bluuebunny/crossref_metadata_2025 huggingface dataset:
The Exercise of Nurses' Clinical Leadership in Hospital Care Units: A Qualitative Multiple Case Study
Authors: Boutin Geneviève , Pepin Jacinthe , Brault Isabelle
Published: October 2024

Aims

This study aims to describe the exercise of clinical leadership by nurses within hospital care units, identify the factors influencing it and explore how nurses perceive its impact.

Design

Qualitative multiple case study.

Method

The study involved 36 interviews, 120 h of observation and documentary analyses with nurses across various roles within three nursing teams to capture collective leadership. Thematic and cross‐case analyses were also conducted.

Results

Nurses' clinical leadership was manifested in five distinct forms, irrespective of their role: (1) initiating actions involving reflective thinking and intervention, (2) influencing others through coaching, (3) actively participating in and mobilising efforts to enhance the quality of care, (4) fostering optimal synergy and team cohesion, and (5) leveraging personal and collaborative capacities. Factors influencing this leadership included clinical, human and material resources, time, a work environment that promotes autonomy and a positive work climate. Nurses perceived their leadership as having a positive impact on patients, themselves, the interdisciplinary team and the organisation. These findings were integrated into a modellisation of the exercise of nurses' clinical leadership based on Le Moigne's (La Théorie du Système Général. Théorie de la Modélisation. Paris: Presses Universitaires de France, 2006) philosophical approach.

Conclusion

This study provides a perspective on nurses' collective clinical leadership in hospital care units, emphasising its leverage effect and the achievement of positive impacts. The proposed model serves as a valuable tool for nurse managers to better understand and support the exercise of clinical leadership.

Implications for the Profession

The model can guide nurse managers in supporting clinical leadership within teams, assist individual nurses in associating clinical leadership with their practice and assist with mobilising their leadership skills.

Impact

This study explores how nurses across various roles within a hospital care unit exercise clinical leadership.

The findings reveal five active forms of nurses' clinical leadership, perceived by nurses to positively impact patients, the interdisciplinary team and the organisation.

Nurses and managers can use these five forms to foster a collective approach to clinical leadership.

Patient or Public Contribution

None.

What Does This Paper Contribute to the Wider Community?

This study introduces an innovative model for understanding and promoting nurses' clinical leadership.

It provides insights into the positive impact of this leadership approach and the significance of promoting it.

Reporting Method

Standards for Reporting Qualitative Research [SRQR] (O'Brien et al. Academic Medicine, 89, 2014 and 1245).

Trial and Protocol Registration

Not registered
“Creatures of kek:” Affordance and enregisterment within “kek” on 4chan's “/pol/” board
Authors: Ludemann Dillon
Published: October 2024

This paper examines the relation of affordance and enregisterment in the socialization of users through the popular 4chan phrase “kek.” This word, overwhelmingly used as an equivalent for “lol” (netspeak for “laugh out loud”), has taken up several other meanings within “/pol/,” the politically incorrect subforum on 4chan, an anonymous imageboard forum. Drawing from both enregisterment and affordance theory, I claim that the processes of mobilizing kek in very community‐specific ways allow for users within this digital media space to not only enregister what a /pol/ user should “sound like,” but that it creates an environment which socializes a very specific kind of user itself. These branching paths of kek explored in this article situate kek as first, an affective assessment marker within interactive speech; then, as a lamination of the word, and deification of chaos magic and mischief celebrated on 4chan, represented by the frog‐headed Egyptian god Kek; and finally, as a sovereign nation, known as “Kekistan.” Through these examples, I argue that a “creature of kek” is a socially constructed, enregistered framework of “knowing,” by which users on /pol/ legitimize themselves to new users, and in broader digital spaces.
Tongue and Lip Strength and Endurance in Healthy Young Adults With and Without Orofacial Myofunctional Disorders
Authors: Van der Straeten Charis , Verbeke Jolien , Bettens Kim , De Pauw Guy , Van Lierde Kristiane
Published: October 2024

Background/Objectives

Based on the premise that tongue and lip force is affected in individuals with orofacial myofunctional disorders (OMDs), orofacial myofunctional therapy (OMT) programs typically include the strengthening of orofacial muscles through isometric and isotonic exercises. The purpose of this study is to examine whether there is indeed a measurable difference in maximum tongue and lip strength and endurance between subjects with and without OMDs, as well as to explore Oral Health‐Related Quality of Life (OHRQoL) in this population.

Methods

Sixty healthy young adults (mean age 18.9 years, SD 0.69 years, range 18.0–21.4 years) participated in this study. Perceptual evaluation of orofacial functions was conducted using the Orofacial Myofunctional Evaluation with Scores (OMES) protocol. Participants were divided into three groups, namely those with physiological orofacial functions (POF; n = 20), those with inconsistent orofacial functions (IOF; n = 11), and those with consistent OMDs (OMD; n = 29). Maximum isometric pressure and endurance of tongue and lips were measured using the Iowa Oral Performance Instrument (IOPI). OHRQoL was assessed using the Oral Health Impact Profile (OHIP‐14).

