bluuebunny/crossref_metadata_2025 huggingface dataset:
Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction
Authors: Li Cun , Yu Yifei , Wan Zhixin , Chiu Man Chun , Huang Jingjing , Zhang Shuxin , Zhu Xiaoxin , Lan Qiaoshuai , Deng Yanlin , Zhou Ying , Xue Wei , Yue Ming , Cai Jian-Piao , Yip Cyril Chik-Yan , Wong Kenneth Kak-Yuen , Liu Xiaojuan , Yu Yang , Huang Lin , Chu Hin , Chan Jasper Fuk-Woo , Clevers Hans , Yuen Kwok Yung , Zhou Jie
Published: December 2024

The lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention. Nasal organoids are more susceptible to HRV-C than airway organoids. Intriguingly, upon HRV-C infection, we observe an innate immune response that is stronger in airway organoids than in nasal organoids, which is reproduced in a Poly(I:C) stimulation assay. Treatment with α-CDHR3 and antivirals significantly reduces HRV-C viral growth in airway and nasal organoids. Additionally, an organoid-based immunofluorescence assay is established to titrate HRV-C infectious particles. Collectively, we develop an organoid-based system to reproducibly propagate the poorly cultivable HRV-C, followed by a comprehensive characterization of HRV-C infection and innate immunity in physiologically active respiratory organoids. The organoid-based HRV-C infection model can be extended for developing antiviral strategies. More importantly, our study has opened an avenue for propagating and studying other uncultivable human and animal viruses.
Cytokine-armed pyroptosis induces antitumor immunity against diverse types of tumors
Authors: Orehek Sara , Ramuta Taja Železnik , Lainšček Duško , Malenšek Špela , Šala Martin , Benčina Mojca , Jerala Roman , Hafner-Bratkovič Iva
Published: December 2024

Inflammasomes are defense complexes that utilize cytokines and immunogenic cell death (ICD) to stimulate the immune system against pathogens. Inspired by their dual action, we present cytokine-armed pyroptosis as a strategy for boosting immune response against diverse types of tumors. To induce pyroptosis, we utilize designed tightly regulated gasdermin D variants comprising different pore-forming capabilities and diverse modes of activation, representing a toolbox of ICD inducers. We demonstrate that the electrogenic transfer of ICD effector-encoding plasmids into mouse melanoma tumors when combined with intratumoral expression of cytokines IL-1β, IL-12, or IL-18, enhanced anti-tumor immune responses. Careful selection of immunostimulatory molecules is, however, imperative as a combination of IL-1β and IL-18 antagonized the protective effect of pyroptosis by IFNγ-mediated upregulation of several immunosuppressive pathways. Additionally, we show that the intratumoral introduction of armed pyroptosis provides protection against distant tumors and proves effective across various tumor types without inducing systemic inflammation. Deconstructed inflammasomes thus serve as a powerful, tunable, and tumor-agnostic strategy to enhance antitumor response, even against the most resilient types of tumors.
Robust and inducible genome editing via an all-in-one prime editor in human pluripotent stem cells
Authors: Wu Youjun , Zhong Aaron , Sidharta Mega , Kim Tae Wan , Ramirez Bernny , Persily Benjamin , Studer Lorenz , Zhou Ting
Published: December 2024

Prime editing (PE) allows for precise genome editing in human pluripotent stem cells (hPSCs), such as introducing single nucleotide modifications, small insertions or deletions at a specific genomic locus. Here, we systematically compare a panel of prime editing conditions in hPSCs and generate a potent prime editor, “PE-Plus”, through co-inhibition of mismatch repair and p53-mediated cellular stress responses. We further establish an inducible prime editing platform in hPSCs by incorporating the PE-Plus into a safe-harbor locus and demonstrated temporal control of precise editing in both hPSCs and differentiated cells. By evaluating disease-associated mutations, we show that this platform allows efficient creation of both monoallelic and biallelic disease-relevant mutations in hPSCs. In addition, this platform enables the efficient introduction of single or multiple edits in one step, demonstrating potential for multiplex editing. Our method presents an efficient and controllable multiplex prime editing tool in hPSCs and their differentiated progeny.
Magnetosensitivity of tightly bound radical pairs in cryptochrome is enabled by the quantum Zeno effect
Authors: Denton Matt C. J. , Smith Luke D. , Xu Wenhao , Pugsley Jodeci , Toghill Amelia , Kattnig Daniel R.
Published: December 2024

The radical pair mechanism accounts for the magnetic field sensitivity of a large class of chemical reactions and is hypothesised to underpin numerous magnetosensitive traits in biology, including the avian compass. Traditionally, magnetic field sensitivity in this mechanism is attributed to radical pairs with weakly interacting, well-separated electrons; closely bound pairs were considered unresponsive to weak fields due to arrested spin dynamics. In this study, we challenge this view by examining the FAD-superoxide radical pair within cryptochrome, a protein hypothesised to function as a biological magnetosensor. Contrary to expectations, we find that this tightly bound radical pair can respond to Earth-strength magnetic fields, provided that the recombination reaction is strongly asymmetric—a scenario invoking the quantum Zeno effect. These findings present a plausible mechanism for weak magnetic field effects in biology, suggesting that even closely associated radical pairs, like those involving superoxide, may play a role in magnetic sensing.
Observation of 1H-1H J-couplings in fast magic-angle-spinning solid-state NMR spectroscopy
Authors: Torodii Daria , Holmes Jacob B. , Grohe Kristof , de Oliveira-Silva Rodrigo , Wegner Sebastian , Sakellariou Dimitrios , Emsley Lyndon
Published: December 2024

