bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome mining for drug discovery: progress at the front end
Authors: Baltz Richard H
Published: July 2021

Microbial genome mining for drug discovery and development has been accelerating in recent years, driven by technical advancements in genome sequencing, bioinformatics, metabolomics/metabologenomics, and synthetic biology. Microbial genome mining is a multistep process that starts with the sequencing of microbes that encode multiple secondary metabolites and identifying new and novel secondary metabolite biosynthetic gene clusters (BGCs) to pursue. The initial steps in the process are critical for the overall success, and they encompass the most innovative new technologies to revitalize natural product discovery. As microbial genome mining has matured in recent years, unvalidated conjectures about what microbes to pursue, how to identify legitimate secondary metabolite BGCs, and how to sequence DNA to satisfactory levels of completion have been identified. The solutions to correct the misconceptions around these topics are beginning to be implemented.
Nonribosomal peptide synthetases and their biotechnological potential in Penicillium rubens
Authors: Iacovelli Riccardo , Bovenberg Roel A L , Driessen Arnold J M
Published: July 2021

Nonribosomal peptide synthetases (NRPS) are large multimodular enzymes that synthesize a diverse variety of peptides. Many of these are currently used as pharmaceuticals, thanks to their activity as antimicrobials (penicillin, vancomycin, daptomycin, echinocandin), immunosuppressant (cyclosporin) and anticancer compounds (bleomycin). Because of their biotechnological potential, NRPSs have been extensively studied in the past decades. In this review, we provide an overview of the main structural and functional features of these enzymes, and we consider the challenges and prospects of engineering NRPSs for the synthesis of novel compounds. Furthermore, we discuss secondary metabolism and NRP synthesis in the filamentous fungus Penicillium rubens and examine its potential for the production of novel and modified β-lactam antibiotics.
Core and Whole-Body Vibration Exercise Improve Military Foot March Performance in Novice Trainees: A Randomized Controlled Trial
Authors: Lyons Kaitlin D , Parks Aaron G , Dadematthews Oluwagbemiga D , Zandieh Nilophar L , McHenry Paige A , Games Kenneth E , Goodlett Michael D , Murrah William M , Roper Jaimie A , Sefton JoEllen M
Published: July 2021

Introduction

The purpose of the present study was to investigate core exercise training and whole-body vibration (WBV) as a training method to improve performance and recovery from an 8-km military foot march in novice trainees.

Materials and Methods

A 3 × 5 repeated measures randomized control trial was used to evaluate the effects of core exercise training and WBV on performance and recovery from an 8-km foot march. Thirty-nine participants were randomized into three groups: core exercise (Ex), WBV with core exercise (WBVEx), and control. Each participant completed two 8-km foot marches (FM1 and FM2) with a 35 pound rucksack, separated by 4 weeks. Participants in the Ex and WBVEx groups completed 3 weeks of core exercise training, three times per week in between FM1 and FM2. Performance time, creatine kinase (CK), and interleukin-6 (IL-6) were measured. The Auburn University Institutional Review Board approved all aspects of this study (protocol number: 19-211 MR 1907).

Results

Performance time (P < .001) and CK (P = .005) were significantly improved during FM2 as compared to FM1. The Ex (d = −0.295) and WBVEx (d = −0.645) treatments had a large effect on performance time. CK (P < .001) and IL-6 (P < .001) were significantly elevated at the completion of the foot march regardless of group. Only CK remained elevated for 2 days (P < .001) following the foot march.

Conclusions

Core exercise training with or without WBV improved 8-km foot march performance time by 5-6 minutes. The improvements are likely because of an increase in trunk stability. Additionally, this study showed that completing two identical foot marches a month apart increases performance and improves recovery.
Correcting correlation functions for redshift-dependent interloper contamination
Authors: Farrow Daniel J , Sánchez Ariel G , Ciardullo Robin , Cooper Erin Mentuch , Davis Dustin , Fabricius Maximilian , Gawiser Eric , Grasshorn Gebhardt Henry S , Gebhardt Karl , Hill Gary J , Jeong Donghui , Komatsu Eiichiro , Landriau Martin , Liu Chenxu , Saito Shun , Snigula Jan , Wold Isak G B
Published: July 2021

The construction of catalogues of a particular type of galaxy can be complicated by interlopers contaminating the sample. In spectroscopic galaxy surveys this can be due to the misclassification of an emission line; for example in the Hobby–Eberly Telescope Dark Energy Experiment (HETDEX) low-redshift [O ii] emitters may make up a few per cent of the observed Ly α emitter (LAE) sample. The presence of contaminants affects the measured correlation functions and power spectra. Previous attempts to deal with this using the cross-correlation function have assumed sources at a fixed redshift, or not modelled evolution within the adopted redshift bins. However, in spectroscopic surveys like HETDEX, where the contamination fraction is likely to be redshift dependent, the observed clustering of misclassified sources will appear to evolve strongly due to projection effects, even if their true clustering does not. We present a practical method for accounting for the presence of contaminants with redshift-dependent contamination fractions and projected clustering. We show using mock catalogues that our method, unlike existing approaches, yields unbiased clustering measurements from the upcoming HETDEX survey in scenarios with redshift-dependent contamination fractions within the redshift bins used. We show our method returns autocorrelation functions with systematic biases much smaller than the statistical noise for samples with at least as high as 7 per cent contamination. We also present and test a method for fitting for the redshift-dependent interloper fraction using the LAE–[O ii] galaxy cross-correlation function, which gives less biased results than assuming a single interloper fraction for the whole sample.
The GALAH survey: accreted stars also inhabit the Spite plateau
Authors: Simpson Jeffrey D , Martell Sarah L , Buder Sven , Bland-Hawthorn Joss , Casey Andrew R , De Silva Gayandhi M , D’Orazi Valentina , Freeman Ken C , Hayden Michael , Kos Janez , Lewis Geraint F , Lind Karin , Schlesinger Katharine J , Sharma Sanjib , Stello Dennis , Zucker Daniel B , Zwitter Tomaž , Asplund Martin , Da Costa Gary , Čotar Klemen , Tepper-García Thor , Horner Jonathan , Nordlander Thomas , Ting Yuan-Sen , Wyse Rosemary F G ,   The GALAH Collaboration
Published: July 2021

