bluuebunny/crossref_metadata_2025 huggingface dataset:
Mayor re-election and earnings management: evidence from Portuguese municipalities
Authors: Ferreira Augusta
Published: December 2023

Purpose

The aim of this paper is to investigate whether Mayors in Portugal engage in earnings management close to zero with the motivation of re-election.

Design/methodology/approach

The data used in this study were annual financial information from Portuguese municipalities from 2005 to 2016, as well as data on elections and Mayor re-elections involving three political cycles. The methodologies employed were quantitative, including graphical and panel data regressions.

Findings

The results indicate that municipalities used discretionary accruals to engage in earnings management to report net earnings close to zero, and re-election seems to be a motivation for earnings management behaviour. Furthermore, the results suggest that municipalities in which the Mayor is re-elected are less likely to report positive net earnings close to zero.

Originality/value

This paper makes a valuable contribution to the literature on earnings management in municipalities. At the theoretical level, it makes it possible to identify whether re-election is a motivation for earnings management and, in this sense, to identify patterns of behaviour by managers. On a practical level, the knowledge of a manager's behaviour patterns will help to anticipate his or her future behaviour and, consequently, may prevent inefficiencies.
SDG commentary: services that provide opportunity for all humans
Authors: Raciti Maria M. , Alkire Linda , Beatson Amanda
Published: December 2023

Purpose

This paper is part of the Special Issue series Improving Life on Planet Earth – A Call to Action for Service Research to Achieve the Sustainable Development Goals (SDG). This paper aims to provide the groundwork for Service Research Theme 2 – services that provide OPPORTUNITY for all humans. Service Research Theme 2 comprises SDG4, quality education; SDG5, gender equality; and SDG10, reduced inequalities and seeks to mobilize ServCollab’s aspirations to reduce human suffering, improve human well-being and enable well-becoming.

Design/methodology/approach

A scoping review appraising existing service research related to SDG4, SDG5 and SDG10 was conducted, establishing interlinkages, identifying patterns within each SDG and then assembling a research agenda for service researchers.

Findings

The scoping review identifies 18 patterns in service research (six patterns per SDG) pertaining to Service Research Theme 2. Common patterns among the SDG4, SDG5 and SDG10 included underrepresentation, consumer-centricity, the absence of explicit SDG linkages, the predominance of one theoretical anchor and the preference for quantitative studies, particularly surveys. Overall, the scoping review found that service research related to Service Research Theme 2 is patchy in that it is overdeveloped in some topics, methodologies and methods yet underdeveloped or silent in others.

Originality/value

The high-level research problem of Service Research Theme 2 is as follows: How have services provided OPPORTUNITY for all humans? This paper analyzes patterns in service research and, from these patterns, assembles a research agenda that sparks and guides further research.
Developing and validating a cashless transaction adoption model (CTAM)
Authors: Raj L. Vimal , S. Amilan , K. Aparna
Published: December 2023

Purpose

This paper aims to develop and validate a cashless transaction adoption model (CTAM) that integrates all essential elements to investigate the adoption of “cashless transactions (CLT)”.

Design/methodology/approach

The researchers surveyed 375 respondents from each of Bengaluru’s eight zones in India. In addition, using the respondents’ replies, a “partial least squares-based structural equation modelling (PLS-SEM)” technique was used to analyse the relationship between the components.

Findings

The results of CTAM reveal that 12 independent variables explain 84.7% of the variation in behavioural intention to adopt CLT. In addition, performance expectancy is the strongest predictor of users’ intentions to embrace CLT, followed by perceptions of the economy’s security and economic offence reduction, social influence, perceived trustworthiness, the expected level of effort and innovativeness. Furthermore, in terms of impediments, perceived risk and cost are the negative influence factors that affect behavioural intention to adopt CLT.

Originality/value

The research successfully developed and validated a comprehensive CTAM that integrates essential elements to investigate the adoption of CLT. Consequently, this research, for the first time, elucidates the precise role of “Perceived Economic Offense Reduction (PEOR)”, “Perceived Economic Benefit (PEB)” and “Perceived Economy’s Security (PES)” in influencing individuals’ behavioural intentions towards adopting CLT. Accordingly, this CTAM offers a more in-depth explanation than any other research for understanding why individuals embrace CLT systems.
Overlap relationship between the priority of land consolidation and the floodplain wetland potential in paddy field
Authors: Osawa Takeshi
Published: December 2023

