bluuebunny/crossref_metadata_2025 huggingface dataset:
Incentivizing Private Antitrust Enforcement to Promote Leniency Applications
Authors: Lai Sinchit
Published: April 2021

Both leniency programs and private antitrust enforcement are essential in combating cartels. The literature demonstrates that society benefits from both increased private actions and leniency applications. However, the present view is that private enforcement discourages cartel members from seeking leniency. Proponents of this view blame follow-on civil actions in the wake of successful public antitrust enforcement cases. This concern hinders the development of private antitrust enforcement. Nevertheless, the literature that expresses such a concern fails to consider standalone civil actions’ impact. Building on a game theory model of leniency programs by Professor Joseph E. Harrington, this article reinvestigates the relationship between the two seemingly contradictory procedural devices of leniency programs and private enforcement. Considering a revised leniency game, this article reveals that incentivizing private antitrust enforcement does not necessarily discourage leniency applications. Accordingly, this article proposes ways for legislators to use private enforcement as a tool to promote leniency applications.
The ancestral duplicated DL/CRC orthologs, PeDL1 and PeDL2, function in orchid reproductive organ innovation
Authors: Chen You-Yi , Hsiao Yu-Yun , Li Chung-I , Yeh Chuan-Ming , Mitsuda Nobutaka , Yang Hong-Xing , Chiu Chi-Chou , Chang Song-Bin , Liu Zhong-Jian , Tsai Wen-Chieh
Published: April 2021

Orchid gynostemium, the fused organ of the androecium and gynoecium, and ovule development are unique developmental processes. Two DROOPING LEAF/CRABS CLAW (DL/CRC) genes, PeDL1 and PeDL2, were identified from the Phalaenopsis orchid genome and functionally characterized. Phylogenetic analysis indicated that the most recent common ancestor of orchids contained the duplicated DL/CRC-like genes. Temporal and spatial expression analysis indicated that PeDL genes are specifically expressed in the gynostemium and at the early stages of ovule development. Both PeDLs could partially complement an Arabidopsis crc-1 mutant. Virus-induced gene silencing (VIGS) of PeDL1 and PeDL2 affected the number of protuberant ovule initials differentiated from the placenta. Transient overexpression of PeDL1 in Phalaenopsis orchids caused abnormal development of ovule and stigmatic cavity of gynostemium. PeDL1, but not PeDL2, could form a heterodimer with Phalaenopsis equestris CINCINNATA 8 (PeCIN8). Paralogous retention and subsequent divergence of the gene sequences of PeDL1 and PeDL2 in P. equestris might result in the differentiation of function and protein behaviors. These results reveal that the ancestral duplicated DL/CRC-like genes play important roles in orchid reproductive organ innovation.
Different repartition of the cryptic species of black aspergilli according to the anatomical sites in human infections, in a French University hospital
Authors: Gits-Muselli Maud , Hamane Samia , Verillaud Benjamin , Cherpin Elisa , Denis Blandine , Bondeelle Louise , Touratier Sophie , Alanio Alexandre , Garcia-Hermoso Dea , Bretagne Stéphane
Published: April 2021

Black aspergilli of the section Nigri are rarely differentiated at the species level when originating from human specimens. We wondered whether some cryptic species could be more frequently observed in some clinical entities. We analyzed the 198 black isolates consecutively collected from the external ear canal (EEC; n = 66), respiratory specimens (n = 99), and environment (n = 33). DNA was extracted and species identification was performed upon the partial calmodulin gene. We identified by decreasing frequency: Aspergillus welwitschiae (35.3%), Aspergillus tubingensis (34.3%), Aspergillus niger (17.2%), Aspergillus luchuensis (4%), Aspergillus aff. welwitschiae (3%), Aspergillus neoniger (2%), Aspergillus piperis (1.5%), Aspergillus japonicus (1.0%), Aspergillus vadensis (0.5%), and two Aspergillus tubingensis clade (1%). The distribution of the three main cryptic species was different between EEC and respiratory samples (P < 0.001) but not different between respiratory and environment samples (P = 0.264). Aspergillus welwitschiae was more often associated with EEC (54.5%), whereas A. tubingensis and A. niger were predominant in respiratory samples (39.4 and 26.3%, respectively). Among the 99 respiratory isolates, only 10 were deemed responsible for probable invasive aspergillosis, of which six were mixed with other pathogenic moulds. This study shows the interest to pursue the identification of clinical isolates in the Aspergillus section Nigri to unravel some specific associations with clinical entities. The association of A. welwitschiae with otomycosis suggests a better fitness to infect/colonize the ear canal. Also, members of the Aspergillus section Nigri alone are rarely responsible for invasive aspergillosis.