While 1H-1H J-couplings are the cornerstone of all spectral assignment methods in solution-state NMR, they are yet to be observed in solids. Here we observe 1H-1H J-couplings in plastic crystals of (1S)-(−)-camphor in solid-state NMR at magic angle spinning (MAS) rates of 100 kHz and above. This is enabled in this special case because the intrinsic coherence lifetimes at fast MAS rates become longer than the inverse of the 1H-1H J couplings. For example, at 160 kHz MAS the coherence lifetimes are longer than 20 ms, corresponding to refocused linewidths of less than 15 Hz. As a result, we are able to record two-dimensional 1H-1H J resolved spectra that allow the observation and measurement of 1H-1H J-couplings in solid camphor. The J-couplings also lead to unambiguous through-bond correlations in 1H-1H refocused incredible natural abundance double quantum transfer (INADEQUATE) and uniform-sign cross-peak double-quantum-filtered correlation spectroscopy (UC2QFCOSY) experiments.
DNA replication initiation drives focal mutagenesis and rearrangements in human cancers
Authors: Murat Pierre , Guilbaud Guillaume , Sale Julian E.
Published: December 2024

The rate and pattern of mutagenesis in cancer genomes is significantly influenced by DNA accessibility and active biological processes. Here we show that efficient sites of replication initiation drive and modulate specific mutational processes in cancer. Sites of replication initiation impede nucleotide excision repair in melanoma and are off-targets for activation-induced deaminase (AICDA) activity in lymphomas. Using ductal pancreatic adenocarcinoma as a cancer model, we demonstrate that the initiation of DNA synthesis is error-prone at G-quadruplex-forming sequences in tumours displaying markers of replication stress, resulting in a previously recognised but uncharacterised mutational signature. Finally, we demonstrate that replication origins serve as hotspots for genomic rearrangements, including structural and copy number variations. These findings reveal replication origins as functional determinants of tumour biology and demonstrate that replication initiation both passively and actively drives focal mutagenesis in cancer genomes.
Short tandem repeats delineate gene bodies across eukaryotes
Authors: Reinar William B. , Krabberød Anders K. , Lalun Vilde O. , Butenko Melinka A. , Jakobsen Kjetill S.
Published: December 2024

Short tandem repeats (STRs) have emerged as important and hypermutable sites where genetic variation correlates with gene expression in plant and animal systems. Recently, it has been shown that a broad range of transcription factors (TFs) are affected by STRs near or in the DNA target binding site. Despite this, the distribution of STR motif repetitiveness in eukaryote genomes is still largely unknown. Here, we identify monomer and dimer STR motif repetitiveness in 5.1 billion 10-bp windows upstream of translation starts and downstream of translation stops in 25 million genes spanning 1270 species across the eukaryotic Tree of Life. We report that all surveyed genomes have gene-proximal shifts in motif repetitiveness. Within genomes, variation in gene-proximal repetitiveness landscapes correlated to the function of genes; genes with housekeeping functions were depleted in upstream and downstream repetitiveness. Furthermore, the repetitiveness landscapes correlated with TF binding sites, indicating that gene function has evolved in conjunction with cis-regulatory STRs and TFs that recognize repetitive sites. These results suggest that the hypermutability inherent to STRs is canalized along the genome sequence and contributes to regulatory and eco-evolutionary dynamics in all eukaryotes.
Rapid lightsheet fluorescence imaging of whole Drosophila brains at nanoscale resolution by potassium acrylate-based expansion microscopy
Authors: Tian Xuejiao , Lin Tzu-Yang , Lin Po-Ting , Tsai Min-Ju , Chen Hsin , Chen Wen-Jie , Lee Chia-Ming , Tu Chiao-Hui , Hsu Jui-Cheng , Hsieh Tung-Han , Tung Yi-Chung , Wang Chien-Kai , Lin Suewei , Chu Li-An , Tseng Fan-Gang , Hsueh Yi-Ping , Lee Chi-Hon , Chen Peilin , Chen Bi-Chang
Published: December 2024

Taking advantage of the good mechanical strength of expanded Drosophila brains and to tackle their relatively large size that can complicate imaging, we apply potassium (poly)acrylate-based hydrogels for expansion microscopy (ExM), resulting in a 40x plus increased resolution of transgenic fluorescent proteins preserved by glutaraldehyde fixation in the nervous system. Large-volume ExM is realized by using an axicon-based Bessel lightsheet microscope, featuring gentle multi-color fluorophore excitation and intrinsic optical sectioning capability, enabling visualization of Tm5a neurites and L3 lamina neurons with photoreceptors in the optic lobe. We also image nanometer-sized dopaminergic neurons across the same intact iteratively expanded Drosophila brain, enabling us to measure the 3D expansion ratio. Here we show that at a tile scanning speed of ~1 min/mm3 with 1012 pixels over 14 hours, we image the centimeter-sized fly brain at an effective resolution comparable to electron microscopy, allowing us to visualize mitochondria within presynaptic compartments and Bruchpilot (Brp) scaffold proteins distributed in the central complex, enabling robust analyses of neurobiological topics.
Time-bin entangled Bell state generation and tomography on thin-film lithium niobate
Authors: Finco Giovanni , Miserocchi Filippo , Maeder Andreas , Kellner Jost , Sabatti Alessandra , Chapman Robert J. , Grange Rachel
Published: December 2024

