bluuebunny/crossref_metadata_2025_split huggingface dataset:
5-Fluorouracil blocks quorum-sensing of biofilm-embedded methicillin-resistantStaphylococcus aureusin mice
Authors: Sedlmayer Ferdinand , Woischnig Anne-Kathrin , Unterreiner Vincent , Fuchs Florian , Baeschlin Daniel , Khanna Nina , Fussenegger Martin 
Published: March 2021

AbstractAntibiotic-resistant pathogens often escape antimicrobial treatment by forming protective biofilms in response to quorum-sensing communication via diffusible autoinducers. Biofilm formation by the nosocomial pathogen methicillin-resistant Staphylococcus aureus (MRSA) is triggered by the quorum-sensor autoinducer-2 (AI-2), whose biosynthesis is mediated by methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) and S-ribosylhomocysteine lyase (LuxS). Here, we present a high-throughput screening platform for small-molecular inhibitors of either enzyme. This platform employs a cell-based assay to report non-toxic, bioavailable and cell-penetrating inhibitors of AI-2 production, utilizing engineered human cells programmed to constitutively secrete AI-2 by tapping into the endogenous methylation cycle via ectopic expression of codon-optimized MTAN and LuxS. Screening of a library of over 5000 commercial compounds yielded 66 hits, including the FDA-licensed cytostatic anti-cancer drug 5-fluorouracil (5-FU). Secondary screening and validation studies showed that 5-FU is a potent quorum-quencher, inhibiting AI-2 production and release by MRSA, Staphylococcus epidermidis, Escherichia coli and Vibrio harveyi. 5-FU efficiently reduced adherence and blocked biofilm formation of MRSA in vitro at an order-of-magnitude-lower concentration than that clinically relevant for anti-cancer therapy. Furthermore, 5-FU reestablished antibiotic susceptibility and enabled daptomycin-mediated prevention and clearance of MRSA infection in a mouse model of human implant-associated infection.
Trade Sanctions
Authors: Lodge Hugo D 
Published: March 2021

Abstract
In the UK, trade sanctions should be distinguished from arms embargoes. The latter comprise a ban on the export of military arms and related material, e.g. ammunition, weapons, and other military goods. Thus, embargoes relate to all goods and technologies on a ‘UK military list’. Certain similar goods though not listed may also require a licence either under ‘military end-use controls’ or ‘weapons of mass destruction’ end-use controls.
Partial melting of granodiorite: insights from ediacaran granulite-facies metamorphism in Southern Brazil
Authors: Pavan M , Sawyer E W , Moraes R , Faleiros F M 
Published: March 2021

AbstractIn the Southern Ribeira Belt (Brazil), the Itatins Complex, composed of ortho- and para-derived migmatites record granulite facies metamorphism. Our work focuses on the ortho-derived migmatite, which displays features indicative of partial melting ranging from in-situ melting (cm-thick lenses and veins) to accumulations of melt as leucosomes and patches of diatexite. The unit comprises a biotite felsic granulite (metagranodiorite) with a residual neosome and a leucocratic neosome, generally referred to as leucosome. Phase equilibria modelling using a modified bulk composition from the geochemical standard JG-1 (granodiorite) was carried out to evaluate whether a protolith of granodiorite bulk composition could produce the mineral assemblages observed in the residual neosome and the compositions of melt and residue produced by the partial melting. Isopleth thermobarometry of plagioclase, biotite and orthopyroxene points to P-T conditions of 0.7–1.0 GPa and 845–872 ºC. The modified granodiorite bulk composition generated just 10 mol % melt at these conditions, far lower than the amount estimated from outcrops (around 32 %). A T-XH2O pseudosection shows that increasing H2O content enhances the fertility of the bulk composition and it can become capable of producing melt volumes similar to that observed in outcrop. The melt compositions determined for partial melting of the modified granodiorite bulk composition in open- and closed-systems using THERMOCALC are granitic, and peraluminous. The melts have SiO2 contents between 52.02 mol % and 77.27 mol. % and show XFe values of 0.68 and 0.86. In K2O vs. Na2O+CaO, K2O vs. XFe and K2O-(FeO+MgO)-(Na2O+CaO) space natural samples (5 from the residual neosome and 2 from leucosome) from the Itatins Complex plot in the direction of the trends for melt and residue compositions obtained from modelling of the modified granodiorite bulk composition. The differences between modeled compositions and real rocks are interpreted to result from the interaction of melt with its residual counterpart. Chondrite normalized REE patterns from the residual neosome shows considerably greater depletion of HREE than geochemical standard JG-1 (granodiorite), and the two analyzed leucosomes show lower HREE contents. Zircon rims have REE patterns interpreted to indicate metamorphic recrystallization. U-Pb zircon Concordia ages indicate that the protolith formed during the Paleoproterozoic (2137 Ma) but that metamorphic recrystallization is Neoproterozoic (between 632 and 601 Ma). The metamorphic age pre-dates the intense granitic magmatism that affected the Southern Ribeira Belt between 600 and 570 Ma.
Indonesian Autonomies: Explaining Divergent Self-Government Outcomes in Aceh and Papua
Authors: Barter Shane Joshua , Wangge Hipolitus Ringgi 
Published: March 2021

