bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-parameter bifurcations analysis of a delayed high-temperature superconducting maglev model with guidance force
Authors: Dai Qinrui
Published: August 2022

A modified high-temperature superconducting maglev model is studied in this paper, mainly considering the influence of time delay on the dynamic properties of the system. For the original model without time delay, there are periodic equilibrium points. We investigate its stability and Hopf bifurcation and study the bifurcation properties by using the center manifold theorem and the normal form theory. For the delayed model, we mainly study the co-dimension two bifurcations (Bautin and Hopf–Hopf bifurcations) of the system. Specifically, we prove the existence of Bautin bifurcation and calculate the normal form of Hopf–Hopf bifurcation through the bifurcation theory of functional differential equations. Finally, we numerically simulate the abundant dynamic phenomena of the system. The two-parameter bifurcation diagram in the delayed model is given directly. Based on this, some nontrivial phenomena of the system, such as periodic coexistence and multistability, are well presented. Compared with the original ordinary differential equation system, the introduction of time delay makes the system appear chaotic behavior, and with the increase in delay, the variation law between displacement and velocity becomes more complex, which provides further insights into the dynamics of the high-temperature superconducting maglev model.
Physical mechanisms for delaying condensation freezing on grooved and sintered wicking surfaces
Authors: Stallbaumer-Cyr Emily M. , Derby Melanie M. , Betz Amy R.
Published: August 2022

Heat pipes are passive heat transfer devices crucial for systems on spacecraft; however, they can freeze when exposed to extreme cold temperatures. The research on freezing mechanisms on wicked surfaces, such as those found in heat pipes, is limited. Surface characteristics, including surface topography, have been found to impact freezing. This work investigates freezing mechanisms on wicks during condensation freezing. Experiments were conducted in an environmental chamber at 22 °C and 60% relative humidity on three types of surfaces (i.e., plain copper, sintered heat pipe wicks, and grooved heat pipe wicks). The plain copper surface tended to freeze via ice bridging—consistent with other literature—before the grooved and sintered wicks at an average freezing time of 4.6 min with an average droplet diameter of 141.9 ± 58.1 μm at freezing. The grooved surface also froze via ice bridging but required, on average, almost double the length of time the plain copper surface took to freeze, 8.3 min with an average droplet diameter of 60.5 ± 27.9 μm at freezing. Bridges could not form between grooves, so initial freezing for each groove was stochastic. The sintered wick's surface could not propagate solely by ice bridging due to its topography, but also employed stochastic freezing and cascade freezing, which prompted more varied freezing times and an average of 10.9 min with an average droplet diameter of 97.4 ± 32.9 μm at freezing. The topography of the wicked surfaces influenced the location of droplet nucleation and, therefore, the ability for the droplet-to-droplet interaction during the freezing process.
Nigerian English as a Lingua Franca
Authors: Müller Julia , Mair Christian
Published: August 2022

This paper investigates the use of Nigerian English in lingua-franca interaction in Germany, focussing on the perspective of the German listener. Fifty-eight German-speaking respondents were asked to transcribe short extracts from English interviews recorded with Nigerian immigrants and sojourners resident in Germany. In addition to testing comprehension, respondents were requested to rate samples along parameters designed to measure speaker likability and competence. The study’s two major findings are that, in spite of the absence of contextual clues, respondents perform better than expected in the comprehension task, but that the single greatest obstacle to comprehension is the presence of German-language material in the stimulus. As realistic English as a Lingua Franca (ELF) interaction in Germany necessarily involves a level of English-German mixing, the experiment thus points to a major practical problem in ELF interaction. The study also yields provisional findings on gender (with male voices being understood better than female ones) and interactions between assumptions about speakers and transcription performance that should be revisited in future research.
Feeling for speaking
Authors: Müller Cornelia , Marienfeld Benjamin
Published: August 2022

In this paper, attention is drawn to the embodied experiences that are mobilized when speakers are
asked to describe emotions. By analyzing how people use expressive body movements and language when thinking
and speaking about emotion concepts, light is thrown on “People’s subjective, felt experiences of their
bodies in action” (Gibbs, 2005: 9). It illustrates how experiencing emotion
concepts bodily provides “part of the fundamental grounding for language and thought.” (Gibbs, 2005: 9). The title of this chapter alludes to Daniel I. Slobin’s reformulation of the
linguistic relativity hypothesis. Slobin counters Wilhelm von Humboldt and Benjamin L. Whorf
static understanding of the relationship between “thought and language” with a dynamic idea of this relation which he
terms Thinking for speaking (Slobin, 1996: 76). We report
a small study indicating that speakers not only express affective experiences as conceptual content, but perform or
indicate expressive body movements before or while describing a specific emotion. The chapter thus suggests a very
concrete way of understanding Gibbs’ assumption of an “embodiment premise for language and thought”.
Defaultness vs. constructionism
Authors: Giora Rachel
Published: August 2022