Results

The OMES total scores did not differ significantly between the three groups, though the subscale ‘function’ showed significant differences (13.637; p = 0.001). No statistically significant differences in maximum isometric pressure or endurance for tongue and lips, nor for OHIP scores, were measured between the three groups.

Conclusions

Although orofacial muscle strengthening is commonly part of OMT, current findings suggest the superfluity of these types of exercises in the treatment of OMDs in healthy young adults and may indicate the need to focus on awareness and rehabilitation of pathological functions in these individuals. Re‐evaluation of the efficacy of OMT programs in different populations may be an important strategy going forward.
How do institutional gender regimes affect formal reporting processes for sexual harassment? A qualitative study of UK higher education
Authors: Bull Anna , Shannon Erin
Published: October 2024

Formal complaints and disciplinary processes constitute a mandatory aspect of organizational responses for addressing sexual harassment in many jurisdictions. However, previous research has found that reporting parties are not well served by such processes. In particular, Ahmed (Complaint!; 2021) argues that the institutional climate that enables harassment or discrimination to occur—including its gendered dynamics—also shapes how complaints about harassment are handled. Building on Ahmed's work, this article analyses how gender “gets into” formal reporting processes for sexual harassment within organizations. It draws on interviews with 18 students and staff who went through a formal institutional reporting process for gender‐based violence or harassment in UK higher education between 2016 and 2021. Using Connell's theorization of “gender regimes,” we outline how “dimensions of gender” within organizations affected different stages of formal reporting processes, including how evidence was gathered during reporting processes, as well as how it was assessed. These findings demonstrate that gender regimes—via gender relations of power, gendered “attachments and investments,” and “gender‐neutral” processes—can override formal processes and affect outcomes of sexual harassment reporting. These findings explain how gender regimes contribute to the failure of sexual harassment complaints to be upheld within organizations.
Rural development as the propagation of regional ‘communities of values’: A case study of local discourses promoting social innovation and social sustainability
Authors: Stoustrup Sune Wiingaard
Published: October 2024

Discourses on rural areas and their development concurrently encompass both negative narratives of them dying out and discussions on how to constitute future visions for a ‘living’, ‘good’ and ‘sustainable’ countryside to work towards. As a solution, ‘social innovation’ has been proposed to counter the economic, demographic and sociocultural challenges disadvantaged rural regions are facing. Accordingly, this article contributes to the growing literature on the dynamics of social innovation initiatives by investigating how rural areas and their communities are communicatively re‐constructed, as part of socio‐spatial processes emerging from the work of rural development initiatives, fostering potential social change towards more sustainable societies. Building on fieldwork from the rural Austrian region of Mühlviertel, it is shown how social innovation aiming at instigating positive territorial developments is linked to intertwined processes of the re‐figuration of social bonds and re‐figuration of space, which is centred around the propagation of regional ‘community of values’ founded on ideas about changing values and social sustainability.
Replication kinetics and cytopathic effect of feline calicivirus in feline corneal epithelial cells
Authors: Saade Daniela I. , Liu Chin‐Chi , Mills Erinn P. , Stanfield Brent , Thieulent Côme J. , Chouljenko Vladimir N. , Emelogu Ugochi , Carter Renee T. , Camacho‐Luna Pilar , Lewin Andrew C.
Published: October 2024

Objective

To determine the replication kinetics and cytopathic effect (CPE) of feline calicivirus (FCV) in feline corneal epithelial cells (FCEC).

Animals Studied

Seven archived FCV isolates and one archived feline herpesvirus type 1 (FHV‐1) isolate, previously obtained from eight domestic short hair cats.

Procedures

FCV RNA was extracted for sequencing using Illumina MiSeq, to identify three genomically diverse isolates for further testing. Following reference‐based assembly, viral genomes were annotated and assessed. Superficial keratectomies were performed to isolate the corneal epithelium of cats and the cells were cultured in vitro. FCEC were infected with the three chosen FCV isolates and one FHV‐1 isolate at two different multiplicity of infection ratios (MOIs, 0.1 and 0.01 PFU/cell) and virus titration was assessed at 0, 2, 6, 12, 24, and 48 h post‐infection (hpi). Viral identity was confirmed by RT‐qPCR.

Results

Three genomically diverse FCV isolates were chosen for further assessment in the FCEC model. All infections of FCEC with FCV led to visible CPE, characterized by epithelial cell rounding and detachment from the plate by 24 hpi, while FHV‐1 led to visible CPE within 48 hpi. All three of the FCV isolates replicated effectively in FCEC at both 0.1 and 0.01 MOI, with a peak increase in titer approximately 12–24 hpi.