Lay summary

We analyzed 198 black aspergilli isolates collected from different samples type to determine their species identification. We observe a different distribution of species between ear canal and respiratory samples (P < 0.001), suggesting a better fitness of A. welwitschiae to infect the ear canal.
Giant molecular cloud formation at the interface of colliding supershells in the large magellanic cloud
Authors: Fujii Kosuke , Mizuno Norikazu , Dawson J R , Inoue Tsuyoshi , Torii Kazufumi , Onishi Toshikazu , Kawamura Akiko , Muller Erik , Minamidani Tetsuhiro , Tsuge Kisetsu , Fukui Yasuo
Published: April 2021

We investigate the H i envelope of the young, massive GMCs in the star-forming regions N48 and N49, which are located within the high column density H i ridge between two kpc-scale supergiant shells, LMC 4 and LMC 5. New long-baseline H i 21 cm line observations with the Australia Telescope Compact Array (ATCA) were combined with archival shorter baseline data and single dish data from the Parkes telescope, for a final synthesized beam size of 24.75 arcsec by 20.48 arcsec, which corresponds to a spatial resolution of ∼6 pc in the LMC. It is newly revealed that the H i gas is highly filamentary and that the molecular clumps are distributed along filamentary H i features. In total 39 filamentary features are identified and their typical width is ∼21 (8–49) [pc]. We propose a scenario in which the GMCs were formed via gravitational instabilities in atomic gas which was initially accumulated by the two shells and then further compressed by their collision. This suggests that GMC formation involves the filamentary nature of the atomic medium.
The evolution of the mass–metallicity relations from the VANDELS survey and the gaea semi-analytic model
Authors: Fontanot Fabio , Calabrò Antonello , Talia Margherita , Mannucci Filippo , Castellano Marco , Cresci Giovanni , De Lucia Gabriella , Gallazzi Anna , Hirschmann Michaela , Pentericci Laura , Xie Lizhi , Amorin Ricardo , Bolzonella Micol , Bongiorno Angela , Cucciati Olga , Cullen Fergus , Fynbo Johan P U , Hathi Nimish , Hibon Pascale , McLure Ross J , Pozzetti Lucia
Published: April 2021

In this work, we study the evolution of the mass–metallicity relations (MZRs) as predicted by the GAlaxy Evolution and Assembly (gaea) semi-analytic model. We contrast these predictions with recent results from the VANDELS survey, which allows us to expand the accessible redshift range for the stellar MZR up to z ∼ 3.5. We complement our study by considering the evolution of the gas-phase MZR in the same redshift range. We show that gaea is able to reproduce the observed evolution of the z < 3.5 gas-phase MZR and z < 0.7 stellar MZR, while it overpredicts the stellar metallicity at z ∼ 3.5. Furthermore, gaea also reproduces the so-called fundamental metallicity relation (FMR) between gas-phase metallicity, stellar mass, and star formation rate (SFR). In particular, the gas-phase FMR in gaea is already in place at z ∼ 5 and shows almost no evolution at lower redshift. gaea predicts the existence of a stellar FMR that is, however, characterized by a relevant redshift evolution, although its shape follows closely the gas-phase FMR. We also report additional unsolved tensions between model and data: the overall normalization of the predicted MZR agrees with observations only within ∼0.1 dex; the largest discrepancies are seen at z ∼ 3.5 where models tend to slightly overpredict observed metallicities; the slope of the predicted MZR at fixed SFR is too steep below a few M⊙ yr−1. Finally, we provide model predictions for the evolution of the MZRs at higher redshifts, which would be useful in the context of future surveys, like those that will be performed with James Webb Space Telescope.
What controls the UV-to-X-ray continuum shape in quasars?
Authors: Timlin III John D , Brandt W N , Laor Ari
Published: April 2021

We present an investigation of the interdependence of the optical-to-X-ray spectral slope (αox), the  He ii equivalent-width (EW), and the monochromatic luminosity at 2500 Å (L2500). The values of αox and  He ii EW are indicators of the strength/shape of the quasar ionizing continuum, from the ultraviolet (UV; 1500–2500 Å), through the extreme ultraviolet (EUV; 300–50 Å), to the  X-ray (2 keV) regime. For this investigation, we measure the  He ii EW of 206 radioquiet quasars devoid of broad absorption lines that have high-quality spectral observations of the UV and 2 keV X-rays. The sample spans wide redshift (≈0.13–3.5) and luminosity (log(L2500) ≈ 29.2–32.5 erg s−1 Hz−1) ranges. We recover the well-known αox–L2500 and  He ii EW–L2500 anticorrelations, and we find a similarly strong correlation between αox and  He ii EW, and thus the overall spectral shape from the UV, through the EUV, to the  X-ray regime is largely set by luminosity. A significant αox– He ii EW correlation remains after removing the contribution of L2500 from each quantity, and thus the emission in the EUV and the X-rays are also directly tied. This set of relations is surprising, since the UV, EUV, and  X-ray emission are expected to be formed in three physically distinct regions. Our results indicate the presence of a redshift-independent physical mechanism that couples the continuum emission from these three different regions, and thus controls the overall continuum shape from the UV to the  X-ray regime.
KIC 5359678: a detached eclipsing binary with starspots
Authors: Wang Jiaxin , Fu Jianning , Niu Hubiao , Pan Yang , Li Chunqian , Zong Weikai , Hou Yonghui
Published: April 2021