Ecosystems that offer several ecosystem services can be used as green infrastructure for human well‐being. In recent years, human activities have substantially engineered ecosystems to produce the desired ecosystem services. However, such efforts could lead to losses of other ecosystem services. Paddy fields are a seminatural ecosystem that can provide several ecosystem services other than rice production. Land consolidation in paddy fields aim to increase the efficiency of food production as a provisioning service, but it could depress the quality of wetland habitat as a supporting service. Recently, the Japanese government aimed to agricultural production with biodiversity conservation. Therefore, prioritizing a control strategy for future land consolidation is needed. Land consolidation work is effective for large areas and may incorporate the paddy field, previously a floodplain wetland that played a crucial role in regional biodiversity. However, land consolidation could result in the loss of this function. In this study, I investigated the spatial overlapping between land consolidation and paddy fields, which were previously natural floodplain wetlands in Kanagawa Prefecture, Japan. Here, terrain parameters and flow accumulation value (FAV), that can reflect wetland potential, along with the latest land use map, were used. The consolidation records in 1‐km cell for the whole of Kanagawa prefecture were used to test the hypothesis. Results showed that high FAV area with high wetland potential has large paddy fields and was heavily consolidated. Thus, there is need for drastic policy changes to align both food production and biodiversity in paddy fields in Japan.
Anthropology is good
Authors: Ingold Tim
Published: December 2023

Anthropology does not just study people; it studies with people, drawing them into a conversation, of concern to everyone, about how to live. But this means turning the academic model of knowledge production outside in. As a way of knowing from the inside, through participant observation, anthropological study exposes its practitioners to other ways of being with the aim to learn from them, not to write them up. Its true purpose, then, is not ethnographic but educational. It requires of all of us to place our anthropic selves at the center of a shared world while acknowledging the exceptional responsibility we bear for its future flourishing.
Optogenetic action potentials and intrinsic pacemaker interplay in retrogradely identified midbrain dopamine neurons
Authors: Hammer Niklas , Vogel Pascal , Lee Sanghun , Roeper Jochen
Published: December 2023

Dissecting the diversity of midbrain dopamine (DA) neurons by optotagging is a promising addition to better identify their functional properties and contribution to motivated behavior. Retrograde molecular targeting of DA neurons with specific axonal projection allows further refinement of this approach. Here, we focus on adult mouse DA neurons in the substantia nigra pars compacta (SNc) projecting to dorsal striatum (DS) by demonstrating the selectivity of a floxed AAV9‐based retrograde channelrhodopsin‐eYFP (ChR‐eYFP) labeling approach in DAT‐cre mice. Furthermore, we show the utility of a sparse labeling version for anatomical single‐cell reconstruction and demonstrate that ChR‐eYFR expressing DA neurons retain intrinsic functional properties indistinguishable from conventionally retrogradely red‐beads‐labeled neurons. We systematically explore the properties of optogenetically evoked action potentials (oAPs) and their interaction with intrinsic pacemaking in this defined subpopulation of DA neurons. We found that the shape of the oAP and its first derivative, as a proxy for extracellularly recorded APs, is highly distinct from spontaneous APs (sAPs) of the same neurons and systematically varies across the pacemaker duty cycle. The timing of the oAP also affects the backbone oscillator of the intrinsic pacemaker by introducing transient “compensatory pauses”. Characterizing this systematic interplay between oAPs and sAPs in defined DA neurons will also facilitate a refinement of DA neuron optotagging in vivo.
Non‐linear thresholds in the effect of area on three dimensions of diversity of herpetofauna in the West Indies
Authors: Gao De , Wang Yanping
Published: December 2023

Aim

The small‐island effect (SIE) describes an anomalous feature of the species–area relationship (SAR) on smaller compared to larger islands. However, previous studies on SIEs mainly focused on taxonomic diversity and overlooked phylogenetic and functional diversity. In this study, we explored SIEs in three dimensions of diversity. We expect to see the non‐linear thresholds in the effect of area on three dimensions of diversity as well as on community structures, because the dominant assembly processes vary across spatial scales.

Location

The West Indies.

Taxon

Herpetofauna.

Methods

We derived data on the presence/absence of 199 amphibian species on 163 islands and 614 reptile species on 748 islands in the West Indies. We built a species‐level phylogenetic tree and a species‐level functional tree to estimate six taxonomic, phylogenetic and functional diversity indices. Four community metrics on behalf of the phylogenetic and functional community structure of each island were calculated using a null modelling framework and was quantified using the standardized effect size (SES). We explored the non‐linear thresholds in the effect of area for each of the diversity indices and SES values of community metrics by comparing six piecewise regression models with a linear regression model and a null model.

Results

We found evidence of SIEs in four diversity indices representing all three dimensions of diversity. Besides, area thresholds were also found in the phylogenetic and functional community structure for both amphibians and reptiles. Random extinction, competitive exclusion and adaptive radiation are the dominant processes structuring reptile communities on small, intermediate and large islands respectively.

Main Conclusions

To conduct a comprehensive biodiversity conservation plan concerning taxonomic, phylogenetic and functional diversity, we suggest it is necessary to explore the SIEs in various diversity indices representing all three dimensions of diversity and apply the lowest threshold value to make management strategies.
Microglia‐derived extracellular vesicles in homeostasis and demyelination/remyelination processes
Authors: Wies Mancini V. S. B. , Mattera V. S. , Pasquini J. M. , Pasquini L. A. , Correale J. D.
Published: December 2023