Conclusions

The results support the possible role of FCV as a primary pathogen of the feline ocular surface. FCV replicates in FCEC in vitro, leading to profound CPE.
Rational noncrossing Coxeter–Catalan combinatorics
Authors: Galashin Pavel , Lam Thomas , Trinh Minh‐Tâm , Williams Nathan
Published: October 2024

We solve two open problems in Coxeter–Catalan combinatorics. First, we introduce a family of rational noncrossing objects for any finite Coxeter group, using the combinatorics of distinguished subwords. Second, we give a type‐uniform proof that these noncrossing Catalan objects are counted by the rational Coxeter–Catalan number, using the character theory of the associated Hecke algebra and the properties of Lusztig's exotic Fourier transform. We solve the same problems for rational noncrossing parking objects.
Material Removal Rate of Face-Milled Bevel Gears Based on a Ring-Dexel Cutting Simulation
Authors: Shih Yi-Pei , Wang Yu-Chieh , Wei Bo-Lin , Chen Kuan-Hung
Published: October 2024

Face milling is not only a primary machining technique for the mass production of bevel gears, but it has also become a standardized process integrated into computer numerical control (CNC) bevel gear-cutting machines in the last two decades. Controlling suitable feed rates for face milling is one of the most direct and pivotal factors influencing processing efficiency for CNC machines. Despite being programmed through numerical codes, the feed rates provided by the gear machines most rely on experiential insights rather than optimization. Therefore, leveraging material removal rate (MRR) directly correlates with machining power and will hold immense potential for optimizing feed rates and enhancing efficiency. Because commercial software solutions cannot accurately predict the MRR for face milling operations, this paper uses a novel ring-dexel-based model for cutting simulation to address this issue. The main aim of this model is to provide a more precise prediction of the MRR across all face milling cuttings. By controlling the cutting depth and generating angle, the ring gear's plunging process and the pinion's single-roll generating process were successfully simulated. Thus, the MRRs through all cutting processes were calculated. Experimental results showed that tool torques are positively correlated with the MRRs. Finally, by appropriately increasing the cutting feed rate based on the MRR, the pinion and ring gear machining times were reduced by 44% and 18%, respectively.
Modeling Stochastical Particle Rebound Based on High-Velocity Experiments
Authors: Hartmann Jan , Koch Christian , Staudacher Stephan
Published: October 2024

Solid particle erosion is a major deterioration process which contributes to performance deterioration of modern axial compressors. The prediction of this deterioration process requires the correct computation of particle movement through the machine and their resulting impacts on the effected components. Especially for particles with high Stokes numbers, the movement is determined mainly by the particle-wall interaction, which is described by coefficients of restitution. Today, they are derived from experiments featuring high particle velocities and target materials, which are representative for turbomachinery applications. In this study, an already published rebound model is optimized for particle materials and velocities within high-pressure compressors. The statistical spread of the rebound experiment is evaluated and the implementation into the rebound model is shown, which improves the prediction capability of the model. The model is implemented into a computational fluid dynamics (CFD) software and numerical simulations are performed. The model is applied to a cylinder test specimen within a sand blast facility. The simulation shows the importance of the stochastics of the rebound, which is often neglected in particle-wall models. Moreover, the numerical study shows requirements for the test specimen and its positioning in the experimental setup, which are prerequisites for the derivation of the coefficients of restitution using two-dimensional particle evaluation equipment.
The Effect of Thermal Cycling on Deposition in an Impingement/Effusion Cooling Geometry
Authors: Gogidze George J. , Bons Jeffrey P. , Lundgreen Ryan
Published: October 2024

Experiments were conducted in a high-pressure deposition facility to study the effect of engine cycling on the successive buildup of deposits as aircraft shut down and power up. The test facility simulates the pressure and temperature environment of a combustor liner or turbine vane cooling circuit. The coolant flow temperature reaches 894 K (1150 °F) and discharges into a 17-atm (250-psi) cavity pressure at a nominal pressure ratio of 1.027. AFRL05 test dust with a 0- to 10-µm size distribution is added to the coolant gas stream. The cooling circuit consists of a double-walled impingement/effusion cooling plate with nominal hole sizes on the order of 0.5 mm. To simulate cycling, the facility is brought up to the desired operating conditions where the first batch of dust is delivered (2–8 g). The facility is then ramped down to ambient conditions. Following a “dwell” period of approximately 24 h, another batch of dust is delivered once the facility is brought back up to the desired operating condition. Test data were acquired for one, two, and four cycles with different dust masses delivered. Values such as discharge coefficient, pressure ratio, Reynolds number, and temperature are used to evaluate the effects of dust deposition on the impingement/effusion plate setup. Dust capture efficiency is shown to be insensitive to cycling whereas flow blockage is negatively impacted by an increased number of cycles for the same total mass delivered. The sloughing of deposit structures during cooling circuit cool down is postulated to be responsible for the observed behavior.
Third-octave analyses describing two perceptual dimensions of sound reproduction and the resulting overall perceived dissimilarity between loudspeakers or headphones
Authors: Szwarcberg Nathan , Lavandier Mathieu
Published: October 2024

Many objective measurements have been proposed to evaluate sound reproduction, but it is often difficult to link measured differences with the differences perceived by listeners. In the literature, the best correlations with perception were obtained for measures involving an auditory model. The present study investigated simpler measurements to highlight the signal processing steps required to make the link with perception. It is based on dissimilarity evaluations from two previous studies: 1 study comparing 12 single loudspeakers using 3 musical excerpts, 1 study comparing 21 headphones using 2 musical excerpts, and both studies highlighting 2 perceptual dimensions associated with the relative strengths of bass and midrange. The objective approach compared several signal analyses computing the dissimilarity between the spectra of the recorded sound reproductions. The results show that a third-octave analysis can accurately describe the overall dissimilarity between the loudspeakers or headphones and the two underlying perceptual dimensions.
AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action
Authors: Cerro-Herreros Estefanía , Núñez-Manchón Judit , Naldaiz-Gastesi Neia , Carrascosa-Sàez Marc , García-Rey Andrea , Losilla Diego Piqueras , González-Martínez Irene , Espinosa-Espinosa Jorge , Moreno Kevin , Poyatos-García Javier , Vilchez Juan J. , de Munain Adolfo López , Suelves Mònica , Nogales-Gadea Gisela , Llamusí Beatriz , Artero Rubén
Published: October 2024