We study the detached eclipsing binary, KIC 5359678, with starspot modulation using the high-quality Kepler photometry and LAMOST spectroscopy. The phoebe model, optimal for this binary, reveals that this system is a circular detached binary, composed of two F-type main-sequence stars. The masses and radii of the primary and the secondary are M1 = 1.31 ± 0.05 M⊙, R1 = 1.52 ± 0.04 R⊙, M2 = 1.12 ± 0.04 M⊙, and R2 = 1.05 ± 0.06 R⊙, respectively. The age of this binary is estimated to be about 2 Gyr, a value much longer than the synchronization time-scale of 17.8 Myr. The residuals of light curves show quasi-sinusoidal signals, which could be induced by starspots. We apply autocorrelation function analysis on the out-of-eclipse residuals and find that the spot with rotational period close to the orbital period, while, the decay time-scale of starspots is longer than that on the single stars with the same temperature, period range, and rms scatter. A two-starspot model is adopted to fit the signals with two-dip pattern, whose result shows that the longitude decreases with time.
The splashback boundary of haloes in hydrodynamic simulations
Authors: O’Neil Stephanie , Barnes David J , Vogelsberger Mark , Diemer Benedikt
Published: April 2021

The splashback radius, Rsp, is a physically motivated halo boundary that separates infalling and collapsed matter of haloes. We study Rsp in the hydrodynamic and dark matter-only IllustrisTNG simulations. The most commonly adopted signature of Rsp is the radius at which the radial density profiles are steepest. Therefore, we explicitly optimize our density profile fit to the profile slope and find that this leads to a $\sim 5{{\ \rm per\ cent}}$ larger radius compared to other optimizations. We calculate Rsp for haloes with masses between 1013 and 15 M⊙ as a function of halo mass, accretion rate, and redshift. Rsp decreases with mass and with redshift for haloes of similar M200 m in agreement with previous work. We also find that Rsp/R200 m decreases with halo accretion rate. We apply our analysis to dark matter, gas, and satellite galaxies associated with haloes to investigate the observational potential of Rsp. The radius of steepest slope in gas profiles is consistently smaller than the value calculated from dark matter profiles. The steepest slope in galaxy profiles, which are often used in observations, tends to agree with dark matter profiles but is lower for less massive haloes. We compare Rsp in hydrodynamic and N-body dark matter-only simulations and do not find a significant difference caused by the addition of baryonic physics. Thus, results from dark matter-only simulations should be applicable to realistic haloes.
A constraint on light primordial black holes from the interstellar medium temperature
Authors: Kim Hyungjin
Published: April 2021

Primordial black holes are a viable dark matter candidate. They decay via Hawking evaporation. Energetic particles from the Hawking radiation interact with interstellar gas, depositing their energy as heat and ionization. For a sufficiently high Hawking temperature, fast electrons produced by black holes deposit a substantial fraction of energy as heat through the Coulomb interaction. Using the dwarf galaxy Leo T, we place an upper bound on the fraction of primordial black hole dark matter. For $M \lt 5 \times 10^{-17}\, \mathrm{M}_\odot$, our bound is competitive with or stronger than other bounds.
Two conserved oligomer interfaces of NSP7 and NSP8 underpin the dynamic assembly of SARS-CoV-2 RdRP
Authors: Biswal Mahamaya , Diggs Stephen , Xu Duo , Khudaverdyan Nelli , Lu Jiuwei , Fang Jian , Blaha Gregor , Hai Rong , Song Jikui
Published: April 2021

Replication of the ∼30 kb-long coronavirus genome is mediated by a complex of non-structural proteins (NSP), in which NSP7 and NSP8 play a critical role in regulating the RNA-dependent RNA polymerase (RdRP) activity of NSP12. The assembly of NSP7, NSP8 and NSP12 proteins is highly dynamic in solution, yet the underlying mechanism remains elusive. We report the crystal structure of the complex between NSP7 and NSP8 of SARS-CoV-2, revealing a 2:2 heterotetrameric form. Formation of the NSP7-NSP8 complex is mediated by two distinct oligomer interfaces, with interface I responsible for heterodimeric NSP7-NSP8 assembly, and interface II mediating the heterotetrameric interaction between the two NSP7-NSP8 dimers. Structure-guided mutagenesis, combined with biochemical and enzymatic assays, further reveals a structural coupling between the two oligomer interfaces, as well as the importance of these interfaces for the RdRP activity of the NSP7-NSP8-NSP12 complex. Finally, we identify an NSP7 mutation that differentially affects the stability of the NSP7-NSP8 and NSP7-NSP8-NSP12 complexes leading to a selective impairment of the RdRP activity. Together, this study provides deep insights into the structure and mechanism for the dynamic assembly of NSP7 and NSP8 in regulating the replication of the SARS-CoV-2 genome, with important implications for antiviral drug development.
Integrating multiple references for single-cell assignment
Authors: Duan Bin , Chen Shaoqi , Chen Xiaohan , Zhu Chenyu , Tang Chen , Wang Shuguang , Gao Yicheng , Fu Shaliu , Liu Qi
Published: April 2021

Efficient single-cell assignment is essential for single-cell sequencing data analysis. With the explosive growth of single-cell sequencing data, multiple single-cell sequencing data sources are available for the same kind of tissue, which can be integrated to further improve single-cell assignment; however, an efficient integration strategy is still lacking due to the great challenges of data heterogeneity existing in multiple references. To this end, we present mtSC, a flexible single-cell assignment framework that integrates multiple references based on multitask deep metric learning designed specifically for cell type identification within tissues with multiple single-cell sequencing data as references. We evaluated mtSC on a comprehensive set of publicly available benchmark datasets and demonstrated its state-of-the-art effectiveness for integrative single-cell assignment with multiple references.
LigAdvisor: a versatile and user-friendly web-platform for drug design
Authors: Pinzi Luca , Tinivella Annachiara , Gagliardelli Luca , Beneventano Domenico , Rastelli Giulio
Published: April 2021

