bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Establishment of Butterfly-Type Bifurcation Set Equation for Chip-Splitting Catastrophe in Cylindrical Turning
Authors: Xu Mingxian , Xiong Liangshan , Cheng Dongdong , Zhang Shaonan
Published: January 2025

The catastrophic phenomenon in chip-splitting that occurs during cylindrical turning can lead to a significant reduction in cutting force and cutting power, which has great potential for utilization. The establishment of a bifurcation set equation that can predict the occurrence of chip-splitting catastrophe is the basis for controlling and utilizing it. Based on this, this paper proposes a method to establish a butterfly-type bifurcation set equation for chip-splitting catastrophe in cylindrical turning using experimental data on critical conditions for chip-splitting catastrophe. This method is based on the regularized bifurcation set equation of butterfly-type catastrophe, and uses the tool rake angle γ0, tool included angle εr, feedrate f and depth of cut ap as actual control variables. Firstly, 246 sets of observation experiments on chip-splitting catastrophe phenomenon when cylindrically turning 6061 T6 aluminum workpieces with PCD straight double-edged turning tools were designed and completed, and 152 sets of experimental data on critical conditions for chip-splitting catastrophe were obtained. Secondly, the diffeomorphism transformation between actual control variables and theoretical control variables is assumed to be a set of linear mapping functions with undetermined coefficients, and the mapping function is used to convert the actual critical control points obtained through critical condition experimental data into theoretical critical control points. Finally, using optimization techniques, the undetermined coefficients of the mapping function are solved and substituted into the regularized butterfly-type catastrophe bifurcation set equation to obtain the cylindrical turning chip-splitting catastrophe bifurcation set equation represented by actual control variables. The verification experiment found that there is good consistency between the critical depth of cut value of chip-splitting catastrophe predicted by the established equation and the actual measured value.
Investigating Nonlinear Neurodynamics Hierarchical Evolution: Novel Insights for Control and Computation
Authors: Shettigar Nandan , Suh C. Steve
Published: January 2025

Biological neural networks engage upon a variety of complex tasks proficiently demonstrated by the wealth, flair and grace of many human undertakings (technological or social). A deeper insight upon the fundamental physical and mathematical architecture can enable reproducing these capabilities in current technological applications. Not all neural dynamic capabilities are desirable; however, there are certain subsects of tasks which are performed with high accuracy, speed and minimal energy consumption such as visual or audio recognition, autonomous driving (or other machinery operations), generative languages and behaviors capable of transmitting information demonstrating varying degrees of intelligence. The objective of this paper is to provide a fundamental approach towards feasibly characterizing relevant neural dynamics whose architectures endows intelligent behavioral operations. Furthermore, this can elucidate how the underlying information processing functions enabling reproducing its desirable characteristics (low power consumption and high reliability) in our own technical operations. Thus, quantifying the microscopic energetic consumption and defining the macroscopic level of information entropy will enable identifying a physical structure that can maximize influence upon the global state of information entropy upon an open system while minimizing the associated energetic consumptions. Enabling such a structure allows maximizing the r information capacity of a system given finite constraints on resources. Therefore, this approach can further provide insight towards generating novel computing architectures which address the current bottlenecks in conventional computing schemes. That is, alleviation memory and CPU interaction bottlenecks which are increasingly becoming apparent as it becomes more and more difficult to keep up the pace of Moore’s Law. The importance is further exemplified by the exponentially increasing computational demands in the recent advent of artificial intelligence.
Kinetics and mechanism of surface plutonium oxycarbide formation
Authors: Roussel Paul
Published: January 2025

Initial studies of plutonium oxycarbide surface films on metal have been reported to slow the rate of metal corrosion in dry conditions. Exploiting this property presents a unique opportunity in the safe storage of this radioactive and toxic material; however, more fundamental work is required. The plutonium, carbon, and oxygen ratio of these surface films is investigated here using x-ray photoelectron spectroscopy (XPS) and is shown to be nonstoichiometric. The origin of the carbon in the formation of surface plutonium oxycarbide films is probed using a combination of XPS, x-ray diffraction, and secondary ion mass spectrometry and is shown to occur from the metal interstitial impurity. The kinetics of plutonium oxycarbide film growth for a specific bulk carbon concentration have been determined.
Challenges and insights in growing epitaxial FeSn thin films on GaAs(111) substrate using molecular beam epitaxy
Authors: Chatterjee P. , Nord M. , He J. , Meier D. , Brüne C.
Published: January 2025

FeSn is a room-temperature antiferromagnet composed of alternating Fe3Sn kagome layers and honeycomb Sn layers. Its distinctive lattice allows the formation of linearly dispersing Dirac bands and topological flatbands in its electronic band structure, positioning FeSn as an ideal candidate for investigating the interplay between magnetism and topology. In this study, we investigate the epitaxial growth of FeSn thin films on GaAs(111) substrates by molecular beam epitaxy. A significant challenge in this growth process is the diffusion of Ga and As from the substrate into the deposited films and the diffusion of Fe into the substrate. This diffusion complicates the formation of a pure FeSn phase. Through a comprehensive analysis—including reflection high energy electron diffraction, high-resolution x-ray diffraction, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometry—we demonstrate that the Sn evaporation temperature plays a critical role in influencing crystallinity, surface morphology, and magnetic behavior of the films. Our results show that while it is difficult to grow a single-phase FeSn film on GaAs due to diffusion, optimizing the Sn evaporation temperature can enhance the dominance of the FeSn phase, partially overcoming these challenges.
The spinorial ball: A macroscopic object of spin-1/2
Authors: Bernard-Bernardet Samuel , Dumas Emily , Apffel Benjamin
Published: January 2025