Optical quantum communication technologies are making the prospect of unconditionally secure and efficient information transfer a reality. The possibility of generating and reliably detecting quantum states of light, with the further need of increasing the private data-rate is where most research efforts are focusing. The physical concept of entanglement is a solution guaranteeing the highest degree of security in device-independent schemes, yet its implementation and preservation over long communication links is hard to achieve. Lithium niobate-on-insulator has emerged as a revolutionising platform for high-speed classical telecommunication and is equally suited for quantum information applications owing to the large second-order nonlinearities that can efficiently produce entangled photon pairs. In this work, we generate maximally entangled quantum states in the time-bin basis using lithium niobate-on-insulator photonics at the fibre optics telecommunication wavelength, and reconstruct the density matrix by quantum tomography on a single photonic integrated circuit. We use on-chip periodically-poled lithium niobate as source of entangled qubits with a brightness of 242 MHz/mW and perform quantum tomography with a fidelity of 91.9 ± 1.0 %. Our results, combined with the established large electro-optic bandwidth of lithium niobate, showcase the platform as perfect candidate to realise fibre-coupled, high-speed time-bin quantum communication modules that exploit entanglement to achieve information security.
Variation of gene ratios in mock communities constructed with purified 16S rRNA during processing
Authors: Nammoura Neto Georges Mikhael , Schneider René Peter
Published: December 2024

16S ribosomal nucleic acid (16S rRNA) analysis allows to specifically target the metabolically active members of microbial communities. The stability of the ratios between target genes in the workflow, which is essential for the bioprocess-relevance of the data derived from this analysis, was investigated using synthetic mock communities constructed by mixing purified 16S rRNA from Bacillus subtilis (Bs), Staphylococcus aureus (Sa), Pseudomonas aeruginosa (Pa), Klebsiella pneumoniae (Kp) and Burkholderia cepacia (Bc) in different proportions. The RT reaction yielded one copy of cDNA per rRNA molecule for Pa, Bc and Sa but only 2/3 of the expected cDNA from 16S rRNAs of Bs and Kp. The combination of Taq DNA Platinum polymerase with subcycling PCR (scPCR) produced uniform yields of approximately 70% for second strand PCR synthesis from all target cDNAs. The proportion between templates in multicycle PCR was best preserved after 10 cycle scPCR followed by cloning. With MiSeq sequencing, correct proportions for about two thirds of templates were recovered after 10 cycle scPCR with Taq Platinum. 30 cycles standard PCR (stdPCR) or scPCR proved particularly harmful to proportion data and should be avoided.
Rectal mucosal inflammation, microbiome, and wound healing in men who have sex with men who engage in receptive anal intercourse
Authors: Van Doren Vanessa E. , Ackerley Cassie G. , Arthur Robert A. , Murray Phillip M. , Smith S. Abigail , Hu Yi-Juan , Kelley Colleen F.
Published: December 2024

Mucosal injury is common during consensual intercourse and induces an inflammatory response that could contribute to pathogen transmission including HIV. Here, we compared mucosal immune and microbiome responses to experimentally induced mucosal injury between men who have sex with men engaging in receptive anal intercourse (MSM-RAI) and men who do not engage in RAI (controls), all without HIV. Rectal mucosal secretions were collected from adult MSM-RAI (n = 19) and controls (n = 6) via anoscopy before and up to eight days after experimentally induced injury. Mucosal healing was evaluated by repeated injury surface area measurements with digital imaging. MSM-RAI demonstrated overall significantly higher concentrations of pro-inflammatory cytokines and a distinct rectal microbiome compared with controls. Wound healing was numerically faster in MSM-RAI but did not meet statistical significance (p = 0.09). Different cytokine injury response patterns were observed between MSM-RAI and controls; however, IL-6 and IP-10 were important mediators in both groups. Microbial guilds, particularly from the Lachnospiraceae and Prevotellaceae families, were associated with rectal mucosal inflammation. This work is the first experimental study of rectal mucosal injury and the immune environment in healthy humans and provides a more nuanced understanding of rectal mucosal inflammation after injury, which can inform our understanding of HIV transmission.
Lyophilization of ASFV vaccine candidate ASFV-G-ΔI177L offers long term stability
Authors: Espinoza Nallely , Spinard Edward , Rai Ayushi , Ramirez-Medina Elizabeth , Valladares Alyssa , Meyers Amanda , Borca Manuel V. , Gladue Douglas P.
Published: December 2024

For over a century African swine fever (ASF) has been causing outbreaks leading to devastating losses for the swine industry. The current pandemic of ASF has shown no signs of stopping and continues to spread causing outbreaks in additional countries. Currently control relies mostly on culling infected farms, and strict biosecurity procedures. Recently a vaccine, ASFV-G-ΔI177L was approved for use in Vietnam. In this study we evaluate the long-term stability of lyophilized ASFV-G-ΔI177L. Understanding the stability of different formulations of vaccines is information necessary for deployment of vaccines to ASF outbreak areas, particularly those that do not have a reliable well established cold chain to ensure conservation of vaccine quality. In this report, we determined that ASFV-G-ΔI177L, when lyophilized under specific conditions, is stable for up to one year at 4 °C, with similar vaccine titers after storage. Next-generation sequencing analysis also determined that lyophilization and long-term storage under these conditions had no effect on the genome of ASFV as the genome remained genetically identical to the original non-lyophilized form.
Identifying and understanding the nonlinear behavior of memristive devices
Authors: Yarragolla Sahitya , Hemke Torben , Jalled Fares , Gergs Tobias , Trieschmann Jan , Arul Tolga , Mussenbrock Thomas
Published: December 2024