Although several tools facilitating in silico drug design are available, their results are usually difficult to integrate with publicly available information or require further processing to be fully exploited. The rational design of multi-target ligands (polypharmacology) and the repositioning of known drugs towards unmet therapeutic needs (drug repurposing) have raised increasing attention in drug discovery, although they usually require careful planning of tailored drug design strategies. Computational tools and data-driven approaches can help to reveal novel valuable opportunities in these contexts, as they enable to efficiently mine publicly available chemical, biological, clinical, and disease-related data. Based on these premises, we developed LigAdvisor, a data-driven webserver which integrates information reported in DrugBank, Protein Data Bank, UniProt, Clinical Trials and Therapeutic Target Database into an intuitive platform, to facilitate drug discovery tasks as drug repurposing, polypharmacology, target fishing and profiling. As designed, LigAdvisor enables easy integration of similarity estimation results with clinical data, thereby allowing a more efficient exploitation of information in different drug discovery contexts. Users can also develop customizable drug design tasks on their own molecules, by means of ligand- and target-based search modes, and download their results. LigAdvisor is publicly available at https://ligadvisor.unimore.it/.
Environmental and sex-specific molecular signatures of glioma causation
Authors: Claus Elizabeth B , Cannataro Vincent L , Gaffney Stephen G , Townsend Jeffrey P
Published: April 2021

Background

The relative importance of genetic and environmental risk factors in gliomagenesis remains uncertain.

Methods

Using whole-exome sequencing data from 1105 adult gliomas, we evaluate the relative contribution to cancer cell lineage proliferation and survival of single-nucleotide mutations in tumors by IDH mutation subtype and sex. We also quantify the contributions of COSMIC cancer mutational signatures to these tumors, identifying possible risk exposures.

Results

IDH-mutant tumors exhibited few unique recurrent substitutions—all in coding regions, while IDH wild-type tumors exhibited many substitutions in non-coding regions. The importance of previously reported mutations in IDH1/2, TP53, EGFR, PTEN, PIK3CA, and PIK3R1 was confirmed; however, the largest cancer effect in IDH wild-type tumors was associated with mutations in the low-prevalence BRAF V600E. Males and females exhibited mutations in a similar set of significantly overburdened genes, with some differences in variant sites—notably in the phosphoinositide 3-kinase (PI3K) pathway. In IDH-mutant tumors, PIK3CA mutations were located in the helical domain for females and the kinase domain for males; variants of import also differed by sex for PIK3R1. Endogenous age-related mutagenesis was the primary molecular signature identified; a signature associated with exogenous exposure to haloalkanes was identified and noted more frequently in males.

Conclusions

Cancer-causing mutations in glioma primarily originated as a consequence of endogenous rather than exogenous factors. Mutations in helical vs kinase domains of genes in the phosphoinositide 3-kinase (PI3K) pathway are differentially selected in males and females. Additionally, a rare environmental risk factor is suggested for some cases of glioma—particularly in males.
Proper protein folding in the endoplasmic reticulum is required for attachment of a glycosylphosphatidylinositol anchor in plants
Authors: Shin Yun-Ji , Vavra Ulrike , Strasser Richard
Published: April 2021

Endoplasmic reticulum (ER) quality control processes recognize and eliminate misfolded proteins to maintain cellular protein homeostasis and prevent the accumulation of defective proteins in the secretory pathway. Glycosylphosphatidylinositol (GPI)-anchored proteins carry a glycolipid modification, which provides an efficient ER export signal and potentially prevents the entry into ER-associated degradation (ERAD), which is one of the major pathways for clearance of terminally misfolded proteins from the ER. Here, we analyzed the degradation routes of different misfolded glycoproteins carrying a C-terminal GPI-attachment signal peptide in Arabidopsis thaliana. We found that a fusion protein consisting of the misfolded extracellular domain from Arabidopsis STRUBBELIG and the GPI-anchor attachment sequence of COBRA1 was efficiently targeted to hydroxymethylglutaryl reductase degradation protein 1 complex-mediated ERAD without the detectable attachment of a GPI anchor. Non-native variants of the GPI-anchored lipid transfer protein 1 (LTPG1) that lack a severely misfolded domain, on the other hand, are modified with a GPI anchor and targeted to the vacuole for degradation. Impaired processing of the GPI-anchoring signal peptide by mutation of the cleavage site or in a GPI-transamidase-compromised mutant caused ER retention and routed the non-native LTPG1 to ERAD. Collectively, these results indicate that for severely misfolded proteins, ER quality control processes are dominant over ER export. For less severely misfolded proteins, the GPI anchor provides an efficient ER export signal resulting in transport to the vacuole.
Identifying parameters associated with delayed diagnosis in axial spondyloarthritis: data from the European map of axial spondyloarthritis
Authors: Garrido-Cumbrera Marco , Navarro-Compán Victoria , Bundy Christine , Mahapatra Raj , Makri Souzi , Correa-Fernández José , Christen Laura , Delgado-Domínguez Carlos Jesús , Poddubnyy Denis ,   the EMAS Working Group
Published: April 2021

Objective

To identify the parameters associated with self-reported diagnostic delay (DD) in axial spondyloarthritis (axSpA) patients across Europe.