In quantum physics lectures, half-integer spins are generally introduced as “objects that do not come back to their original state after one full turn but that do after two.” As a consequence, students often consider this behavior to be purely quantum mechanical. However, spin-1/2 is above all a geometrical property of the rotations group and can, therefore, also have practical consequences at the macroscopic scale. To illustrate this, we introduce and describe in this work a new pedagogical tool named the spinorial ball. It allows students to concretely manipulate a macroscopic 1/2-spin, which helps them to build intuition as to how the latter behaves under rotations. This object can also be used to introduce several general concepts from the theory of Lie groups, such as group homomorphism and homotopy classes of loops through the example of the groups SU(2) and SO(3). The spinorial ball provides a macroscopic visualization of all these concepts, which are ubiquitous in quantum physics.
Investigating the influence of a bubble curtain on the underwater sound wave field generated by offshore pile driving
Authors: Bohne Tobias , Rolfes Raimund
Published: January 2025

Pile driving for offshore wind turbines typically generates high sound levels in the water column. Bubble curtains are frequently employed to protect marine fauna. This study aims to investigate the effect of a bubble curtain on the generated sound wave field. A recently developed seismo-acoustic model was extended by incorporating an established acoustic model of the bubble curtain. Subsequently, a detailed analysis of the sound wave field at an offshore wind farm construction site was conducted using both simulated and measured data. The results indicate a distance- and depth-dependent insertion loss, with reductions of approximately 2 to 4 dB observed at greater distances from the pile. For a more detailed analysis, a metric based on the concept of transmission loss was introduced. This demonstrates that the insertion loss caused by a bubble curtain can be formulated as a sum of two components: the loss due to the interaction between the bubbles and the sound wave field, and the altered bottom loss resulting from the scattering of the sound wave as it passes through the bubble curtain. Analysis of the simulation data highlights that sound scattering and the resulting altered bottom loss significantly contribute to the efficiency of the bubble curtain.
Antarctic krill vertical migrations modulate seasonal carbon export
Authors: Smith A. J. R. , Wotherspoon S. , Ratnarajah L. , Cutter G. R. , Macaulay G. J. , Hutton B. , King R. , Kawaguchi S. , Cox M. J.
Published: January 2025

Vertical migrations by marine organisms contribute to carbon export by consumption of surface phytoplankton followed by defecation in the deep ocean. However, biogeochemical models lack observational data, leading to oversimplified representation of carbon cycling by migrating organisms, such as Antarctic krill (
Euphausia superba
). Using a numerical model informed by 1 year of acoustic observations in the East Antarctic, we estimated the total particulate organic carbon (POC) flux from krill fecal pellets to be 9.68 milligrams of carbon per square meter per day (mg C m
−2
day
−1
). A maximum of 25% of krill migrated to depths >200 m with a strong seasonality component, transporting <10% of the total krill POC flux (1.28 mg C m
−2
day
−1
) to the deep ocean. Accurate carbon flux estimates are essential to inform climate policy and mitigation strategies, and models that include vertical migration will overestimate carbon export if this seasonality is not captured.
Highly multiplexed spatial transcriptomics in bacteria
Authors: Sarfatis Ari , Wang Yuanyou , Twumasi-Ankrah Nana , Moffitt Jeffrey R.
Published: January 2025

Single-cell decisions made in complex environments underlie many bacterial phenomena. Image-based transcriptomics approaches offer an avenue to study such behaviors, yet these approaches have been hindered by the massive density of bacterial messenger RNA. To overcome this challenge, we combined 1000-fold volumetric expansion with multiplexed error-robust fluorescence in situ hybridization (MERFISH) to create bacterial-MERFISH. This method enables high-throughput, spatially resolved profiling of thousands of operons within individual bacteria. Using bacterial-MERFISH, we dissected the response of
Escherichia coli
to carbon starvation, systematically mapped subcellular RNA organization, and charted the adaptation of a gut commensal
Bacteroides thetaiotaomicron
to micrometer-scale niches in the mammalian colon. We envision that bacterial-MERFISH will be broadly applicable to the study of bacterial single-cell heterogeneity in diverse, spatially structured, and native environments.
Physico-chemical properties and substrate specificity of α-(1→3)-
d
-glucan degrading recombinant mutanase from
Trichoderma harzianum
expressed in
Penicillium verruculosum
Authors: Sinitsyna Olga A. , Volkov Pavel V. , Zorov Ivan N. , Rozhkova Alexandra M. , Emshanov Oleg V. , Romanova Yulia M. , Komarova Bozhena S. , Novikova Natalia S. , Nifantiev Nikolay E. , Sinitsyn Arkady P.
Published: January 2025