This study evaluated therapeutic antimiRs in primary myoblasts from patients with myotonic dystrophy type 1 (DM1). DM1 results from unstable CTG repeat expansions in the
DMPK
gene, leading to variable clinical manifestations by depleting muscleblind-like splicing regulator protein MBNL1. AntimiRs targeting natural repressors miR-23b and miR-218 boost MBNL1 expression but must be optimized for a better pharmacological profile in humans. In untreated cells, miR-23b and miR-218 were up-regulated, which correlated with CTG repeat size, supporting that active MBNL1 protein repression synergizes with the sequestration by CUG expansions in
DMPK
. AntimiR treatment improved RNA toxicity readouts and corrected regulated exon inclusions and myoblast defects such as fusion index and myotube area across CTG expansions. Unexpectedly, the treatment also reduced
DMPK
transcripts and ribonuclear foci. A leading antimiR reversed 68% of dysregulated genes. This study highlights the potential of antimiRs to treat various DM1 forms across a range of repeat sizes and genetic backgrounds by mitigating MBNL1 sequestration and enhancing protein synthesis.
Self-limiting multimerization of α-synuclein on membrane and its implication in Parkinson’s diseases
Authors: Ma Dong-Fei , Zhang Shenqing , Xu Si-Yao , Huang Zi , Tao Yuanxiao , Chen Feiyang , Zhang Shengnan , Li Dan , Chen Tongsheng , Liu Cong , Li Ming , Lu Ying
Published: October 2024

α-Synuclein (α-syn), a crucial molecule in Parkinson’s disease (PD), is known for its interaction with lipid membranes, which facilitates vesicle trafficking and modulates its pathological aggregation. Deciphering the complexity of the membrane-binding behavior of α-syn is crucial to understand its functions and the pathology of PD. Here, we used single-molecule imaging to show that α-syn forms multimers on lipid membranes with huge intermultimer distances. The multimers are characterized by self-limiting growth, manifesting in concentration-dependent exchanges of monomers, which are fast at micromolar concentrations and almost stop at nanomolar concentrations. We further uncovered movement patterns of α-syn’s occasional trapping on membranes, which may be attributed to sparse lipid packing defects. Mutations such as E46K and E35K may disrupt the limit on the growth, resulting in larger multimers and accelerated amyloid fibril formation. This work emphasizes sophisticated regulation of α-syn multimerization on membranes as a critical underlying factor in the PD pathology.
Bidirectional regulation of motor circuits using magnetogenetic gene therapy
Authors: Unda Santiago R. , Pomeranz Lisa E. , Marongiu Roberta , Yu Xiaofei , Kelly Leah , Hassanzadeh Gholamreza , Molina Henrik , Vaisey George , Wang Putianqi , Dyke Jonathan P. , Fung Edward K. , Grosenick Logan , Zirkel Rick , Antoniazzi Aldana M. , Norman Sofya , Liston Conor M. , Schaffer Chris , Nishimura Nozomi , Stanley Sarah A. , Friedman Jeffrey M. , Kaplitt Michael G.
Published: October 2024

Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)–mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor–Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing Cre into the globus pallidus led to similar circuit specificity and motor responses. Last, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in the subthalamic nucleus in PitX2-Cre parkinsonian mice resulted in reduced
c-fos
expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits noninvasively in vivo using clinically available devices.
Single ambipolar OECT–based inverter with volatility and nonvolatility on demand
Authors: Cong Shengyu , Chen Junxin , Xie Miao , Deng Ziyi , Chen Chaoyue , Liu Riping , Duan Jiayao , Zhu Xiuyuan , Li Zhengke , Cheng Yuhua , Huang Wei , McCulloch Iain , Yue Wan
Published: October 2024

Organic electrochemical transistor (OECT)–based inverter introduces new prospects for energy-efficient brain-inspired artificial intelligence devices. Here, we report single-component OECT-based inverters by incorporating ambipolar p(gDPP-V). Notably, p(gDPP-V) shows state-of-the-art ambipolar OECT performances in both conventional (p/n-type mode transconductance of 29/25 S cm
−1
) and vertical (transconductance of 297.2/292.4 μS μm
−2
under p/n operation) device architectures. Especially, the resulting highly stable vertical OECT–based inverter shows a high voltage gain of 105 V V
−1
under a low driving voltage of 0.8 V. The inverter exhibits undiscovered voltage-regulated dual mode: volatile receptor and nonvolatile synapse. Moreover, applications of physiology signal recording and demonstrations of NAND/NOR logic circuits are investigated within the volatile feature, while neuromorphic simulations with a convolutional neural network and image memorizing capabilities are explored under the nonvolatile behavior. The ambipolar OECT–based inverter, capable of both volatile and nonvolatile operations, provides possibilities for the applications of reconfigurable complementary logic circuits in novel neuromorphic computing paradigms.
Temperature-adaptive dual-modal photonic textiles for thermal management
Authors: Zhu Kaixuan , Yao Houze , Song JiaJia , Liao Qihua , He Shuang , Guang Tianlei , Wang Haiyan , Hao Xuanzhang , Lu Bing , Lin Tengyu , Cheng Huhu , Liu Xin , Qu Liangti
Published: October 2024