Nonlinearity is a crucial characteristic for implementing hardware security primitives or neuromorphic computing systems. The main feature of all memristive devices is this nonlinear behavior observed in their current-voltage characteristics. To comprehend the nonlinear behavior, we have to understand the coexistence of resistive, capacitive, and inertia (virtual inductive) effects in these devices. These effects originate from corresponding physical and chemical processes in memristive devices. A physics-inspired compact model is employed to model and simulate interface-type RRAMs such as Au/BiFeO$$_{3}$$/Pt/Ti, Au/Nb$$_{\textrm{x}}$$O$$_{\textrm{y}}$$/Al$$_{2}$$O$$_{3}$$/Nb, while accounting for the modeling of capacitive and inertia effects. The simulated current-voltage characteristics align well with experimental data and accurately capture the non-zero crossing hysteresis generated by capacitive and inductive effects. This study examines the response of two devices to increasing frequencies, revealing a shift in their nonlinear behavior characterized by a reduced hysteresis range Fourier series analysis utilizing a sinusoidal input voltage of varying amplitudes and frequencies indicates harmonics or frequency components that considerably influence the functioning of RRAMs. Moreover, we propose and demonstrate the use of the frequency spectra as one of the fingerprints for memristive devices.
Deep-learning-based extraction of circle of Willis topology with anatomical priors
Authors: Alblas Dieuwertje , Vos Iris N. , Lipplaa Micha M. , Brune Christoph , van der Schaaf Irene C. , Velthuis Mireille R. E. , Velthuis Birgitta K. , Kuijf Hugo J. , Ruigrok Ynte M. , Wolterink Jelmer M.
Published: December 2024

The circle of Willis (CoW) is a circular arrangement of arteries in the human brain, exhibiting significant anatomical variability. The CoW is extensively studied in relation to neurovascular pathologies, with certain anatomical variants previously linked to ischemic stroke and intracranial aneurysms. In an individual CoW, arteries might be absent (aplasia) or underdeveloped (hypoplasia, diameter < 1 mm). As the assessment of such variations is time-consuming and susceptible to subjectivity, robust automatic extraction of personalized CoW topology from time-of-flight magnetic resonance angiography (TOF-MRA) images would highly benefit large-scale clinical investigations. Previous work has sought to extract CoW topology from voxel-based semantic segmentation masks. However, hypoplastic arteries are challenging to recover in voxel-based segmentation. Instead, we propose using a complete CoW as an anatomical prior for extracting all possible CoW arteries as shortest paths between automatically identified anatomical landmarks, guided by automatically determined artery orientation vector fields. These fields are obtained using a scale-invariant and rotation-equivariant mesh-CNN-based model (SIRE). For a 3D TOF-MRA volume, a potentially overcomplete graph of the CoW is thus extracted in which each edge represents an artery. Subsequently, a binary Random Forest classifier labels each artery as normal or hypo-/aplastic. The model was optimized and validated using a data set of 351 3D TOF-MRA scans in a cross-validation setup. We showed that using a shortest path algorithm with a cost function based on local artery orientations results in continuous artery paths, even in hypoplastic cases. We tracked the correct path in the posterior communicating arteries in 70–74% of the cases, an artery that is known to pose challenges in voxel-based segmentation models. Our downstream artery path classifier obtained an average F1 score of 0.91, demonstrating the potential of our proposed framework to extract personalized CoW topology automatically.
Role of P2X7 receptor in the progression and clinicopathological characteristics of gastric cancer
Authors: Zhang Wen-jun , Pi Xiong-wei , Le Yi-guan , Li Teng-zheng
Published: December 2024

P2X7 receptor (P2X7R) plays a role in regulating tumor progression, but it is unclear whether P2X7R affects the pathological characteristics of patients with gastric cancer and the activity of gastric cancer cells. Therefore, this study preliminarily investigated the relationship between P2X7R and clinicopathological features of patients with gastric cancer, and further explored the effect of P2X7R on the proliferation, migration and invasion of gastric cancer cells through functional experiments. The results showed that P2X7R was highly expressed in gastric cancer tissues and gastric cancer cells. High expression of P2X7R was closely related to lymphatic metastasis, vascular invasion and Tumor-Node-Metastasis (TNM) stage in patients with gastric cancer. High expression of P2X7R predicted poor overall survival in patients. Moreover, the activation of P2X7R by ATP and its analogue BzATP increased the calcium current of gastric cancer cells, enhanced YF actin stress and cell viability, and promoted the proliferation, migration and invasion of gastric cancer cells. While P2X7R antagonists (A438079 and AZD9056) inhibited the proliferation, migration and invasion of gastric cancer cells induced by ATP. Therefore, the data obtained in this experiment suggest that P2X7R may be another potential molecular target for the prevention and treatment of gastric cancer.
Estimation of the size, density, and demographic distribution of the UK pet dog population in 2019
Authors: McMillan Kirsten M. , Harrison Xavier A. , Wong David C. , Upjohn Melissa M. , Christley Robert M. , Casey Rachel A.
Published: December 2024