The gene
mutAW
encoding
Trichoderma harzianum
fungus mutanase (MutA, GH71 family, α-1,3-glucanase, EC 3.2.1.59) was cloned and heterologously expressed by the highly productive
Penicillium verruculosum
fungus.
P. verruculosum MutA
strain secreted crude enzyme preparations with the recombinant MutA content of 40% of the total secreted protein, and the specific activity increased 150 folds compared to that of enzyme preparation obtained by the host strain. Homogeneous MutA had molecular mass of 70 kDa and displayed maximum of the activity on mutan at pH 5.0 and 50°C, with
K
m
and
k
cat
being 1.0 g/L and 30 s
−1
, respectively. At 40-50°C, the MutA was stable for at least 3 h. Glucose was the main product of long-term mutan hydrolysis. HPLC analysis of hydrolysis product of oligo-α-(1→3)-D-glucosides bearing UV-detectable
N
-
trans
-cinnamoyl residue in the aglycon clearly indicated that MutA has an endo-processive hydrolytic mode of action. It was demonstrated that MutA can destroy the polysaccharide matrix of both gram-positive and gram-negative pathogenic bacteria biofilms.

IMPORTANCE

The manuscript describes the properties of a novel recombinant GH71 mutanase Mut A from
Trichoderma harzianum
. Gene
mutAW
encoding mutanase was heterologously expressed in the host strain
Penicillium verruculosum
B1-537 (ΔniaD). The recipient strain has a high secretory ability and allowed to obtain preparations containing the target recombinant enzyme up to 80% of the total protein pool. MutA exhibited a high activity against mutan and negligible or zero activity toward other types of glucans including α-(1→4)-, β-(1→3)-, β-(1→4)-, and β-(1→6)-glucans. By using a series of synthetic oligo-α-(1→3)-D-glucosides, we demonstrated that MutA is an endo-processive enzyme, which hydrolyzes the internal glucosidic bonds and releases glucose from the reducing end sliding into the non-reducing end. MutA recognizes tetrasaccharide as a minimal substrate and hydrolyzes it to trisaccharide and glucose. The effectiveness of the use of MutA for the destruction of clinical isolates of gram-positive and gram-negative bacteria is also described.
Laboratory evolution in
Novosphingobium aromaticivorans
enables rapid catabolism of a model lignin-derived aromatic dimer
Authors: Allemann Marco N. , Kato Ryo , Carper Dana L. , Hochanadel Leah H. , Alexander William G. , Giannone Richard J. , Kamimura Naofumi , Masai Eiji , Michener Joshua K.
Published: January 2025

Lignin contains a variety of interunit linkages, leading to a range of potential decomposition products that can be used as carbon and energy sources by microbes. β-O-4 linkages are the most common in native lignin, and associated catabolic pathways have been well characterized. However, the fate of the mono-aromatic intermediates that result from β-O-4 dimer cleavage has not been fully elucidated. Here, we used experimental evolution to identify mutant strains of
Novosphingobium aromaticivorans
with improved catabolism of a model aromatic dimer containing a β-O-4 linkage, guaiacylglycerol-β-guaiacyl ether (GGE). We identified several parallel causal mutations, including a single nucleotide polymorphism in the promoter of an uncharacterized gene that roughly doubled the growth yield with GGE. We characterized the associated enzyme and demonstrated that it oxidizes an intermediate in GGE catabolism, β-hydroxypropiovanillone, to vanilloyl acetaldehyde. Identification of this enzyme and its key role in GGE catabolism furthers our understanding of catabolic pathways for lignin-derived aromatic compounds.

IMPORTANCE

Lignin degradation is a key step for both carbon cycling in nature and biomass conversion to fuels and chemicals. Bacteria can catabolize lignin-derived aromatic compounds, but the complexity of lignin means that full mineralization requires numerous catabolic pathways and often results in slow growth. Using experimental evolution, we identified an uncharacterized enzyme for the catabolism of a lignin-derived aromatic monomer, β-hydroxypropiovanillone. A single nucleotide polymorphism in the promoter of the associated gene significantly increased bacterial growth with either β-hydroxypropiovanillone or a related lignin-derived aromatic dimer. This work expands the repertoire of known aromatic catabolic genes and demonstrates that slow catabolism of lignin-derived aromatic compounds may be due to misregulation under laboratory conditions rather than inherent catabolic challenges.
The interplay between
Acinetobacter baumannii
ZigA and SltB promotes zinc homeostasis and cell envelope integrity
Authors: Critchlow Jeanette M. , Barraza Juan P. , Munneke Matthew J. , Krystofiak Evan , Green Erin R. , Skaar Eric P.
Published: January 2025