AbstractA form of power-sharing, territorial autonomy is essential for managing separatism. Indonesia provides two non-Western cases to illuminate what makes autonomy work. In Aceh, autonomy helped to overcome conflict and can be regarded as successful, while in Papua, autonomy has failed, evident in continued unrest. Within the same country, the same institutional response to violent separatism has generated divergent self-government outcomes. Why has autonomy succeeded in Aceh, but failed in Papua? Utilizing within-case and temporal comparisons, we suggest that the content of autonomy may be less important than the process through which it unfolds. The powers granted to Aceh and Papua are similar, although how self-government was negotiated and whom it empowered varied. Early in Aceh and in Papua, autonomy was essentially imposed, empowering corrupt leaders, and sidelining dissidents. Aceh’s ultimately successful autonomy was negotiated and saw popular former rebels take the reins of self-government.
Institutionalized insecurity: post-war employment restructuring and the symbolic power of the local business climate
Authors: Hanley Caroline 
Published: March 2021

Abstract
This article investigates an early case of the institutionalization of insecurity by examining labor-management struggles over capital mobility at the General Electric Company (GE) in Schenectady, NY during the 1950s and 1960s. During this period, GE expanded production in the US South and Southwest, reducing employment in Northern plant communities. In the union stronghold of Schenectady, GE’s strategic use of the emergent ‘business climate’ concept undermined union power to resist employment restructuring by reshaping the local politics of employment security: it mobilized community actors against labor’s framing of the problem and enhanced the Company’s ability to present its position as non-political or disinterested, which aided its operation of symbolic power. This article advances our understanding of the sources of legitimacy in claims-making and shows how cultural processes can contribute to change in the distribution of workplace rewards.
Viromics of extant insect orders unveil the evolution of the flavi-like superfamily
Authors: Paraskevopoulou Sofia , Käfer Simon , Zirkel Florian , Donath Alexander , Petersen Malte , Liu Shanlin , Zhou Xin , Drosten Christian , Misof Bernhard , Junglen Sandra 
Published: March 2021

