bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Characterization of a Bladeless Air Compressor
Authors: Tiwari Ravi Nath , Reggio Federico , Ferrari Mario Luigi , De Paepe Ward , Traverso Alberto
Published: September 2024

The Tesla compressor is an innovative technology that offers a unique approach to fluid compression. Unlike traditional compressors that use rotating blades, bladeless compressors utilize closely spaced disks to create compression. The purpose of this article is to design a prototype Tesla air compressor with optimal design parameters and investigate the performance and loss characteristics based on numerical analysis and experimental demonstration. The prototype model has been numerically investigated at different rotational speeds, and the results have been compared with those obtained in experiments. Computational fluid dynamics (CFD) simulations indicate that the rotor-only efficiency is greater than 90% at very low mass flowrates, while the coupling of the rotor and volute leads to a total-to-static efficiency of approximately 58% (without losses) at 14 g/s. At a nominal mass flow of 4 g/s, the highest total-to-static pressure ratio would be around 1.27. Experimental results indicate leakage losses greatly reduce net mass flow, while pressure ratio values are in good agreement with CFD predictions. During this experiment, a maximum isentropic efficiency of 32.4% is measured. Indeed, the prototype included ventilation and leakage losses, which were not modeled in the CFD analysis. It is remarkable that the compressor does not show any unstable behavior down to zero mass flow (closed valve test), where the CFD and the experiment show consistent pressure ratios. An estimation of the losses from end-wall friction and leakage flow is carried out using numerical simulations at different exit radial clearances. Increasing radial clearance results in an increase in leakage and end-wall power loss, the latter being driven mainly by the axial clearance with the casing, which remained unchanged. To minimize leakage, a Teflon ring has been used as a first measure. Numerical calculations have indicated that the leakage rate is approximately 6 g/s at design speed. A brush seal-type solution can improve the sealing system to reduce leakage.
Insights Into Turbocharger Centrifugal Compressor Stability Using High-Fidelity Computational Fluid Dynamics and a Novel Impeller Diffusion Factor
Authors: Liu Yiming , Spence Stephen , Horsley John , Mann Stuart , Stuart Charles
Published: September 2024

Turbocharger technologies are widely applied in the modern automotive industry to meet increasingly stringent carbon emission standards. To support the continuous enhancement of these tactics, delivering improvement to the performance and stability of turbocharger compressors at low mass flowrate regimes is of paramount importance. This chapter investigates the stability of a turbocharger compressor stage equipped with a ported shroud, using high-fidelity computational fluid dynamics (CFD) simulations. It was found that the recirculated flow passing through the ported shroud device had primary influence on the flow condition in the vicinity of the impeller tip region (80–100% span). This discovery facilitated the definition of a modified impeller diffusion factor (DF), which was applied to the CFD results for three different compressor geometry configurations to lead to the provision of quantitative metrics for impeller stability. Furthermore, the observed change in the limiting impeller DF along the compressor surge line indicated that the dominant components governing the instability of the entire stage had switched, i.e., the stalling behavior of the compressor stage had transitioned from impeller dominated stall to vaneless diffuser dominated stall. Additionally, the limiting impeller DF clearly showed that one of the compressor configurations with a change in the hub endwall recess around the rear of the impeller improved the impeller stability by 3%. By comparison, another configuration with a change to strut geometry in the ported shroud recirculation channel reduced the impeller stability by 10%. The present work addressed the gap in the understanding about the stability of different compressor configurations equipped with a ported shroud, and was useful for determining the changes in compressor global and local instability through a quantitative parameter based on a modified definition of DF.
A primer on participatory research for health professional education
Authors: Paxino Julie , Eppich Walter , Bolton Joanne , Woodward-Kron Robyn , Denniston Charlotte
Published: September 2024

Participatory research methodologies are gaining traction in health professional education research (HPER) due to their ability to foster collaboration and inclusivity with communities involved in or affected by the issues being studied. This paper provides an introduction for researchers new to participatory research in HPER. It aims to guide researchers in the thoughtful integration of participatory methods into their research practices. We define participatory research as a diverse approach that engages health professionals, students, patients and other community members as co-researchers actively involved in shaping the research process. Drawing on examples from the field, we explore the potential benefits of participatory research, including the co-production of knowledge, improved relevance of findings and enhanced impact on practice. However, we also acknowledge the complexities and challenges, including the need for researcher flexibility, ethical considerations and appropriate levels of participation, depending on project goals and funding constraints. To support researchers, we outline key questions that prompt critical deliberation when considering participatory approaches. Ultimately, this paper encourages researchers to reflect on the epistemic shifts required to adopt participatory methodologies and to consider how these approaches can foster more inclusive, collaborative and meaningful contributions to health professional education and research.
Complete mitochondrial genomes of two Phoretic mites (Parasitidae: Poecilochirus) on burying beetle: Genome characterization and phylogenetic analysis
Authors: Zhao Pei-Yue , Liang Lang , Yi Tian-Ci , Bai Ming
Published: September 2024