Default responses play a major role in affecting processing, pleasantness, and cueing of
nondefault alternatives. Default responses are activated automatically, initially and directly, faster than nondefault
counterparts, irrespective of degree of negation, novelty, nonliteralness, or contextual support (Giora et al., 2015c). No wonder default automatic responses may be initially
involved in processing nondefault counterparts. This involvement of defaultness in processing nondefaultness slows
down the latter while rendering it Optimal Innovative and therefore pleasing, even if highly dependent on context or
cueing for its derivation. Findings here are discussed in terms of the Defaultness Hypothesis (Giora et al., 2015c, 2017), Construction Grammar
(e.g., Goldberg, 1995, 1996,
2006, 2013; Johnson & Goldberg, 2013), and pragmatic effects.
Second-Harmonic Response in Magnetic Nodal-Line Semimetal Fe3GeTe2
Authors: Esin V. D. , Avakyants A. A. , Timonina A. V. , Kolesnikov N. N. , Deviatov E. V.
Published: August 2022

We experimentally investigate second-harmonic transverse voltage response to ac electrical current for a magnetic nodal-line semimetal Fe3GeTe2 (FGT). For zero magnetic field, the observed second-harmonic voltage behaves as a square of the longitudinal current, as it should be expected for nonlinear Hall effect. The magnetic field behavior is found to be sophisticated: while the first-harmonic response shows the known anomalous Hall hysteresis in FGT, the second-harmonic Hall voltage is characterized by the pronounced high-field hysteresis and flat (B-independent) region with curves touching at low fields. The high-field hysteresis strongly depends on the magnetic field sweep rate, so it reflects some slow relaxation process. For the lowest rates, it is also accomplished by multiple crossing points. Similar shape of the second-harmonic hysteresis is known for skyrmion spin textures in nonlinear optics. Since skyrmions have been demonstrated for FGT by direct visualization techniques, we can connect the observed high-field relaxation with deformation of the skyrmion lattice. Thus, the second-harmonic Hall voltage response can be regarded as a tool to detect spin textures in transport experiments.
Controlling LIPSS formation on Ni surface using near-infrared laser beam and its low-order harmonics
Authors: Khalil Baha , Boltaev Ganjaboy S , Abu Baker Aya , Abbasi Naveed , Alnaser Ali S
Published: August 2022

Ultrafast laser ablation of metal surfaces is a common physical process used to generate periodic surface structures with tuneable multifunctionality for various applications in science and technology. In this work, the formation of femtosecond laser-induced periodic surface structures (LIPSSs) is investigated with 50 kHz repetition rate laser of 40 fs pulse duration and a central wavelength (

λ

w

=
1030

nm

) along with its second (

λ

2

w

=
515

nm

) and third

(

λ

3

w

=
343

nm

) harmonic components. The variation in the LIPSS periodicity is demonstrated by changing the wavelength of the ablating laser pulses. LIPSS with periodicity ∼0.85

μ

m at the fundamental ablating pulses, ∼0.42

μ

m periodicity at the second harmonic, and ∼0.35

μ

m periodicity at the third harmonic were observed. The third harmonic radiation was generated in an air-filament with minimal temporal delay with respect to the fundamental driving pulses to structure Nickel surfaces at ambient conditions. The approach demonstrates the potential for generating very fine LIPSS on materials’ surfaces using the efficient high-order harmonics of an infrared fundamental laser beam.
Application of impedance spectroscopy in exploring electrical properties of dielectric materials under high pressure
Authors: Zhao Lin , Liu Hao , Tong Shuang , Wang Jia , Han Tao , Liu Cailong , Gao Chunxiao , Han Yonghao
Published: August 2022

Impedance spectroscopy (IS) is an indispensable method of exploring electrical properties of materials. In this review, we provide an overview on the specific applications of IS measurement in the investigations of various electrical properties of materials under high pressure, including electric conduction in bulk and grain boundary, dielectric properties, ionic conduction, and electrostrictive effect. Related studies are summarized to demonstrate the method of analyzing different electrical transport processes with various designed equivalent circuits of IS and reveal some interesting phenomena of electrical properties of materials under high pressure.
Soft-margin hyperdisk tensor machine and its application to the intelligent fault diagnosis of rotating machinery
Authors: Liu Hailong , Yang Yu , Hu Niaoqing , Cheng Zhe , Cheng Junsheng
Published: August 2022

Compared with a support vector machine, a hyperdisk (HD) classification model is a more effective model for intelligent fault diagnosis. But due to its defect of a hard margin, the formed category area sometimes does not approximate the real category area well, which means that the HD model has poor anti-interference ability, generalization ability and stability. Therefore, in order to overcome the above defects, a soft-margin HD tensor machine (SHDTM) is proposed. Firstly, by introducing the adaptive weight, the HD margin can be adaptively adjusted, that is, the details of the HD margin are added to obtain a soft margin so that it can better approximate the real category region and improve its anti-interference ability for outliers and samples with noise. Secondly, the model input is extended from vector data to tensor data. This can further improve the generalization ability and stability of the model by increasing the richness of the input information. The results of the rotating machinery fault diagnosis experiments fully prove the effectiveness of the proposed model. The SHDTM model has excellent resistance to outliers and noise interference, and also obtains good diagnostic results when diagnosing unbalanced datasets.
Progress on the electro-thermo-mechanical instability and its role as seed on plasma instabilities
Authors: Kaselouris E , Skoulakis A , Dimitriou V , Fitilis I , Chatzakis J , Bakarezos M , Papadogiannis N A , Tatarakis M
Published: August 2022