Microglia (MG) play a crucial role as the predominant myeloid cells in the central nervous system and are commonly activated in multiple sclerosis. They perform essential functions under normal conditions, such as actively surveying the surrounding parenchyma, facilitating synaptic remodeling, engulfing dead cells and debris, and protecting the brain against infectious pathogens and harmful self‐proteins. Extracellular vesicles (EVs) are diverse structures enclosed by a lipid bilayer that originate from intracellular endocytic trafficking or the plasma membrane. They are released by cells into the extracellular space and can be found in various bodily fluids. EVs have recently emerged as a communication mechanism between cells, enabling the transfer of functional proteins, lipids, different RNA species, and even fragments of DNA from donor cells. MG act as both source and recipient of EVs. Consequently, MG‐derived EVs are involved in regulating synapse development and maintaining homeostasis. These EVs also directly influence astrocytes, significantly increasing the release of inflammatory cytokines like IL‐1β, IL‐6, and TNF‐α, resulting in a robust inflammatory response. Furthermore, EVs derived from inflammatory MG have been found to inhibit remyelination, whereas Evs produced by pro‐regenerative MG effectively promote myelin repair. This review aims to provide an overview of the current understanding of MG‐derived Evs, their impact on neighboring cells, and the cellular microenvironment in normal conditions and pathological states, specifically focusing on demyelination and remyelination processes.
Emerging patterns of accumulation in land redistribution in South Africa
Authors: Mtero Farai , Gumede Nkanyiso , Ramantsima Katlego
Published: December 2023

This article contributes to the wider debates on the impacts and outcomes of state efforts to create agrarian capitalists in land reform and agriculture in most countries of the global South. Specifically, this article presents empirical evidence on South Africa's State Land Lease and Disposal Policy (SLLDP) and analyses emerging accumulation dynamics in land redistribution. The evidence presented demonstrates that most of the SLLDP farm beneficiaries are capitalists from non‐agrarian sectors who increasingly see land reform as the new frontier for accumulation with significant opportunities to access state land and production support. Other agrarian capitalists leverage political influence and accumulate through privileged access to public resources. In contrast, accumulation from below through the reinvestment of farming proceeds remains constrained. Promoting a small segment of already wealthy capitalists greatly limits the potential of land reform to transform social relations in property in favour of historically marginalised social classes.
climenv: Download, extract and visualise climatic and elevation data
Authors: Tsakalos James Lee , Smith Martin Ross , Luebert Federico , Mucina Ladislav
Published: December 2023

Understanding the relationship between climate and vegetation requires climate data to be linked with ecological data, including habitat types and vegetation mapping. Our new R package climenv allows researchers to efficiently acquire, extract and visualise data sets that are commonly used by researchers to quantify the climatic envelope of vegetation. climenv offers integrated downloading and processing capabilities for three globally recognised data sets: WorldClim 2, CHELSA and the National Aeronautics and Space Administration's (NASA) Shuttle Radar Topography Mission (SRTM) elevation data. The package allows users to easily download and extract these data sets for single and multi‐geospatial polygon and point data sets, facilitating studies that explore the relationship between vegetation and climate. Furthermore, climenv allows users to plot traditional Holdridge life zone classification, Walter–Lieth climate diagrams and new customised plots, which combine aspects of both these systems with other biologically relevant climate variables. By enhancing the usability and flexibility of these data sets, climenv helps to explore the intricacies of the relationships between climate and vegetation. Our package is accessible from CRAN (https://CRAN.R‐project.org/package=climenv) or GitHub (https://github.com/jamestsakalos/climenv).
A mutually communicable external system resource in remote monitoring for cardiovascular implantable electronic devices
Authors: Hasumi Eriko , Fujiu Katsuhito , Nakamura Kentaro , Yumino Dai , Nishii Nobuhiro , Imai Yasushi , Shoda Morio , Komuro Issei
Published: December 2023

Background

Using third‐party resources to manage remote monitoring (RM) data from implantable cardiac electronic devices (CIEDs) can assist in device clinic workflows. However, each hospital‐acquired data is not used for further analysis as big data.

Methods and results

We developed a real‐time and automatically centralized system of CIED information from multiple hospitals. If the extensive data‐based analysis suggests individual problems, it can be returned to each hospital. To show its feasibility, we prospectively analyzed data from six hospitals. For example, unexpected abnormal battery levels were easily illustrated without recall information.

Conclusions

The centralized RM system could be a new platform that promotes the utilization of device data as big data, and that information could be used for each patient's practice.
Rising from the shadows: Selective foraging in model shoot parasitic plants
Authors: Bawin Thomas , Krause Kirsten
Published: December 2023

Despite being sessile, plants nonetheless forage for resources by modulating their growth. Adaptative foraging in response to changes in resource availability and presence of neighbours has strong implications for performance and fitness. It is an even more pressing issue for parasitic plants, which draw resources directly from other plants. Indeed, parasitic plants were demonstrated over the years to direct their growth towards preferred hosts and invest resources in parasitism relative to host quality. In contrast to root parasites that rely mostly on chemical cues, some shoot parasites seem to profit from the ability to integrate different types of abiotic and biotic cues. While significant progress in this field has been made recently, there are still many open questions regarding the molecular perception and the integration of diverse signalling pathways under different ecological contexts. Addressing how different cues are integrated in parasitic plants will be important when unravelling variations in plant interaction pathways, and essential to predict the spread of parasites in natural and agricultural environments. In this review, we discuss this with a focus on Cuscuta species as an emerging parasitic model, and provide research perspectives based on the recent advances in the topic and plant–plant interactions in general.
Direct reference and the Goldbach puzzle
Authors: Rinner Stefan
Published: December 2023