There is limited knowledge about the size of the UK dog population. This makes it difficult to reliably monitor population dynamics and management. A repeatable method of measuring the UK dog population, including owned and unowned dogs i.e., those housed long term by animal welfare charities, would help inform interventions to reduce risks to dog welfare such as poor breeding practices and the illegal import of young or pregnant dogs. However, estimating the total dog population in the UK is not straightforward. Although several estimates of dog numbers have been previously suggested, differing methodologies and limited public access to data sources makes comparison and replication difficult. In this study, we compiled a comprehensive dataset of UK pet dogs in 2019, from multiple sources, including a breed registry, veterinary corporations, pet insurance companies, animal welfare charities and an academic institution. Using a hierarchical Bayesian N-mixture model, we estimate 12.64 million (mean, 95% CI 8.54–15.16 million; median, 13.03 million, 95% CI 8.51–15.24 million) owned and unowned pet dogs within the UK in 2019. Estimates were modelled at the postcode area scale, allowing for aggregation to region or country level, as well as providing associated metrics of uncertainty. Furthermore, we provide spatial demographic estimates, regarding age, breed, cephalic index, and body size. Establishing a population baseline offers significant analytical benefits to welfare, veterinary, epidemiological, and business stakeholders alike: as it provides the spatial data required to underpin robust canine welfare strategies and campaigns. We plan to repeat the described process, in order to provide ongoing estimates: allowing for the interrogation of changes to the UK pet dog population over space and time.
A systematic review of circulating IP-10/CXCL10 in patients with Plasmodium infections in relation to disease severity
Authors: Kotepui Manas , Mahittikorn Aongart , Masangkay Frederick Ramirez , Kotepui Kwuntida Uthaisar
Published: December 2024

Interferon γ-induced protein 10 kDa (IP-10) or C–X–C motif chemokine 10 (CXCL10) is produced and secreted from specific leukocytes such as neutrophils, eosinophils, and monocytes, which play key roles in the immune response to Plasmodium infections. This systematic review aimed to collate and critically appraise the current evidence on IP-10 levels in malaria patients. It provided insights into its role in malaria pathogenesis and potential as a biomarker for Plasmodium infections and disease severity. The protocol for this systematic review was registered in PROSPERO (number CRD42024556087). A comprehensive literature search was conducted across multiple databases, including Embase, PubMed, Scopus, Ovid, ProQuest, and MEDLINE, to identify relevant studies examining the role of IP-10 in patients with Plasmodium infections. A narrative synthesis was applied to summarize key findings and to provide an overview of the relationship between IP-10/CXCL10 levels and Plasmodium infection and disease severity. A total of 1933 records were identified, and 26 studies were included in the synthesis. The studies collectively indicated that IP-10 levels are elevated in patients with Plasmodium infections compared to healthy or non-malarial controls. Most studies reported that increased IP-10 levels were associated with increased disease severity. However, a few studies found no significant difference or decreased levels in patients with severe Plasmodium infections compared to those with uncomplicated or mild malaria. Additionally, several studies indicated that IP-10 levels were elevated in cerebral malaria. The systematic review suggests that IP-10 is elevated in patients with Plasmodium infections. However, the variability in findings across different studies regarding the association between IP-10 and severe malaria, particularly cerebral malaria, highlights the need for further comprehensive studies. Addressing confounding factors will be crucial in future research to better understand the role of IP-10 in Plasmodium infections and the pathogenesis of severe disease.
Biocompatible ionized air alleviates rat osteoarthritis by modulating polarization from M1 to M2 macrophages
Authors: Yu Haoran , Ding Chengbiao , Hu Zhongyao , Liu Qi , Gu Xuesong , He Junyan , Yan Yiqun , Yu Shenrui , Gao Lin , Cheng Wendan , Wu Zhengwei , Jing Juehua
Published: December 2024

The imbalance in the proportion of M1/M2 macrophage polarization is a crucial contributor to the persistent progression of osteoarthritis (OA). This study aimed to evaluate the effects of low-dose biocompatible ionized air (BIA) on macrophage polarization and its subsequent chondroprotective effects, thereby validating the potential of BIA in slowing the progression of OA. In vitro experiments demonstrated that BIA modulates the polarization of M1 macrophages toward the M2 phenotype via the ROS-mediated STAT6 pathway. This shift reduces the expression of pro-inflammatory mediators while increasing the expression of anti-inflammatory mediators and pro-chondrogenic factors, leading to an improved microenvironment surrounding chondrocytes. The direct benefits of this improved microenvironment include enhanced chondrocyte viability, inhibition of apoptosis, and reduced degradation of the extracellular matrix. In vivo studies in rats showed that BIA inhibited M1 macrophage infiltration in the synovium, upregulated the proportion of M2 macrophages, alleviated cartilage degeneration, and delayed OA progression. This gas-based regulatory strategy may open new avenues for the treatment of OA.
Effects of exercise on vascular remodelling and fetal growth in uncomplicated and abortion-prone mouse pregnancies
Authors: Lovell Evangeline A. K. , Hosking Shanna L. , Groome Holly M. , Moldenhauer Lachlan M. , Robertson Sarah A. , Gatford Kathryn L. , Care Alison S.
Published: December 2024