It was recently demonstrated that a newly explored instability, which was named electro-thermo-mechanical (ETM) instability, was developed in the solid elastic phase in the case of an electrically exploded conductor in the skin effect mode. Here, we present new advances in the exploration of the role of the ETM instability as seed of the magneto-hydro-dynamic instabilities that are later observed in the plasma phase. Our study, through analytical calculations, simulations and experiments, demonstrates the whole evolution dynamics of the instability amplitude, from the solid to the plasma phase, including the phase transitions. It is validated that the sustained axial wavelength modes in the plasma phase lie in the range of values of those of the ETM instability developed in the solid phase. The results are of significant importance for understanding the role of the ETM instability as seeding for the later observed instabilities in the plasma phase.
Acceleration of polaron induced by site effective mass increment in organic ferromagnets
Authors: Miao Yuanyuan , Yu Daiwei , Li Dan , Zhang Huiqing , Ren Junfeng , Hu Guichao
Published: August 2022

The polaron dynamics in organic ferromagnets (OFs) is investigated theoretically by considering the increment of site effective mass originating from the attachment of spin radicals. In spite of the increase of polaron effective mass, the results reveal two opposite effects on the polaron velocity caused by the increment of site effective mass. One is the normal decrease of the polaron velocity with the increment of site effective mass. The other is the abrupt acceleration of the polaron from below the sound velocity to the supersonic velocity upon a critical value of the site effective mass increment. Mechanism analysis shows that the acceleration of the polaron is attributed to the reduction of critical decoupling field for optical and acoustic deformations caused by the site effective mass increment. The second effect further depends on the polaron spin due to the existence of spin-dependent intrinsic dipole of the polarons. This work indicates the potential of high polaron mobility and efficient spin filtering effect under low electric fields in OFs.
Amyloid-β levels and cognitive trajectories in non-demented pTau181-positive subjects without amyloidopathy
Authors: Oberstein Timo Jan , Schmidt Manuel Alexander , Florvaag Anna , Haas Anna-Lena , Siegmann Eva-Maria , Olm Pauline , Utz Janine , Spitzer Philipp , Doerfler Arnd , Lewczuk Piotr , Kornhuber Johannes , Maler Juan Manuel
Published: August 2022

Phosphorylated Tau181 (pTau181) in CSF and recently in plasma has been associated with Alzheimer’s disease. In the absence of amyloidopathy, individuals with increased total Tau levels and/or temporal lobe atrophy experience no or only mild cognitive decline compared with biomarker-negative controls, leading to the proposal to categorize this constellation as suspected non-Alzheimer's disease pathophysiology (SNAP). We investigated whether the characteristics of SNAP also applied to individuals with increased CSF-pTau181 without amyloidopathy.

In this long-term observational study, 285 non-demented individuals, including 76 individuals with subjective cognitive impairment and 209 individuals with mild cognitive impairment, were classified based on their CSF levels of pTau181 (T), total Tau (N), amyloid-β42 (Aβ42) and Aβ42/Aβ40 ratio (A) into A+T+N±, A+T–N±, A–T+N±, and A–T–N–. The longitudinal analysis included 154 subjects with a follow-up of more than 12 months who were followed to a median of 4.6 years (interquartile range = 4.3 years). We employed linear mixed models on psychometric tests and region of interest analysis of structural MRI data.

Cognitive decline and hippocampal atrophy rate were significantly higher in A+T+N± compared to A–T+N±, whereas there was no difference between A–T+N± and A–T–N–. Furthermore, there was no significant difference between A–T+N± and controls in dementia risk [hazard ratio 0.3, 95% confidence interval (0.1, 1.9)]. However, A–T+N± and A–T–N– could be distinguished based on their Aβ42 and Aβ40 levels. Both Aβ40 and Aβ42 levels were significantly increased in A–T+N± compared to controls.

Long term follow-up of A–T+N± individuals revealed no evidence that this biomarker constellation was associated with dementia or more severe hippocampal atrophy rates compared to controls. However, because of the positive association of pTau181 with Aβ in the A–T+N± group, a link to the pathophysiology of Alzheimer’s disease cannot be excluded in this case. We propose to refer to these individuals in the SNAP group as ‘pTau and Aβ surge with subtle deterioration’ (PASSED).

The investigation of the circumstances of simultaneous elevation of pTau and Aβ might provide a deeper insight into the process under which Aβ becomes pathological.
Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study
Authors: Taquet Maxime , Harrison Paul J
Published: August 2022

Post-COVID cognitive deficits (often referred to as ‘brain fog’) are common and have large impacts on patients’ level of functioning. No specific intervention exists to mitigate this burden.

This study tested the hypothesis, inspired by recent experimental research, that post-COVID cognitive deficits can be prevented by inhibiting receptor-interacting protein kinase. Using electronic health record data, we compared the cognitive outcomes of propensity score-matched cohorts of patients with epilepsy taking phenytoin (a commonly used receptor-interacting protein kinase inhibitor) versus valproate or levetiracetam at the time of COVID-19 diagnosis. Patients taking phenytoin at the time of COVID-19 were at a significantly lower risk of cognitive deficits in the 6 months after COVID-19 infection than a matched cohort of patients receiving levetiracetam (hazard ratio 0.78, 95% confidence interval 0.63–0.97, P = 0.024) or valproate (hazard ratio 0.73, 95% confidence interval 0.58–0.93, P = 0.011). In secondary analyses, results were robust when controlling for subtype of epilepsy, and showed specificity to cognitive deficits in that similar associations were not seen with other ‘long-COVID’ outcomes such as persistent breathlessness or pain. These findings provide pharmacoepidemiological support for the hypothesis that receptor-interacting protein kinase signaling is involved in post-COVID cognitive deficits. These results should prompt empirical investigations of receptor-interacting protein kinase inhibitors in the prevention of post-COVID cognitive deficits.
Transient disruption of functional connectivity and depression of neural fluctuations in a mouse model of acute septic encephalopathy
Authors: Brier L M , Chen S , Sherafati A , Bice A R , Lee J M , Culver J P
Published: August 2022