Acinetobacter baumannii
is an opportunistic human pathogen that acquires nutrient metals from the vertebrate host amid infection. During zinc (Zn) scarcity,
A. baumannii
upregulates the expression of the predicted Zn metallochaperone,
zigA
. Loss of
zigA
compromises fitness during Zn deficiency, highlighting its role in this condition. To assess the contribution of ZigA to Zn-deficient
A. baumannii
, a multiparallel transposon sequencing and genetic interaction mapping approach was used. Transposon insertions in
A1S_3027
, encoding a predicted soluble lytic transglycosylase that tailors the bacterial cell wall, were enriched in the Zn-starved Δ
zigA
transposon library. Based on previous studies as well as structural and sequence homology, we designated A1S_3027 as
s
oluble
l
ytic
t
ransglycosylase
B
(SltB). Further analyses revealed that inactivating
sltB
rescued Δ
zigA
fitness defects during Zn starvation. An
A. baumannii
Δ
zigA
Δ
sltB
mutant demonstrated altered cell envelope structures and increased cellular permeability, highlighting the roles of ZigA and SltB in maintaining cell envelope integrity. Furthermore, these mutants exhibited heightened resistance to β-lactam antibiotics and other cell wall-targeting agents. Alterations in cell envelope integrity in the Δ
zigA
Δ
sltB
mutant improved fitness in a murine pneumonia infection model, emphasizing the contribution of ZigA and SltB to
A. baumannii
pathogenesis. This study elucidates how functional interactions between ZigA and SltB modulate cell envelope integrity and pathogenesis of
A. baumannii
during Zn depletion. These findings reveal an interplay between metal homeostasis and cell envelope integrity, offering insights into how
A. baumannii
ZigA contributes to these critical cellular processes.
Gut phages and their interactions with bacterial and mammalian hosts
Authors: Godsil Marshall , Ritz Nathaniel L. , Venkatesh Siddarth , Meeske Alexander J.
Published: January 2025

The mammalian gut microbiome is a dense and diverse community of microorganisms that reside in the distal gastrointestinal tract. In recent decades, the bacterial members of the gut microbiome have been the subject of intense research. Less well studied is the large community of bacteriophages that reside in the gut, which number in the billions of viral particles per gram of feces, and consist of considerable unknown viral “dark matter.” This community of gut-residing bacteriophages, called the gut “phageome,” plays a central role in the gut microbiome through predation and transformation of native gut bacteria, and through interactions with their mammalian hosts. In this review, we will summarize what is known about the composition and origins of the gut phageome, as well as its role in microbiome homeostasis and host health. Furthermore, we will outline the interactions of gut phages with their bacterial and mammalian hosts, and plot a course for the mechanistic study of these systems.
MA104 cell line is permissive for human bocavirus 1 infection
Authors: Tang Jielin , Chen Sijie , Deng Yijun , Liu Junjun , Huang Dan , Fu Muqing , Xue Bao , Liu Canyu , Wu Chunchen , Wang Fan , Zhou Yuan , Yang Qi , Chen Xinwen
Published: January 2025

Human bocavirus 1 (HBoV1) has appeared as an emerging pathogen, causing mild to life-threatening respiratory tract infections, acute otitis media, and encephalitis in young children and immunocompromised individuals. The lack of cell lines suitable for culturing replicative viruses hinders research on HBoV1. Here, we characterized the susceptibility to HBoV1 of 29 human and 7 animal cell lines, and identified a permissive cell line, MA104. The complete HBoV1 life cycle was achieved in MA104 cells, including viral entry, complete replication, and infectious progeny virion production. Additionally, the suppression of the interferon pathway facilitated the viral genome replication in MA104 cells. RNA-sequencing showed that innate immunity, inflammation, the PI3K-Akt and MAPK signaling pathways, and the cellular membrane system were mobilized in response to HBoV1 infection. Overall, our study is the first to identify a cell line, MA104, that supports the complete HBoV1 life cycle, which will promote research on HBoV1 virology and pathogenesis and benefit drug and vaccine development.

IMPORTANCE

HBoV1 is an emerging pathogen that mainly causes respiratory tract infections, while the lack of cell lines suitable for culture replicative viruses hindered research on HBoV1. Here, we identify a permissive cell line for HBoV1 infection, MA104, and reveal that the complete life cycle of HBoV1 was supported in MA104 cells. Our findings provide a suitable cell model for the study of HBoV1 and explore its application for antiviral drug evaluation, which is vital for research on HBoV1 virology and pathogenesis, as well as for drug and vaccine development.
Surveillance for
Chlamydia trachomatis
variants escaping detection with the Aptima Combo 2 assay in Canada from 2019 to 2021
Authors: Roy Felicia , Beirnes Jennifer , LeBlanc Jason J. , Gibbons Suzanne , Sivro Aida , Severini Alberto ,   On behalf of the Canadian Public Health Laboratory Network (CPHLN) Chlamydia Variant Working Group
Published: January 2025

Nucleic acid amplification tests (NAATs) are the method of choice for
Chlamydia trachomatis
diagnosis, but these strategies are susceptible to target site mutations.
C. trachomatis
variants escaping detection with the Aptima Combo 2 (AC2) assay on the Hologic Panther instrument from 23S rRNA mutations have been reported in Nordic countries, England, Japan, and the United States. Given the potential for false negative results, this study investigated whether strains of
C. trachomatis
with AC2 target site mutations were present in Canada. Surveillance was conducted in Canadian laboratories from 2019 to 2021. Specimens suspected of AC2 target site mutations included those with low-value detections on the AC2 assay, with subsequent high-value detections on the Aptima Chlamydia Trachomatis (ACT) assay used for confirmatory testing. Specimens with AC2/ACT discrepant results were subjected to sequencing of the AC2 target (i.e., 23S rRNA). Sequencing revealed 15 (4.8%) diagnostic escape variants which were carrying either C1514T, G1523A, or G1526A mutations. All specimens with
a
diagnostic escape mutation were detected with a reformulated version of the AC2 assay. Overall, while the prevalence of
C. trachomatis
variants was rare, their presence in the Canadian population supports the use of the new AC2 kit formulation and the need for ongoing genetic surveillance for NAAT-based assays.