A pair of intriguing phoretic instances are the burying beetle and Poecilochirus mites. Their interaction is environment-dependent and can be either mutualistic or antagonistic hostile depending on various biological and physical circumstances. In this study, we sequenced the complete mitogenomes of two Poecilochirus mite species, P. davydovae and P. mrciaki, which are associated with burying beetles, using Illumina HiSeq sequencing technology. Each mitochondrial genome comprised 37 typical genes, including 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and one control region (CR). The size of these mitogenomes were determined to be 14,489 bp and 14,517 bp, respectively. These two mitochondrial genomes contain a notable AT bias in their nucleotide composition, with positive AT and negative GC skews in the deflection index of mitochondrial genomes, and a unique incomplete stop codon T- in both protein-coding genes. The DHU arm of tRNA-S1 (AGN) only forms a simple loop structure, while the secondary structures of 21 tRNA genes in both species showed the conventional cloverleaf structures, like those of most metazoans. The phylogenetic tree of Gamasina was constructed using Maximum likelihood and Bayesian inference based on two rRNA genes and 13 PCGs. Based on the existing data, the Parasitidae forms a monophyletic, and Poecilochirus and Parasitus are closely related, possibly belonging to the same genus.
Bodily Uncertainty, Precarious Body: An Embodied Narrative of a Physical Education Teacher From an Autobiographical Perspective
Authors: González-Calvo Gustavo , Gerdin Göran
Published: September 2024

School physical education (PE) is influenced by different discourses that play a crucial role not only in the (re)production of PE practices but also in shaping teacher subjectivities. This paper aims to explore how a PE teacher responds to, lives, and negotiates his embodied professional subjectivity over time. To achieve this, we employ an autobiographical approach to delve into the first author’s life story of becoming and being a PE teacher over time, grappling with the unease generated by the knowledge that his body may have an “expiry date.” Through narrative analysis, we discuss and reflect on the complex experience of teaching a physical and corporeal subject such as PE, focusing on four themes: (1)reflecting his life as a PE teacher“the young, healthy and athletic body,” (2) “the uncertain body,” (3) “the precarious body,” and (4) “the shut-up and just-do-it body.”
Challenges and opportunities of phage therapy for
Klebsiella pneumoniae
infections
Authors: Kou Xin , Yang Xiaoyu , Zheng Rui
Published: September 2024

Traditional antibiotics have been effective in many cases. However, the rise in multidrug-resistant bacteria has diminished their therapeutic efficacy, signaling the dawn of an era beyond antibiotics. The challenge of multidrug resistance in
Klebsiella pneumoniae
is particularly critical, with increasing global mortality and resistance rates. Therefore, the development of alternative therapies to antibiotics is urgently needed. Phages, which are natural predators of bacteria, have inherent advantages. However, comprehensive information on
K. pneumoniae
phages is lacking in current literature. This review aims to analyze and summarize relevant studies, focusing on the present state of phage therapy for
K. pneumoniae
infections. This includes an examination of treatment methodologies, associated challenges, strategies, new phage technologies, clinical trial safety and efficacy, regulatory issues, and future directions for phage therapy development. Enhancing phage technology is crucial for addressing the evolving threat of multidrug-resistant
K. pneumoniae
.
The human gut microbiome in health and disease: time for a new chapter?
Authors: Lee Jee-Yon , Bays Derek J. , Savage Hannah P. , Bäumler Andreas J.
Published: September 2024

The gut microbiome, composed of the colonic microbiota and their host environment, is important for many aspects of human health. A gut microbiome imbalance (gut dysbiosis) is associated with major causes of human morbidity and mortality. Despite the central part our gut microbiome plays in health and disease, mechanisms that maintain homeostasis and properties that demarcate dysbiosis remain largely undefined. Here we discuss that sorting taxa into meaningful ecological units reveals that the availability of respiratory electron acceptors, such as oxygen, in the host environment has a dominant influence on gut microbiome health. During homeostasis, host functions that limit the diffusion of oxygen into the colonic lumen shelter a microbial community dominated by primary fermenters from atmospheric oxygen. In turn, primary fermenters break down unabsorbed nutrients into fermentation products that support host nutrition. This symbiotic relationship is disrupted when host functions that limit the luminal availability of host-derived electron acceptors become weakened. The resulting changes in the host environment drive alterations in the microbiota composition, which feature an elevated abundance of facultatively anaerobic microbes. Thus, the part of the gut microbiome that becomes imbalanced during dysbiosis is the host environment, whereas changes in the microbiota composition are secondary to this underlying cause. This shift in our understanding of dysbiosis provides a novel starting point for therapeutic strategies to restore microbiome health. Such strategies can either target the microbes through metabolism-based editing or strengthen the host functions that control their environment.
Autoproteolytic mechanism of CdiA toxin release reconstituted
in vitro
Authors: Tiu Ana Katrina Y. , Conroy Grace C. , Bobst Cedric E. , Hagan Christine L.
Published: September 2024

Contact-dependent inhibition (CDI) is a mechanism of interbacterial competition in Gram-negative bacteria. Bacteria that contain CDI systems produce a large, filamentous protein, CdiA, on their cell surfaces. CdiA contains a C-terminal toxin domain that is transported across the outer membranes (OMs) of neighboring bacteria. Once inside a target bacterium, the toxin is released from the CdiA protein via a proteolytic mechanism that has not been well characterized. We have developed an
in vitro
assay to monitor this toxin release process and have identified several conserved amino acids that play critical roles in the autocatalytic mechanism. Our results indicate that a hydrophobic, membrane-like environment is required for CdiA to fold, and the proteolysis occurs through an asparagine cyclization mechanism. Our
in vitro
assay thus provides a starting point for analyzing the conformational state of the CdiA protein when it is inserted into a target cell’s OM and engaged in transporting the toxin across that membrane.