Maintaining a thermally comfortable living and working environment with renewable energy sources is crucial for human health. However, achieving temperature self-regulation in individual textiles without external interventions remains a challenge. Here, we present a dual-modal photonic textile capable of autonomously achieving both low-temperature solar heating and high-temperature radiative cooling under sunlight. This innovative textile is primarily composed of textile fibers that are functionalized with thermochromic microcapsules encapsulated in graphene and barium sulfate coatings, which exhibit approximately 80% visible light optical modulation when integrated into the fabric. We demonstrate that garment and tent (3.5 m × 2.9 m × 1.3 m) fabricated from these textiles can achieve temperature-adaptive, all-weather thermal management, expanding the thermal comfort range by 8.5°C. This research showcases notable potential for applications in fabric-related heat management and highlights the importance of exploring temperature-adaptive solutions for a sustainable and healthy lifestyle.
DNA cytosine methylation suppresses meiotic recombination at the sex-determining region
Authors: Ge Tong , Gui Xiuqi , Xu Jia-Xi , Xia Wei , Wang Chao-Han , Yang Wenqiang , Huang Kaiyao , Walsh Colum , Umen James G. , Walter Jörn , Du Ya-Rui , Chen Hui , Shao Zhen , Xu Guo-Liang
Published: October 2024

Meiotic recombination between homologous chromosomes is vital for maximizing genetic variation among offspring. However, sex-determining regions are often rearranged and blocked from recombination. It remains unclear whether rearrangements or other mechanisms might be responsible for recombination suppression. Here, we uncover that the deficiency of the DNA cytosine methyltransferase DNMT1 in the green alga
Chlamydomonas reinhardtii
causes anomalous meiotic recombination at the mating-type locus (
MT
), generating haploid progeny containing both
plus
and
minus
mating-type markers due to crossovers within
MT
. The deficiency of a histone methyltransferase for H3K9 methylation does not lead to anomalous recombination. These findings suggest that DNA methylation, rather than rearrangements or histone methylation, suppresses meiotic recombination, revealing an unappreciated biological function for DNA methylation in eukaryotes.
Assessment of the activity and mechanisms of resistance to cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, taniborbactam, zidebactam, nacubactam, xeruborbactam, and ANT3310 in emerging double-carbapenemase-producing Enterobacterales
Authors: Blanco-Martín Tania , López-Hernández Inmaculada , Aracil Belén , González-Pinto Lucía , Aja-Macaya Pablo , Alonso-García Isaac , Rodríguez-Pallares Salud , Sánchez-Peña Lucía , Outeda-García Michelle , Pérez-Vázquez María , Vázquez-Ucha Juan Carlos , Beceiro Alejandro , Pascual Álvaro , Bou Germán , López-Cerero Lorena , Oteo-Iglesias Jesús , Arca-Suárez Jorge ,   on behalf of the GEMARA-SEIMC/CIBERINFEC Study Group on the activity and resistance mechanisms to new β-lactams and β-lactamase inhibitors (PROTECT)
Published: October 2024

We aimed to investigate the activity of and mechanisms of resistance to cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations in a nationwide collection of double-carbapenemase-producing Enterobacterales. In all, 57 clinical isolates co-producing two carbapenemases collected from Spanish hospitals during the period 2017–2022 were analyzed. Minimum inhibitory concentration (MIC) values for ceftazidime, ceftazidime/avibactam, aztreonam, aztreonam/avibactam, aztreonam/nacubactam, cefiderocol, cefepime, cefepime/taniborbactam, cefepime/zidebactam, cefepime/nacubactam, imipenem, imipenem/relebactam, meropenem, meropenem/vaborbactam, meropenem/xeruborbactam, and meropenem/ANT3310 were determined by reference broth microdilution. Genetic drivers of resistance were analyzed by whole-genome sequencing (WGS). The collection covered nine carbapenemase associations: VIM + OXA-48 (21/57), NDM + OXA-48 (11/57), KPC + VIM (10/57), KPC + OXA-48 (6/57), IMP + OXA-48 (3/57), NDM + KPC (2/57), NDM + VIM (2/57), NDM + GES (1/57), and KPC + IMP (1/57). Ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam were the least active options. Aztreonam/avibactam and aztreonam/nacubactam were active against the whole collection and yielded MIC
50
/MIC
90
values of ≤0.25/0.5 mg/L and 1/2 mg/L, respectively. Cefepime/zidebactam (56/57 susceptible), meropenem/xeruborbactam (56/57 susceptible), cefepime/nacubactam (55/57 susceptible), and cefiderocol (53/57 susceptible) were also highly active, with MIC
50
/MIC
90
values ranging from ≤0.25–2 mg/L to 2–4 mg/L, respectively. Meropenem/ANT3310 (MIC
50
/MIC
90
= 0.5/≥64 mg/L; 47/57 susceptible) and cefepime/taniborbactam (MIC
50
/MIC
90
= 0.5/16 mg/L; 44/57 susceptible) also retained high levels of activity, although they were affected by NDM-type enzymes in combination with porin deficiency. Our findings highlight that cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, nacubactam, taniborbactam, zidebactam, xeruborbactam, and ANT3310 show promising activity against double-carbapenemase-producing Enterobacterales.
AAV2 can replicate its DNA by a rolling hairpin or rolling circle mechanism, depending on the helper virus
Authors: Lkharrazi Anouk , Tobler Kurt , Marti Sara , Bratus-Neuenschwander Anna , Vogt Bernd , Fraefel Cornel
Published: October 2024