So‐called Neo‐Russellians, such as Salmon, Braun, Crimmins, and Perry, hold that the semantic content of ‘ is ’ in a context is the singular proposition o, P, where is the referent of the name in , and is the property expressed by the predicate in . This is also known as the Neo‐Russellian theory. Using truth ascriptions with names designating propositions, such as ‘Goldbach's conjecture’, in this paper, I will argue that, together with highly plausible principles regarding a priori knowledge, the Neo‐Russellian theory leads to unacceptable consequences. I will call this ‘the Goldbach puzzle’. Since the solution to the Goldbach puzzle cannot be to reject the discussed principles regarding a priori knowledge, the puzzle will undermine the Neo‐Russellian theory.
A substantial number of patients with rest pain, ulceration or gangrene are unable to undergo current non‐invasive perfusion testing—Could another modality be utilised?
Authors: Hart Odette , Hong Qiantai , Lee Khai Tuck , Gormley Sinead , Tehan Peta , Sommerset Jill , Khashram Manar
Published: December 2023

Rest pain, ulceration and gangrene are hallmark features of chronic limb‐threatening ischaemia (CLTI). Wound healing can be challenging, and this is compounded by an inability to measure lower limb perfusion via non‐invasive tools such as toe pressure (TP). Novel perfusion tests, such as pedal acceleration time (PAT), may overcome some limitations. This study aimed to quantify the proportion of patients with CLTI that were unable to undergo TP measurement. Over a three‐year duration, 344 consecutive patients with CLTI underwent PAT assessment (403 limbs). Overall, 32% of limbs were unable to undergo first toe TP, and 12.9% were unable to undergo first and second toe TP due to forefoot/digit amputation or tissue loss. Inability to measure first toe TP disproportionately impacted CLTI patients with diabetes compared to patients without diabetes (39.6% limbs (106/268); vs. 17% limbs (23/135); p < 0.001). Novel modalities may provide a useful tool for assessing perfusion in CLTI.
Feasibility of a Wearable Soft Robot Triggered by Brain-Computer Interface for Stroke Upper Extremity Rehabilitation
Authors: Cantillo-Negrete Jessica , Carino-Escobar Ruben I. , Yao Wei
Published: December 2023

Conventional robot designs have been applied as feedback stages in brain-computer interfaces (BCI) for stroke upper limb neurorehabilitation, showing promising results. Soft -robotic devices can be simpler and less expensive to manufacture, and provide ergonomic advantages over traditional designs, allowing to increase the efficacy and availableness of BCI systems for stroke neurorehabilitation. However, patients' degrees of control, neurophysiological activity, and system's usability with a BCI, using a soft robotic device as feedback, have not been assessed in stroke. For these reasons, a BCI system with a soft robotic feedback device was assessed in stroke patients. Fifty trials were acquired to setup the system, and another fifty trials were performed for evaluating patients' BCI control and cortical activity during movement intention (MI) and robotic feedback. User experience with the BCI was also assessed. Classification accuracy was in the range of 71.3% to 97.5%. Significant decrease in alpha power was observed during both motor intention and robotic feedback, but significant decrease in beta power was only observed during motor intention. BCI performance was high and in the range of reported BCI stroke interventions that used traditional robotics as feedback. Power decrease observed predominantly in alpha during soft robotic feedback was likely due to the eliciting of motor-related mechanisms. Quantification of user experience with the BCI implied that the system complexity is adequate for stroke patients. Therefore, a BCI system aimed at stroke neurorehabilitation can incorporate a soft robotic design as feedback and has potential for upper extremity interventions.
Dynamic Modeling of the Ball-on-Flexible Beam Using Euler–Lagrangian Formulation
Authors: Choi Du-Soon , Chung Seong Youb , Ryu Ji-Chul
Published: December 2023

Nonprehensile manipulation involves moving objects without physical grasping using methods such as rolling, sliding, pushing, and throwing. In the context of rolling manipulation, a novel nonconventional type manipulator, referred to as the ball-on-flexible beam system, is presented in this paper. A flexible beam with multiple linear actuating rods attached to the underside of it can be controlled to move an overlying ball using rolling manipulation. Since the absence of physical grasping in nonprehensile manipulation often requires taking into account the dynamics of the system, we focus on the derivation of the dynamic model of the ball-on-flexible beam in this paper. The dynamic model is derived using the Euler–Lagrangian formulation. In the calculation of the kinetic and potential energies of the beam and the ball, the deflection of the flexible beam is taken into account based on the Euler–Bernoulli beam theory. The accuracy of the derived model is verified through a finite element analysis (FEA) case study.
Swirl Enhancement Effect on Turbine Rim Seal Performance
Authors: Choi Mingeun , Goo Bonhan , Cho GeonHwan , Song Seung Jin
Published: December 2023