Studies in humans and rodents show exercise in pregnancy can modulate maternal blood pressure, vascular volume, and placental efficiency, but whether exercise affects early uteroplacental vascular adaptations is unknown. To investigate this, CBA/J female mice mated with BALB/c males to generate healthy uncomplicated pregnancies (BALB/c-mated) or mated with DBA/2J males to generate abortion-prone pregnancies (DBA/2J-mated), were subjected to treadmill exercise (5 days/week, 10 m/min, 30 min/day for 6 weeks before and throughout pregnancy), or remained sedentary. In uncomplicated pregnancies, exercise caused symmetric fetal growth restriction in fetuses evidenced by reductions in fetal weight, crown-to-rump length, abdominal girth and biparietal diameter. Placental insufficiency was indicated by reduced fetal: placental weight ratio and increased glycogen cell content in the junctional zone of placentas of exercised BALB/c-mated mice on gestational day (GD)18.5. In abortion-prone pregnancy, exercise increased placental efficiency, but the number of late-pregnancy resorptions were elevated. Effects of paternal genotype independent of exercise were evidenced by a greater number of resorptions, poorer spiral artery remodelling, and larger placentas in the DBA/2J-mated compared to BALB/c-mated mice. Effects of exercise independent of paternal genotype included increased implantation sites at both mid and late pregnancy, accompanied by decreased junctional zone areas of placentas. Our findings show that exercise before and during pregnancy in mice can have different effects on fetal outcomes, depending on the paternal and/or fetal genotype. This suggests that the underlying mechanisms are responsive to fetal cues.
Symmetry breaking organizes the brain’s resting state manifold
Authors: Fousek Jan , Rabuffo Giovanni , Gudibanda Kashyap , Sheheitli Hiba , Petkoski Spase , Jirsa Viktor
Published: December 2024

Spontaneously fluctuating brain activity patterns that emerge at rest have been linked to the brain’s health and cognition. Despite detailed descriptions of the spatio-temporal brain patterns, our understanding of their generative mechanism is still incomplete. Using a combination of computational modeling and dynamical systems analysis we provide a mechanistic description of the formation of a resting state manifold via the network connectivity. We demonstrate that the symmetry breaking by the connectivity creates a characteristic flow on the manifold, which produces the major data features across scales and imaging modalities. These include spontaneous high-amplitude co-activations, neuronal cascades, spectral cortical gradients, multistability, and characteristic functional connectivity dynamics. When aggregated across cortical hierarchies, these match the profiles from empirical data. The understanding of the brain’s resting state manifold is fundamental for the construction of task-specific flows and manifolds used in theories of brain function. In addition, it shifts the focus from the single recordings towards the brain’s capacity to generate certain dynamics characteristic of health and pathology.
Research on floating object classification algorithm based on convolutional neural network
Authors: Yang Jikai , Li Zihan , Gu Ziyan , Li Wei
Published: December 2024

With the advancement of artificial intelligence technology, unmanned boats utilizing deep learning models have shown significant potential in water surface garbage classification. This study employs Convolutional Neural Network (CNN) to extract features of water surface floating objects and constructs the VGG16-15 model based on the VGG-16 architecture, capable of identifying 15 common types of water surface floatables. A garbage classification dataset was curated to obtain 5707 images belonging to 15 categories, which were then split into training and validation sets in a 4:1 ratio. Customized improvements were made on the base VGG-16 model, including adjusting the neural network structure to suit 15 floating object categories, applying learning rate decay and early stopping strategies for model optimization, and using data augmentation to enhance model generalization. By tweaking certain parameters, the study analyzed the impact of the number of epochs and batch sizes on the model’s classification effectiveness. The results show that the model achieves the best performance with 20 epochs and a batch size of 64, reaching a recognition accuracy of 93.86%. This is a 10.09% improvement over the traditional VGG-16 model and a 4.91% increase compared to the model without data augmentation, demonstrating the effectiveness of model improvements and data augmentation in enhancing image recognition capabilities. Additionally, the few-shot test demonstrates the fine-tuned model’s improved generalization capability. This research illustrates the applicability of transfer learning in the task of water surface garbage classification and provides technical support for the application of unmanned boats in environmental protection.
A machine learning-based clinical predictive tool to identify patients at high risk of medication errors
Authors: Abdo Ammar , Gallay Lyse , Vallecillo Thibault , Clarenne Justine , Quillet Pauline , Vuiblet Vincent , Merieux Rudy
Published: December 2024

A medication error is an inadvertent failure in the drug therapy process that can cause serious harm to patients by increasing morbidity and mortality and are associated with significant economic costs to the healthcare system. Medication reconciliation is the most cost-effective intervention and can result in a 66% reduction in medication errors. To improve patient safety, we developed a machine learning-based tool that prioritizes patients at risk of medication errors upon admission to the hospital to ensure that they undergo medication reconciliation by clinical pharmacists. The data were collected from the electronic health records of patients admitted to Reims University Hospital who underwent medication reconciliation between 2017 and 2023. The data from 7200 patients were used to train four machine learning-based models based on 52 variables in the development dataset. These models were used to prioritize admitted patients according to their likelihood of being exposed to a medication error. Our models, particularly the voting classifier model, demonstrated good performance (a recall of 0.75, precision of 0.65, F1 score of 0.70, AUROC of 0.74 and AUCPR of 0.75). In a retrospective evaluation simulating real-life use, the voting classifier model successfully identified 45% of the total patients selected who were found to have at least one unintended discrepancy compared to 21% when using the existing tool. The positive experimental results of this tool showed a superior improvement of 113% over the existing tool by targeting patients at risk of medication errors upon admission to Reims University Hospital.
Exploring salinity induced adaptations in marine diatoms using advanced photonic techniques
Authors: Cvjetinovic Julijana , Bedoshvili Yekaterina D. , Davidovich Nickolai A. , Maksimov Eugene G. , Prikhozhdenko Ekaterina S. , Todorenko Daria A. , Bodunova Daria V. , Davidovich Olga I. , Sergeev Igor S. , Gorin Dmitry A.
Published: December 2024

