In classical RM, endonucleolytic DNA cleavage follows detection of unprotected sites on entering DNA. Recent investigation has uncovered BREX systems, RM-like activities that employ host protection by DNA modification but replication arrest without evident nuclease action on unmodified phage DNA. We show that the historical stySA RM locus of Salmonella enterica sv Typhimurium is a BREX homolog. The stySA29 allele of the hybrid strain LB5000 carries a mutated version of the ancestral LT2 BREX system. Surprisingly, both a restriction and a methylation defect are observed for this lineage despite lack of mutations in brxX, the modification gene homolog. Instead, flanking genes pglZ and brxC each carry multiple mutations (μ) in C-terminal domains. To avoid plasmid artifacts and potential stoichiometric interference, we chose to investigate this system in situ, replacing the mutated pglZμ and brxCμ genes with wild type (WT). PglZ-WT supports methylation in the presence of either BrxCμ or BrxC-WT but not in the presence of a deletion/insertion allele, ΔbrxC::cat. Restriction of phage L requires both BrxC-WT and PglZ-WT, implicating the BrxC C-terminus specifically in restriction activity. Disruption of four other CDS with cat cassettes still permitted modification, suggesting that BrxC, PglZ and BrxX are principal components of the modification activity. BrxL is required for restriction only. A partial disruption of brxL disrupts transcription globally.
School teachers’ perception and challenges towards online teaching during COVID-19 pandemic in India: an econometric analysis
Authors: Kamal Tuba , Illiyan Asheref 
Published: November 2021

PurposeCoronavirus disease 2019 (COVID-19) outbreak has impacted catastrophically every sector of the economy throughout the world. And, the education sector is not leftover from the devastating effects of lockdown, especially in South Asia. It has led to the prolonged closure of schools/universities, subsequently, traditional teaching expeditiously transformed into online teaching. In the light of the events, this study is pertinent to examine teachers’ perceptions of online teaching and the obstacles they face in online teaching during this pandemic.Design/methodology/approachThe research takes a quantitative and sample survey approach. A Google Form Questionnaire was used to obtain a sample of 200 Delhi school teachers in March and April 2021. Data were analyzed in SPSS by using Descriptive Statistics, Factor Analysis, Reliability and Chi-Square test, etc.FindingsThe result of the study indicates that on average, teachers have a positive perception about virtual teaching amid COVID-19 for reducing the learning gap and shaping pupils’ future during the crisis. Nevertheless, they encountered several obstacles in online teaching such as technical obstacles, difficulties in online exams and assessment, etc.Practical implicationsThe findings of this study would persuade educational institutions and policymakers for enhancing the quality of online teaching by embracing the newest instructional strategies and providing continuous training to teachers.Originality/valueSeveral studies described obstacles confronted by instructors in virtual teaching in higher education during the Coronavirus while disregarding the perception and challenges of school teachers toward e-learning in an ongoing outbreak. The present study replenishes this gap.
Objectives and measures of performance of Islamic microfinance banks in Indonesia: the stakeholders' perspectives
Authors: Akbar Taufik , Siti-Nabiha A.K. 
Published: November 2021

PurposeThis study investigates both internal and external stakeholders' views on the objectives and measures of performance of Indonesian Islamic microfinance banks (IMFBs).Design/methodology/approachThis study uses a qualitative approach. In-depth interviews were conducted with a wide range of internal and external stakeholders of IMFBs in Indonesia. The primary stakeholders interviewed comprised the board of directors of IMFBs located in several provinces in Indonesia, including rural and urban areas. The external stakeholders were the regulators/supervisors, represented by the Indonesian Financial Services Authority and Sharīʿah advisors of the National Sharīʿah Board as well as Muslim scholars. The data were analysed using CAQDAS, a computer-assisted tool for qualitative analysis.FindingsThe objectives of the IMFBs are seen to represent more than profits or economic well-being. Their objectives also comprise spirituality and daʿwah (Islamic propagation). Daʿwah is conducted through the provision of funding and services that are aligned with Sharīʿah (Islamic law), the dissemination of information about Islamic financing, which is based on Islamic values and principles, and the payment of zakat (Islamic alms) and charitable contributions. The measures of performance are considered to be more holistic than those of conventional banks. Profit and growth are deemed important as the means to achieve social well-being objectives.Research limitations/implicationsBetter insights into the objectives and measures of IMFBs could be achieved from interviews with other stakeholder categories, such as customers and the community. This could be the focus of future research.Originality/valueThis study added a new discussion to the limited empirical literature on IMFBs by investigating the views of stakeholders on the objectives and performance of IMFBs in Indonesia.
Alleviating the impact of SNS fatigue on user discontinuance
Authors: Lee One-Ki Daniel , Lee Seoyoun , Suh Woojong , Chang Younghoon 
Published: November 2021

PurposeSocial networking services (SNSs) have become deeply ingrained into our daily life. However, it has often been reported that users experience negative feelings regarding SNS usage. This phenomenon presents challenges for SNS providers in retaining or increasing their customer base. This study focuses on SNS fatigue, a negative psychological state that can lead to discontinuance intention among SNS users. This study proposes two distinctive SNS-specific contexts and investigates how they alleviate the negative effect of SNS fatigue on user behavior.Design/methodology/approachDrawing upon the context-specific theorization perspective, a model involving moderation effects of the SNS-specific contexts on the relationship between user's SNS fatigue and discontinuance intention was proposed. The model was tested using survey data of active SNS users.FindingsThe results indicate that SNS fatigue leads to user discontinuance intention. However, the SNS-specific contexts, such as social interaction context and platform service context, negatively moderate the relationship between SNS fatigue and user discontinuance intention.Originality/valueThe findings of this study are expected to help SNS providers develop strategies to improve their services for effective user retention.