In gas turbines, sealing flow is extracted from the high-pressure compressor and supplied into the turbine wheel-space to suppress hot gas ingestion. Such hot gas ingestion is thought to be driven by the difference in either the static pressure or swirl between the mainstream and wheel-space flows. For the first time, experiments have been conducted in a low-speed single-stage axial turbine with a single-radial clearance rim seal and a “swirler” on the rotor disk. The objective is to evaluate the impact of enhanced wheel-space flow swirl on the rim seal performance. The swirler does not affect the mainstream flow. In the wheel-space, however, the swirler reduces static pressure; increases swirl; and improves rim seal performance (i.e., reduces the minimum sealing flowrate needed for hot gas ingestion prevention). Thus, the seal performance improvement occurs with increased difference in pressure and reduced difference in swirl between the mainstream and wheel-space flows. Therefore, it can be inferred that the rim seal performance depends more strongly on swirl than pressure. Preliminary gas turbine cycle performance studies indicate that net cycle efficiency benefits can be obtained.
ADVISE: Accelerating the Creation of Evidence Syntheses for Global Development Using Natural Language Processing-Supported Human-Artificial Intelligence Collaboration
Authors: Edwards Kristen M. , Song Binyang , Porciello Jaron , Engelbert Mark , Huang Carolyn , Ahmed Faez
Published: December 2023

When designing evidence-based policies and programs, decision-makers must distill key information from a vast and rapidly growing literature base. Identifying relevant literature from raw search results is time and resource intensive, and is often done by manual screening. In this study, we develop an artificial intelligence (AI) agent based on a bidirectional encoder representations from transformers (BERT) model and incorporate it into a human team designing an evidence synthesis product for global development. We explore the effectiveness of the human–AI hybrid team in accelerating the evidence synthesis process. To further improve team efficiency, we enhance the human–AI hybrid team through active learning (AL). Specifically, we explore different sampling strategies, including random sampling, least confidence (LC) sampling, and highest priority (HP) sampling, to study their influence on the collaborative screening process. Results show that incorporating the BERT-based AI agent into the human team can reduce the human screening effort, i.e., the number of documents that humans need to screen, by 68.5% compared to the case of no AI assistance and by 16.8% compared to the industry-standard case of using a frequency-based language model and support vector machine-based classifier for identifying 80% of all relevant documents. When we apply the HP sampling strategy, the human screening effort can be reduced even more: by 78.3% for identifying 80% of all relevant documents compared to no AI assistance. We apply the AL-enhanced human–AI hybrid teaming workflow in the design process of three evidence gap maps for U.S. Agency for International Development and find it to be highly effective. These findings demonstrate how AI can accelerate the development of evidence synthesis products and promote timely evidence-based decision-making in global development.
Entrepreneurial Bricolage and Innovation in Sport for Development and Peace Organizations
Authors: Andersson Fredrik O. , Svensson Per G. , Faulk Lewis
Published: December 2023

Many sport for development and peace organizations operate with limited resources and in low-resource environments. While resource constraints impede some organizations, others demonstrate an adaptive behavior, known as bricolage, to repurpose and flexibly engage existing resources to accomplish their goals. In this study, we ask what distinguishes organizations that engage in bricolage from others. We specifically test whether sport for development and peace nonprofits that engage in bricolage are more likely to engage in social innovation, and we test those findings against organizational size, age, and characteristics of organizations’ operating environments. Using data from an international sample of 161 sport for development and peace nonprofits, we find that organizations employing greater levels of bricolage also demonstrate significantly higher levels of innovation, except for process-focused innovations, which are significantly associated with environmental turbulence. Organizational size itself does not appear to influence the use of bricolage or the relationship between bricolage and innovation.
GluD1 binds GABA and controls inhibitory plasticity
Authors: Piot Laura , Heroven Christina , Bossi Simon , Zamith Joseph , Malinauskas Tomas , Johnson Chris , Wennagel Doris , Stroebel David , Charrier Cécile , Aricescu A. Radu , Mony Laetitia , Paoletti Pierre
Published: December 2023

Fast synaptic neurotransmission in the vertebrate central nervous system relies primarily on ionotropic glutamate receptors (iGluRs), which drive neuronal excitation, and type A γ-aminobutyric acid receptors (GABA
A
Rs), which are responsible for neuronal inhibition. However, the GluD1 receptor, an iGluR family member, is present at both excitatory and inhibitory synapses. Whether and how GluD1 activation may affect inhibitory neurotransmission is unknown. In this work, by using a combination of biochemical, structural, and functional analyses, we demonstrate that GluD1 binds GABA, a previously unknown feature of iGluRs. GluD1 activation produces long-lasting enhancement of GABAergic synaptic currents in the adult mouse hippocampus through a non-ionotropic mechanism that is dependent on trans-synaptic anchoring. The identification of GluD1 as a GABA receptor that controls inhibitory synaptic plasticity challenges the classical dichotomy between glutamatergic and GABAergic receptors.
Delivering drugs with microrobots
Authors: Nelson Bradley J. , Pané Salvador
Published: December 2023