Septic encephalopathy leads to major and costly burdens for a large percentage of admitted hospital patients. Elderly patients are at an increased risk, especially those with dementia. Current treatments are aimed at sedation to combat mental status changes and are not aimed at the underlying cause of encephalopathy. Indeed, the underlying pathology linking together peripheral infection and altered neural function has not been established, largely because good, acutely accessible readouts of encephalopathy in animal models do not exist. Behavioral testing in animals lasts multiple days, outlasting the time frame of acute encephalopathy. Here, we propose optical fluorescent imaging of neural functional connectivity (FC) as a readout of encephalopathy in a mouse model of acute sepsis. Imaging and basic behavioral assessment were performed at baseline, Hr8, Hr24, and Hr72 following injection of either lipopolysaccharide or phosphate buffered saline. Neural FC strength decreased at Hr8 and returned to baseline by Hr72 in motor, somatosensory, parietal, and visual cortical regions. Additionally, neural fluctuations transiently declined at Hr8 and returned to baseline by Hr72. Both FC strength and fluctuation tone correlated with neuroscore indicating this imaging methodology is a sensitive and acute readout of encephalopathy.
Site-dependent shaping of field potential waveforms
Authors: Herreras Oscar , Torres Daniel , Martín-Vázquez Gonzalo , Hernández-Recio Sara , López-Madrona Víctor J , Benito Nuria , Makarov Valeri A , Makarova Julia
Published: August 2022

The activity of neuron populations gives rise to field potentials (FPs) that extend beyond the sources. Their mixing in the volume dilutes the original temporal motifs in a site-dependent manner, a fact that has received little attention. And yet, it potentially rids of physiological significance the time-frequency parameters of individual waves (amplitude, phase, duration). This is most likely to happen when a single source or a local origin is erroneously assumed. Recent studies using spatial treatment of these signals and anatomically realistic modeling of neuron aggregates provide convincing evidence for the multisource origin and site-dependent blend of FPs. Thus, FPs generated in primary structures like the neocortex and hippocampus reach far and cross-contaminate each other but also, they add and even impose their temporal traits on distant regions. Furthermore, both structures house neurons that act as spatially distinct (but overlapped) FP sources whose activation is state, region, and time dependent, making the composition of so-called local FPs highly volatile and strongly site dependent. Since the spatial reach cannot be predicted without source geometry, it is important to assess whether waveforms and temporal motifs arise from a single source; otherwise, those from each of the co-active sources should be sought.
Neural decoding dissociates perceptual grouping between proximity and similarity in visual perception
Authors: Hua Lin , Gao Fei , Leong Chantat , Yuan Zhen
Published: August 2022

Unlike single grouping principle, cognitive neural mechanism underlying the dissociation across two or more grouping principles is still unclear. In this study, a dimotif lattice paradigm that can adjust the strength of one grouping principle was used to inspect how, when, and where the processing of two grouping principles (proximity and similarity) were carried out in human brain. Our psychophysical findings demonstrated that similarity grouping effect was enhanced with reduced proximity effect when the grouping cues of proximity and similarity were presented simultaneously. Meanwhile, EEG decoding was performed to reveal the specific cognitive patterns involved in each principle by using time-resolved MVPA. More importantly, the onsets of dissociation between 2 grouping principles coincided within 3 time windows: the early-stage proximity-defined local visual element arrangement in middle occipital cortex, the middle-stage processing for feature selection modulating low-level visual cortex such as inferior occipital cortex and fusiform cortex, and the high-level cognitive integration to make decisions for specific grouping preference in the parietal areas. In addition, it was discovered that the brain responses were highly correlated with behavioral grouping. Therefore, our study provides direct evidence for a link between the human perceptual space of grouping decision-making and neural space of brain activation patterns.
Early-onset post-cardiotomy severe constrictive pericarditis: a case report
Authors: Mikhail Philopatir , Meere William , Howden Nicklas , Spina Roberto
Published: August 2022

Background

Constrictive pericarditis (CP) can be one of the most challenging conditions to diagnose within cardiovascular medicine. Iatrogenic causes of CP are increasingly recognized in higher income countries. This case provides insight into the need for clinical suspicion when diagnosing this relatively under recognized clinical entity as well as the need for multimodality imaging combined with invasive haemodynamic assessment.

Case summary

A 68-year-old man presented with decompensated heart failure 4 weeks after open-heart surgery. A diagnosis of early-onset post-cardiotomy CP was made using multimodality imaging and invasive haemodynamic assessment, which demonstrated the cardinal features of constrictive physiology. Surgical intervention with two pericardiectomy procedures was pursued given the aggressive and recalcitrant nature of his presentation. Our patient died shortly after his second surgery due to progressive multi-organ dysfunction.