Adeno-associated virus type 2 (AAV2) is a small, non-pathogenic, helper virus-dependent parvovirus with a single-stranded (ss) DNA genome of approximately 4.7 kb. AAV2 DNA replication requires the presence of a helper virus such as adenovirus type 5 (AdV5) or herpes simplex virus type 1 (HSV-1) and is generally assumed to occur as a strand-displacement rolling hairpin (RHR) mechanism initiated at the AAV2 3′ inverted terminal repeat (ITR). We have recently shown that AAV2 replication supported by HSV-1 leads to the formation of double-stranded head-to-tail concatemers, which provides evidence for a rolling circle replication (RCR) mechanism. We have revisited AAV2 DNA replication and specifically compared the formation of AAV2 replication intermediates in the presence of either HSV-1 or AdV5 as the helper virus. The results confirmed that the AAV2 DNA replication mechanism is helper virus-dependent and follows a strand-displacement RHR mechanism when AdV5 is the helper virus and primarily an RCR mechanism when HSV-1 is the helper virus. We also demonstrate that recombination plays a negligible role in AAV2 genome replication. Interestingly, the formation of high-molecular-weight AAV2 DNA concatemers in the presence of HSV-1 as the helper virus was dependent on an intact HSV-1 DNA polymerase.

IMPORTANCE

AAV is a small helper virus-dependent, non-pathogenic parvovirus. The AAV genome replication mechanism was extensively studied in the presence of AdV as the helper virus and described to proceed using RHR. Surprisingly, HSV-1 co-infection facilitates RCR of the AAV2 DNA. We directly compared AdV5 and HSV-1 supported AAV2 DNA replication and showed that AAV2 can adapt its replication mechanism to the helper virus. A detailed understanding of the AAV replication mechanism expands our knowledge of virus biology and can contribute to increase gene therapy vector production.
Acidocalcisome localization of membrane transporters and enzymes in
Trypanosoma brucei
Authors: Huang Guozhong , Docampo Roberto
Published: October 2024

Acidocalcisomes of
Trypanosoma brucei
are membrane-bounded organelles characterized by their acidity and high content of polyphosphate and cations, like calcium and magnesium. They have important roles in cation and phosphorus storage, osmoregulation, autophagy initiation, calcium signaling, and virulence. Acidocalcisomes of
T. brucei
possess several membrane transporters, pumps, and channels, some of which were identified by proteomic and immunofluorescence analyses and validated as acidocalcisome proteins by their colocalization with the acidocalcisome marker vacuolar proton pyrophosphatase (VP1). Here, we report that a set of membrane transporters and enzymes, which were proposed to be present in acidocalcisomes by the morphological appearance of tagged proteins, colocalize with VP1, validating their character as acidocalcisome proteins.

IMPORTANCE

Acidocalcisomes are acidic organelles rich in polyphosphate and calcium present in a variety of eukaryotes and important for osmoregulation and calcium signaling. Several proteins were postulated to localize to acidocalcisomes based on their morphological characteristics. We provide validation of the localization of ten10 acidocalcisome proteins by their co-localization with enzymatic markers. These findings reveal the roles of acidocalcisomes in the storage of toxic metals, and the presence of enzymes involved in palmitoylation and polyphosphate metabolism.
Universal Adapter Protein Bag3 and Small Heat Shock Proteins
Authors: Zamotina Maria A. , Muranova Lidia K. , Zabolotskii Artur I. , Tyurin-Kuzmin Pyotr A. , Kulebyakin Konstantin Yu. , Gusev Nikolai B.
Published: October 2024

Bag3 (Bcl-2-associated athanogene 3) protein contains a number of functional domains and interacts with a wide range of different partner proteins, including small heat shock proteins (sHsps) and heat shock protein Hsp70. The ternary Bag3–sHsp–and Hsp70 complex binds denatured proteins and transports them to phagosomes, thus playing a key role in the chaperone-assisted selective autophagy (CASA). This complex also participates in the control of formation and disassembly of stress granules (granulostasis) and cytoskeleton regulation. As Bag3 and sHsps participate in multiple cellular processes, mutations in these proteins are often associated with neurodegenerative diseases and cardiomyopathy. The review discusses the role of sHsps in different processes regulated by Bag3.
Testing General Relativity with Black Hole X-Ray Data
Authors: Bambi C.
Published: October 2024

