bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Height Estimation on Tidal Volume Calculation for Protective Ventilation—A Prospective Observational Study
Authors: Alexandre André R. , Rocha Filipa R. , Landeiro Luís , Mota Pedro , Jones Joana , Gomes José A. 
Published: May 2021

Objectives:
The current standard of care to deliver invasive mechanical ventilation support is the protective ventilation approach. One pillar of this approach is the limitation of tidal volume to less than 6 mL/Kg of predicted body weight. Predicted body weight is calculated from patient’s height. Yet, little is known about the potential impact of errors arising from visual height estimation, a common practice, to calculate tidal volumes. The aim of this study was to evaluate that impact on tidal volume calculation to use during protective ventilation.

Design:
Prospective observational study.

Setting:
An eight-bed polyvalent ICU.

Patients:
Adult patients (≥ 18 yr).

Interventions:
None.

Measurements and Main Results:
Tidal volumes were calculated from visual height estimates made by physicians, nurses, and patients themselves and compared with tidal volumes calculated from measured heights. Comparisons were made using the paired t test. Modified Bland-Altman plots were used to assess agreement between height estimates and measurements. One-hundred patients were recruited. Regardless of the height estimator, all the mean tidal volumes would be greater than 6 mL/Kg predicted body weight (all p < 0.001). Additionally, tidal volumes would be greater than or equal to 6.5 mL/Kg predicted body weight in 18% of patients’ estimates, 25% of physicians’ estimates, and 30% of nurses’ estimates. Patients with lower stature (< 165 cm), older age, and surgical typology of admission were at increased risk of being ventilated with tidal volumes above protective threshold.

Conclusions:
The clinical benefit of the protective ventilation strategy can be offset by using visual height estimates to calculate tidal volumes. Additionally, this approach can be harmful and potentially increase mortality by exposing patients to tidal volumes greater than or equal to 6.5 mL/Kg predicted body weight. In the interest of patient safety, every ICU patient should have his or her height accurately measured.
Artificial Intelligence Sepsis Prediction Algorithm Learns to Say “I don’t know”
Authors: Shashikumar Supreeth P. , Wardi Gabriel , Malhotra Atul , Nemati Shamim 
Published: May 2021

AbstractSepsis is a leading cause of morbidity and mortality worldwide. Early identification of sepsis is important as it allows timely administration of potentially life-saving resuscitation and antimicrobial therapy. We present COMPOSER (COnformal Multidimensional Prediction Of SEpsis Risk), a deep learning model for the early prediction of sepsis, specifically designed to reduce false alarms by detecting unfamiliar patients/situations arising from erroneous data, missingness, distributional shift and data drifts. COMPOSER flags these unfamiliar cases as ‘indeterminate’ rather than making spurious predictions. Six patient cohorts (515,720 patients) curated from two healthcare systems in the United States across intensive care units (ICU) and emergency departments (ED) were used to train and externally and temporally validate this model. In a sequential prediction setting, COMPOSER achieved a consistently high area under the curve (AUC) (ICU: 0.925–0.953; ED: 0.938–0.945). Out of over 6 million prediction windows roughly 20% and 8% were identified as ‘indeterminate’ amongst non-septic and septic patients, respectively. COMPOSER provided early warning within a clinically actionable timeframe (ICU: 12.2 [3.2 22.8] and ED: 2.1 [0.8 4.5] hours prior to first antibiotics order) across all six cohorts, thus allowing for identification and prioritization of patients at high risk for sepsis.
Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain
Authors: Desai Mitul , Sharma Jitendra , Slusarczyk Adrian L. , Chapin Ashley , Wiśniowska Agata , Ohlendorf Robert , Sur Mriganka , Jasanoff Alan 
Published: May 2021