Methods

Data from 2652 patients from 13 countries who participated in the European Map of Axial Spondyloarthritis (EMAS) were collected through an online survey (2017–2018). DD was calculated as the difference between age at diagnosis and age at symptom onset reported by participants. Associations between DD and sociodemographic characteristics, as well as disease-related factors were explored through univariable and multivariable linear regression analysis.

Results

Average DD was 7.4  (8.4) years with a variation between countries. The variables associated with longer DD in the final multivariable regression model were: younger age at symptom onset (b = −0.26; 95% CI: −0.28, −0.23), female gender (b = 1.34; 95% CI: 0.73, 1.96) and higher number of health-care professionals (HCPs) seen before diagnosis (b = 1.19; 95% CI: 0.95, 1.43). There was a significant interaction between the female gender and the number of HCPs seen before diagnosis. A substantial variation of the DD across European countries was observed.

Conclusion

In this sample of axSpA patients, average DD was greater than 7 years. Younger age at symptom onset, female gender, higher number of HCPs seen before diagnosis, and being diagnosed by rheumatologist were the parameters associated with a longer DD in axSpA. These findings indicate a need for continuing efforts dedicated to recognition of patients with a high probability of axSpA on the level of non-rheumatology specialists and facilitating referral to a rheumatologist for timely diagnosis.
Transforming Lives of Former Foster Youths: A Campus-Based Support Program Grounded in Social Work Values
Authors: Lee Madeline Y , Mickelson James , Quijada Leigh , Orr Laurie
Published: April 2021

Support programs to improve higher education outcomes for former foster youths have emerged in the past 20 years, but literature to guide their development and implementation is limited. This conceptual article presents the program logic model for ACE [Achieving College Excellence] Scholars Services, the comprehensive, campus-based program supporting former foster youths grounded in social work values at California State University San Marcos (CSUSM). ACE has a noncompetitive application process that accepts an unrestricted number of students, known as ACE Scholars. To focus on the unique needs of former foster youths, students who are on probation, experiencing homeless, and unaccompanied minors are included if they have also experienced foster care. Funded by private donors, the Center for ACE Scholars on CSUSM’s campus provides an inviting, welcoming space that reflects the inclusive support ACE Scholars receive. By increasing educational attainment and opportunities for this vulnerable population, ACE aims to improve outcomes for former foster youths and their next generation. Articulating this program logic model provides implications for developing and implementing support programs for former foster youths on college campuses and sets the foundation for evaluating the impact of ACE Scholars Services.
Converging Roles of the Aryl Hydrocarbon Receptor in Early Embryonic Development, Maintenance of Stemness, and Tissue Repair
Authors: Zablon Hesbon A , Ko Chia-I , Puga Alvaro
Published: April 2021

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor well-known for its adaptive role as a sensor of environmental toxicants and mediator of the metabolic detoxification of xenobiotic ligands. In addition, a growing body of experimental data has provided indisputable evidence that the AHR regulates critical functions of cell physiology and embryonic development. Recent studies have shown that the naïve AHR—that is, unliganded to xenobiotics but activated endogenously—has a crucial role in maintenance of embryonic stem cell pluripotency, tissue repair, and regulation of cancer stem cell stemness. Depending on the cellular context, AHR silences the expression of pluripotency genes Oct4 and Nanog and potentiates differentiation, whereas curtailing cellular plasticity and stemness. In these processes, AHR-mediated contextual responses and outcomes are dictated by changes of interacting partners in signaling pathways, gene networks, and cell-type-specific genomic structures. In this review, we focus on AHR-mediated changes of genomic architecture as an emerging mechanism for the AHR to regulate gene expression at the transcriptional level. Collective evidence places this receptor as a physiological hub connecting multiple biological processes whose disruption impacts on embryonic development, tissue repair, and maintenance or loss of stemness.
Safety of Nitrous Oxide Anesthesia in a Selected Group of Patients Undergoing Neurosurgery: An Exploratory Subgroup Analysis of the ENIGMA Trials
Authors: Patel Kishan K. , Sun Xin , Cheng Joseph , Schaller Karl , Tessitore Enrico , Gondar Renato , Gaudet John , Myles Paul S. , Leslie Kate , Nouri Aria
Published: April 2021

Background:

The Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia (ENIGMA)-I and ENIGMA-II were randomized clinical trials that assessed the safety of nitrous oxide anesthesia in patients undergoing noncardiac surgery. In this study, we performed an exploratory pooled analysis of both ENIGMA trials to assess the safety of nitrous oxide in a selected group of patients undergoing neurosurgery.

Methods:

Data from each ENIGMA trial were collated into a single database. Information regarding patient demographics, comorbidities, medication use, anesthesia, surgical procedure, and postoperative complications was extracted. Multivariate logistic regression was conducted for postoperative complications to assess the risk associated with nitrous oxide.