Biomedical microrobots could overcome current challenges in targeted therapies
Far-right election win worries Dutch academics
Authors: de Vrieze Jop
Published: December 2023

A government led by Geert Wilders could restrict international students and scrap key climate policies
Tumor-killing viruses score rare success in late-stage trial
Authors: Leslie Mitch
Published: December 2023

Bladder cancer results suggest that after decades of failure, the viruses could finally reach their potential
Population pharmacokinetics and target attainment analysis of vancomycin after intermittent dosing in adults with cystic fibrosis
Authors: Yellepeddi Venkata K. , Lindley Bryn , Radetich Emi , Kumar Shaun , Bhakta Zubin , Leclair Laurie , Parrot Madison , Young David C.
Published: December 2023

Vancomycin is the first-line agent to treat pulmonary infections caused by methicillin-resistant
Staphylococcus aureus
(MRSA) in people with cystic fibrosis (PwCF). However, there is no consensus on vancomycin initial dosing in this population among health institutions, and there is a large variability in initial dosing across the United States. In this study, we characterized the pharmacokinetics (PK) of vancomycin in PwCF using a population PK approach. The clinical PK data to develop the population PK model were obtained from vancomycin therapeutic monitoring data from PwCF undergoing treatment for infections due to MRSA. The population PK model was then used to perform comprehensive Monte Carlo simulations to evaluate the probability of target attainment (PTA) of 12 different initial dosing scenarios. The area under the curve to minimum inhibitory concentration (MIC) ratio ≥400 mg*h/L and <650 mg*h/L were used as efficacy and toxicity targets for PTA analysis. A total of 181 vancomycin plasma concentrations were included in the analysis. A one-compartment model with first-order elimination best described the data. Weight significantly influenced the vancomycin PK (
P
< 0.05). In the final model, clearance was estimated as 5.52 L/h/70 kg, and the volume of distribution was 31.5 L/70 kg. The PTA analysis showed that at MIC = 1 µg/mL, doses 1,500 q8h and 2,000 q12h showed the highest %PTA in achieving both efficacy and toxicity targets. The PTA results from this study may potentially inform the initial dosing regimens of vancomycin to treat pulmonary infections due to MRSA in PwCF.
Bacteriophage infection and killing of intracellular
Mycobacterium abscessus
Authors: Schmalstig Alan A. , Wiggins Andrew , Badillo Debbie , Wetzel Katherine S. , Hatfull Graham F. , Braunstein Miriam
Published: December 2023

Mycobacterium abscessus
is a nontuberculous mycobacteria that contributes to the decline and death of patients with lung diseases such as cystic fibrosis and other muco-obstructive airway diseases.
M. abscessus
is challenging to treat due to its extensive antibiotic resistance and ability to survive inside mammalian cells. An alternative to antibiotics is the therapeutic use of bacteriophages (phages). There are recent cases of phage therapy being used to treat
M. abscessus
infections in people under compassionate-use conditions. However, little is known about the ability of phages to kill bacteria, such as
M. abscessus
, which reside in an intracellular environment. Here, we used
M. abscessus
strains and phages from recent phage therapy cases to determine if phages can enter mammalian cells and if they can infect and kill intracellular
M. abscessus
. Using fluorescence microscopy, we demonstrate phage uptake by macrophages and lung epithelial cells, and we further demonstrate phage infection of intracellular
M. abscessus
with fluorescent reporter phages. Transmission electron microscopy was additionally used to image phage infection of intracellular
M. abscessus
. Together, these findings provide the first visualizations of phage-
M. abscessus
interactions in an intracellular environment. Finally, we show that phage treatment can significantly reduce the intracellular burden of
M. abscessus
in a manner that depends on both the specific phage and mammalian cell type involved. These results demonstrate the potential to use phage therapy to treat intracellular bacteria, specifically
M. abscessus
, while also highlighting the importance of prescreening phage therapy candidates for activity in an intracellular environment.

IMPORTANCE

As we rapidly approach a post-antibiotic era, bacteriophage (phage) therapy may offer a solution for treating drug-resistant bacteria.
Mycobacterium abscessus
is an emerging, multidrug-resistant pathogen that causes disease in people with cystic fibrosis, chronic obstructive pulmonary disease, and other underlying lung diseases.
M. abscessus
can survive inside host cells, a niche that can limit access to antibiotics. As current treatment options for
M. abscessus
infections often fail, there is an urgent need for alternative therapies. Phage therapy is being used to treat
M. abscessus
infections as an option of last resort. However, little is known about the ability of phages to kill bacteria in the host environment and specifically in an intracellular environment. Here, we demonstrate the ability of phages to enter mammalian cells and to infect and kill intracellular
M. abscessus
. These findings support the use of phages to treat intracellular bacterial pathogens.
Integrated Re-Os, Ar/Ar, and U-Pb geochronology directly dates the timing of mineralization at the Mina Justa and Marcona deposits, Peru
Authors: Rodríguez-Mustafa María A. , Simon Adam C. , Holder Robert M. , Stein Holly , Kylander-Clark Andrew R.C. , Jicha Brian R. , Blakemore Daniel , Machado Edson L.B.
Published: December 2023