IMPORTANCE

Molecular tests are commonly used for the detection of sexually transmitted infections (STIs) like
Chlamydia trachomatis
. Mutations impacting
C. trachomatis
molecular target detection on the Hologic Panther AC2 assay have been reported in several countries, raising concerns about potential false negative results. This study showed
C. trachomatis
target detection failures in specimens submitted for
C. trachomatis
testing in Canadian laboratories from 2019 to 2021. A reformulated version of the AC2 molecular test is now available that can identify
C. trachomatis
strains harboring target site mutations that were impacted by the previous test formulation. While target site mutations were rare in Canada, revealing their presence is important to ensure accurate molecular detection of
C. trachomatis
with existing testing methods. This study supports ongoing genetic monitoring of
C. trachomatis
molecular test target sites, as well as the use of the reformulated test to avoid false negative results and subsequent transmissions.
Variation and assembly mechanisms of
Rhinolophus ferrumequinum
skin and cave environmental fungal communities during hibernation periods
Authors: Leng Haixia , Li Aoqiang , Li Zhongle , Hoyt Joseph R. , Dai Wentao , Xiao Yanhong , Feng Jiang , Sun Keping
Published: January 2025

Animal skin acts as the barrier against invasion by pathogens and microbial colonizers. Environmental microbiota plays a significant role in shaping these microbial communities, which, in turn, have profound implications for host health. Previous research has focused on characterizing microorganisms on bats’ skin and in their roosting environments, particularly bacterial communities. The emergence of white-nose syndrome, caused by the fungal-pathogen
Pseudogymnoascus destructans
, highlights the importance of understanding fungal dynamics in cave ecosystems and on bats’ skin. In this study, we employed ITS amplicon sequencing to investigate the fungal community associated with the skin of
Rhinolophus ferrumequinum
and surfaces within hibernacula. In addition, we utilized neutral community and null models to assess the relative importance of stochastic and deterministic processes in fungal community assembly. The infection status of
P. destructans
did not significantly impact fungal community composition either on bat skin or cave environments. However, fungal diversity was significantly higher in cave environments compared to bat skin. Notably, potentially inhibitory genera of fungal pathogens were present in both bats and cave environments during hibernation. Furthermore, the composition and structure of fungal communities on both bat skin and cave environments varied across hibernation periods. Our findings suggest neutral processes primarily drive the assembly of fungal communities associated with hibernating
R. ferrumequinum
and cave environments, with dispersal limitation exerting a significant influence. This study provides insights into the fungal communities associated with hibernating
R. ferrumequinum
and cave environments.

IMPORTANCE

Animal habitats provide sources and reservoirs for host microorganisms, making it critical to understand changes in microbial communities between habitats and hosts. While most studies have focused on bacterial microorganisms, research on fungal communities is lacking. This study investigated how community dynamics and assembly processes differ between the skin of hibernating
Rhinolophus ferrumequinum
and the cave environments under pathogen stress. We found significant differences in the composition and structure of the fungal communities between bat skin and roosting cave environments. Fungal genera with potential inhibitory effects on pathogens were found in all bat skin and cave environments. In addition, dispersal limitations during stochastic processes were a key factor in the formation of environmental fungal communities on bat skin and in caves. These findings offer new insights for exploring pathogen-host-environment-microbe interactions.
Fluid fluctuations assessed with artificial intelligence during the maintenance phase impact anti-vascular endothelial growth factor visual outcomes in a multicentre, routine clinical care national age-related macular degeneration database
Authors: Martin-Pinardel Ruben , Izquierdo-Serra Jordi , Bernal-Morales Carolina , De Zanet Sandro , Garay-Aramburu Gonzaga , Puzo Martin , Arruabarrena Carolina , Sararols Laura , Abraldes Maximino , Broc Laura , Escobar-Barranco Jose Juan , Figueroa Marta , Zapata Miguel Angel , Ruiz-Moreno José M , Parrado-Carrillo Alba , Moll-Udina Aina , Alforja Socorro , Figueras-Roca Marc , Gómez-Baldó Laia , Ciller Carlos , Apostolopoulos Stefanos , Mishchuk Anastasiia , Casaroli-Marano Ricardo P , Zarranz-Ventura Javier
Published: January 2025

Aim

To evaluate the impact of fluid volume fluctuations quantified with artificial intelligence in optical coherence tomography scans during the maintenance phase and visual outcomes at 12 and 24 months in a real-world, multicentre, national cohort of treatment-naïve neovascular age-related macular degeneration (nAMD) eyes.

Methods

Demographics, visual acuity (VA) and number of injections were collected using the Fight Retinal Blindness tool. Intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), total fluid (TF) and central subfield thickness (CST) were quantified using the RetinAI Discovery tool. Fluctuations were defined as the SD of within-eye quantified values, and eyes were distributed according to SD quartiles for each biomarker.

Results

A total of 452 naïve nAMD eyes were included. Eyes with highest (Q4) versus lowest (Q1) fluid fluctuations showed significantly worse VA change (months 3–12) in IRF −3.91 versus 3.50 letters, PED −4.66 versus 3.29, TF −2.07 versus 2.97 and CST −1.85 versus 2.96 (all p<0.05), but not for SRF 0.66 versus 0.93 (p=0.91). Similar VA outcomes were observed at month 24 for PED −8.41 versus 4.98 (p<0.05), TF −7.38 versus 1.89 (p=0.07) and CST −10.58 versus 3.60 (p<0.05). The median number of injections (months 3–24) was significantly higher in Q4 versus Q1 eyes in IRF 9 versus 8, SRF 10 versus 8 and TF 10 versus 8 (all p<0.05).