Abstract
Insects are the most diversified and species-rich group of animals and harbor an immense diversity of viruses. Several taxa in the flavi-like superfamily, such as the genus Flavivirus, are associated with insects; however, systematic studies on insect virus genetic diversity are lacking, limiting our understanding of the evolution of the flavi-like superfamily. Here, we examined the diversity of flavi-like viruses within the most complete and up-to-date insect transcriptome collection comprising 1,243 insect species by employing a Flaviviridae RdRp profile hidden Markov model search. We identified seventy-six viral sequences in sixty-one species belonging to seventeen insect, one entognathan, and one arachnidan orders. Phylogenetic analyses revealed that twenty-seven sequences fell within the Flaviviridae phylogeny but did not group with established genera. Despite the large diversity of insect hosts studied, we only detected one virus in a blood-feeding insect, which branched within the genus Flavivirus, indicating that this genus likely diversified only in hematophagous arthropods. Nine new jingmenviruses with novel host associations were identified. One of the jingmenviruses established a deep rooting lineage additional to the insect- and tick-associated clades. Segment co-segregation phylogenies support the separation of tick- and insect-associated groups within jingmenviruses, with evidence for segment reassortment. In addition, fourteen viruses grouped with unclassified flaviviruses encompassing genome length of up to 20 kb. Species-specific clades for Hymenopteran- and Orthopteran-associated viruses were identified. Forty-nine viruses populated three highly diversified clades in distant relationship to Tombusviridae, a plant-infecting virus family, suggesting the detection of three previously unknown insect-associated families that contributed to tombusvirus evolution.
ONT-Based Draft Genome Assembly and Annotation of Alternaria atra
Authors: Bonthala Bhawna , Small Corinn S. , Lutz Maximilian A. , Graf Alexander , Krebs Stefan , Sepúlveda German , Stam Remco 
Published: March 2021

Species of Alternaria (phylum Ascomycota, family Pleosporaceae) are known as serious plant pathogens, causing major losses on a wide range of crops. Alternaria atra (previously known as Ulocladium atrum) can grow as a saprophyte on many hosts and causes Ulocladium blight on potato. It has been reported that it can also be used as a biocontrol agent against Botrytis cinerea. Here, we present a scaffold-level reference genome assembly for A. atra. The assembly contains 43 scaffolds with a total length of 39.62 Mbp, with scaffold N50 of 3,893,166 bp, L50 of 4, and the longest 10 scaffolds containing 89.9% of the assembled data. RNA-sequencing-guided gene prediction using BRAKER resulted in 12,173 protein-coding genes with their functional annotation. This first high-quality reference genome assembly and annotation for A. atra can be used as a resource for studying evolution in the highly complicated Alternaria genus and might help in understanding the mechanisms defining its role as pathogen or biocontrol agent. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Dose-Dependent Inhibition of CYP2D6 by Bupropion in Patients With Depression
Authors: Hole Kristine , Arnestad Marianne , Molden Espen , Haslemo Tore 
Published: March 2021

Abstract

Purpose
The aim of this study was to investigate the potential dose-dependent CYP2D6 inhibition by bupropion (BUP) in patients with depression.

Methods
Patients combining BUP with venlafaxine were included from a therapeutic drug monitoring (TDM) database at the Diakonhjemmet Hospital (Oslo, Norway). The O/N-desmethylvenlafaxine metabolic ratio measured in TDM samples was used as a biomarker for CYP2D6 phenotype and was compared between patients treated with BUP 150 mg/d and 300 mg/d or greater. In addition, reference groups of venlafaxine-treated patients genotyped as CYP2D6 poor metabolizers (PMs, no CYP2D6 activity) and normal metabolizers (NMs, fully functional CYP2D6 activity) were included.

Findings
A total of 221 patients were included in the study. The median O/N-desmethylvenlafaxine metabolic ratio was significantly higher in patients treated with BUP 150 mg/d (n = 59) versus 300 mg/d or greater (n = 34, 1.77 vs 0.96, P < 0.001). In CYP2D6 NMs (n = 62) and PMs (n = 66), the median metabolic ratios were 40.55 and 0.48, respectively. For patients treated with BUP 150 mg/d, 11 (19%) of the 59 patients were phenoconverted to PMs, whereas this was the case for 17 (50%) of the 34 patients treated with BUP 300 mg/d or greater.