The European Space Agency (ESA) Gaia mission has enabled the remarkable discovery that a large fraction of the stars near the solar neighbourhood are debris from a single in-falling system, the so-called Gaia-Sausage-Enceladus (GSE). This discovery provides astronomers for the first time with a large cohort of easily observable, unevolved stars that formed in a single extragalactic environment. Here we use these stars to investigate the ‘Spite plateau’ – the near-constant lithium abundance observed in unevolved metal-poor stars across a wide range of metallicities (−3 < [Fe/H] < −1). Our aim is to test whether individual galaxies could have different Spite plateaus – e.g. the interstellar medium could be more depleted in lithium in a lower galactic mass system due to it having a smaller reservoir of gas. We identified 93 GSE dwarf stars observed and analysed by the GALactic Archaeology with HERMES (GALAH) survey as part of its Data Release 3 (DR3). Orbital actions were used to select samples of GSE stars, and comparison samples of halo and disc stars. We find that the GSE stars show the same lithium abundance as other likely accreted stars and in situ Milky Way stars. Formation environment leaves no imprint on lithium abundances. This result fits within the growing consensus that the Spite plateau, and more generally the ‘cosmological lithium problem’ – the observed discrepancy between the amount of lithium in warm, metal-poor dwarf stars in our Galaxy, and the amount of lithium predicted to have been produced by big bang nucleosynthesis – is the result of lithium depletion processes within stars.
Radiative transfer in atmospheres with a large chaotic magnetic field
Authors: Silant’ev N A , Alekseeva G A , Ananjevskaja Yu K
Published: July 2021

We derive the radiative transfer equations for all Stokes parameters of continuum radiation in atmospheres with any value of homogeneous magnetic field $\boldsymbol{B}$. The explicit formulas for cross-sections and the phase shifts are given with allowance for absorption effects. We consider the scattering of non-polarized radiation in an optically thin envelope with a dipole magnetic field. The presented theory is valid for magnetic fields B ≤ 1010G. In general, a magnetic field consists of the mean value $\boldsymbol{B_0}$ and the chaotic part $\boldsymbol{ B^{\prime }}$. The latter is assumed to have an isotropic distribution over directions and a Gaussian-type distribution over the value B′. It is shown that for B0(G)λ(μm) ≪ 108, the fluctuations play a dominating role. This case is considered in detail. First of all, we derive the system of transfer equations for observed averaged Stokes parameters. The averaging procedure consists of two stages: the averaging of fluctuations $\boldsymbol{B }^{\prime }$ over values and the averaging of these over all directions. The averaging over Gaussian fluctuations B′ is carried out using the exponential Fourier transform of polarizability tensor components and the known formula for the averaged exponential. This technique is available for arbitrary values of a magnetic field, both large and small. The system of transfer equations for four averaged Stokes parameters, I, Q, U and V, splits up into two independent systems – for I, Q and V, U parameters. The form of equations for the case of large magnetic fluctuations differs strongly from the Thomson scattering. These equations describe the large decrease of linear and circular polarization of observed radiation.
Probing the progenitors of Type Ia supernovae using circumstellar material interaction signatures
Authors: Clark Peter , Maguire Kate , Bulla Mattia , Galbany Lluís , Sullivan Mark , Anderson Joseph P , Smartt Stephen J
Published: July 2021

This work aims to study different probes of Type Ia supernova (SN Ia) progenitors that have been suggested to be linked to the presence of circumstellar material (CSM). In particular, we have investigated, for the first time, the link between narrow blueshifted Na i D absorption profiles and the presence and strength of the broad high-velocity Ca ii near-infrared triplet absorption features seen in SNe Ia around maximum light. With the probes exploring different distances from the SN; Na i D > 1017cm, high-velocity Ca ii features < 1015cm. For this, we have used a new intermediate-resolution X-shooter spectral sample of 15 SNe Ia. We do not identify a link between these two probes, implying either that, one (or both) is not physically related to the presence of CSM or that the occurrence of CSM at the distance explored by one probe is not linked to its presence at the distance probed by the other. However, the previously identified statistical excess in the presence of blueshifted (over redshifted) Na i D absorption is confirmed in this sample at high significance and is found to be stronger in SNe Ia hosted by late-type galaxies. This excess is difficult to explain as being from an interstellar-medium origin as has been suggested by some recent modelling, as such an origin is not expected to show a bias for blueshifted absorption. However, a circumstellar origin for these features also appears unsatisfactory based on our new results, given the lack of link between the two probes of CSM investigated.
High-resolution synthetic UV–submm images for simulated Milky Way-type galaxies from the Auriga project
Authors: Kapoor Anand Utsav , Camps Peter , Baes Maarten , Trčka Ana , Grand Robert J J , van der Wel Arjen , Cortese Luca , De Looze Ilse , Barrientos Daniela
Published: July 2021