IMPORTANCE

It is challenging to develop new antibiotics capable of killing Gram-negative bacteria because their outer membranes are impermeable to many small molecules. Some Gram-negative bacteria, however, deliver much larger protein toxins through the outer membranes of competing bacteria in their environments using contact-dependent inhibition (CDI) systems. How these toxins traverse the outer membranes of their targets is not well understood. We have therefore developed a method to study the toxin delivery process in a highly simplified system using a fragment of a CDI protein. Our results indicate that the CDI protein assembles into a structure in the target membrane that catalyzes the release of the toxin. This CDI protein fragment enables further studies of the toxin delivery mechanism.
Early extensional salt tectonics controls deep-water sediment dispersal
Authors: Oppo Davide , Jackson Christopher A.-L. , Maselli Vittorio
Published: September 2024

Predicting the distribution of sedimentary facies during the early stages of deformation of salt-detached continental margins is key to constraining the location and stratigraphic architecture of hydrocarbon and CO2 reservoirs, as well as to understanding the oceanic carbon cycle. Despite its importance, we still have a relatively poor understanding of salt-sediment interactions during the early phases of extensional salt tectonics, mainly because subsequent salt-related deformation and/or deep burial of the related stratigraphic succession means the related deposits are poorly imaged in seismic reflection data and/or not penetrated by borehole data. We investigated the interplay between early extension-related salt deformation and deep-water sediment dispersal using 3-D seismic reflection data from the northern Levant Basin offshore Lebanon. Our results indicate that salt tectonics has two contrasting impacts: Whereas slope-parallel faults favor early sediment transfer along downslope-oriented corridors to the abyssal plain, slope-normal faults and ramp-syncline basins trap land-derived sediments, hampering or delaying their transport to the abyssal plain. These results help refine source-to-sink models of turbidite systems developing in young salt basins, highlighting the crucial role of extensional tectonics in controlling sediment dispersal and the development of intra-slope depocenters and emphasizing the impact of fault strike, ramp-syncline basin evolution, and salt thinning. Our study has significant implications for predicting the location of deep-water coarse-grained sediment and the preservation of land-derived organic carbon in mature, more structurally complex, salt basins.
Sarin exposure, mortality and cancer incidence in UK military veterans involved in human experiments at Porton Down: 52-year follow-up
Authors: Archer Gemma , Keegan Thomas , Wessely Simon , Venables Katherine M , Fear Nicola T
Published: September 2024

Objectives

We investigated whether UK military personnel exposed to sarin during the ‘Service Volunteer Programme’ at Porton Down had increased rates of mortality or cancer incidence over a 52-year follow-up.

Methods

A historical cohort study assembled from UK military records, comprising male veterans exposed to sarin during the ‘Service Volunteer Programme’ at Porton Down, UK (n=2975) and a comparison group of similar veterans who did not attend (n=2919). Mortality and cancer incidence data were obtained from national registries up to December 2019. Analysis was conducted using Cox regression adjusted for age, year of birth and service characteristics.

Results

Over a median follow-up of 52.2 years (range 2 days to 74.6 years), 1598 (53.7%) sarin-exposed veterans and 1583 (54.3%) non-exposed veterans died. Adjusted HRs for all-cause mortality were raised for any sarin exposure (HR=1.08, 95% CI 1.01 to 1.16), two or more exposures (HR=1.25, 95% CI 1.04 to 1.49) and higher doses (air >15 mg.min/m3) (HR=1.15, 95% CI 1.02 to 1.30). For cause-specific mortality, sarin exposure was associated with deaths from ‘other’ circulatory diseases (excludes ischaemic and cerebrovascular diseases) (HR=1.41, 95% CI 1.06 to 1.87) and alcohol-attributable deaths (HR=2.66, 95% CI 1.40 to 5.07). There was no association between sarin exposure and overall cancer incidence (HR=1.01, 95% CI 0.93 to 1.10), but cancer incidence was higher for alcohol-related neoplasms (HR=1.24, 95% CI 1.01 to 1.51).

Conclusions

Sarin exposure was associated with increased rates of mortality over a 50-year follow-up. The strongest associations were observed for deaths attributable to alcohol and ‘other’ circulatory diseases.
Application and Research of Mine Safety Management Strategy Based on the BP Network Model
Authors: Wan Xiangyun , Tang Yiju , Liu Sheng
Published: September 2024

Coal mine safety production is undoubtedly the cornerstone of the healthy, table, and sustainable development of China’s coal industry, and it also profoundly affects the effective implementation of the national energy strategy. In this context, exploring the application of network models in coal mine safety management strategies not only has significant practical significance, but also has profound development value. By integrating these factors, we can have a more comprehensive understanding of the causes of coal mine safety accidents and provide a scientific basis for formulating effective preventive measures. By collecting and analyzing various data in real-time during the coal mine production process, we can promptly detect abnormal situations, predict potential safety risks, and take corresponding measures for intervention and prevention. This dynamic monitoring and early warning mechanism can not only improve the safety of coal mine production, but also enhance the efficiency and efficiency of coal mine production. In the analysis process, we particularly focused on the advantages of Back Propagation (BP) neural network models in mine safety evaluation. BP neural network models can handle uncertainty and fuzzy information and have strong learning and adaptive capabilities. By constructing a safety evaluation model based on BP neural networks, we can more accurately evaluate the safety risks in the coal mine production process, providing strong support for formulating more scientific and reasonable safety management strategies.
The Potential Role of Artemisinins Against Neurodegenerative Diseases
Authors: Xia Lei , Qiu Yiqiong , Li Junjie , Xu Mingliang , Dong Zhifang
Published: September 2024