Results:

A total of 830 patients were included in our analysis: 417 received nitrous oxide anesthesia, and 413 received nitrous oxide-free anesthesia. Baseline patient and perioperative characteristics were comparable. Procedural data were available for 535 patients (64%); of these, 507 (95%) underwent spinal neurosurgery and 28 (5%) underwent cranial neurosurgery. Patients in the nitrous oxide group had lower inspired oxygen concentration (30% vs. 38%; P<0.001) and end-tidal volatile agent concentration (0.56 vs. 0.89 minimal alveolar concentration equivalents; P<0.001) compared with the nitrous oxide-free group. Use of nitrous oxide was not associated with increased risk of postoperative complications (myocardial infarction, cardiac arrest, stroke, infection, severe vomiting, fever, pneumonia, pneumothorax, blood transfusion, venous thromboembolism, or death) (odds ratio: 1.22; 95% confidence interval: 0.89-1.65; P=0.22) or prolonged length of hospital stay (median 5.0 vs. 4.2 d for nitrous oxide and nitrous oxide-free groups; P=0.28).

Conclusion:

Nitrous oxide did not increase the risk of postoperative complications or prolonged length of hospital stay in the neurosurgical cohort enrolled in the ENIGMA-I and ENIGMA-II trials.
System of Psychological Support Based on Positive Suggestions to the Critically Ill Using ICU Doulas
Authors: Karnatovskaia Lioudmila V. , Schultz Jason M. , Niven Alexander S. , Steele Amanda J. , Baker Brittany A. , Philbrick Kemuel L. , del Valle Kathryn T. , Johnson Kimberly R. , Gajic Ognjen , Varga Katalin
Published: April 2021

Background:

Surviving critical illness often creates a lasting psychological impact, including depression, anxiety, and post-traumatic stress. Memories of frightening and delusional experiences are the largest potentially modifiable risk factor, but currently, there is no proven intervention to improve these inciting factors. Psychological support based on positive suggestion is a psychotherapeutic approach that can be provided even to patients in altered cognitive states and is therefore a viable psychotherapy intervention throughout the ICU stay. Traditional ICU care team members have limited time and training to provide such psychological support to patients. Doulas are trained supportive companions who have been effectively used to provide patient advocacy and emotional support in other clinical settings and may address this need. Our aim was to train and implement a psychological support based on positive suggestion program for the critically ill using doulas, and measure acceptance of this intervention through stakeholder feedback.

Methods:

Doula training included three objectives: an introduction to ICU practice structure and policies; education about fundamental aspects of critical care conditions and procedures; and didactic and hands-on learning experiences in effective use of psychological support based on positive suggestion in the critically ill. Doulas were evaluated at the end of their training and during subsequent clinical activities using competency-based assessments as well as through survey-based questions and interviews with key stakeholders.

Results:

The ICU doulas performed psychological support based on positive suggestion on 43 critically ill patients in the ICU setting. Stakeholder feedback from nurses, patients, and patient families was positive. The majority (28/32) of surveyed bedside ICU nurses reported that the doulas’ involvement was helpful for both patients and nurses alike. All interviewed family members offered positive comments about the ICU doula presence and of the 40 patients who recalled the intervention 37 found it comforting.

Conclusions:

Our program successfully trained two doulas to work effectively in the ICU setting performing patient-centered psychological support based on positive suggestion interventions. Their training improved their skill sets and was reported as beneficial by patients, families, and critical care nursing. This training program offers a proof of concept that could be applied in other medical centers, bringing doulas more commonly into the ICU practice to help humanize the experience for patients, families, and medical teams.
Respiratory Support Adjustments and Monitoring of Mechanically Ventilated Patients Performing Early Mobilization: A Scoping Review
Authors: González-Seguel Felipe , Camus-Molina Agustín , Jasmén Anita , Molina Jorge , Pérez-Araos Rodrigo , Graf Jerónimo
Published: April 2021

Objectives:

This scoping review is aimed to summarize current knowledge on respiratory support adjustments and monitoring of metabolic and respiratory variables in mechanically ventilated adult patients performing early mobilization.

Data Sources:

Eight electronic databases were searched from inception to February 2021, using a predefined search strategy.

Study Selection:

Two blinded reviewers performed document selection by title, abstract, and full text according to the following criteria: mechanically ventilated adult patients performing any mobilization intervention, respiratory support adjustments, and/or monitoring of metabolic/respiratory real-time variables.

Data Extraction:

Four physiotherapists extracted relevant information using a prespecified template.

Data Synthesis:

From 1,208 references screened, 35 documents were selected for analysis, where 20 (57%) were published between 2016 and 2020. Respiratory support settings (ventilatory modes or respiratory variables) were reported in 21 documents (60%). Reported modes were assisted (n = 11) and assist-control (n = 9). Adjustment of variables and modes were identified in only seven documents (20%). The most frequent respiratory variable was the Fio
2, and only four studies modified the level of ventilatory support. Mechanical ventilator brand/model used was not specified in 26 documents (74%). Monitoring of respiratory, metabolic, and both variables were reported in 22 documents (63%), four documents (11%) and 10 documents (29%), respectively. These variables were reported to assess the physiologic response (n = 21) or safety (n = 13). Monitored variables were mostly respiratory rate (n = 26), pulse oximetry (n = 22), and oxygen consumption (n = 9). Remarkably, no study assessed the work of breathing or effort during mobilization.