We present redshift-zero synthetic observational data considering dust attenuation and dust emission for the 30 galaxies of the Auriga project, calculated with the skirt radiative transfer code. The post-processing procedure includes components for star-forming regions, stellar sources, and diffuse dust taking into account stochastic heating of dust grains. This allows us to obtain realistic high-resolution broad-band images and fluxes from ultraviolet (UV) to submillimetre (submm) wavelengths. For the diffuse dust component, we consider two mechanisms for assigning dust to gas cells in the simulation. In one case, only the densest or the coldest gas cells are allowed to have dust, while in the other case this condition is relaxed to allow a larger number of dust-containing cells. The latter approach yields galaxies with a larger radial dust extent and an enhanced dust presence in the interspiral regions. At a global scale, we compare Auriga galaxies with observations by deriving dust scaling relations using spectral energy distribution fitting. At a resolved scale, we make a multiwavelength morphological comparison with nine well-resolved spiral galaxies from the DustPedia observational data base. We find that for both dust assignment methods, although the Auriga galaxies show a good overall agreement with observational dust properties, they exhibit a slightly higher specific dust mass. The multiwavelength morphological analysis reveals a good agreement between the Auriga and the observed galaxies in the optical wavelengths. In the mid- and far-infrared wavelengths, Auriga galaxies appear smaller and more centrally concentrated in comparison to their observed counterparts. We publicly release the multi-observer images and fluxes in 50 commonly used broad-band filters.
Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse
Authors: Richardson Stacey , Hill Rebecca M , Kui Christopher , Lindsey Janet C , Grabovksa Yura , Keeling Claire , Pease Louise , Bashton Matthew , Crosier Stephen , Vinci Maria , André Nicolas , Figarella-Branger Dominique , Hansford Jordan R , Lastowska Maria , Zakrzewski Krzysztof , Jorgensen Mette , Pickles Jessica C , Taylor Michael D , Pfister Stefan M , Wharton Stephen B , Pizer Barry , Michalski Antony , Joshi Abhijit , Jacques Thomas S , Hicks Debbie , Schwalbe Edward C , Williamson Daniel , Ramaswamy Vijay , Bailey Simon , Clifford Steven C
Published: July 2021

Background

Less than 5% of medulloblastoma (MB) patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initial genome-wide investigations have suggested significant genetic divergence of the relapsed disease.

Methods

We undertook large-scale integrated characterization of the molecular features of rMB—molecular subgroup, novel subtypes, copy number variation (CNV), and driver gene mutation. 119 rMBs were assessed in comparison with their paired diagnostic samples (n = 107), alongside an independent reference cohort sampled at diagnosis (n = 282). rMB events were investigated for association with outcome post-relapse in clinically annotated patients (n = 54).

Results

Significant genetic evolution occurred over disease-course; 40% of putative rMB drivers emerged at relapse and differed significantly between molecular subgroups. Non-infant MBSHH displayed significantly more chromosomal CNVs at relapse (TP53 mutation-associated). Relapsed MBGroup4 demonstrated the greatest genetic divergence, enriched for targetable (eg, CDK amplifications) and novel (eg, USH2A mutations) events. Importantly, many hallmark features of MB were stable over time; novel subtypes (>90% of tumors) and established genetic drivers (eg, SHH/WNT/P53 mutations; 60% of rMB events) were maintained from diagnosis. Critically, acquired and maintained rMB events converged on targetable pathways which were significantly enriched at relapse (eg, DNA damage signaling) and specific events (eg, 3p loss) predicted survival post-relapse.

Conclusions

rMB is characterised by the emergence of novel events and pathways, in concert with selective maintenance of established genetic drivers. Together, these define the actionable genetic landscape of rMB and provide a basis for improved clinical management and development of stratified therapeutics, across disease-course.
Ultrathin two-dimensional hybrid perovskites toward flexible electronics and optoelectronics
Authors: Zhang Junran , Song Xuefen , Wang Lin , Huang Wei
Published: July 2021

Ultrathin hybrid perovskites combine the advantages of 2D morphology and organic-inorganic components. This perspective article provides an updated summary and new insights for their development in flexible electronics and optoelectronics.
Native vs Prosthetic Valve Histoplasma capsulatum Infective Endocarditis: A Case Report and Systemic Literature Review Comparing Patient Presentation, Treatment Modalities, Clinical Outcomes, and Diagnostic Laboratory Testing
Authors: Boyanton Bobby L , Boamah Harry , Lauter Carl B
Published: July 2021