Iron oxide–copper–gold (IOCG) and iron oxide–apatite (IOA) deposits are important sources of Cu and Fe, respectively. They contain abundant Fe-oxides and may contain Au, Ag, Co, rare earth elements (REEs), U, Ni, and V as economically important by-products. In Peru, the Mina Justa IOCG deposit is located next to the giant Marcona IOA deposit. Constraining the timing of Fe and Cu mineralization at Mina Justa is fundamental to understanding the duration and type of processes that generated this mineral deposit, and ultimately to testing the genetic link with other deposits in the area. Previous authors used alteration minerals to indirectly date Cu mineralization at Mina Justa at around 100 Ma. We report Ar/Ar dates of actinolite, U-Pb dates of magnetite, apatite, and titanite collected by in situ laser-ablation–multicollector–inductively coupled plasma–mass spectrometry, and Re-Os thermal ionization mass spectrometry dates for sulfides. These results indicate that Cu mineralization at Mina Justa occurred at ca. 160 Ma and that Fe mineralization is older and coeval with the neighboring Marcona IOA deposit, consistent with Cu mineralization overprinting IOA-style mineralization at Mina Justa.
Multicentric evaluation of a specific intrathecal anti-Treponema pallidumIgG index as a diagnostic biomarker of neurosyphilis: results from a retro-prospective case–control study
Authors: Alberto Chloé , Lambeng Nathalie , Deffert Christine , Breville Gautier , Gayet-Ageron Angèle , Lalive Patrice , Calmy Alexandra , Coste Alix , Papadimitriou-Olivgeris Matthaios , Braun Dominique , Lienhard Reto , Bosshard Philipp Peter , Fontao Lionel , Toutous Trellu Laurence
Published: December 2023

Background and objectives

The diagnosis of neurosyphilis (NS) lacks a true ‘gold standard’, making the diagnosis challenging while consequences of a misdiagnosis are potentially severe. The aim of this study was to evaluate the diagnostic performance of measuring an antibody index (AI) for the intrathecal synthesis of specific anti-Treponema pallidum(T. pallidum) IgG for the diagnosis of NS.

Methods

Specific anti-T. pallidumIgG were measured simultaneously in paired cerebrospinal fluid (CSF)–serum samples collected retrospectively and prospectively between 2007 and 2022, from patients suspected of NS, in Switzerland. An AI was calculated to account for blood–brain barrier integrity. Area under the receiver operating characteristic curve, sensitivity/specificity and positive/negative predictive values of AI test were estimated. Two NS definitions were used: NS1 included patients with NS suspicion presenting with neurological symptoms and/or acute neurosensory signs, and positiveT. PallidumHemagglutinations Assay (TPHA)/T. pallidumparticle agglutination assay (TPPA) serology and CSF-TPHA/TPPA ≥320, and either CSF-leucocytes >5 cells/mm3and/or CSF-protein >0.45 g/L and/or a reactive CSF-venereal disease research laboratory (VDRL)/rapid plasma reagin (RPR) test. NS2 included patients with suspected NS presenting with acute ocular and/or otologic symptoms, and positive TPHA/TPPA serology, and a favourable response to NS treatment. Controls were patients diagnosed with any other central nervous system (CNS) pathologies and with positive TPHA/TPPA serology.

Results

The study included 71 NS (43 NS1 and 28 NS2) and 110 controls. With a threshold of ≥1.7, sensitivity and specificity of the specific AI test were 90.7% (CI 77.7 to 97.4) and 100% (CI 96.7 to 100.0), respectively, for NS1 and 14.3% (CI 4 to 32.7) and 100% (CI 96.7 to 100.0) for NS2. In patients suspected of NS with a CNS involvement (NS1 group), NS could be confirmed by the positivity of this specific AI.

Conclusions

Measurement of an intrathecal synthesis index of specific anti-T. pallidumIgG in patients with CSF inflammatory signs appears to be a valuable diagnostic test. However, in otic or ocular syphilis, presenting few CSF abnormalities, AI is not sufficient alone to confirm NS diagnosis.

Trial registration

Swiss Association of Research Ethics Committees number 2019-00232.
Short peripheral blood leukocyte telomere length in rheumatoid arthritis-interstitial lung disease
Authors: Doyle Tracy J , Juge Pierre-Antoine , Peljto Anna L , Lee Seoyeon , Walts Avram D , Esposito Anthony Joseph , Poli Sergio , Gill Ritu , Hatabu Hiroto , Nishino Mizuki , Dellaripa Paul F , Weinblatt Michael E , Shadick Nancy A , Demoruelle M Kristen , Sparks Jeffrey A , Rosas Ivan O , Granger Benjamin , Deane Kevin D , Crestani Bruno , Wolters Paul J , Dieudé Philippe , Lee Joyce S
Published: December 2023

Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.
Physarum polycephalum: Smart Network Adaptation
Authors: Le Verge-Serandour Mathieu , Alim Karen
Published: December 2023