Conclusions:

Little information on respiratory support adjustments during mobilization of mechanically ventilated patients was identified. Monitoring of metabolic and respiratory variables is also scant. More studies on the effects of adjustments of the level/mode of ventilatory support on exercise performance and respiratory muscle activity monitoring for safe and efficient implementation of early mobilization in mechanically ventilated patients are needed.
Development of a Computer Application Used by Visiting Nurses, Physicians, and Patients/Caregivers to Prevent Indwelling Urinary Catheter Occlusion in the Community
Authors: Maeda Shuko , Fukuda Moriyoshi , Moriyama Manabu T. , Nakamura Miho
Published: April 2021

This study aimed to develop a computer application (software) for use by visiting nurses, physicians, and patients/caregivers, to support their care of long-term indwelling urinary catheters in the community. Development of this application involved: (1) confirmation of the intended purpose, users, and application construction; (2) establishment of the functional requirements for data sharing and communication among visiting nurses, physicians, and patients/caregivers; (3) design of three constituent “versions” of the application to be used by visiting nurses, physicians, and patients/caregivers, respectively; and (4) testing of the data sharing and communication functions. The application was designed to facilitate the prevention, assessment, and response to occlusion of indwelling urinary catheters during long-term use at home. This application is characterized by: (1) a unique design of three application “versions” that each reflect the specific care roles of its respective user group; (2) data sharing among the three groups according to their respective roles; and (3) the inclusion of caregivers as users. This article proposes a model that can inform the design of future applications for nursing professionals and patients and caregivers and provide a basis for future research on the development of healthcare applications supporting improvements in care.
Long-term Outcomes after Postnatal Cytomegalovirus Infection in Low Birthweight Preterm Infants
Authors: Stark Ashley , Cantrell Sarah , Greenberg Rachel G. , Permar Sallie R. , Weimer Kristin E. D.
Published: April 2021

Background:

Cytomegalovirus (CMV) is the most common viral infection seen in newborns. Although postnatally acquired CMV (pCMV) infection rarely results in serious manifestations in term infants, preterm infants can develop severe clinical illness. However, the long-term implications of pCMV infection of preterm infants are unknown. Few robust studies on long-term outcomes of pCMV infection have been performed, and those reported often present conflicting results. Our objective was to assess the long-term outcomes for low birthweight (LBW) preterm infants after pCMV infection.

Methods:

A systematic review of English and non-English articles using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science was conducted. Search strategies included a mix of keywords and database-specific subject headings for CMV and LBW infants. Editorials, comments, reviews and animal-only studies were excluded. Case reports, observational, experimental and randomized controlled trials that examined pCMV in preterm or VLBW infants and long-term (>1 month) impact of pCMV were included.

Results:

pCMV infection in preterm infants is associated with increased risk for pulmonary and neurologic complications and increases length of stay. There is less evidence to suggest that pCMV is associated with necrotizing enterocolitis, ophthalmologic, audiologic and anthropomorphic complications in preterm infants.

Conclusions:

Preterm infants with pCMV, especially those with symptomatic infection, may have long-term pulmonary and neurodevelopmental morbidity compared with their pCMV negative counterparts. Our results highlight the importance of pCMV detection and prevention in preterm infants in the neonatal intensive care unit. Large prospective studies are needed to fully define outcomes and determine if treatment improves outcomes.
COVID-19-Associated Cerebral White Matter Injury in a Newborn Infant With Afebrile Seizure
Authors: Yildiz Harun , Yarci Erbu , Bozdemir Sefika Elmas , Ozdinc Kizilay Nesrin , Mengi Senay , Beskardesler Naciye , Korukluoglu Gulay , Mueller Andreas , Bagci Soyhan
Published: April 2021

Coronavirus disease 2019 (COVID-19) symptoms in newborn infants are incompletely described. We present the first case of neuroradiologic abnormality associated with COVID-19 in a newborn infant with afebrile seizure. This case underlines the possible neurologic involvement of severe acute respiratory syndrome coronavirus 2 in this age group.
The Role of Facets of Job Satisfaction in the National and Socioeconomic Differences in Overall Job Satisfaction
Authors: Tatsuse Takashi , Sekine Michikazu , Yamada Masaaki , Cable Noriko , Chandola Tarani , Marmot Michael G.
Published: April 2021

Objective:

To explore national and socioeconomic differences in overall job satisfaction, we examined whether those differences can be explained by what job-related factors.

Methods:

Our datasets for this study are from the Whitehall II study and the Japan Civil Servant Study. Of the participants who were 5540 cases, with 3250 people from Great Britain and 2290 from Japan.

Results:

The odds ratio for job dissatisfaction was more than double in Japan compared with Britain. However, after adjusting the related factors—especially the facets of job satisfaction variables—the difference was reversed. Also, regarding the occupational differences, lower occupational grades had lower risks of overall job dissatisfaction, after adjusting for related factors.

Conclusions:

The national and socioeconomic differences in overall job satisfaction were strongly related to facets of job satisfaction rather than job stress factors.
The Forgotten Health-Care Occupations at Risk of Burnout—A Burnout, Job Demand-Control-Support, and Effort-Reward Imbalance Survey
Authors: Sérole Claire , Auclair Candy , Prunet Denis , Charkhabi Morteza , Lesage François-Xavier , Baker Julien S. , Mermillod Martial , Gerbaud Laurent , Dutheil Frédéric
Published: April 2021

Aims:

We conducted a cross-sectional study on healthcare workers from the University Hospital in Clermont-Ferrand. They received a self-report questionnaire consisting of the Maslach Burnout Inventory, Job Demand Control Support, Effort-Reward Imbalance model, and questions about ethical conflict in order to investigate on burnout.