Conclusion

Constrictive pericarditis is a challenging but important clinical entity to diagnose. Differentiating CP from restrictive cardiomyopathy is important as there are key differences in management and prognosis. Our case supports the clinical utility of multimodality imaging combined with invasive haemodynamic assessment in patients with suspected CP.
Trametinib as a promising therapeutic option in alleviating vascular defects in an endothelial KRAS-induced mouse model
Authors: Nguyen Ha-Long , Boon Laurence M , Vikkula Miikka
Published: August 2022

Somatic activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations have been reported in patients with arteriovenous malformations. By producing LSL-Kras (G12D); Cdh5 (PAC)-CreERT2 [iEC-Kras (G12D*)] mice, we hoped to activate KRAS within vascular endothelial cells (ECs) to generate an arteriovenous malformation mouse model. Neonatal mice were treated daily with tamoxifen from postnatal (PN) days 1–3. Mortality and phenotypes varied amongst iEC-Kras (G12D*) pups, with only 31.5% surviving at PN14. Phenotypes (focal lesions, vessel dilations) developed in a consistent manner, although with unpredictable severity within multiple soft tissues (such as the brain, liver, heart and brain). Overall, iEC-Kras (G12D*) pups developed significantly larger vascular lumen areas compared with control littermates, beginning at PN8. We subsequently tested whether the MEK inhibitor trametinib could effectively alleviate lesion progression. At PN16, iEC-Kras (G12D*) pup survival improved to 76.9%, and average vessel sizes were closer to controls than in untreated and vehicle-treated mutants. In addition, trametinib treatment helped normalize iEC-Kras (G12D*) vessel morphology in PN14 brains. Thus, trametinib could act as an effective therapy for KRAS-induced vascular malformations in patients.
Cefepime-induced neurotoxicity: systematic review
Authors: Maan Gozun , Keitoku Koichi , Kimura Nobuhiko , Sawada Haruki , Pham Andrew , Yeo Jihun , Hagiya Hideharu , Nishimura Yoshito
Published: August 2022

Background

Cefepime-induced neurotoxicity (CIN) has been well acknowledged among clinicians, although there are no clear diagnostic criteria or specific laboratory testing to help with its diagnosis. We aimed to summarize the existing evidence regarding CIN and provide future agendas for research.

Methods

Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and Embase for all peer-reviewed articles using keywords including ‘cefepime’, ‘neurotoxicity’, ‘encephalopathy’ and ‘seizure’, from their inception to 20 January 2022.

Results

We included 92 articles, including 23 observational studies and 69 cases from case reports and case series, in the systematic review. Among 119 patients with CIN, 23.5% were in the ICU at the time of diagnosis and nearly 90% of the cases showed renal dysfunction.

Cefepime overdoses were described in 41%. The median latency period of developing CIN from cefepime initiation was 4 days, and about 12% developed CIN during empirical treatment. CIN patients commonly manifested altered mental status (93%), myoclonus (37%) and non-convulsive seizure epilepticus (28%). A serum cefepime trough level of >20 mg/L would put patients at risk for CIN. CIN-related symptoms were ameliorated in 97.5% by dose reduction or discontinuation of cefepime, with median time to improvement of 3 days. No CIN-associated deaths were reported.

Conclusions

This systematic review summarizes the current evidence and characteristics of CIN. In the current situation where there are no CIN diagnostic criteria and the drug monitoring platform is not routinely available, candidates for cefepime should be carefully selected. Also, based on these findings, it needs to be appropriately dosed to avoid the development of CIN.
In vitro activity of fosfomycin against bacterial pathogens isolated from urine specimens in Canada from 2007 to 2020: CANWARD surveillance study
Authors: Karlowsky James A , Baxter Melanie R , Walkty Andrew J , Lagacé-Wiens Philippe R S , Bay Denice , Adam Heather J , Zhanel George G
Published: August 2022

Background

Multiple susceptible breakpoints are published to interpret fosfomycin MICs: ≤64 mg/L for Escherichia coli and Enterococcus faecalis grown from urine (CLSI M100); ≤32 mg/L for Enterobacterales and staphylococci when parenteral fosfomycin is prescribed (EUCAST); and ≤8 mg/L for uncomplicated urinary tract infection with E. coli when oral fosfomycin is used (EUCAST). Clinical laboratories are frequently requested to test fosfomycin against antimicrobial-resistant urinary isolates not included in standard documents.

Methods

The in vitro activity of fosfomycin was determined using the CLSI agar dilution method for a 2007–20 collection of clinically significant Gram-negative (3656 Enterobacterales; 140 Pseudomonas aeruginosa) and Gram-positive (346 E. faecalis; 94 Staphylococcus aureus) urinary isolates from the CANWARD surveillance study. Comparator agents were tested using CLSI broth microdilution.

Results

Using the CLSI MIC breakpoint (≤64 mg/L), 99.2% of E. coli (n = 2871; MIC90, 4 mg/L), including 96.7% of ESBL-positive isolates, were fosfomycin susceptible. Similarly, 95.8% of E. coli, including 95.2% of ESBL-positive isolates, were fosfomycin susceptible at ≤8 mg/L (EUCAST oral susceptible MIC breakpoint). All other species of Enterobacterales (except Citrobacter freundii) and P. aeruginosa had higher fosfomycin MICs (MIC90s, 64 to >512 mg/L) than E. coli. Using published breakpoints, 88.4% of E. faecalis (MIC ≤64 mg/L) and 97.9% of S. aureus (MIC ≤32 mg/L) isolates were fosfomycin susceptible.