ABSTRACTMolecular imaging could have great utility for detecting, classifying, and guiding treatment of brain disorders, but existing probes offer limited capability for assessing relevant physiological parameters. Here we describe a potent approach for noninvasive mapping of cancer-associated enzyme activity using a molecular sensor that acts on the vasculature, providing a diagnostic readout via local changes in hemodynamic image contrast. The sensor is targeted at the fibroblast activation protein (FAP), an extracellular dipeptidase and clinically relevant biomarker of brain tumor biology. Optimal FAP sensor variants were identified by screening a series of prototypes for responsiveness in a cell-based bioassay. The best variant was then applied for quantitative neuroimaging of FAP activity in rats, where it reveals nanomolar-scale FAP expression by xeno-grafted tumor cells. The activated probe also induces robust hemodynamic contrast in nonhuman primate brain. This work thus demonstrates a translatable strategy for ultrasensitive functional imaging of molecular targets in neuromedicine.
A comprehensive landscape of 60S ribosome biogenesis factors
Authors: Sailer Carolin , Jansen Jasmin , Erzberger Jan P. , Stengel Florian 
Published: May 2021

SummaryEukaryotic ribosome biogenesis is facilitated and regulated by numerous ribosome biogenesis factors (RBFs). High-resolution cryo-EM maps have defined the molecular interactions of RBFs during maturation, but many transient and dynamic interactions, particularly during early assembly, remain uncharacterized. Using quantitative proteomics and crosslinking coupled to mass spectrometry (XL-MS) data from a extensive set of pre-ribosomal particles, we derived a comprehensive and time-resolved interaction map of RBF engagement during 60S maturation. A novel filter that efficiently eliminates false positive interactions and integration of our MS data with known structural information allowed us to localize 22 unmapped RBFs to specific biogenesis intermediates and to identify 9 proteins that represent potentially new RBFs. Our analysis reveals an extensive interaction network for the casein kinase complex in 60S maturation and elucidates the timing and molecular function of 60S engagement by DEAD-box ATPases. Our data provide a powerful resource for future studies of 60S ribosome biogenesis.
CRISPR activation and interference screens in primary human T cells decode cytokine regulation
Authors: Schmidt Ralf , Steinhart Zachary , Layeghi Madeline , Freimer Jacob W. , Nguyen Vinh Q. , Blaeschke Franziska , Marson Alexander 
Published: May 2021

AbstractThe pathways that regulate cytokine responses in T cells are disrupted in autoimmunity, immune deficiencies, and cancer, and include immunotherapy targets. Systematic discovery of cytokine regulators requires both loss-of-function and gain-of-function studies, which have been challenging in primary human cells. We now have accomplished genome-wide pooled CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) screens in primary human T cells to map gene networks controlling Interleukin-2 and Interferon-γ production. Arrayed CRISPRa confirmed key hits and enabled multiplexed T cell secretome characterization, revealing reshaped cytokine responses driven by individual regulators. CRISPRa uncovered genes not canonically expressed in T cells, including the transcription factor FOXQ1, whose overexpression promoted the expression of most cytokines, while selectively dampening T helper 2 (Th2) cytokines. Paired CRISPRa and CRISPRi screens reveal signaling components that tune critical immune cell functions, which could inform design of future immunotherapies.
Neocortical Localization and Thalamocortical Modulation of Neuronal Hyperexcitability in Fragile X Syndrome
Authors: Pedapati Ernest V , Schmitt Lauren M. , Ethridge Lauren E. , Liu Rui , Smith Elizabeth , Sweeney John A , Shaffer Rebecca C. , Dominick Kelli C. , Gilbert Donald L. , Wu Steve W. , Horn Paul S. , Binder Devin , Lamy Martine , Axford Megan , Miyakoshi Makoto , Erickson Craig A. 
Published: May 2021