Results:

We included 1774 workers. Overinvestment was the only factor explaining the increase in emotional exhaustion, depersonalization, and the decrease in personal accomplishment. Taking into account the absence of burnout as a reference, overinvestment multiplied the risk of high burnout by 22.0 (5.10 to 94.7).

Conclusion:

Some “forgotten” occupations among healthcare workers are at risk of burnout. Overinvestment was the main factor explaining the increase in the tree dimensions of burnout. Moreover, the two main models of stress at work were highly predictive of burnout.
Updated Use of Maggots for Debridement
Authors: Juanillo Kate Isabel
Published: April 2021

Historical and modern-day use of maggots for debridement is described. Included are benefits of maggot therapy based on the evidence. This article also includes method for procurement.
Efficacy and Safety of Eculizumab for Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis
Authors: Zhou Shuang , Dong Xiu , Chen Chaoyang , Ma Lingyun , Wu Ye , Zhou Ying , Cui Yimin
Published: April 2021

Background:

Eculizumab is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). This study aimed to evaluate the efficacy and safety of eculizumab in patients with PNH.

Methods:

PubMed, EMBASE, The Cochrane Library, and ClinicalTrials.gov were searched for prospective interventional studies treating PNH with eculizumab. The primary outcome was the change in lactate dehydrogenase (LDH) levels, whereas secondary outcomes included the change in hemoglobin (Hb) levels, transfusion rates, and adverse drug events.

Results:

Patients (n=235) from 6 studies were included in this meta-analysis. LDH and Hb levels and transfusion rates decreased significantly at 12, 26 weeks, 12, 15, and >15 months. The most frequent adverse events included nasopharyngitis (effect size [ES]: 0.53; 95% confidence intervals [CI]: 0.47 to 0.60; P=0.00), headache (ES: 0.47; 95% CI: 0.25 to 0.69; P=0.00), upper respiratory tract infection (ES: 0.37; 95% CI: 0.27 to 0.46; P=0.00), nausea (ES: 0.31; 95% CI: 0.24 to 0.38; P=0.00), fatigue, diarrhea, cough, pyrexia, abdominal pain, pain in extremities, and contusion.

Conclusion:

Eculizumab is an effective and well-tolerated treatment for patients with PNH. It is effective at decreasing LDH levels and transfusion rates while increasing Hb levels. Further studies are needed to explore the safety of eculizumab.
Effects of Transcranial Direct Current Stimulation Combined With Neuromuscular Electrical Stimulation on Upper Extremity Motor Function in Patients With Stroke
Authors: Wei Ya-Ying , Koh Chia-Lin , Hsu Miao-Ju , Lo Sing-Kai , Chen Chia-Hsin , Lin Jau-Hong
Published: April 2021

Objective

The aim of the study was to investigate the treatment effects of transcranial direct current stimulation combined with neuromuscular electrical stimulation on the motor function of upper extremity in persons with stroke.

Design

This study was a pilot double-blind randomized controlled trial. Twenty-six patients due to stroke onset of more than 6 mos were randomly allocated to three groups: transcranial direct current stimulation combined with neuromuscular electrical stimulation group, transcranial direct current stimulation group, or control group. In addition to conventional rehabilitation, all subjects received one of the three protocols in a total of 15 sessions for 3 wks.

Results

A significant difference among the three groups was found for the change scores of the Fugl-Meyer Assessment upper extremity subscale from pretreatment to 1-mo follow-up (P = 0.02), in favor of the transcranial direct current stimulation combined with neuromuscular electrical stimulation group. Moreover, the transcranial direct current stimulation combined with neuromuscular electrical stimulation group showed significant within-group improvement on the Fugl-Meyer Assessment upper extremity (from preintervention to postintervention, P = 0.01) and the Action Research Arm Test (from preintervention to postintervention and to 1-mo postintervention, P = 0.03 and P = 0.04, respectively).

Conclusions

This preliminary study reveals that combining transcranial direct current stimulation and neuromuscular electrical stimulation with regular rehabilitation programs may enhance better upper extremity functional improvement than regular rehabilitation programs alone in patients with chronic stroke.
The opioid overdose crisis as a global health challenge
Authors: Krausz R. Michael , Westenberg Jean Nicolas , Ziafat Kimia
Published: April 2021

Purpose of review

To assess the current state of the opioid overdose crisis along three major axes: drug markets and patterns of use, the effectiveness of systems of care, and international developments.

Recent findings

Overdose is a major contributor to mortality and disability among people who use drugs. The increasing number of opioid overdoses in North America especially is an indication of changing drug markets and failing regional systems of care. Globally, we see three clusters of overdose prevalence: (1) a group of countries led by the United States with historically high rates of opioid overdose, (2) a group of countries with increasing rates within a concerning range, (3) a group with very low rates. The contamination of street drugs, the quality and accessibility of treatment, and the overall system of care all contribute to the prevalence of overdose.

Drug markets and pattern of consumption in parts of the world are shifting towards contamination and opioids like fentanyl as the drug of choice, which dismantles insufficient and largely ineffective systems of care. Furthermore, outside of North America, more countries like Estonia, Lithuania, Sweden, Finland, and Norway show very concerning numbers. Without a consistent system response, effects will be devastating.