Conclusions

Fosfomycin demonstrated in vitro activity against frequently encountered Gram-positive and Gram-negative urinary pathogens; however, the extrapolation of current CLSI and EUCAST MIC breakpoints to pathogens not specified by standard methods requires further study and is currently not recommended.
Establishment of RCPA national guidelines for selective reporting of antimicrobials: processes, challenges and measuring the impact
Authors: Graham Maryza , Graves Debra , Cooley Louise , Elvy Juliet , Kelley Peter , Maley Michael , Porter Michelle , Robson Jennifer , Turnidge John
Published: August 2022

Objectives

In 2016, The Royal College of Pathologists of Australasia (RCPA) initiated the formation of a working group comprising medical microbiologists to establish guidelines to assist Australian laboratories to implement selective and cascade reporting of antimicrobials—the first guidelines of this type in the world.

Methods

A 2017 audit of antimicrobial reporting in Australian and New Zealand laboratories identified significant opportunities for improvement and standardization of selective reporting.

Results

The first draft of the RCPA Selective Reporting Guidelines was circulated to all RCPA Microbiology fellows for feedback in August 2018 and the first version was published in February 2019. Subsequently, version two of the guidelines has recently been published in Australia, and New Zealand adapted these guidelines for formulation of their own national guidelines to accommodate local needs.

Conclusions

Here we describe the processes, acceptance and challenges associated with the establishment of these guidelines and measurement of their impact.
A new synthetic protegrin as a promising peptide with antibacterial activity against MDR Gram-negative pathogens
Authors: Moreno-Morales Javier , Guardiola Salvador , Ballesté-Delpierre Clara , Giralt Ernest , Vila Jordi
Published: August 2022

Objectives

Protegrins are a family of natural peptides from the innate immune system of vertebrates, with broad-spectrum antimicrobial activity. However, the toxicity and haemolysis of protegrin-1 (PG-1) at low concentrations renders it useless for therapeutic application. We rationally designed PLP-3, a novel synthetic PG-1-like peptide, comprising key activity features of protegrins in a constrained bicyclic structure. Our main objective was to investigate PLP-3’s activity against MDR strains of Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae and to analyse its haemolysis and cytotoxicity.

Methods

Peptide synthesis was performed via solid phase and intramolecular ligation in solution, and the correct folding of the peptide was verified by circular dichroism. Antimicrobial activity was performed through broth microdilution. The test panel contained 45 bacterial strains belonging to A. baumannii, P. aeruginosa and K. pneumoniae (15 strains per species) comprising colistin-resistant and MDR strains. Cytotoxicity was assessed by XTT cell viability assays using HeLa and A549 cells and haemolysis of human erythrocytes.

Results

PLP-3 was successfully synthesized, and its antiparallel β-sheet conformation was confirmed. Antimicrobial activity screening showed MIC90 values of 2 mg/L for A. baumannii, 16 mg/L for K. pneumoniae and 8 mg/L for P. aeruginosa. The haemolysis IC50 value was 48.53 mg/L. Cytotoxicity against human HeLa and A549 cells showed values of ca. 200 mg/L in both cell lines resulting in a 100-fold selectivity window for bacterial over human cells.

Conclusions

PLP-3 has potent antimicrobial activity, especially against A. baumannii, while maintaining low haemolysis and toxicity against human cell lines at antimicrobial concentrations. These characteristics make PLP-3 a promising peptide with an interesting therapeutic window.
Quaternary organization of the human eEF1B complex reveals unique multi-GEF domain assembly
Authors: Bondarchuk Tetiana V , Shalak Vyacheslav F , Lozhko Dmytro M , Fatalska Agnieszka , Szczepanowski Roman H , Liudkovska Vladyslava , Tsuvariev Oleksandr Yu , Dadlez Michal , El'skaya Anna V , Negrutskii Boris S
Published: August 2022

Protein synthesis in eukaryotic cell is spatially and structurally compartmentalized that ensures high efficiency of this process. One of the distinctive features of higher eukaryotes is the existence of stable multi-protein complexes of aminoacyl-tRNA synthetases and translation elongation factors. Here, we report a quaternary organization of the human guanine-nucleotide exchange factor (GEF) complex, eEF1B, comprising α, β and γ subunits that specifically associate into a heterotrimeric form eEF1B(αβγ)3. As both the eEF1Bα and eEF1Bβ proteins have structurally conserved GEF domains, their total number within the complex is equal to six. Such, so far, unique structural assembly of the guanine-nucleotide exchange factors within a stable complex may be considered as a ‘GEF hub’ that ensures efficient maintenance of the translationally active GTP-bound conformation of eEF1A in higher eukaryotes.
3D (x-y-t) Raman imaging of tomato fruit cuticle: Microchemistry during development
Authors: González Moreno Ana , Domínguez Eva , Mayer Konrad , Xiao Nannan , Bock Peter , Heredia Antonio , Gierlinger Notburga
Published: August 2022