Histoplasma capsulatum is a rare cause of fungal endocarditis that affects both native and prosthetic valves. It is associated with a high mortality rate if not diagnosed early and treated with a combination of antifungal therapy and surgical intervention. We present a case of a 47-year-old man with histoplasmosis infective endocarditis. He was successfully treated with antifungal therapy and surgical replacement of the infected bioprosthetic aortic valve. Our systemic literature review includes 52 articles encompassing 60 individual cases of H. capsulatum infective endocarditis from 1940 to 2020. Patient presentations, diagnostic laboratory testing accuracy, treatment modalities, and patient outcomes comparing and contrasting native and prosthetic valve infection are described.
Rapid Base-Specific Calling of SARS-CoV-2 Variants of Concern Using Combined RT-PCR Melting Curve Screening and SIRPH Technology
Authors: Tierling Sascha , Kattler Kathrin , Vogelgesang Markus , Pfuhl Thorsten , Lohse Stefan , Lo Porto Christina , Schmitt Beate , Nastasja Seiwert , Salhab Abdulrahman , Smola Sigrun , Walter Jörn
Published: July 2021

Background

The emergence of novel variants of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demands fast and reliable detection of such variants in local populations.

Methods

Here we present a cost-efficient and fast workflow combining a prescreening of SARS-CoV-2-positive samples using reverse transcription polymerase chain reaction melting curve analysis with multiplexed IP-RP-HPLC-based single nucleotide primer extensions.

Results

The entire workflow from positive SARS-CoV-2 testing to base-specific identification of variants requires about 24 hours.

Conclusions

We applied the sensitive method to monitor local variant of concern outbreaks in SARS-CoV-2-positive samples collected in a confined region of Germany.
Metapopulation connectivity retains genetic diversity following a historical bottleneck in a federally endangered seabird
Authors: Dayton Jacob , Szczys Patricia
Published: July 2021

Despite intensive management since the 1970s, recovery of the endangered northwestern Atlantic population of the Roseate Tern (Sterna dougallii dougallii) has not offset low productivity from a female-biased sex ratio, low adult survival, and habitat constriction. Now, >90% of individuals breed at three sites within 200 km from Long Island, NY, to Buzzards Bay, MA (warm-water subregion). To characterize the impact of historical bottlenecks, metapopulation structure, and demographic fluctuations on genetic variation, Roseate Terns from the warm-water (1870s, 1970s, 1997, 2016) and cold-water (Nova Scotia, Canada; 2018) subregions were genotyped at 8–16 microsatellites and 2–3 mitochondrial regions. Diversity declined in the warm-water subregion from the 1870s (expected heterozygosity [HE] = 0.44, allelic richness [AR] = 2.86) and 1970s (HE = 0.53, AR = 3.25) to 1997 (HE = 0.38, AR = 2.58). Genetic signatures of bottlenecks persisted in 1997 (P = <0.001–0.003) and 2016 (P = <0.001–0.005), but an increase in variation occurred by 2016 (HE = 0.50, AR = 2.85). Weak structure was detected between contemporary warm- and cold-water subregions (θ = 0.06) and within the warm-water subregion (θ = 0.04). Both demographic (3,439–3,821) and genetic (3,040) estimates suggested effective population size (Ne) stability over the last 100 years, despite large fluctuations in census size (4,000–8,662). Results suggest that 50 years of management (restoring habitat, preventing gull encroachment, controlling predators) at colony sites supported a small, stable Ne and maintained a hierarchical metapopulation that allowed gene flow to redistribute genetic variation throughout the northwest Atlantic. The metapopulation remains highly vulnerable to stochastic events but harbors resiliency and redundancy through gene flow and a stable Ne. For long-term persistence from a genetic perspective, managers must maintain the major source colonies, increase the availability of high-quality peripheral breeding sites, and protect concentrated nonbreeding sites that facilitate gene flow.
N enrichment affects the arbuscular mycorrhizal fungi-mediated relationship between a C4 grass and a legume
Authors: Liu Hongfei , Wu Yang , Xu Hongwei , Ai Zemin , Zhang Jiaoyang , Liu Guobin , Xue Sha
Published: July 2021

Arbuscular mycorrhizal fungi (AMF) regulate soil nutrient cycling, directly supplying a host plant with nitrogen (N). AMF can also affect the outcome of interspecific interactions, but a mechanistic understanding of how soil N availability affects AMF-mediated interspecific relationships is currently lacking. We selected one dominant (Bothriochloa ischaemum; C4 grass) and one subordinate (Lespedeza davurica; legume) species in a natural grassland climax community to investigate the mechanism by which AMF influence interspecific interaction (mixed and monoculture) under three levels of N addition (0, low, and high N addition). Under the non-N addition treatment, AMF preferentially supplied N to the roots of B. ischaemum at the expense of N uptake by L. davurica, resulting in inhibited AMF benefits for L. davurica shoot growth. Under the low N addition treatment, interspecific interaction via AMF promoted L. davurica growth. Compared to the non-N addition treatment, N addition largely mitigated the effects, both positive (for B. ischaemum) and negative (for L. davurica), of AMF-mediated interspecific interaction on plant N uptake via AMF. When soil N availability severely limited plant growth, preferential N supply to the C4 grass by AMF was important for maintaining the abundance of the dominant species. When the N limitation for plant growth was alleviated by N addition, the interaction between AMF and soil microorganisms improved nutrient availability for the legume by stimulating activity of the enzyme responsible for soil organic matter mineralization, which is important for maintaining the abundance of the subordinate species. These data could influence strategies for maintaining biodiversity.
Trading off consumer preferences induced by cultural and colonial heritage: Lessons from New Rice for Africa (NERICA) in Casamance, Senegal
Authors: Britwum Kofi , Demont Matty
Published: July 2021