The theory of General Relativity has successfully passed a large number of observational tests without requiring any adjustment from its original version proposed by Einstein in 1915. The past 8 years have seen significant advancements in the study of the strong-field regime, which can now be tested with gravitational waves, X-ray data, and black hole imaging. This is a compact and pedagogical review on the state-of-the-art of the tests of General Relativity with black hole X-ray data.
On the Principle of Relativity of Inertia in Both General and Entangled Relativities
Authors: Minazzoli O.
Published: October 2024

Entangled Relativity is a novel theory of relativity that offers a more economical approach than General Relativity. It successfully recovers both General Relativity and standard quantum field theory within a specific (yet generic) limit. Furthermore, Entangled Relativity precludes the existence of spacetime devoid of the matter that permeates it. Consequently, I argue that Entangled Relativity is not only preferable from the standpoint of Occam’s razor, due to its economical nature, but it also aligns more closely with Einstein’s original vision for a satisfactory theory of relativity.
Systematic review of interventions for mental health, cognition and psychological well-being in long COVID
Authors: Hawke Lisa D , Nguyen Anh T P , Wang Wei , Brown Eric E , Xu Dandan , Deuville Susan , Goulding Suzie , Ski Chantal F , Rossell Susan L , Thompson David R , Rodak Terri , Strudwick Gillian , Castle David
Published: October 2024

Aims

This systematic review aims to identify and synthesise the publicly available research testing treatments for mental health, cognition and psychological well-being in long COVID.

Methods

The following databases and repositories were searched in October–November 2023: Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Internet, WANFANG Data, Web of Science’s Preprint Citation Index, The Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Articles were selected if they described participants with long COVID symptoms at least 4 weeks after SAR-CoV-19 infection, reported primary outcomes on mental health, cognition and/or psychological well-being, and were available with at least an English-language summary. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews were followed.

Results

Thirty-three documents representing 31 studies were included. Seven tested psychosocial interventions, five pharmaceutical interventions, three natural supplement interventions, nine neurocognitive interventions, two physical rehabilitation interventions and five integrated interventions. While some promising findings emerged from randomised controlled trials, many studies were uncontrolled; a high risk of bias and insufficient reporting were also frequent.

Conclusions

The published literature on treatments for mental health, cognition and psychological well-being in long COVID show that the interventions are highly heterogeneous and findings are inconclusive to date. Continued scientific effort is required to improve the evidence base. Regular literature syntheses will be required to update and educate clinicians, scientists, interventionists and the long COVID community.
Development of prediction models of COVID-19 vaccine uptake among Lebanese and Syrians in a district of Beirut, Lebanon: a population-based study
Authors: Ragi Marie-Elizabeth , Ghattas Hala , Shamas Hazar , DeJong Jocelyn , Melhem Nada M , McCall Stephen J
Published: October 2024

Introduction

Vaccines are essential to prevent infection and reduce the morbidity of infectious diseases. Previous evidence has shown that migrants and refugees are particularly vulnerable to exclusion and discrimination, and low COVID-19 vaccine intention and uptake were observed among refugees globally. This study aimed to develop and internally validate prediction models of COVID-19 vaccine uptake by nationality.

Methods

This is a nested prognostic population-based cross-sectional analysis. Data were collected between June and October 2022 in Sin-El-Fil, a district of Beirut, Lebanon. The study population included a random sample of Lebanese adults and all Syrian adults residing in areas of low socioeconomic status. Data were collected through a telephone survey. The main outcome was the uptake of at least one dose of the COVID-19 vaccine. Predictors of COVID-19 vaccine uptake were assessed using the Least Absolute Shrinkage and Selection Operator regression for Lebanese and Syrian nationalities in separate models.

Results

Of 2028 participants, 79% were Lebanese, 18% Syrians and 3% of other nationalities. COVID-19 vaccination uptake was higher among Lebanese (85% (95% CI 82% to 86%) compared to Syrians (47% (95% CI 43% to 51%)) (p<0.001); adjusted OR 6.2 (95% CI 4.9 to 7.7). Predictors of uptake of one or more COVID-19 vaccine doses for Lebanese were older age, presence of an older adult in the household, higher education, greater asset-based wealth index, private healthcare coverage, feeling susceptible to COVID-19, belief in the safety and efficacy of vaccines and previous receipt of the influenza vaccine. For Syrians, predictors were older age, male sex, completing school or higher education, receipt of cash assistance, presence of chronic illness, belief in the safety and efficacy of vaccines, previous receipt of the influenza vaccine and possession of a legal residency permit in Lebanon.

Conclusions

These findings indicate barriers to vaccine uptake among Syrian refugees and migrants, including legal residency status. These findings call for urgent action to enable equitable access to vaccines by raising awareness about the importance of vaccination and the targeting of migrant and refugee populations through vaccination campaigns.
Exploration of preferences among people with COPD to inform resource allocation: a discrete choice experiment study
Authors: Ettinger Jack , Patel Anita , Ohrnberger Julius , Moore Chris , Bhudiya Manjula , Smith Wayne
Published: October 2024

Introduction

Treatment options for chronic obstructive pulmonary disease (COPD) are numerous but adherence remains a key challenge. We performed a discrete choice experiment (DCE) of patients’ preferences in accessing care for the management of COPD. The aim of this study was to understand patients’ preferences for modes of accessing care for the management of COPD. This piece of work was then used to inform resource allocation decisions in five integrated care systems (ICSs) in England.