The cuticle is a protective extracellular matrix that covers the above-ground epidermis of land plants. Here, we studied the cuticle of tomato (Solanum lycopersicum L.) fruits in situ using confocal Raman microscopy. Microsections from cuticles isolated at different developmental stages were scanned to visualize cuticle components with a spatial resolution of 342 nm by univariate and multivariate data analysis. Three main components, cutin, polysaccharides, and aromatics, were identified, with the latter exhibiting the strongest Raman scattering intensity. Phenolic acids and flavonoids were differentiated within the cuticle, and three schematic cuticle models were identified during development. Phenolic acids were found across the entire cuticle at the earliest stage of development, i.e. during the formation of the procuticle layer. Based on a mixture analysis with reference component spectra, the phenolic acids were identified as mainly esterified p-coumaric acid together with free p-hydroxybenzoic acid. During the cell expansion period of growth, phenolic acids accumulated in an outermost layer of the cuticle and in the middle region of the pegs. In these stages of development, cellulose and pectin were detected next to the inner cuticle region, close to the epidermal cell where flavonoid impregnation started during ripening. In the first ripening stage, chalconaringenin was observed, while methoxylated chalcones were chosen by the algorithm to fit the mature cuticle spectra. The colocation of carbohydrates, esterified p-coumaric acid, and methoxylated chalconaringenin suggests that the latter two link polysaccharide and cutin domains. Elucidating the different distribution of aromatics within the cuticle, suggests important functions: (1) overall impregnation conferring mechanical and thermal functions (2) the outermost phenolic acid layer displaying UV-B protection of the plant tissue.
AtPRMT5-mediated AtLCD methylation improves Cd2+ tolerance via increased H2S production in Arabidopsis
Authors: Cao Haiyan , Liang Yali , Zhang Liping , Liu Zhiqiang , Liu Danmei , Cao Xiaofeng , Deng Xian , Jin Zhuping , Pei Yanxi
Published: August 2022

Arabidopsis (Arabidopsis thaliana) PROTEIN ARGININE METHYLTRANSFERASE5 (PRMT5), a highly conserved arginine (Arg) methyltransferase protein, regulates multiple aspects of the growth, development, and environmental stress responses by methylating Arg in histones and some mRNA splicing-related proteins in plants. Hydrogen sulfide (H2S) is a recently characterized gasotransmitter that also regulates various important physiological processes. l-cysteine desulfhydrase (LCD) is a key enzyme of endogenous H2S production. However, our understanding of the upstream regulatory mechanisms of endogenous H2S production is limited in plant cells. Here, we confirmed that AtPRMT5 increases the enzymatic activity of AtLCD through methylation modifications during stress responses. Both atprmt5 and atlcd mutants were sensitive to cadmium (Cd2+), whereas the overexpression (OE) of AtPRMT5 or AtLCD enhanced the Cd2+ tolerance of plants. AtPRMT5 methylated AtLCD at Arg-83, leading to a significant increase in AtLCD enzymatic activity. The Cd2+ sensitivity of atprmt5-2 atlcd double mutants was consistent with that of atlcd plants. When AtPRMT5 was overexpressed in the atlcd mutant, the Cd2+ tolerance of plants was significantly lower than that of AtPRMT5-OE plants in the wild-type background. These results were confirmed in pharmacological experiments. Thus, AtPRMT5 methylation of AtLCD increases its enzymatic activity, thereby strengthening the endogenous H2S signal and ultimately improving plant tolerance to Cd2+ stress. These findings provide further insights into the substrates of AtPRMT5 and increase our understanding of the regulatory mechanism upstream of H2S signals.
Chronic Pelvic Pain Profiles in Women Seeking Care in a Tertiary Pelvic Pain Clinic
Authors: Li Rui , Kreher Donna A , Gubbels Ashley L , Palermo Tonya M
Published: August 2022

Objective

Female chronic pelvic pain (CPP) has multiple pain generators and significant psychosocial sequalae. Biopsychosocial-based phenotyping could help identify clinical heterogeneity that may inform tailored patient treatment. This study sought to identify distinct CPP profiles based on routinely collected clinical information and evaluate the validity of the profiles through associations with social histories and subsequent health care utilization.

Methods

Women (18–77 years, n = 200) seeking care for CPP in a tertiary gynecological pelvic pain clinic between 2017 and 2020 were included. Baseline data of pain intensity, interference, catastrophizing, acceptance, overlapping pelvic pain syndromes, and co-occurring psychiatric disorders were subject to a partition around medoids clustering to identify patient profiles. Profiles were compared across social history and subsequent treatment modality, prescribed medications, and surgeries performed.

Results

Two profiles with equal proportion were identified. Profile 1 was vulvodynia and myofascial pelvic pain-dominant characterized by lower pain burden and better psychological functioning. Profile 2 was visceral pain-dominant featuring higher pain interference and catastrophizing, lower pain acceptance, and higher psychiatric comorbidity. Patients in Profile 2 had 2–4 times higher prevalence of childhood and adulthood abuse history (all P < .001), were more likely to subsequently receive behavioral therapy (46% vs 27%, P = .005) and hormonal treatments (34% vs 21%, P = .04), and were prescribed more classes of medications for pain management (P = .045) compared to patients in Profile 1.

Conclusions

Treatment-seeking women with CPP could be separated into two groups distinguished by pain clusters, pain burden, pain distress and coping, and co-occurring mental health disorders.
Tofacitinib to Treat Severe Acute Refractory Colitis in a Teenager: Case Report and Review of the Literature
Authors: Girard Chloé , Dirks Martha , Deslandres Colette
Published: August 2022

Objectives:

Acute severe colitis (ASC) may occur within 3 months of ulcerative colitis diagnosis in 9%–15% of children and the rate of colectomy is up to 40%–50% within 5 years after an ASC. The aim of this publication is to present recent and relevant data on the success of medical treatment with tofacitinib in ASC.