Life evolved organisms to adapt dynamically to their environment and autonomously exhibit behaviors. Although complex behaviors in organisms are typically associated with the capability of neurons to process information, the unicellular organism Physarum polycephalum disabuses us by solving complex tasks despite being just a single although gigantic cell shaped into a mesmerizing tubular network. In Physarum, smart behaviors arise as network tubes grow or shrink due to the mechanochemical coupling of contractile tubes, fluid flows, and transport across the network. Here, from a physicist's perspective, we introduce the biology and active chemomechanics of this living matter network. We review Physarum's global response in migration and dynamic state to its environment before revisiting its network architecture and flow and transport patterns. Finally, we summarize recent studies on storing and processing information to mount well-informed behaviors.
Electrocatalytic Degradation of Acyclovir by Three-Dimensional Porous Lead Dioxide Anodes: Condition Optimization, Kinetic Analysis and Degradation Mechanisms
Authors: Wei Lanlan , Wang Lin , Chen Lu , Ru Yifan , Shen Lianzhong , Ye Yu , Li Zhouwei , Dai Qizhou
Published: December 2023

A three-dimensional porous lead dioxide electrode (3D-PbO2) was developed by the template electrodeposition approach. Polystyrene microspheres were prepared by microemulsion polymerization, and then the polystyrene template was loaded on the PbO2 electrode by electrodeposition. Finally, a porous structure was formed by removing the template. Under these optimized conditions, the degradation of acyclovir could achieve complete removal, while the removal of COD was 29.59%. The electrochemical degradation process of acyclovir was consistent with the proposed primary reaction kinetics. The 3D-PbO2 electrode was comprehensively characterized using SEM, XRD, and XPS techniques. The SEM analysis revealed the presence of well-defined porous structures on the electrode surface, while the XRD results indicated a reduction in electrode crystal sizes. Additionally, the XPS analysis demonstrated a higher proportion of reactive oxygen species on the 3D-PbO2 electrode. The electrochemical properties of the electrode were investigated using CV and EIS. The experimental findings demonstrate that the 3D-PbO2 electrode exhibits a higher oxygen evolution potential and lower charge transfer resistance than the conventional PbO2 electrode. This study presents a viable approach to enhance the electrochemical oxidation performance of lead dioxide.
Limitation of cerebral blood flow by increased venous outflow resistance in elevated ICP
Authors: Zadka Yuliya , Rosenthal Guy , Doron Omer , Barnea Ofer
Published: December 2023

The goal of this study was to investigate the effects of venous compression caused by elevated intracranial pressure (ICP) due to cerebral edema, validated through animal experiments. The flow control zone model highlights the impact of cerebral venous compression on cerebral blood flow (CBF) during elevated ICP. The cerebral venous outflow resistance-to-cerebrovascular resistance ratio may indicate when venous outflow compression becomes the dominant factor limiting CBF. CBF regulation descriptions should consider how arterial or venous factors may predominantly influence flow in different clinical scenarios.
Niosomal-Based Drug Delivery Platforms: A Promising Therapeutic Approach to Fight Staphylococcus aureus Drug Resistance
Authors: Hemmati Jaber , Chegini Zahra , Arabestani Mohammad Reza
Published: December 2023

Staphylococcus aureus, a prominent bacterial pathogen, presents formidable medical challenges owing to its rapid development of resistance. The emergence of multidrug resistant (MDR) S. aureus strains has become a pressing concern for healthcare systems, driving researchers to explore novel therapeutic strategies for managing infections associated with this pathogen. In this pursuit, niosomal-based platforms have emerged as promising candidates to effectively target S. aureus and fight conventional antimicrobial resistance. Niosomes comprise a bilayer membrane formed by nonionic surfactants, which can encapsulate both hydrophilic and hydrophobic drugs. These nanoparticles are known as vesicular delivery systems and have many advantages, such as low cost, less toxicity, and more flexibility and stability. Moreover, niosomes, being an effective drug delivery system, can directly interact with the bacterial cell envelope, thereby enhancing the pharmacokinetic activities of drugs at infected sites. A niosome-based delivery system can effectively treat S. aureus infections by destroying the biofilm community, increasing intracellular targeting, and enhancing the antibacterial activity. The main mechanisms of action of niosomes against resistant S. aureus strains involve the ability to resist enzymatic degradation, controlled release profile, and targeted drug delivery, which can provide an effective dosage of antimicrobial agents at the site of actions. In addition, niosomes have the potential to transfer wide-spectrum materials from different classes of antibiotics to nonantibiotic antimicrobial agents, such as natural compounds, antimicrobial peptides, and metallic nanoparticles. The combination of polymeric materials in the structure of a niosomal formulation could improve their bioavailability, loading capacity, and therapeutic efficacy for different applications. Furthermore, niosomes could find application in photodynamic therapy, offering a promising alternative to conventional treatments for eradicating drug-resistant S. aureus isolates. Finally, niosomal nanocarriers can be developed for delivering the drugs to desired sites by different routes of administration and could be considered a powerful strategy for overcoming the therapeutic obstacles caused by MDR S. aureus.