AbstractFragile X Syndrome (FXS) is a monogenetic form of intellectual disability and autism in which well-established knockout (KO) animal models point to neuronal hyperexcitability and abnormal gamma-frequency physiology as a basis for key disorder features. Translating these findings into patients may identify tractable treatment targets. Using source modeling of resting-state electroencephalography data, we report novel findings in FXS, including 1) increases in localized gamma activity, 2) pervasive changes of theta/alpha activity, indicative of disrupted thalamocortical modulation coupled with elevated gamma power, 3) stepwise moderation of these abnormalities based on female sex, and 4) relationship of this physiology to intellectual disability and neuropsychiatric symptoms. Our observations extend findings in Fmr1-/- KO mice to patients with FXS and raise a novel role for disrupted thalamocortical modulation in local hyperexcitability. This systems-level mechanism has received limited preclinical attention but has significant implications for understanding fundamental disease mechanisms.
One Hundred and Fifty Years of Warming on Caribbean Coral Reefs
Authors: Bove Colleen B. , Mudge Laura , Bruno John F. 
Published: May 2021

AbstractAnthropogenic climate change is rapidly altering the characteristics and dynamics of biological communities. This is especially apparent in marine systems as the world’s oceans are warming at an unprecedented rate, causing dramatic changes to coastal marine systems, especially on coral reefs of the Caribbean. We used three complementary ocean temperature databases (HadISST, Pathfinder, and OISST) to quantify change in thermal characteristics of Caribbean coral reefs over the last 150 years (1871–2020). These sea surface temperature (SST) databases included combinedin situand satellite-derived SST (HadISST, OISST), as well as satellite-only observations (Pathfinder) at multiple spatial resolutions. We also compiled a Caribbean coral reef database identifying 5,326 unique reefs across the region. We found that Caribbean reefs have warmed on average by 0.20 °C per decade since 1987, the calculated year that rapid warming began on Caribbean reefs. Further, geographic variation in warming rates ranged from 0.17 °C per decade on Bahamian reefs to 0.26 °C per decade on reefs within the Southern and Eastern Caribbean ecoregions. If this linear rate of warming continues, these already threatened ecosystems would warm by anadditional1.6 °C on average by 2100. We also found that marine heatwave (MHW) events are increasing in both frequency and duration across the Caribbean. Caribbean coral reefs now experience on average 5 MHW events annually, compared to 1 per year in the early 1980s. Combined, these changes have caused a dramatic shift in the composition and function of Caribbean coral reef ecosystems. If reefs continue to warm at this rate, we are likely to lose even the remnant Caribbean coral reef communities of today in the coming decades.
Protein contact map prediction using multiple sequence alignment dropout and consistency learning for sequences with fewer homologs
Authors: Liu Xuyang , Jin Lei , Gao Shenghua , Zhao Suwen 
Published: May 2021

AbstractThe prediction of protein contact map needs enough normalized number of effective sequence (Nf) in multiple sequence alignment (MSA). When Nf is small, the predicted contact maps are often not satisfactory. To solve this problem, we randomly selected a small part of sequence homologs for proteins with large Nf to generate MSAs with small Nf. From these MSAs, input features were generated and were passed through a consistency learning network, aiming to get the same results when using the features generated from the MSA with large Nf. The results showed that this method effectively improves the prediction accuracy of protein contact maps with small Nf.
Patterns of serum immune biomarkers during elephant endotheliotropic herpesvirus viremia in Asian and African elephants
Authors: Edwards Katie L. , Latimer Erin M. , Siegal-Willott Jessica , Kiso Wendy , Padilla Luis R. , Sanchez Carlos R. , Schmitt Dennis , Brown Janine L. 
Published: May 2021