Photonic-based methods are crucial in biology and medicine due to their non-invasive nature, allowing remote measurements without affecting biological specimens. The study of diatoms using advanced photonic methods remains a relatively underexplored area, presenting significant opportunities for pioneering discoveries. This research provides a comprehensive analysis of marine diatoms, specifically Nitzschia sp., across varying salinity levels, integrating fluorescence lifetime imaging microscopy (FLIM), combined photoacoustic and fluorescence tomographies (PAFT), and ultrastructural examinations using transmission electron microscopy. Key findings include a systematic shift in the mean fluorescence lifetime from 570 ps at 20‰ to 940 ps at 80‰, indicating functional adaptations in chlorophyll molecules within light-harvesting complexes. At 60‰ salinity, anomalies are observed in the development of silica valves and polysaccharide layers, suggesting abnormalities in valve morphogenesis. Lipid droplets within the cells display a minimum diameter at 40‰, indicating metabolic adjustments to osmotic stress. The intensity of both fluorescence and photoacoustic signals increases with increasing salinity levels. These insights enhance understanding of the ecological implications of salinity stress on diatom communities and pave the way for future research on leveraging the unique adaptive mechanisms of microalgae for environmental monitoring and sustainable biotechnological applications.
Exploratory testing of functional blood oxygenation level dependent-MRI to image the renoprotective effect of Remote Ischaemic PreConditioning during partial nephrectomy
Authors: Heuzeroth Frederick , Wetterauer Christian , Boll Daniel , Westhoff Timm H. , Dreher Maeve , Seifert Helge , Rentsch Cyrill , Ebbing Jan
Published: December 2024

Urinary biomarker studies in cardiothoracic and kidney-sparing surgery have demonstrated renal protection by Remote Ischaemic PreConditioning (RIPC). RIPC intervention generates cycles of ischaemia and reperfusion of the limbs before the actual ischaemia of the target organ (e.g. kidney) is initiated. This explorative trial aims to investigate whether Blood Oxygenation Level Dependent-MRI (BOLD-MRI) can be a suitable technique to image and quantify the renoprotective effect of RIPC on ischaemia/reperfusion injury (IRI) after partial nephrectomy (PN). Overall, 15 patients were enrolled in this randomized controlled trial. Randomization was 1:1, with RIPC in the intervention arm. Urinary neutrophil gelatinase-associated lipocalin (NGAL), a sensitive biomarker for renal tubular damage was measured preoperatively and for the first 5 days after surgery. Functional BOLD-MRI was successfully performed preoperatively and 48 h after PN in 11 patients. BOLD-MRI uses ∆R2* to express acute tubular damage induced by IRI. The more the ∆R2* values have decreased postoperatively, the more damage the renal tubuli have taken. The cumulative urinary concentration of NGAL in the first 5 postoperative days was significantly lower in the RIPC group (p = 0.02) as compared to the control arm, indicating that the RIPC maneuver performed was effective. The highest difference was seen 6 h after surgery with NGAL being 65% lower in the RIPC arm. IRI of the operated kidney expressed by ∆R2* in BOLD-MRI was 2.1 times less pronounced in the RIPC group as compared to the noRIPC group (∆R2* in % preop/postop RIPC: 14.73/12.57 vs. noRIPC 16.33/11.82, p = 0.36). We were able to demonstrate the potential of BOLD-MRI in measuring IRI. For the first time, it was shown that the renoprotective effects of RIPC can be visualized and measured using BOLD-MRI. Larger studies are required to validate these initial findings.
Temporal evolution of insecticide resistance and bionomics in Anopheles funestus, a key malaria vector in Uganda
Authors: Oruni Ambrose , Tchouakui Magellan , Tagne Carlos S. Djoko , Hearn Jack , Kayondo Jonathan , Wondji Charles S.
Published: December 2024

Insecticide resistance escalation is decreasing the efficacy of vector control tools. Monitoring vector resistance is paramount in order to understand its evolution and devise effective counter-solutions. In this study, we monitored insecticide resistance patterns, vector population bionomics and genetic variants associated with resistance over 3 years from 2021 to 2023 in Uganda. Anopheles funestus s.s was the predominant species in Mayuge but with evidence of hybridization with other species of the An. funestus group. Sporozoite infection rates were relatively very high with a peak of 20.41% in March 2022. Intense pyrethroid resistance was seen against pyrethroids up to 10-times the diagnostic concentration but partial recovery of susceptibility in PBO synergistic assays. Among bednets, only PBO-based nets (PermaNet 3.0 Top and Olyset Plus) and chlorfenapyr-based net (Interceptor G2) had high mortality rates. Mosquitoes were fully susceptible to chlorfenapyr and organophosphates, moderately resistant to clothianidin and resistant to carbamates. The allele frequency of key P450, CYP9K1, resistance marker was constantly very high but that for CYP6P9A/b were very low. Interestingly, we report the first detection of resistance alleles for Ace1 gene (RS =  ~ 13%) and Rdl gene (RS =  ~ 21%, RR =  ~ 4%) in Uganda. The qRT-PCR revealed that Cytochrome P450s CYP9K1, CYP6P9A, CYP6P9b, CYP6P5 and CYP6M7 were consistently upregulated while a glutathione-S-transferase gene (GSTE2) showed low expression. Our study shows the complexity of insecticide resistance patterns and underlying mechanisms, hence constant and consistent spatial and temporal monitoring is crucial to rapidly detect changing resistance profiles which is key in informing deployment of counter interventions.
Small spheroids for head and neck cartilage tissue engineering
Authors: Reutter Sven , Kern Johann , Jakob Yvonne , Rotter Nicole , Gvaramia David
Published: December 2024