Breeders face the challenging task of tailoring crop varieties to complex consumer preferences shaped through culture and history. The Casamance rice sector in Senegal is an interesting case; while the region is endowed with a 3,000-year-old cultural heritage of African rice domestication, it has also been exposed to century-long colonial import substitution policies, leading to massive influx of cheap, broken Asian rice. Markets have responded to the amalgam of consumer preferences that have emerged as a result of cultural and colonial heritage by offering three standard grades of rice: 100 per cent broken, semi-broken (35–60 per cent broken), and unbroken. To disentangle the trade-off between indigenous and ‘imported’ traits and inform breeding priorities, we conducted framed field experiments with urban women in the Casamance. We assessed consumers’ revealed price premiums for replacing imported, broken Asian rice with three locally produced New Rice for Africa (NERICA) hybrids between African and Asian rice: (i) broken, fragrant NERICA 1; (ii) broken NERICA 4; and (iii) unbroken NERICA 6 featuring medium/bold grain shape. Consumers with genealogical lineages tracing back to the original domesticators of African rice put significantly higher value on locally produced NERICAs relative to immigrants from the north and northeast, who put premiums on ‘imported’ traits such as rice fragrance. Driven by preferences for both broken and unbroken rice, NERICA 6 outcompeted all other varieties as it mimics the grain shape of semi-broken rice while being unbroken. The latter exemplifies how breeders can strike an optimal compromise in the trade-off between cultural and colonial heritage-induced preferences.
Derivation and Molecular Characterization of a Morphological Subpopulation of Human iPSC Astrocytes Reveal a Potential Role in Schizophrenia and Clozapine Response
Authors: Akkouh Ibrahim A , Hribkova Hana , Grabiec Marta , Budinska Eva , Szabo Attila , Kasparek Tomas , Andreassen Ole A , Sun Yuh-Man , Djurovic Srdjan
Published: July 2021

Astrocytes are the most abundant cell type in the human brain and are important regulators of several critical cellular functions, including synaptic transmission. Although astrocytes are known to play a central role in the etiology and pathophysiology of schizophrenia, little is known about their potential involvement in clinical response to the antipsychotic clozapine. Moreover, astrocytes display a remarkable degree of morphological diversity, but the potential contribution of astrocytic subtypes to disease biology and drug response has received little attention. Here, we used state-of-the-art human induced pluripotent stem cell (hiPSC) technology to derive a morphological subtype of astrocytes from healthy individuals and individuals with schizophrenia, including responders and nonresponders to clozapine. Using functional assays and transcriptional profiling, we identified a distinct gene expression signature highly specific to schizophrenia as shown by disease association analysis of more than 10 000 diseases. We further found reduced levels of both glutamate and the NMDA receptor coagonist d-serine in subtype astrocytes derived from schizophrenia patients, and that exposure to clozapine only rescued this deficiency in cells from clozapine responders, providing further evidence that d-serine in particular, and NMDA receptor-mediated glutamatergic neurotransmission in general, could play an important role in disease pathophysiology and clozapine action. Our study represents a first attempt to explore the potential contribution of astrocyte diversity to schizophrenia pathophysiology using a human cellular model. Our findings suggest that specialized subtypes of astrocytes could be important modulators of disease pathophysiology and clinical drug response, and warrant further investigations.
Structural and Functional Default Mode Network Connectivity and Antipsychotic Treatment Response in Medication-Naïve First Episode Psychosis Patients
Authors: Maximo Jose O , Kraguljac Nina V , Rountree Boone G , Lahti Adrienne C
Published: July 2021

Introduction

Only a few studies have comprehensively characterized default mode network (DMN) pathology on a structural and functional level, and definite conclusions cannot be drawn due to antipsychotic medication exposure and illness chronicity. The objective of this study was to characterize DMN pathology in medication-naïve first episode psychosis (FEP) patients, and determine if DMN structural and functional connectivity (FC) have potential utility as a predictor for subsequent antipsychotic treatment response.

Methods

Diffusion imaging and resting state FC data from 42 controls and 52 FEP were analyzed. Patients then received 16 weeks of antipsychotic treatment. Using region of interest analyses, we quantified FC of the DMN and structural integrity of the white matter tracts supporting DMN function. We then did linear regressions between DMN structural and FC indices and antipsychotic treatment response.

Results

We detected reduced DMN fractional anisotropy and axial diffusivity in FEP compared to controls. No DMN FC abnormalities nor correlations between DMN structural and FC were found. Finally, DMN fractional anisotropy and radial diffusivity were associated with response to treatment.