Artemisinin (ART) and its derivatives, collectively referred to as artemisinins (ARTs), have been approved for the treatment of malaria for decades. ARTs are converted into dihydroartemisinin (DHA), the only active form, which is reductive in vivo. In this review, we provide a brief overview of the neuroprotective potential of ARTs and the underlying mechanisms on several of the most common neurodegenerative diseases, particularly considering their potential application in those associated with cognitive and motor impairments including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). ARTs act as autophagy balancers to alleviate AD and PD. They inhibit neuroinflammatory responses by regulating phosphorylation of signal transduction proteins, such as AKT, PI3K, ERK, NF-κB, p38 MAPK, IκBα. In addition, ARTs regulate GABAergic signaling in a dose-dependent manner. Although they competitively inhibit the binding of gephyrin to GABAergic receptors, low doses of ARTs enhance GABAergic signaling. ARTs can also inhibit ferroptosis, activate the Akt/Bcl-2, AMPK, or ERK/CREB pathways to reduce oxidative stress, and maintain mitochondrial homeostasis, protecting neurons from oxidative stress injury. More importantly, ARTs structurally combine with and suppress β-Amyloid (A[Formula: see text]-induced neurotoxicity, reduce P-tau, and maintain O-GlcNAcylation/Phosphorylation balance, leading to relieved pathological changes in neurodegenerative diseases. Collectively, these natural properties endow ARTs with unique potential for application in neurodegenerative diseases.
Visualizing and Quantifying Electronic Accessibility in Composite Battery Electrodes using Electrochemical Fluorescent Microscopy
Authors: Negrete Karla , Tang Maureen H.
Published: September 2024

Electronic connections between active material particles and the conductive carbon binder domain govern high-energy commercial Li-ion batteries' rate capability and lifetime (LIB). This work develops an in situ electrochemical fluorescent microscopy (EFM) technique that maps fluorescence intensity to these local electronic connections. Specifically, rapid redox kinetics of an electrofluorophore translates to reaction distributions limited by the electronic accessibility of battery electrode regions and individual active material particles. This technique can visualize hot spots, dead zones, and isolated particles on the electrode surface. EFM characterization of a series of LiNi0.33Mn0.33Co0.33O2 electrodes across processing parameters finds a significant negative correlation between the number of disconnected active particles and the rate capability. This low-cost technique provides quantitative mesoscale characterization of commercial LIB electrodes with fast throughput (<60 s) to facilitate rapid research and development and provide manufacturing quality control.
Perspective – Leveraging the Versatility of DNA Origami and Electrochemistry for New Sensing Modalities
Authors: Lukeman Philip S.
Published: September 2024

Electrochemical biosensors are uniquely positioned to offer real-time in vivo molecular sensing due to their robustness to both biofluids and contaminants found in biofluids, and their adaptability for the detection of different analytes by their use of oligonucleotides or proteins as binding moiety. DNA Origami, the folding of a long DNA scaffold by hundreds of shorter oligonucleotide “staple” strands, allows the construction of nanoscale molecular objects of essentially arbitrary form, flexibility and functionality. We describe work at the intersection of these two fields and their—hopefully—bright future together.
A Cross‐Sectional Survey of Swedish Primary Healthcare Nurses’ Discontent With Their Current Job
Authors: Karlsson Elin , Karlsson Nadine , Fernemark Hanna , Seing Ida , Skagerström Janna , Brulin Emma , Nilsen Per
Published: September 2024

Nursing staff turnover is an increasing problem for healthcare globally. In Sweden, the shortage of nurses in primary healthcare has increased significantly in recent years. This development is alarming because primary healthcare, both in Sweden and internationally, is responsible for a large part of healthcare. The aim of this study was to explore working conditions (change fatigue, leadership climate, and social support from colleagues) and characteristics of primary care nurses who are discontent with their current job, i.e., those with high turnover intentions and poor job satisfaction in Sweden. This was a cross‐sectional survey of 466 registered nurses working in Swedish primary healthcare. Data were analyzed using descriptive statistics and logistic regression. The results demonstrate that 21.1% of the responding nurses are discontent with their current job and have considered quitting. Being discontent had significant associations with poor leadership climate (p < 0.001), lack of social support from colleagues (p < 0.001), change fatigue (p < 0.001), poor health (p < 0.001), and working more than 40 h per week (p = 0.02). The results have implications for how healthcare organizations structure the work of nurses in primary healthcare and how they can attract and retain future staff to these workplaces.
Hermitian Matrix Diagonalization and Its Symmetry Properties
Authors: Chiu S. H. , Kuo T. K.
Published: September 2024