Conclusions
Bupropion exhibits a clear dose-dependent CYP2D6 inhibitory effect during treatment of patients with depression. This finding is of clinical relevance when adjusting dosing of CYP2D6 substrates during comedication with BUP. Half of the patients treated with high-dose BUP are converted to CYP2D6 PM phenotype. Because of the variability in CYP2D6 inhibition, TDM of CYP2D6 substrates should be considered to provide individualized dose adjustments during comedication with BUP.
Recognition, Evaluation, and Management of Pediatric Hereditary Angioedema
Authors: Krack Andrew T. , Bernstein Jonathan A. , Ruddy Richard M. 
Published: March 2021

Abstract
Hereditary angioedema (HAE) is a rare, often underrecognized genetic disorder caused by either a C1 esterase inhibitor deficiency (type 1) or mutation (type 2). This leads to overproduction of bradykinin resulting in vasodilation, vascular leakage, and transient nonpitting angioedema occurring most frequently in the face, neck, upper airway, abdomen, and/or extremities. Involvement of the tongue and laryngopharynx has been associated with asphyxiation and death. Hereditary angioedema is an autosomal-dominant condition; therefore, there is a 50% chance an offspring will inherit this disorder. Any patient presenting with isolated angioedema should be screened with a C4 measurement, as 25% of cases have no family history of HAE. All patients with HAE will have a functional deficiency of C1 esterase inhibitor. Contributors that delay the diagnosis of HAE include recognition delay by clinicians who confuse this condition with histaminergic angioedema, the disease's varied presentations, and limitations to timely testing. Pediatric emergency clinicians should be knowledgeable about how to distinguish between bradykinin- and histamine-mediated angioedema, as there are significant differences in the diagnostic testing, treatment, and clinical response between these 2 different conditions. Evidence indicates that early diagnosis and treatment of HAE reduces morbidity and mortality. Clinician recognition of the mechanistically different problems will ensure patients are appropriately referred to an expert for outpatient management.
Decline in Pediatric Emergency Department Behavioral Team Activations After Institution of an Agitation Protocol
Authors: Pavlov Hannah , Santillanes Genevieve , Claudius Ilene 
Published: March 2021

Objective
Aggressive behavior among pediatric patients with psychiatric complaints in emergency departments is a growing problem. An agitation protocol was instituted in 1 pediatric emergency department to provide scaled recommendations for differing levels of aggression. The study objective was to determine if the frequency of activation of an emergency behavioral response team changed after protocol initiation.

Methods
A protocol for escalating management of agitation in pediatric patients was introduced in February 2016. The electronic medical record was queried for subsequent behavioral response team activations over the next 16 months. Patient demographics and specific features surrounding the activation were retrospectively recorded from the medical record, including length of stay, medications administered, and documented deescalation techniques. Frequency and features of behavioral team activations were compared with activations from a period before the planning and implementation of the protocol (May 2014 to May 2015).

Results
Twenty-one patient visits were found to require behavioral response team activation over 16 months, compared with 31 for the 13-month preprotocol period. Attempts at verbal/ environmental redirection were seen in 77% and deescalation by medication administration before the activation occurred in 14% of patients. During the behavioral team activation, 81% of the patients were given psychiatric medications and 81% were placed in physical restraints.

Conclusions
A decrease from a baseline of 2.4 to 1.3 behavioral response team activations per month, or a 46% decline, was noted following the institution of a clinical protocol for pediatric agitation.
A National Survey to Assess the Population’s Perception of Breast Implant-Associated Anaplastic Large Cell Lymphoma and Breast Implant Illness
Authors: Azzi Alain J. , Almadani Yasser , Davison Peter 
Published: March 2021

Background:
The goal of this study was to gauge the public’s general perception of breast implants, levels of concern, spontaneous word associations, and misperceptions that might need to be addressed by plastic surgeons regarding breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and breast implant illness (BII).

Methods:
An anonymous survey was completed by a total of 979 female participants in the United States by means of Amazon Mechanical Turk.