Conclusion

Our study highlights the critical role of the DMN in the pathophysiology suggesting that axonal damage may already be present in FEP patients. We also demonstrated that DMN pathology is clinically relevant, as greater structural DMN alterations were associated with a less favorable clinical response to antipsychotic medications.
Complete Genome Resource of Bacillus velezensis J17-4, an Endophyte Isolated from Stem Tissues of Rice
Authors: Shi Zurong , Hong Wanwen , Wang Qingwei
Published: July 2021

Dickeya zeae is the causative agent of rice root rot disease and causes severe harvest and economic losses. In this study, the Bacillus velezensis strain J17-4 with significant antagonism against D. zeae was used to generate DNA for sequencing. After assembly, a high-quality complete genome comprising only a circular chromosome was available. The genome sequence consists of a total of 3,877 prediction coding sequences and nine types of gene clusters involved in secondary metabolite production. This genome data will provide information for understanding the underlying mechanism of strain J17-4 antagonist against D. zeae and a new useful source for comparative genomics studies between strains isolated from various habitats.
GABAergic Neurons in the Dorsal–Intermediate Lateral Septum Regulate Sleep–Wakefulness and Anesthesia in Mice
Authors: Wang Di , Guo Qingchen , Zhou Yu , Xu Zheng , Hu Su-Wan , Kong Xiang-Xi , Yu Yu-Mei , Yang Jun-Xia , Zhang Hongxing , Ding Hai-Lei , Cao Jun-Li
Published: July 2021

Background

The γ-aminobutyric acid–mediated (GABAergic) inhibitory system in the brain is critical for regulation of sleep–wake and general anesthesia. The lateral septum contains mainly GABAergic neurons, being cytoarchitectonically divided into the dorsal, intermediate, and ventral parts. This study hypothesized that GABAergic neurons of the lateral septum participate in the control of wakefulness and promote recovery from anesthesia.

Methods

By employing fiber photometry, chemogenetic and optogenetic neuronal manipulations, anterograde tracing, in vivo electrophysiology, and electroencephalogram/electromyography recordings in adult male mice, the authors measured the role of lateral septum GABAergic neurons to the control of sleep–wake transition and anesthesia emergence and the corresponding neuron circuits in arousal and emergence control.

Results

The GABAergic neurons of the lateral septum exhibited high activities during the awake state by in vivo fiber photometry recordings (awake vs. non–rapid eye movement sleep: 3.3 ± 1.4% vs. –1.3 ± 1.2%, P < 0.001, n = 7 mice/group; awake vs. anesthesia: 2.6 ± 1.2% vs. –1.3 ± 0.8%, P < 0.001, n = 7 mice/group). Using chemogenetic stimulation of lateral septum GABAergic neurons resulted in a 100.5% increase in wakefulness and a 51.2% reduction in non–rapid eye movement sleep. Optogenetic activation of these GABAergic neurons promoted wakefulness from sleep (median [25th, 75th percentiles]: 153.0 [115.9, 179.7] s to 4.0 [3.4, 4.6] s, P = 0.009, n = 5 mice/group) and accelerated emergence from isoflurane anesthesia (514.4 ± 122.2 s vs. 226.5 ± 53.3 s, P < 0.001, n = 8 mice/group). Furthermore, the authors demonstrated that the lateral septum GABAergic neurons send 70.7% (228 of 323 cells) of monosynaptic projections to the ventral tegmental area GABAergic neurons, preferentially inhibiting their activities and thus regulating wakefulness and isoflurane anesthesia depth.

Conclusions

The results uncover a fundamental role of the lateral septum GABAergic neurons and their circuit in maintaining awake state and promoting general anesthesia emergence time.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Patients prefer physician-provided durable medical equipment over third-party vendors: a patient satisfaction survey
Authors: Neral Mithun , Trivedi Nikunj N. , Knapik Derrick M. , Trivedi Amol H. , Karns Michael R. , Gillespie Robert J. , Salata Michael J. , Voos James E.
Published: July 2021

Background:

The purpose of the study was to compare patient satisfaction between patients receiving durable medical equipment (DME) at home from a third-party vendor versus directly from their physician’s office.

Methods:

A prospective 10-question patient satisfaction survey study was provided to 66 consecutive adult patients who met the inclusion criteria of receiving DME after orthopaedic shoulder or knee surgery using either an in-office (n=31 patients) or third party (n=35 patients) DME delivery program. Survey questions were graded on a 1 to 5 Likert scale that assessed the ease of obtaining DME, comfort with delivery method, ease of scheduling fitting, education about DME use and postoperative instructions, concerns about cost, and satisfaction with overall care. Categorical questions evaluated preference of same-day delivery method, patient perceived adequacy of answering of all DME-related questions, and whether cryotherapy was utilized postoperatively.

Results:

All patients (100%; 31 of 31) who received DME in-office reported they would use the same program for their next DME delivery. Six (17.1%; 6 of 35) patients who received DME from a third-party vendor preferred to use the same method in the future (P=0.0001). Scheduling DME fittings was easier in the in-office setting compared with a third-party vendor (P=0.05).

Conclusions:

Patients receiving their DME in the office from their physician were significantly more likely to prefer using the in-office setting again and reported fit-scheduling to be easier when compared with patients using a third-party vendor. DME can be provided by physicians in the office setting without negatively impacting patient satisfaction.