AbstractHemorrhagic disease (HD) caused by a group of elephant endotheliotropic herpesviruses (EEHV) is one of the leading causes of death for young elephants in human care. These viruses are widespread and typically persist latently in adult elephants with no negative effects; however, in juvenile Asian and more recently young African elephants, the onset of disease can be rapid and the mortality rate high. Measuring biomarkers associated with the immune response could be beneficial to understanding underlying disease processes, as well as the management of infection and HD. The goal of this study was to measure acute phase proteins and cytokines in serum collected from elephants infected with EEHV (13 Asian and 1 African) and compare concentrations according to presence, severity and outcome of disease. Serum amyloid A (SAA) and haptoglobin (HP) were higher in elephants with EEHV viremia than those without; concentrations increased with increasing viral load, and were higher in fatal cases compared to those that survived. In Asian elephants, SAA was also higher during EEHV1 viremia compared to EEHV5. Cytokine concentrations were typically low, and no statistical differences existed between groups, perhaps due to insufficient assay sensitivity in this age group. However, in individuals with detectable levels, longitudinal profiles indicated changes in tumor necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) that may reflect an immune response to EEHV infection. These results highlight the potential benefit of measuring circulating biomarker concentrations, such as APPs and cytokines, to improve our understanding of EEHV viremia and HD, assist with monitoring the progression of disease and determining the impact of interventions.
Gaps in global wildlife trade monitoring leave amphibians vulnerable
Authors: Hughes Alice C. , Marshall Benjamin M. , Strine Colin T. 
Published: May 2021

AbstractAs the biodiversity crisis continues, we must redouble efforts to understand and curb pressures pushing species closer to extinction. One major driver is the unsustainable trade of wildlife. Trade in internationally regulated species gains the most research attention, but this only accounts for a minority of traded species and we risk failing to appreciate the scale and impacts of unregulated legal trade. Despite being legal, trade puts pressure on wild species via: direct collection, introduced pathogens, and invasive species. Smaller species-rich vertebrates, such reptiles, fish, and amphibians, may be particularly vulnerable to trading because of gaps in regulations, small distributions, and demand of novel species. Here we combine data from five sources: online web searches in six languages, CITES trade database, LEMIS trade database, IUCN assessments, and a recent literature review, to characterise the global trade in amphibians, and also map use by purpose including meat, pets, medicinal and for research. We show that 1,215 species are being traded (17% of amphibian species), almost three times previous recorded numbers, 345 are threatened, and 100 data deficient or unassessed. Traded species origin hotspots include South American, China, and Central Africa; sources indicate 42% of amphibians are taken from the wild. Newly described species can be rapidly traded (mean time lag of 6.5 years), including threatened and unassessed species. The scale and limited regulation of the amphibian trade, paired with the triptych of connected pressures (collection, pathogens, invasive species), warrants a re-examination of the wildlife trade status-quo, application of the precautionary principle in regards to wildlife trade, and a renewed push to achieve global biodiversity goals.
Functional plasticity coupled with structural predispositions in auditory cortex shape successful music category learning
Authors: Mankel Kelsey , Shrestha Utsav , Tipirneni-Sajja Aaryani , Bidelman Gavin M. 
Published: May 2021

ABSTRACTCategorizing sounds into meaningful groups helps listeners more efficiently process the auditory scene and is a foundational skill for speech perception and language development. Yet, how auditory categories develop in the brain through learning, particularly for nonspeech sounds, is not well understood. Here, we asked musically naïve listeners to complete a brief (∼20 min) training session where they learned to identify sounds from a nonspeech continuum (minor-major 3rd musical intervals). We used multichannel EEG to track behaviorally relevant neuroplastic changes in the auditory event-related potentials (ERPs) pre- to post-training. To rule out mere exposure-induced changes, neural effects were evaluated against a control group of 14 nonmusicians who did not undergo training. We also compared individual categorization performance with structural volumetrics of bilateral primary auditory cortex (PAC) from MRI to evaluate neuroanatomical substrates of learning. Behavioral performance revealed steeper (i.e., more categorical) identification functions in the posttest that correlated with better training accuracy. At the neural level, improvement in learners’ behavioral identification was characterized by smaller P2 amplitudes at posttest, particularly over right hemisphere. Critically, learning-related changes in the ERPs were not observed in control listeners, ruling out mere exposure effects. Learners also showed smaller and thinner PAC bilaterally, indicating superior categorization was associated with structural differences in primary auditory brain regions. Collectively, our data suggest successful auditory categorical learning of nonspeech sounds is characterized by short-term functional changes (i.e., greater post-training efficiency) in sensory coding processes superimposed on preexisting structural differences in bilateral auditory cortex.
Phage-resistant bacteria reveal a role for potassium in root colonization
Authors: Tzipilevich Elhanan , Benfey Philip N. 
Published: May 2021