Conclusion

This multicentre study reports a negative effect in VA outcomes of fluid volume fluctuations during the maintenance phase in specific fluid compartments, suggesting that anatomical and functional treatment response patterns may be fluid-specific.
Triglyceride lowering in patients with different severities of hypertriglyceridaemia-associated acute pancreatitis: secondary analysis of a multicentre, prospective cohort study
Authors: Luo Xiang , Li Xiaoling , Lai Xiaoyan , Mao Wenjian , Ke Lu , Fu Lingyan , Gao Lin , Liu Yaolu
Published: January 2025

Objective

It is controversial whether rapid lowering of triglyceride (TG) levels is associated with clinical benefits in patients with hypertriglyceridaemia-associated acute pancreatitis (HTG-AP). In particular, patients with different severity of disease may respond differently to TG-lowering therapy. In this study, we aimed to explore the association between rapid decline in serum TG levels and organ failure in patients with different severities of HTG-AP.

Methods

This is a secondary analysis of data from a multicentre, prospective registry recruiting HTG-AP patients admitted within 72 hours from the onset of symptoms. Patients were dichotomised into either target reaching (TG≤5.65 mmol/L on study day 3) or not. The primary outcome was the presence of organ failure at day 14. The association between target-reaching and the primary outcome was modelled. Furthermore, subgroup analyses were conducted based on the disease severity of HTG-AP patients at enrolment.

Results

Overall, 413 patients were included for analysis, of whom 192 (46.5%) reached the target on day 3. For the overall study cohort, there was no significant difference in presence of organ failure at day 14 between patients reaching the target or not (3.1% vs 6.8%, p=0.091). In the subgroup of HTG-AP patients with organ failure at enrolment, compared with patients with TG>5.65 mmol/L on day 3, patients who reached the target had significantly lower presence of organ failure at day 14 (7.8% vs 22%, p=0.039) and lower incidence of infected pancreatic necrosis within 60 days (3.1% vs 11.9%, p=0.049). Similar findings were seen in the subgroup with more severe HTG-AP (APACHE II ≥8 at enrolment).

Conclusion

More rapid decline of serum TG levels was associated with decreased presence of organ failure at day 14 in patients with more severe HTG-AP.

Trial registration number

The Chinese Clinical Trial Registry, number ChiCTR2000039541.
Cervical cancer screening by cotesting method for Vietnamese women 25–55 years old: a cost-effectiveness analysis
Authors: Bui Hien Thu , Pham Van Nu Hanh , Vu Thang Hong
Published: January 2025

Background

Cervical cancer (CC) is preventable through regular screening and vaccination against human papillomavirus (HPV). However, CC remains a significant public health issue in low-income and middle-income countries (LMICs) like Vietnam, where financial constraints hinder the widespread implementation of HPV vaccination and screening programmes. Currently, Vietnam lacks both a national CC screening intervention and an HPV vaccination programme for women and girls. To date, cost-effectiveness studies evaluating CC screening methods in Vietnam remain limited.

Objectives

To evaluate the cost-effectiveness of two CC screening strategies for Vietnamese women aged 25–55 years: (1) cotesting combining cytology and HPV testing conducted three times at 5 year intervals (intervention) and (2) cytology-based screening conducted five times at 2 year intervals (comparator). The objective is to provide evidence to inform policy and clinical practice in Vietnam.

Design

Cost-effectiveness analysis using a Markov model with 1 year cycles to simulate the natural progression of CC.

Setting

The Vietnamese healthcare system, modelled from the provider’s perspective, with parameters adapted to the local context through expert consultations.

Participants

A simulated cohort of Vietnamese women aged 25–55 years.

Interventions

The intervention involved cotesting (cytology and HPV testing) three times at 5 year intervals. The comparator was cytology-based screening conducted five times at 2 year intervals.

Primary and secondary outcome measures

The primary outcome measure was quality-adjusted life years (QALYs). Costs and cost-effectiveness ratios were assessed using Vietnam’s gross domestic product (GDP) per capita as the cost-effectiveness threshold (1–3 times GDP per capita). Sensitivity analyses (one-way deterministic and probabilistic) were conducted to account for uncertainties.

Results

The cotesting strategy was less effective and more costly than cytology-based screening across all age groups. Cotesting resulted in higher costs and fewer QALYs than the comparator. Probabilistic sensitivity analyses confirmed that cotesting was not cost-effective under current conditions in Vietnam.

Conclusions

Cytology-based screening conducted five times at 2 year intervals is a more cost-effective option for CC screening in Vietnamese women aged 25–55 years. The cotesting strategy cannot be recommended due to its higher cost and lower effectiveness.
Effect of propofol and ciprofol in patients undergoing bronchoscopy: protocol for a double-blind, randomised controlled trial
Authors: Tang Jinxuan , Chen Fang , Huang Jiayu , Li Dongliang , Li Cheng
Published: January 2025

Introduction

Propofol is a fast-acting intravenous anaesthetic widely used for sedation and anaesthesia in gastrointestinal endoscopy, bronchoscopy, and the induction/maintenance of general anaesthesia in outpatients and inpatients; however, propofol has several undesirable effects, including injection pain, which affects the physical and mental health of patients, and cardiopulmonary depression, characterised by hypotension, bradycardia and apnea, which commonly occur in clinical practice. Ciprofol (HSK3486) is a propofol analogue with good clinical safety, high potency and some advantages over propofol, including lower injection pain and haemodynamic depression in patients undergoing gastroscopy and colonoscopy. This study aims to compare the impact of equivalent effective doses of propofol and ciprofol on haemodynamic changes in patients undergoing bronchoscopy under general anaesthesia.