A Hermitian matrix can be parametrized by a set consisting of its determinant and the eigenvalues of its submatrices. We established a group of equations which connect these variables with the mixing parameters of diagonalization. These equations are simple in structure and manifestly invariant in form under the symmetry operations of dilatation, translation, rephasing, and permutation. When applied to the problem of neutrino oscillation in matter, they produced two new “matter invariants” which are confirmed by available data.
Antibacterial Effect of Silver Nanoparticles on Polymicrobial Biofilms in Endodontics: Systematic Review and Meta Analysis
Authors: Olivares-Acosta Iván , Romero-Sánchez Lilian Beatriz , Marín Nuria Patiño , Orozco Marco Felipe Salas
Published: September 2024

This systematic review investigates the antibacterial effects of silver nanoparticles (AgNPs) on polymicrobial biofilms in endodontics, emphasizing their potential enhancement of traditional treatment methods. Recognizing the limitations of current endodontic disinfectants in fully eradicating complex biofilms, this study focuses on the synergistic potential of AgNPs to improve antimicrobial efficacy. Utilizing a systematic approach based on PRISMA guidelines, the review draws on studies from databases like PubMed, Web of Science, and SCOPUS up to 2024. The included research specifically examines the role of AgNPs in various endodontic applications against resilient biofilms, adhering to strict inclusion criteria that demand clear methodology and measurable outcomes. The results suggest that AgNPs can significantly augment the biofilm disruption capabilities of conventional antimicrobials, potentially due to their ability to modify the biofilm matrix and enhance agent penetration. However, the effectiveness varies depending on the nanoparticle concentration and application technique, indicating a need for further optimized studies. In conclusion, while AgNPs show promise in enhancing endodontic antimicrobial protocols, additional in vivo research is necessary to establish standardized, effective, and safe clinical applications. The review highlights the complex interactions between nanoparticle properties and biofilm biology, underscoring the importance of further investigation in this area.
Supplementary information from Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis
Authors: Ek Torben , Ibrahim Raghda R. , Vogt Hartmut , Georgantzi Kleopatra , Träger Catarina , Gaarder Jennie , Djos Anna , Rahmqvist Ida , Mellström Elisabeth , Pujol-Calderón Fani , Vannas Christoffer , Hansson Lina , Fagman Henrik , Treis Diana , Fransson Susanne , Österlund Tobias , Chuang Tzu-Po , Verhoeven Bronte Manouk , Ståhlberg Anders , Palmer Ruth H. , Hallberg Bengt , Martinsson Tommy , Kogner Per , Dalin Martin
Published: September 2024

Supplementary figures 1-4, supplementary tables 1-4, and supplementary case information
Supplementary data 3 from Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis
Authors: Ek Torben , Ibrahim Raghda R. , Vogt Hartmut , Georgantzi Kleopatra , Träger Catarina , Gaarder Jennie , Djos Anna , Rahmqvist Ida , Mellström Elisabeth , Pujol-Calderón Fani , Vannas Christoffer , Hansson Lina , Fagman Henrik , Treis Diana , Fransson Susanne , Österlund Tobias , Chuang Tzu-Po , Verhoeven Bronte Manouk , Ståhlberg Anders , Palmer Ruth H. , Hallberg Bengt , Martinsson Tommy , Kogner Per , Dalin Martin
Published: September 2024

Sequencing results, ALK hotspot mutation sites
Figure 6 from Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis
Authors: Ek Torben , Ibrahim Raghda R. , Vogt Hartmut , Georgantzi Kleopatra , Träger Catarina , Gaarder Jennie , Djos Anna , Rahmqvist Ida , Mellström Elisabeth , Pujol-Calderón Fani , Vannas Christoffer , Hansson Lina , Fagman Henrik , Treis Diana , Fransson Susanne , Österlund Tobias , Chuang Tzu-Po , Verhoeven Bronte Manouk , Ståhlberg Anders , Palmer Ruth H. , Hallberg Bengt , Martinsson Tommy , Kogner Per , Dalin Martin
Published: September 2024

Early detection of relapse and emergence of an HRAS p.Q61L mutation during lorlatinib treatment in a patient (patient 5) with ALK p.F1174L-positive neuroblastoma. A, MIBG scans at initial diagnosis, at the first relapse, after 4 months of lorlatinib (partial response), and at second relapse after 10.5 months of lorlatinib treatment. B, Allele frequency of HRAS p.Q61L in tumor tissue at different time points. C, Levels of ctDNA. D, Clinical tumor markers, values are normalized to the upper reference limit (URL) for each marker. CGA, chromogranin A; Lorla, lorlatinib; ND, not detected.
Data from Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis
Authors: Ek Torben , Ibrahim Raghda R. , Vogt Hartmut , Georgantzi Kleopatra , Träger Catarina , Gaarder Jennie , Djos Anna , Rahmqvist Ida , Mellström Elisabeth , Pujol-Calderón Fani , Vannas Christoffer , Hansson Lina , Fagman Henrik , Treis Diana , Fransson Susanne , Österlund Tobias , Chuang Tzu-Po , Verhoeven Bronte Manouk , Ståhlberg Anders , Palmer Ruth H. , Hallberg Bengt , Martinsson Tommy , Kogner Per , Dalin Martin
Published: September 2024