AbstractBacteriophage predation is an important factor in bacterial community dynamics and evolution. Phage-bacteria interaction has mainly been studied in lab cultures, while dynamics in natural habitats, and especially in the plant root niche are underexplored. To better understand this process, we characterized infection of the soil bacterium B. subtilis NCBI 3610 by the lytic phage SPO1 during growth in LB medium and compared it to root colonization. Resistance in vitro was primarily through modification of the phage receptor. However, this type of resistance reduced the ability to colonize the root. From a line that survived phage infection while retaining the ability to colonize the root, we identified a plant-specific phage resistance mechanism involving potassium (K+) ion influx modulation and enhanced biofilm formation.
A rapid method to quantify small-scale vegetation patch structure to complement conventional quadrat surveys
Authors: Butler Liam , Sanderson Roy A. 
Published: May 2021

AbstractAimsVegetation sampling typically involves the use of quadrats, often 1m2, to estimate species cover-abundance. Such surveys do not generally record small-scale vegetation patch structure at sub-quadrat scales, for example 10 cm2. Here we test a simple method to quantify patch structure that complements conventional techniques. We compare the two methods, and analyse metrics derived from small-scale patch surveys with environment / management data.LocationNorthumberland, United KingdomMethodsWe recorded cover-abundance of all species in an upland moor with 1m2 quadrats. These were divided into 100 ‘sub-quadrats’, 10 × 10 cm, and the dominant and subdominant species identified. Patch metrics (number, area and shape) for individual species recorded as dominant or subdominant in the sub-quadrat survey were analysed using multivariate generalised linear models with environmental and management data. Sub-quadrat data were also aggregated for each quadrat, to create species composition data. The two sets of compositional data, from whole-quadrat and sub-quadrat aggregations, were compared via Procrustes rotation of ordination scores.ResultsPatch number, area and shape for dominant and subdominant species were all significantly affected by soil pH, soil water content, slope and elevation. Effects of proximity to sheep tracks and drainage ditches were less consistent amongst species. Ordinations of vegetation data from conventional and sub-quadrats were similar, with significant Procrustes R-squared of 67% and 70% for dominant and subdominant species respectively.ConclusionsSub-quadrat surveys can easily be used to complement existing whole-quadrat surveys at little cost in time or resources. Their patch metrics can provide additional insights into the environmental and management drivers that may affect the growth of individual plants or clumps, potentially in relation to plant traits, and thus alter the overall community composition. The methods we describe can readily be adapted to other sizes of quadrats and sub-quadrats in a wide range of vegetation communities.
cAMP controls a trafficking mechanism that directs the neuron specificity and subcellular placement of electrical synapses
Authors: Palumbos Sierra , Skelton Rachel , McWhirter Rebecca , Mitchell Amanda , Swann Isaiah , Heifner Sydney , Von Stetina Steve , Miller David M 
Published: May 2021

SummaryElectrical synapses are established between specific neurons and within distinct subcellular compartments, but the mechanisms that direct gap junction assembly in the nervous system are largely unknown. Here we show that a transcriptional program tunes cAMP signaling to direct the neuron-specific assembly and placement of electrical synapses in the C. elegans motor circuit. For these studies, we use live cell imaging to visualize electrical synapses in vivo and a novel optogenetic assay to confirm that they are functional. In VA motor neurons, the UNC-4 transcription factor blocks expression of cAMP antagonists that promote gap junction miswiring. In unc-4 mutants, VA electrical synapses are established with an alternative synaptic partner and are repositioned from the VA axon to soma. We show that cAMP counters these effects by driving gap junction trafficking into the VA axon for electrical synapse assembly. Thus, our experiments in an intact nervous system establish that cAMP regulates gap junction trafficking for the biogenesis of electrical synapses.