Methods

This prospective, double-blind, randomised, controlled clinical trial will recruit 250 patients aged 18–80 years scheduled for elective bronchoscopy under general anaesthesia. The cohort will be randomised into two groups in a 1:1 ratio: propofol (200 mg/20 mL of saline) and ciprofol (40 mg/20 mL of saline). The primary outcomes are changes in heart rate and blood pressure before and after induction, laryngeal mask airway (LMA) placement and bronchoscopy placement. The secondary outcomes are the incidence of choking and injection pain, the type and dose of vasoactive drugs used during the operation, and the level of postoperative satisfaction among surgeons, anaesthesiologists and patients.

Ethics and dissemination

This trial was approved by the Medical Ethics Committee of Shanghai Fourth People’s Hospital, School of Medicine, Tongji University and registered with the Chinese Clinical Trials Registry (Identifier: ChiCTR2200063048) on 29 August 2022. The findings of this study will be disseminated through various channels. Academic dissemination will include publication in peer-reviewed journals and presentations at national and international conferences.

Trial registration number

ChiCTR2200063048.
Diagnostic performance of the DISQVER metagenomic sequencing tool for the identification of pathogens in febrile neutropenic patients: the ADNEMIA trial
Authors: Pichon Maxime , Burucoa Christophe
Published: January 2025

Introduction

While intensive protocols in onco-haematology have improved survival rates for patients with haematological malignancies, they have also resulted in an increased incidence of infection associated with therapy-induced immunosuppression (including chemotherapy-induced febrile neutropenia; FN). The occurrence of FN, associated with high morbidity and mortality, necessitates broad-spectrum antibiotic therapy, occasioning delayed chemotherapy and resulting in a loss of opportunity for the patient. Considering that without an identified pathogen, a 10% mortality rate can ensue, documentation is essential to the optimisation of antibiotic therapy. However, blood culture (the reference test) is limited for several reasons: such as fastidious culture, antibiotic treatment prior to sampling or insufficient sample volume. Sequencing technologies have led to the development of diagnostic approaches based on the detection of circulating DNA in blood. This study will aim to assess the clinical utility of metagenomic next-generation sequencing (mNGS)-DISQVER technology in detecting pathogenic microorganisms from blood samples of patients undergoing high-risk FN treatment.

Methods and analysis

This nationwide, prospective, multicentre, interventional, proof-of-concept clinical trial will enrol 200 patients. Will include patients≥18 years old, treated for malignancy, at high risk of FN (Multinational Association for Supportive Care in Cancer score≤21) with an expected duration of neutropenia≥7 days. Patients who received antibiotic treatment within 24 hours prior to enrolment, have previously participated and/or have enhanced protection will be excluded. The primary outcome will be determined by considering the microorganisms responsible for this FN, weighted by the assessment of an adjudication committee. Secondary outcomes will evaluate patient management depending on the arm. The second secondary outcome will be determined by the duration of conventional assessment, frequency of microorganisms detected during routine care and percentage distribution of theoretical adjustments made to anti-infective treatment based on microorganisms diagnosed using the mNGS-DISQVER tool as compared with conventional practices. Identifying the pathogens responsible for high-risk FN from a blood sample, using an unbiased technique, can provide microbiological documentation and may even reveal unexpected microorganisms in these profoundly immunocompromised patients.

Ethics and dissemination

The protocol received approval from the Comité de Protection des Personnes Sud-Méditerranée II. All participants will provide informed consent before participation. The trial has been registered on ClinicalTrials.gov (identifierNCT06075888). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Trial registration number

ClinicalTrials.govNCT06075888.
Adapting a consensus process for survivors of domestic abuse and child maltreatment: a brief report about adopting a trauma-informed approach in multistakeholder workshops
Authors: Powell Claire , Szilassy Eszter , Cowan Katherine , Feder Gene , Gilbert Ruth , Howarth Emma , Johns Karen , Lindenberg Ursula , Gregory Alison
Published: January 2025

Purpose

Among health researchers, there is a growing appreciation of the importance of the involvement of service users and members of the public. This recognition has not only resulted in involvement guidelines and improved research ethics but also an increasing use of consensus processes with service users and members of the public to determine research priorities and questions and to agree outcomes to be measured in intervention studies. There is, however, limited advice about how to safely involve survivors of violence and abuse in consensus-based studies.

Methods/results

This commentary provides an overview of the adaptations made to a process of core outcome set development, to ensure that survivors of violence and abuse felt safe, heard and supported, and able to contribute in a meaningful way.