Methods

People with diagnosed COPD in five ICSs were invited to complete an online survey from August to September 2022. An experimental design built on the principles of minimal overlap, level balance and orthogonality was used to create 20 sets of 11 scenarios for participants to assess. Participants were presented with three hypothetical options and asked to select their most preferred or state that none was preferred. Data were analysed using a hierarchal Bayes algorithm.

Results

Of 82 639 patients with COPD in the study area, 520 completed the survey. The mean health-related quality of life score derived using EuroQol 5-Dimensions 5-Level was 0.57 (0.29). The attributes assigned greatest importance were treatment outcomes, treatment delivery and the type of staff who deliver treatment. Mean utility level scores were substantially higher for little relief (22.75 (SD 78.80)) or some relief from symptoms (20.67 (46.77)) than for complete relief (‒43.42 (83.03)). Of the treatment delivery options, in-person individual appointments were preferred (mean utility score 48.34 (SD 48.14)), and care being provided by healthcare professionals was viewed as very important (77.50 (64.39)).

Conclusions

The DCE approach can help resource allocation decisions by indicating attributes most important to patients and trade-offs they are willing to make in treatment access and delivery.
Delayed admission of patients with hip fracture from the emergency department is associated with an increased mortality risk and increased length of hospital stay
Authors: Clement Nicholas D , Farrow Luke , Chen Bin , Duffy Andrew , Murthy Krishna , Duckworth Andrew D
Published: October 2024

Background

The aims of this study were to assess whether delayed admission from the ED influenced mortality risk, length of acute hospital stay, risk of developing delirium and return to domicile for patients presenting with a hip fracture.

Methods

A single centre service evaluation was undertaken including patients aged over 50 years who were admitted to a Scottish hospital through the ED with a hip fracture during a 42-month period (from January 2019 to June 2022). Delay was defined as spending >4 hours in the ED from arrival. Patient demographics and perioperative variables and mortality were collected. Cox regression analysis (adjusting for age, sex, season, socioeconomic status, American Society of Anesthesiologists grade, place of residence, fracture type, delirium and time from ward to theatre) was used to determine the independent association between delayed disposition from the ED and mortality (90 days and final follow-up) as recorded on a regional database.

Results

The cohort consisted of 3266 patients with a mean age of 81 years, of which 2359 (72.2%) were female. 1261 (38.6%) patients stayed >4 hours in ED. The median follow-up was 529 days, during which time there were 1314 (40.2%) deaths. Survival at 90 days was significantly lower (hazard ratio [HR] 0.76, 95% CI 0.63 to 0.91) for patients who stayed >4 hours (92.9%) compared with those who stayed ≤4 hours (95.7%). Delayed disposition was independently associated with an increased mortality risk at 90 days (adjusted HR 1.36, 95% CI 1.12 to 1.63, p=0.001) and at final follow-up (adjusted HR 1.15, 95% CI 1.03 to 1.29, p=0.017). Delay was also associated with a longer length of hospital stay (difference in medians of 1 day, p<0.001). There were no differences in the risk of delirium on the ward (p=0.256) or return to place of residence (p≥0.315).

Conclusion

Delayed disposition from our ED was associated with an increased mortality risk and longer length of hospital stay in patients presenting with a hip fracture.
Effectiveness of rapid access chest pain clinics: a systematic review of patient outcomes and resource utilisation
Authors: Black James Andrew , Eaves Scott , Chapman Niamh , Campbell Julie , Bui Tan Van , Cho Kenneth , Chow Clara K , Sharman James E
Published: October 2024

Background

Rapid Access Chest Pain Clinics (RACPC) are widely used for the outpatient assessment of chest pain, but there appears to be limited high-quality evidence justifying this model of care. This study aimed to review the literature to determine the effectiveness of RACPCs.

Methods

A systematic review of studies evaluating the effectiveness of RACPCs was conducted to assess the quality of the evidence supporting this model. Outcomes related to effectiveness included major adverse cardiovascular events, emergency department reattendance, cost-effectiveness and patient satisfaction. Study quality was assessed using the RoB 2 tool, Newcastle-Ottawa quality assessment tool or the Consolidated Criteria for Reporting Qualitative Studies checklist, as appropriate.

Results

Thirty-two studies were eligible for inclusion, including one randomised trial. Five analytical cohort studies were included, with three comparing outcomes against non-RACPC controls. Three qualitative studies were included. Most reports were descriptive. Findings were consistent with RACPCs being associated with favourable clinical outcomes, reduced emergency department reattendance, cost-effectiveness and high patient satisfaction. However, there was significant heterogeneity in care models, and overall literature quality was low, with a high risk of publication bias.

Conclusion

While the literature suggests RACPCs are safe and efficient, the quality of the available evidence is limited. Further high-quality data from adequately controlled clinical trials or large scare registries are needed to inform healthcare resource allocation decisions.

PROSPERO registration number

CRD42023417110.