Methods:

We report a challenging case of a teenage boy with ASC at diagnosis and conduct a discussion after a review of the literature regarding the use of tofacitinib in inflammatory bowel disease, especially in pediatric patients and in ASC.

Results:

The patient was hospitalized for 10 weeks and was refractory to conventional therapies: intravenous corticosteroids, infliximab, methotrexate, and vedolizumab. He received 7 blood transfusions and also presented with a severe malnutrition requiring a total parenteral nutrition. Tofacitinib was considered as a medical last resort before colectomy and was started at week 8. Thirteen days after starting tofacitinib, he was asymptomatic and was discharged on tofacitinib as sole treatment. By week 9 of tofacitinib, a colonoscopy showed both endoscopic and histological remission. He has remained in clinical remission at 6-month follow-up.

Conclusions:

Tofacitinib may be an alternative medical treatment to avoid colectomy in ASC. It is a small molecule with a rapid onset and few severe adverse events. It has been used for ASC in adult patients, allowing to avoid colectomy in more than 60%. To our knowledge, this is one of the few pediatric patients with refractory ASC at initial diagnosis who responded to tofacitinib.
Specialized germline P-bodies are required to specify germ cell fate in C. elegans embryos
Authors: Cassani Madeline , Seydoux Geraldine
Published: August 2022

In animals with germ plasm, specification of the germline involves “germ granules”, cytoplasmic condensates that enrich maternal transcripts in the germline founder cells. In C. elegans embryos, P granules enrich maternal transcripts, but surprisingly P granules are not essential for germ cell fate specification. Here we describe a second condensate in the C. elegans germ plasm. Like canonical P-bodies found in somatic cells, “germline P-bodies” contain regulators of mRNA decapping and deadenylation and, in addition, the intrinsically-disordered proteins MEG-1 and MEG-2 and the TIS11-family RNA-binding protein POS-1. Embryos lacking meg-1 and meg-2 do not stabilize P-body components, miss-regulate POS-1 targets, miss-specify the germline founder cell, and do not develop a germline. Our findings suggest that specification of the germ line involves at least two distinct condensates that independently enrich and regulate maternal mRNAs in the germline founder cells.
TMsDP: two-stage density peak clustering based on multi-strategy optimization
Authors: Ma Jie , Hao Zhiyuan , Hu Mo
Published: August 2022

Purpose

The density peak clustering algorithm (DP) is proposed to identify cluster centers by two parameters, i.e. ρ value (local density) and δ value (the distance between a point and another point with a higher ρ value). According to the center-identifying principle of the DP, the potential cluster centers should have a higher ρ value and a higher δ value than other points. However, this principle may limit the DP from identifying some categories with multi-centers or the centers in lower-density regions. In addition, the improper assignment strategy of the DP could cause a wrong assignment result for the non-center points. This paper aims to address the aforementioned issues and improve the clustering performance of the DP.

Design/methodology/approach

First, to identify as many potential cluster centers as possible, the authors construct a point-domain by introducing the pinhole imaging strategy to extend the searching range of the potential cluster centers. Second, they design different novel calculation methods for calculating the domain distance, point-domain density and domain similarity. Third, they adopt domain similarity to achieve the domain merging process and optimize the final clustering results.

Findings

The experimental results on analyzing 12 synthetic data sets and 12 real-world data sets show that two-stage density peak clustering based on multi-strategy optimization (TMsDP) outperforms the DP and other state-of-the-art algorithms.

Originality/value

The authors propose a novel DP-based clustering method, i.e. TMsDP, and transform the relationship between points into that between domains to ultimately further optimize the clustering performance of the DP.
Stakeholder perceptions of mentoring in developing girls’ STEM identities: “you do not have to be the textbook scientist with a white coat”
Authors: Millar Victoria , Hobbs Linda , Speldewinde Christopher , van Driel Jan
Published: August 2022

Purpose

Girls are underrepresented in many school science, technology, engineering and mathematics (STEM) subjects, leading to ongoing gender disparity in STEM careers. This issue is not new and has seen a range of initiatives implemented in an attempt to increase girls’ STEM participation. In Australia, a number of these initiatives have emphasised role models and mentors. This paper seeks to understand the influence of role models and mentors on girls’ STEM identities.

Design/methodology/approach

This paper presents qualitative research undertaken with STEM experts into the influences on girls’ STEM identities. Data were collected through three phases involving semi-structured interviews, a forum and focus groups. Thematic analysis identified the importance of mentoring and role modelling in shaping girls’ STEM participation and identities.

Findings

This paper provides a basis for rethinking how and when role models and mentors can assist girls in making decisions about STEM. In particular, it reveals the need for role models and mentors to consider the role of relatability in developing girls’ STEM identities and the need to do this at multiple points throughout girls’ lives.

Originality/value

This article captures the perspectives of multiple experts involved in a variety of STEM professions on the topic of how mentors and role models can influence girls to consider STEM professions. Utilising the concept of identity, this paper sheds new light on girls’ interactions with role models and mentors and the value of storying in role modelling and mentoring relationships as an important component of girls’ identity work in relation to STEM.