Level of Evidence:

Level II.
ABCDEF Bundle Practices for Critically Ill Children: An International Survey of 161 PICUs in 18 Countries*
Authors: Ista Erwin , Redivo Juliana , Kananur Paurav , Choong Karen , Colleti Jose , Needham Dale M. , Awojoodu Ronke , Kudchadkar Sapna R. ,   on behalf of the International PARK-PICU Investigators
Published: July 2021

Objectives:

To evaluate current international practice in PICUs regarding components of the “Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Sedation, Delirium Monitoring/Management, Early Exercise/Mobility, and Family Engagement/Empowerment” (ABCDEF) bundle.

Design:

Online surveys conducted between 2017 and 2019.

Setting:

One-hundred sixty-one PICUs across the United States (n = 82), Canada (n = 14), Brazil (n = 27), and Europe (n = 38) participating in the Prevalence of Acute Rehabilitation for Kids in the PICU study.

Interventions:

None.

Measurements and Main Results:

Of the 161 participating PICUs, 83% were in academic teaching hospitals and 42% were in free-standing children’s hospitals. Median size was 16 beds (interquartile range, 10–24 beds). Only 15 PICUs (9%) had incorporated all six ABCDEF bundle components into routine practice. Standardized pain assessment (A) was the most common (91%), followed by family engagement (F, 88%) and routine sedation assessment (C) with validated scales (84%). Protocols for testing extubation readiness or conducting spontaneous breathing trials (B) were reported in 57%, with 34% reporting a ventilator weaning protocol. Routine delirium monitoring with a validated screening tool (D) was reported by 44% of PICUs, and 26% had a guideline, protocol, or policy for early exercise/mobility (E). Practices for spontaneous breathing trials were variable in 29% of Canadian PICUs versus greater than 50% in the other regions. Delirium monitoring was lowest in Brazilian PICUs (18%) versus greater than 40% in other regions, and family engagement was reported in 55% of European PICUs versus greater than 90% in other regions.

Conclusions:

ABCDEF bundle components have been adopted with substantial variability across regions. Additional research must rigorously evaluate the efficacy of specific elements with a focus on B, D, E, and full ABCDEF bundle implementation. Implementation science is needed to facilitate an understanding of the barriers to ABCDEF implementation and sustainability with a focus on specific cultural and regional differences.
Noninvasive Tidal Volume Measurements, Using a Time-of-Flight Camera, Under High-Flow Nasal Cannula—A Physiological Evaluation, in Healthy Volunteers*
Authors: Le Moigne Guillaume , Nazir Souha , Pateau Victoire , Courtois Emmanuelle , L’Her Erwan
Published: July 2021

OBJECTIVES:

The mechanisms of high-flow nasal cannula are still debated but may be mediated by the generation of low positive end-expiratory pressure and a washout of the airway dead space. The aims of this study were to assess the effects of high-flow nasal cannula on tidal volume using a noninvasive method using a time-of-flight camera, under various conditions.

DESIGN:

A physiologic evaluation in healthy volunteers.

SETTING:

An university hospital ICU.

SUBJECTS:

Ten healthy volunteers were included in a physiologic study (CamOpt study, ClinicalTrials.gov identifier: NCT04096183).

INTERVENTIONS:

All volunteers were submitted to 12 different conditions (i.e., gas flow [baseline = 0; 30–60 L/min]; mouth [open/closed]; respiratory rate [baseline; baseline + 10 breaths/min]). Tidal volume measurements were performed every minute, during a 6-minute recording period. In all combinations, reference respiratory rate was measured by using chronometric evaluation, over a 30-second period (RRREF), and by using the time-of-flight camera (RRTOF).

MEASUREMENTS AND MAIN RESULTS:

Tidal volume increased while increasing gas flow whatever the respiratory rate and mouth condition (p < 0.001). Similar results were observed whatever the experimental conditions (p < 0.01), except one (baseline respiratory rate + 10 breaths/min and mouth closed). Tidal volume increased while decreasing respiratory rate (p < 0.001) and mouth closing (p < 0.05). Proportion of tidal volume greater than 10, 15, and 20 mL/kg changed while increasing the flow. RRTOF was in agreement with RRREF (intraclass correlation coefficient, 0.96), with a low mean bias (0.55 breaths/min) and acceptable deviation.

CONCLUSIONS:

Time-of-flight enables to detect tidal volume changes under various conditions of high-flow nasal cannula application. Tidal volume increased significantly while increasing gas flow and mouth closing. Such technique might be useful to monitor the risk of patient self-inflicted lung injury or under assistance.
Trends in 28-Day Mortality of Critical Care Patients With Coronavirus Disease 2019 in the United Kingdom: A National Cohort Study, March 2020 to January 2021*
Authors: Dennis John M. , McGovern Andrew P. , Thomas Nicholas J. , Wilde Harrison , Vollmer Sebastian J. , Mateen Bilal A.
Published: July 2021

OBJECTIVES:

To determine whether the previously described trend of improving mortality in people with coronavirus disease 2019 in critical care during the first wave was maintained, plateaued, or reversed during the second wave in United Kingdom, when B117 became the dominant strain.

DESIGN:

National retrospective cohort study.

SETTING:

All English hospital trusts (i.e., groups of hospitals functioning as single operational units), reporting critical care admissions (high dependency unit and ICU) to the Coronavirus Disease 2019 Hospitalization in England Surveillance System.

PATIENTS:

A total of 49,862 (34,336 high dependency unit and 15,526 ICU) patients admitted between March 1, 2020, and January 31, 2021 (inclusive).