Conclusions

We advocate for an iterative process of listening to and learning from survivors, as well as buy-in from funders to ensure research studies are appropriately resourced and involve sufficient planning time.
Impact of primary care benefits on healthcare utilisation and estimated out-of-pocket expenses in urban, rural and remote settings in the Philippines
Authors: Panganiban Janelle Micaela S , Camiling-Alfonso Romelei , Sanchez Josephine T , De Mesa Regine Ynez H , Sandigan Gillian , Amit Arianna Maever L , Rey Mia P , Lopez Johanna Faye E , Fabian Noleen Marie , Galingana Cara Lois T , Bernal-Sundiang Nannette , Aquino Maria Rhodora N , Lastrilla Chad Lester , Callo Miguel , Tan-Lim Carol Stephanie Chua , Dans Leonila F , Marfori Jose Rafael A , Paterno Ramon Pedro , Dans Antonio L
Published: January 2025

Background

This study aimed to determine the effects of primary care interventions on healthcare utilisation and estimated out-of-pocket (OOP) expenses in selected urban, rural and remote settings in the Philippines.

Methodology

Context-specific measures relating to expanding healthcare provider networks, augmenting the health human workforce and subsidising transportation costs were implemented to strengthen primary care systems. In this study, two key outcomes were monitored: (1) monthly healthcare utilisation measured by the total number of outpatient consultations per site and (2) change in OOP expenses from baseline to endline within a 1 year study period.

Results

All sites had a positive trend in monthly outpatient consultations in healthcare utilisation over 1 year. The remote site had the steepest increase in outpatient consultations, with a 401% increase compared with the baseline during the peak of consultations at month 7. The urban site had a 62% increase in outpatient consultations from baseline to month 6, while the rural site had a 251% increase from baseline to month 11, which corresponded to the peak month in terms of the number of outpatient consultations. The rural site had the largest decrease in estimated OOP expenses (50.3% reduction, 95% CI −88 to –13), followed by the remote site (33.2% reduction, 95% CI −67,+1) and the urban site (16.0% reduction, 95% CI −65,+33).

Conclusion

The rural site showed a significant reduction in estimated OOP expenses and an increase in healthcare utilisation. The remote site had the steepest increase in utilisation, but the reduction in estimated OOP expenses was not statistically significant. The urban site experienced the lowest increase in utilisation, and the smallest reduction in estimated OOP expenses, which was also not statistically significant. Implementing primary care benefits will necessitate contextualised approaches to avoid the inadvertent aggravation of inequities in healthcare.
Metabolic dysfunction-associated steatotic liver disease in children
Authors: Goyal Nidhi P , Xanthakos Stavra , Schwimmer Jeffrey B
Published: January 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease in children. MASLD encompasses a spectrum of liver disease and can be severe, with 10% of affected children presenting with advanced fibrosis. While biopsy remains the most accurate method for diagnosing and staging the disease, MRI proton density fat fraction and magnetic resonance elastography are the most reliable non-invasive measures for assessing steatosis and fibrosis, respectively. MASLD is associated with multiple comorbidities including type 2 diabetes, hypertension, dyslipidaemia, decreased bone mineral density, obstructive sleep apnoea, anxiety and depression. Currently, there are no pharmacological treatments available for children, highlighting the urgent need for paediatric clinical trials. A diet low in free sugars is promising for reducing steatosis and decreasing alanine aminotransferase, a surrogate marker for hepatic inflammation. Emerging data indicate that steatosis can be present in children under 6 years of age, which was previously considered rare. The intricate interplay of genetics may inform future therapeutics and prognostication, with thePNPLA3gene showing the most evidence for association with the risk and severity of steatotic liver disease and steatohepatitis. MASLD is a complex disease affecting one in ten children and is associated with increased early mortality risk. More dedicated studies are needed in children to advance our understanding of this disease and find effective treatments.
Efficacy and safety of pharmacological treatments in inclusion body myositis: a systematic review
Authors: Santos Eduardo José Ferreira , Farisogullari Bayram , Yapp Nicholas , Townsley Hermaleigh , Sousa Pedro , Machado Pedro M
Published: January 2025

Objective

To identify the best evidence on the efficacy of treatment interventions for inclusion body myositis (IBM) and to describe their safety.

Methods

Systematic review of randomised controlled trials (RCTs) of pharmacological treatments of adults with IBM, conducted according to the Cochrane Handbook, updating a previous Cochrane review. The search strategy was run on Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Assessment of risk of bias, data extraction and synthesis were performed independently by two reviewers. Data pooled in statistical meta-analyses, if possible.

Results

From a total of 487 records, 48 were selected for full-text review, 14 fulfilled the inclusion criteria, but only 2 RCTs were included in meta-analyses due to clinical heterogeneity (different drug interventions or dosages). Treatments included various immunosuppressive and immunomodulatory agents, alongside interventions modulating muscle growth and protein homoeostasis. Efficacy was assessed across multiple outcomes, namely muscle strength, physical function, mobility and muscle trophicity. Trials of methotrexate (MTX), intravenous immunoglobulin, interferon beta-1a and MTX, MTX and anti-T-lymphocyte immunoglobulin, oxandrolone, MTX and azathioprine, bimagrumab, arimoclomol, and sirolimus provided low-quality to high-quality evidence of having no effect on the progression of IBM.

Conclusions

Drug interventions for IBM were not effective for most of the outcomes of interest. We observed inconsistency of outcome measures across trials. More RCTs are needed, of adequate size and duration, and using a standardised set of outcome measures.