Abstract
Patients with anaplastic lymphoma kinase (ALK)–driven neuroblastoma may respond to tyrosine kinase inhibitors, but resistance to treatment occurs and methods currently used for detection of residual disease have limited sensitivity. Here, we present a national unselected cohort of five patients with relapsed or refractory ALK-driven neuroblastoma treated with lorlatinib as monotherapy and test the potential of targeted circulating tumor DNA (ctDNA) analysis as a guide for treatment decisions in these patients. We developed a sequencing panel for ultrasensitive detection of ALK mutations associated with neuroblastoma or resistance to tyrosine kinase inhibitors and used it for ctDNA analysis in 83 plasma samples collected longitudinally from the four patients who harbored somatic ALK mutations. All four patients with ALK p.R1275Q experienced major responses and were alive 35 to 61 months after starting lorlatinib. A fifth patient with ALK p.F1174L initially had a partial response but relapsed after 10 months of treatment. In all cases, ctDNA was detected at the start of lorlatinib single-agent treatment and declined gradually, correlating with clinical responses. In the two patients exhibiting relapse, ctDNA increased 9 and 3 months, respectively, before clinical detection of disease progression. In one patient harboring HRAS p.Q61L in the relapsed tumor, retrospective ctDNA analysis showed that the mutation appeared de novo after 8 months of lorlatinib treatment. We conclude that some patients with relapsed or refractory high-risk neuroblastoma show durable responses to lorlatinib as monotherapy, and targeted ctDNA analysis is effective for evaluation of treatment and early detection of relapse in ALK-driven neuroblastoma.
Significance:
We present five patients with ALK-driven relapsed or refractory neuroblastoma treated with lorlatinib as monotherapy. All patients responded to treatment, and four of them were alive after 3 to 5 years of follow-up. We performed longitudinal ctDNA analysis with ultra-deep sequencing of the ALK tyrosine kinase domain. We conclude that ctDNA analysis may guide treatment decisions in ALK-driven neuroblastoma, also when the disease is undetectable using standard clinical methods.
HLTF/SERPINE1 Axis Plays a Crucial Pro-Oncogenic Role in the Progression from Cervical Precancerous Lesions to Cervical Carcinoma in vitro
Authors: Wang Yong , Tan Yudi , Yang Shasha , Wei Jinkong , Wei Yuying , Chen Junying
Published: September 2024

Objectives: Cervical carcinoma (CC) is prevalent among women worldwide with increasing risk. Finding effective methods for treating CC is of utmost importance. The aim of this study was to investigate the effect of SERPINE1 on the progression of cervical precancerous lesions to CC. Design: This study used transcriptome sequencing and in vitro cell line. Participants/Materials: Cervical precancerous lesions and CC samples and human cervical epithelial immortalized cell line H8, human CC cell lines HeLa, and CaSki were involved in this study. Setting and Methods: Next-generation sequencing was applied to identify 100 differentially expressed genes from cervical precancerous lesions and CC samples. With the application of the Search Tool for the Retrieval of Interacting Genes (STRING) database, we carried out the protein-protein interaction network analysis, thus screening out serine protease inhibitor clade E member 1 (SERPINE1) with significant upregulation in CC cells. The helicase-like transcription factor (HLTF) was predicted as the upstream transcription factor using Human Transcription Factor Database (HumanTFDB). The chromatin immunoprecipitation (ChIP) experiment was conducted to validate the interaction between SERPINE1 and HLTF. The immunohistochemistry was employed to determine the expression of SERPINE1 and HLTF in CC tissues. Following the upregulation or downregulation of SERPINE1 and HLTF, the real-time quantitative reverse transcription polymerase chain reaction was carried out to assess mRNA expression levels of SERPINE1 and HLTF in cells. Cell viability, migration, and invasion were evaluated using MTT assay, cell scratch assay, and Transwell assay, respectively. Western blot analysis was conducted to assess changes in the expression levels of matrix metalloproteinases and proteins related to epithelial-mesenchymal transition (EMT). Results: The ChIP experiment confirmed the interaction between HLTF and SERPINE1. HLTF and SERPINE1 were upregulated in CC tissues and cells, and silencing SERPINE1 inhibited the EMT process and viability, migration, and invasion of CC cells. However, overexpression of SERPINE1 in CC cells showed the opposite trend. Rescue experiments demonstrated that silencing HLTF repressed CC cell viability, migration, and invasion, which could be restored by overexpressing SERPINE1. Limitations: The effect of the HLTF/SERPINE1 axis on CC malignant progression has not been confirmed by in vivo experiments. Conclusion: HLTF transcriptionally activates SERPINE1, promoting the progression from cervical precancerous lesions to CC.
Linear measurements, body proportions, and biomechanical insights: morphological analysis of arabian horses in São Paulo, Brazil
Authors: Siqueira Renata Farinelli de , Cordeiro Nathália de Matos Sousa
Published: September 2024