The demand for cartilage reconstruction in the head and neck region arises frequently due to trauma, malignancies, and hereditary diseases. Traditional tissue engineering produces cartilage from a small biopsy by combining biomaterials and expanded cells. However, this top-down approach is associated with several limitations, including the non-uniform distribution of cells, lack of physiological cell-cell and cell-matrix interactions, and compromised mechanical properties and tissue architecture. The capacity of cells to aggregate into microtissues enables an alternative bottom-up approach to producing cartilage with or without further scaffolding support. Here we explored the optimal conditions for obtaining small spheroids from head and neck cartilage tissues. We used chondrocytes (CCs) and chondroprogenitors (CPCs) isolated from auricular and nasoseptal cartilage to prepare spheroids using ultra-low attachment (ULA) plates or micromass cultures. Different cell densities were tested to estimate the minimal cell number required for optimal spheroid formation. Furthermore, we evaluated the influence of key chondrogenic cytokines, such as transforming growth factor (TGF)-β, connective tissue growth factor (CTGF), and insulin-like growth factor (IGF)-1, on spheroid morphology and the production of cartilage extracellular matrix (ECM) components. Spheroids expressing cartilage markers were formed with 2.5 × 104 cells in a commercially available chondrogenic differentiation medium on ULA plates but not in conventional micromass cultures. Differences were seen in auricular and nasal spheroids with respect to growth patterns and response to cytokine composition. Auricular spheroids were larger and showed size increase in culture, whereas nasal aggregates tended to shrink. Cytokines differentially influenced spheroid growth, and ECM structure and composition. Under all tested conditions, both spheroid types generated one or more cartilage ECM components, including elastin, which was also found in nasal spheroids despite their hyaline origin. Our results suggest that spheroid cultures can offer a viable approach to generating mature cartilage tissue without a biomaterial scaffold. Furthermore, nasal CCs and CPCs can be used to generate elastic cartilage. The findings of the study provide technical insights toward the goal of obtaining cartilage microtissues that can be potentially used for reconstructive procedures of HNC cartilage defects.
Research on the operational properties of the soft gripper pads
Authors: Białek Marcin , Rybarczyk Dominik
Published: December 2024

Grippers are commonly used as a technological tooling for manipulators. They enable robots to interact with objects in their work area. Grippers have a wide range of differentiation focused on the operation performed and the properties (e.g. shape) of the object being gripped. Their design and functionality are constantly being modified, tuned and developed by both academic and industrial units. Consequently, this paper presents a proposal for a lightweight jaw using MR fluid, which can be implemented in a jaw gripper (e.g. Robotiq 2F-140) to form a hybrid soft-rigid structure. In addition, methods are presented for studying the use of soft structures in a jaw gripper. As part of the work carried out, a model of the cushion and jaw of the gripper was developed, the FEM was used to obtain the character of the deformation when the object is axially plunged into it. Experimental plunging tests as well as dynamic tests of object transfer were also carried out. The work carried out allowed to demonstrate several key aspects of the grippers area. The soft structures of the grippers should be studied in terms of the force required to deform them. This determines their applicability to fragile and deformable objects. Dynamic measurements of the handling of objects of different shapes, with simultaneous measurement of force, allow the effectiveness of the use of soft structures in the gripper to be determined. Such experiments will make it possible to determine the measurable stability and repeatability of the grasp. The results of the research and experiments will be particularly applicable to robotic arms with relatively low lifting capacity.
Gradients in cell density and shape transitions drive collective cell migration into confining environments
Authors: Lin Wan-Jung , Yu Hongsheng , Pathak Amit
Published: December 2024

Epithelial cell monolayers rearrange shapes of individual cells to migrate into confining matrices.
Detection and quantification of ergothioneine in human serum using surface enhanced Raman scattering (SERS)
Authors: Fornasaro Stefano , Gotts Nigel , Venturotti Gioia , Muelas Marina Wright , Roberts Ivayla , Sergo Valter , Goodacre Royston , Bonifacio Alois
Published: December 2024

Ergothioneine (ERG) is a natural sulfur-containing amino acid linked to various human physiological processes, such as anti-inflammatory, neuroprotective, and anti-aging effects. ERG can be measured in human serum using SERS in < 20 min employing a highly specific internal standard.
Preliminary studies for the standardization of a pXRF analyzer via ICP-OES for the accurate quantification of Pb in new paint
Authors: Seney Caryn S. , Kiefer Adam M. , Brown Samantha T. , Stair Evan R. , Nelson David G. , Bandoo Lloyd L. , Stewart W. Benjamin , Lara Nuren Z. , Donaldson Clare
Published: December 2024

Relatively inexpensive portable X-ray fluorescence analyzers can be standardized via inductively coupled plasma-optical emission spectroscopy, offering a simple, cost-effective alternative to conventional analyses of Pb in new paint in LMICs.