INTERVENTIONS:

Not applicable.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was inhospital 28-day mortality by calendar month of admission, from March 2020 to January 2021. Unadjusted mortality was estimated, and Cox proportional hazard models were used to estimate adjusted mortality, controlling for age, sex, ethnicity, major comorbidities, social deprivation, geographic location, and operational strain (using bed occupancy as a proxy). Mortality fell to trough levels in June 2020 (ICU: 22.5% [95% CI, 18.2–27.4], high dependency unit: 8.0% [95% CI, 6.4–9.6]) but then subsequently increased up to January 2021: (ICU: 30.6% [95% CI, 29.0–32.2] and high dependency unit, 16.2% [95% CI, 15.3–17.1]). Comparing patients admitted during June–September 2020 with those admitted during December 2020–January 2021, the adjusted mortality was 59% (CI range, 39–82) higher in high dependency unit and 88% (CI range, 62–118) higher in ICU for the later period. This increased mortality was seen in all subgroups including those under 65.

CONCLUSIONS:

There was a marked deterioration in outcomes for patients admitted to critical care at the peak of the second wave of coronavirus disease 2019 in United Kingdom (December 2020–January 2021), compared with the post-first-wave period (June 2020–September 2020). The deterioration was independent of recorded patient characteristics and occupancy levels. Further research is required to determine to what extent this deterioration reflects the impact of the B117 variant of concern.
Use of the Molecular Adsorbent Recirculating System in Acute Liver Failure: Results of a Multicenter Propensity Score-Matched Study*
Authors: MacDonald Andrew J. , Subramanian Ram M. , Olson Jody C. , Speiser Jaime L. , Durkalski-Mauldin Valerie L. , Abraldes Juan G. , Bigam David L. , Flynn Mary M. , Rapaka Babusai , Shropshire Brianne M. , Vora Ravi S. , Karvellas Constantine J. ,   for the U.S. Acute Liver Failure Study Group
Published: July 2021

OBJECTIVES:

The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy.

DESIGN:

Propensity score–matched retrospective cohort analysis.

SETTING:

Tertiary North American liver transplant centers.

PATIENTS:

Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009–2019) and controls from the U.S. Acute Liver Failure Study Group registry.

INTERVENTIONS:

Molecular adsorbent recirculating system treatment versus standard medical therapy (control).

MEASUREMENTS AND MAIN RESULTS:

One-hundred four molecular adsorbent recirculating system patients were propensity score–matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King’s College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07–3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone (“model 2”; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05–3.31; p = 0.033), and further adjustment of the “main model” for mechanical ventilation, and grade 3/4 hepatic encephalopathy (“model 3”; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07–3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 µmol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 µmol/L; p ≤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 µmol/L), creatinine (83.1 vs 133.5 µmol/L), and ammonia (111.5 vs 140.0 µmol/L; p ≤ 0.022 for all).

CONCLUSIONS:

Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure.
Prediction of Postictal Delirium Following Status Epilepticus in the ICU: First Insights of an Observational Cohort Study
Authors: Baumann Sira M. , Semmlack Saskia , Hunziker Sabina , Kaplan Peter W. , De Marchis Gian Marco , Rüegg Stephan , Marsch Stephan , Sutter Raoul
Published: July 2021

OBJECTIVES:

To identify early predictors of postictal delirium in adult patients after termination of status epilepticus.

DESIGN:

Retrospective study.

SETTING:

ICUs at a Swiss tertiary academic medical center.

PATIENTS:

Status epilepticus patients treated on the ICUs for longer than 24 hours from 2012 to 2018.

INTERVENTIONS:

None.

METHODS:

Primary outcome was postictal delirium during post-status epilepticus treatment defined as an Intensive Care Delirium Screening Checklist greater than or equal to 4. Associations with postictal delirium were secondary outcomes. A time-dependent multivariable Cox proportional hazards model was used to identify risks of postictal delirium. It included variables that differed between patients with and without delirium and established risk factors for delirium (age, sex, number of inserted catheters, illness severity [quantified by the Sequential Organ Failure Assessment and Status Epilepticus Severity Score], neurodegenerative disease, dementia, alcohol/drug consumption, infections, coma during status epilepticus, dose of benzodiazepines, anesthetics, and mechanical ventilation).

MEASUREMENTS AND MAIN RESULTS:

Among 224 patients, post-status epilepticus Intensive Care Delirium Screening Checklist was increased in 83% with delirium emerging in 55% with a median duration of 2 days (interquartile range 1–3 d). Among all variables, only the history of alcohol and/or drug consumption was associated with increased hazards for delirium in multivariable analyses (hazard ratio = 3.35; 95% CI, 1.53–7.33).

CONCLUSIONS:

Our study provides first exploratory insights into the risks of postictal delirium in adult status epilepticus patients treated in the ICU. Delirium following status epilepticus is frequent, lasting mostly 2–3 days. Our findings that with the exception of a history of alcohol and/or drug consumption, other risk factors of delirium were not found to be associated with a risk of postictal delirium may be related to the limited sample size and the exploratory nature of our study. Further investigations are needed to investigate the role of established risk factors in other status epilepticus cohorts. In the meantime, our results indicate that the risk of delirium should be especially considered in patients with a history of alcohol and/or drug consumption.