Este estudo, conduzido com meticuloso rigor científico, avaliou medições lineares, proporções corporais e índices corporais em cavalos Árabes para uma melhor compreensão de sua morfologia, aptidão e biomecânica. A amostra foi composta por 168 cavalos Árabes puros adultos (76 machos e 92 fêmeas) alojados em uma fazenda de cavalos no estado brasileiro de São Paulo. Vinte e seis medições lineares foram realizadas usando uma fita métrica, a partir das quais os índices morfométricos foram calculados. Os dados foram meticulosamente analisados utilizando análise de variância e o teste de Tukey, com o nível de significância fixado em 5%. Os resultados deste estudo, respaldados por uma robusta análise estatística, revelaram que os cavalos Árabes são animais geométricos, ligeiramente alongados (ectomorfos), cavalos de trabalho leve e podem suportar cargas equivalentes a 25% de seu peso corporal. O comprimento dorsolombar, da garupa e da coxa mais longos do que as medições lineares dos membros anteriores sugerem uma desproporção corporal. Resultados semelhantes foram relatados em outras raças de cavalos atléticas, como o Quarto de Milha e o Cavalo de Esporte Brasileiro, uma vez que o exercício físico requer mais propulsão do que a equitação de lazer. Os índices dactilo- torácico e de habilidade colocam os cavalos Árabes na categoria de cavalos de trabalho leve, apoiando esta hipótese. Algumas medições e índices diferiram entre os gêneros, com os machos superando as fêmeas na maioria dos casos, exceto no comprimento corporal. As medições lineares se mostraram ferramentas essenciais para a avaliação do movimento e da conformação. Os cavalos Árabes desta amostra não atenderam aos padrões de conforto para equitação, mas foram considerados ter um bom potencial atlético com base em medições lineares e proporções.
Fé em Cena: representatividade na ficção seriada brasileira
Authors: Malta Francisco
Published: September 2024

This study aims to explore the universe of telenovelas as serialized fiction and the elements that drive and make it unique dramatic texts. The complexity of this authorial work, predominantly generated by the author, gives telenovelas a refinement of language and, consequently, a specific aesthetic effect that turns words into images and a space for discussion on social media. This complex process addresses a variety of trends from different professionals working on the concept of the audiovisual chapter. As corpus, we will analyze the telenovela “Vai na fé,” written by Rosane Svartman for TV Globo, and discuss the issue of representation in its plot. To foster discussion, the authors Marlyse Meyer, Fredéric Martel, Maria Immacolata Lopes, among other authors, will be considered.
Entre páginas e telas: a transformação da crítica contemporânea de telenovela no Brasil
Authors: Lima Mariana Marques de
Published: September 2024

O artigo objetiva abordar como a crítica de telenovela se desenvolveu nos principais jornais impressos brasileiros, a partir da década de 1970, apresentando dois principais críticos: Helena da Silveira e Artur da Távola. A partir do mapeamento teórico acerca do que se entende por crítica no meio literário, abordamos a concepção atual de crítica de televisão e de telenovela e como, atualmente, ela tem sido realizada no país no âmbito digital. Apontamos que a transição da crítica entre o analógico (representado pelo jornalismo impresso) e o digital (com os sites de notícias) modificou a maneira como ela é efetuada. Concluímos que a crítica de telenovela contemporânea corresponde ao conjunto de análises sobre a trama, que é passível de alteração a cada episódio, e que, hoje, está em constante diálogo com seu público leitor/espectador.
The Neurophysiological Costs of Learning in a Noisy Classroom: An Ecological Virtual Reality Study
Authors: Levy Orel , Korisky Adi , Zvilichovsky Yair , Zion Golumbic Elana
Published: September 2024

Many real-life situations can be extremely noisy, which makes it difficult to understand what people say. Here, we introduce a novel audiovisual virtual reality experimental platform to study the behavioral and neurophysiological consequences of background noise on processing continuous speech in highly realistic environments. We focus on a context where the ability to understand speech is particularly important: the classroom. Participants (n = 32) experienced sitting in a virtual reality classroom and were told to pay attention to a virtual teacher giving a lecture. Trials were either quiet or contained background construction noise, emitted from outside the classroom window. Two realistic types of noise were used: continuous drilling and intermittent air hammers. Alongside behavioral outcomes, we measured several neurophysiological metrics, including neural activity (EEG), eye-gaze and skin conductance (galvanic skin response). Our results confirm the detrimental effect of background noise. Construction noise, and particularly intermittent noise, was associated with reduced behavioral performance, reduced neural tracking of the teacher's speech and an increase in skin conductance, although it did not have a significant effect on alpha-band oscillations or eye-gaze patterns. These results demonstrate the neurophysiological costs of learning in noisy environments and emphasize the role of temporal dynamics in speech-in-noise perception. The finding that intermittent noise was more disruptive than continuous noise supports a “habituation” rather than “glimpsing” hypothesis of speech-in-noise processing. These results also underscore the importance of increasing the ecologically relevance of neuroscientific research and considering acoustic, temporal, and semantic features of realistic stimuli as well as the cognitive demands of real-life environments.
Lesion Mapping of the Spelling System's Central Cognitive Functions
Authors: Purcell Jeremy , Wiley Robert , Shea Jennifer , Rosenberg Samuel , Martin Randi , Rapp Brenda
Published: September 2024