Results:
Over 91 percent of participants indicated that they had never heard the term BIA-ALCL. Of the respondents who were aware of the term, 37.21 percent reported being moderately or extremely concerned about BIA-ALCL and 85.4 percent were less likely to recommend breast implants to a friend. Awareness of BII was significantly higher at 50.9 percent, whereas almost 40 percent of participants reported being either moderately or extremely concerned about BII. Over 78 percent of participants were less likely to recommend breast implants to a friend because of BII. The most common word association with BII was “pain,” followed by “cancer.” The terms “cancer” and “scary” were the two most common word associations with BIA-ALCL. A significant overlap in word associations was observed between BIA-ALCL and BII, potentially representing a lack of distinction between the two terms. The survey demonstrated a paucity of important knowledge within the general population; notably, 71 percent of respondents who were not aware that, to date, only textured implants/expanders were associated with BIA-ALCL.

Conclusion:
These findings support the need for further targeted awareness to remedy existing misperceptions and fill the knowledge gaps relating to BII and BIA-ALCL.
Intraoperative Fluid Management Implies Insignificant Influence to Surgical Outcomes in Head and Neck Microvascular Reconstruction Cases
Authors: Zheng Gang , Liu Jun , Yu Peirong 
Published: March 2021

Background:
Deliberate fluid administration has been used to maintain a hyperdynamic systemic circulation in free tissue transfer operations. The effects of intraoperative volume loading on postoperative complications have been controversial. The authors hypothesized that increasing intraoperative fluid administration was associated with increased postoperative surgical complications.

Methods:
Free flap operations for head and neck reconstruction between 2004 and 2014 were reviewed. A generalized estimating equation model was used to estimate the effect of intraoperative fluid administration on surgical outcomes. The optimized thresholds of anesthetic time were tested by the Youden index for flap compromise and major complications.

Results:
A total of 2983 consecutive cases were included in the study. The incidences of flap compromise and total loss were 1.5 and 3.3 percent, respectively. Intraoperative fluid administration was not associated with surgical complications (p = 0.195). However, a 1-hour increase in anesthesia time was associated with a 19 percent increased risk of flap compromise (adjusted OR, 1.19; 95 percent CI, 1.10 to 1.29; p < 0.001).

Conclusion:
Prolonged anesthetic time, but not fluid administration, was associated with adverse surgical outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
IL-6 and D-Dimer at Admission Predicts Cardiac Injury and Early Mortality during SARS-CoV-2 Infection
Authors: Si Daoyuan , Du Beibei , Yang Bo , Jin Lina , Ni Lujia , Zhang Qian , Zhang Zhongfan , Azam Mohammed Ali , Lai Patrick F.H. , Massé Stéphane , Sun Huan , Wang Xingtong , Epelman Slava , Lawler Patrick R. , Yang Ping , Nanthakumar Kumaraswamy 
Published: March 2021

AbstractBACKGROUNDWe recently described mortality of cardiac injury in COVID-19 patients. Admission activation of immune, thrombotic biomarkers and their ability to predict cardiacinjury and mortality patterns in COVID-19 is unknown.METHODSThis retrospective cohort study included 170 COVID-19 patients with cardiac injury at admission to Tongji Hospital in Wuhan from January 29–March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed.RESULTSOf 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death were elevate levels of interleukin 6 (IL-6) (p<0.0001), Tumor Necrosis Factor-a (TNF-a) (p=0.0025), and C-reactive protein (CRP) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic pathway activation. Increasing cTnI levels were associated with those of increasing IL-6 (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile.CONCLUSIONSIn COVID-19 patients with cardiac injury, admission IL-6 and D-dimer predicted subsequent elevation of cTnI and early death, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury.Condensed AbstractCOVID-19 with cardiac injury is associated with worse survival. Admission activation of immune, thrombotic biomarkers and their ability to predict cardiac injury and mortality patterns in COVID-19 is unknown. This study proved that cardiac injury in these patients is closely related to the activation of immunological and thrombotic pathways and can be predicted by admission biomarkers of these pathways. This study supports the strategy of biomarker-guided, point-of-care therapy that warrants further studies in a randomized manner to develop anti-immune and anti-thrombotic treatment regimens in severe COVID-19 patients with cardiac injury.