The goal of this study was to improve our understanding of the central cognitive functions of spelling: orthographic long-term memory, phoneme-to-grapheme conversion, and orthographic working memory. To do so, we present a methodological innovation to support vector regression lesion-symptom mapping, which uses a deficit spectrum index to identify brain areas associated with one of each pair of spelling deficits. Using this approach, we find evidence of distinct neural substrates that are selectively associated with each of the three central spelling components, supporting a componential functional architecture of spelling. The specific findings provide neural evidence relevant to various debates regarding the nature of these key cognitive processes and their relationships, namely, questions concerning the degree to which phoneme-to-grapheme conversion is distinct from general phonological processing, the existence of distinct lexical and sublexical routes for translating sound to print, and whether or not working memory is distinct from long-term memory or embedded within it. A better understanding of these issues has clinical implications in terms of our understanding of dysgraphic deficits and approaches to intervention.
Virtual Voting in rfmos: A Procedural Odyssey at the Indian Ocean Tuna Commission
Authors: Schatz Valentin , Perraudeau Maia
Published: September 2024

This article examines, from the perspective of international institutional law, the variety of procedural problems which arose following an online vote by secret ballot taken by the Indian Ocean Tuna Commission (iotc) in 2021. By providing a detailed case-study of this novel instance of practice and the challenges it represents, this article aims to contribute to a better understanding of the institutional governance and procedural legal framework of regional fisheries management organizations (rfmo s). It first analyses the vote and the challenge to its validity. This article then constructs a taxonomy of the various procedural irregularities that were found to have occurred, the responsibility of institutional actors for their occurrence, and their legal consequences. The final substantive sections of this article examine how the iotc ultimately dealt with the situation and what potential role the available dispute settlement procedures could have had in addressing the discussed procedural irregularities.
Temporal scaling of carbon emission accumulations and rates of the Meso-Cenozoic hyperthermal events: implication to the Anthropocene global warming
Authors: HU XIU-MIAN , JIANG JING-XIN , CAI YUAN , HAN ZHONG , XU YI-WEI
Published: September 2024

Anthropocene global warming is largely associated with fossil fuel carbon emissions. Temporal scaling provides a way to place current carbon emissions on a geological scale. The scaling of carbon emissions at the onset of hyperthermal events suggests that we might anticipate higher carbon emission rates over longer time scales than what we currently observe in the Anthropocene. However, this inference is uncertain due to limited data concerning the accumulations and time intervals of carbon emissions of Meso-Cenozoic hyperthermal events. While on the long-time hyperthermal-event scales of several to hundreds of kiloyears, modern carbon accumulations and emission rates are 9 times greater than those of the hyperthermal-event emissions. The present-day carbon release can be effectively compared to the onset of hyperthermal events through temporal scaling. If current carbon emission trends persist, we may reach the carbon emission thresholds for hyperthermal events in one to three hundred years, getting an intensified hydrological cycle, enhanced continental weathering and ocean acidification. And if the situation gets worse, we may reach the upper limit of the carbon emission threshold for hyperthermal events (e.g., Permian-Triassic Boundary event, PTB) with a biotic mass extinction over four to thirteen hundred years. This study offers new insights into current carbon emissions from a temporal scale perspective, enhancing our understanding of contemporary climate change.
Aspergillus capibaribensis (Eurotiales, Trichocomaceae), a new species in section Cremei
Authors: FELIPE MARIA TAMARA C. , BARBOSA RENAN N. , BEZERRA JADSON D.P. , MAGALHÃES OLIANE M.C. , PAIVA LAURA M. , SOUZA-MOTTA CRISTINA M.
Published: September 2024

In this study we describe a new species of Aspergillus in section Cremei deposited in the URM culture collection (Micoteca URM Profa. Maria Auxiliadora Cavalcanti) of the Departamento de Micologia, Universidade Federal de Pernambuco (Recife, Pernambuco, Brazil). Another strain was obtained from samples taken from pollen pots inside nests of Melipona scutellaris (stingless bee). Morphological and phylogenetic evidence based on sequencing of ITS rDNA, BenA, CaM and rpb2 markers supported the description of taxonomic novelty. Aspergillus capibaribensis sp. nov. is morphologically similar and phylogenetically close to A. flaschentraegeri - the distinctive features are uniseriate and hyaline conidiophores, short and smooth conidia and smaller vesicles compared to the micromorphological structures of A. flaschentraegeri. This record also expanded the knowledge of species in Aspergillus section Cremei in a tropical country such as Brazil.
A NEW SPECIES OF SIGMOIDOTROPIS (PAPILIONOIDEAE, LEGUMINOSAE) FROM ATLANTIC FOREST, EASTERN BRAZIL
Authors: SANTOS FELIPE DA SILVA , RIBEIRO CAROLINA LIMA , OLIVEIRA JOSÉ FLORENCIO CERQUEIRA , SOARES KLEBER DE ARAÚJO , QUEIROZ LUCIANO PAGANUCCI DE
Published: September 2024

The Brazilian Atlantic Forest is one of the world’s most biodiverse regions and a key center of endemism for various plant groups. Here, we propose the new species Sigmoidotropis snakiae, which is found in the high-altitude Atlantic Forests of southeastern Brazil. Environmental niche modeling indicates potential areas of distribution that are distinct from the known range of the species, suggesting that these current areas may be remnants of a once-larger, interconnected habitat. The significance of conservation areas such as Parque Nacional do Caparaó and Parque Estadual do Forno Grande for the preservation of this species is emphasized. Sigmoidotropis snakiae, together with S. grandiflora, is only the second species of the genus identified in the Brazilian Atlantic Forest.