bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing a diagnostic prediction model to estimate the severe respiratory syncytial virus pneumonia in children based on machine learning
Authors: Liu Yuanwei , Wu Qiong , Zhou Lifang , Tang Yingyuan , Li Fen , Li Shuangjie
Published: September 2024

Background

Severe respiratory syncytial virus (RSV) pneumonia is a leading cause of hospitalization and morbidity in infants and young children. Early identification of severe RSV pneumonia is crucial for timely and effective treatment by pediatricians. Currently, no prediction model exists for identifying severe RSV pneumonia in children.

Methods

This study aimed to construct a diagnostic prediction model for severe RSV pneumonia in children using a machine learning algorithm. We analyzed data from the Gene Expression Omnibus (GEO) Series, including training dataset GSE246622 and testing dataset GSE105450, to identify differential genes between severe and mild-to-moderate RSV pneumonia in children. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the differential genes, followed by the construction of a protein-protein interaction (PPI) network. An artificial neural network (ANN) algorithm was then used to develop and validate a diagnostic prediction model for severe RSV pneumonia in children.

Results

We identified 34 differentially expressed genes between the severe and mild-to-moderate RSV pneumonia groups. Enrichment analysis revealed that these genes were primarily related to pathogenic infection and immune response. From the PPI network, we identified 10 hub genes and, using the random forest algorithm, screened out 20 specific genes. The ANN-based diagnostic prediction model achieved an area under the curve (AUC) value of 0.970 in the training group and 0.833 in the testing group, demonstrating the model's accuracy.

Conclusions

This study identified specific biomarkers and developed a diagnostic model for severe RSV pneumonia in children. These findings provide a robust foundation for early identification and treatment of severe RSV pneumonia, offering new insights into its pathogenesis and improving pediatric care.
When crayfish make news, headlines are correct but still misleading
Authors: Faulkes Zen
Published: September 2024

Crayfish are well known to many but not often newsworthy, so cases where crayfish are covered in international news provide an example of how science journalism covers a news story about basic research. Headlines have a disproportionately large influence on people’s factual knowledge and perceptions of stories covered in media. I tracked online media coverage of one scientific paper involving marbled crayfish and analyzed the headlines used by the articles. Articles were framed as “news,” but almost no headlines contained “new” facts that first appeared in the target scientific paper. The fact that appeared in the most headlines (that marbled crayfish reproduce by cloning) was over a decade old. Headlines misled readers into thinking a “breakthrough” was made by one team, rather than showing incremental advances by many teams of researchers over years.
Controlled retrieval relies on directed interactions between semantic control regions and visual cortex: MEG evidence from oscillatory dynamics
Authors: Eisenhauer Susanne , Zhang Meichao , Krieger-Redwood Katya , Aveyard Richard , Jackson Rebecca L. , Cornelissen Piers L. , Smallwood Jonathan , Jefferies Elizabeth
Published: September 2024

To navigate the world, we store knowledge about relationships between concepts and retrieve this information flexibly to suit our goals. The semantic control network, comprising left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG), is thought to orchestrate this flexible retrieval by modulating sensory inputs. However, interactions between semantic control and input regions are not sufficiently understood. Moreover, pMTG’s well-formed structural connections to both IFG and visual cortex suggest it as a candidate region to integrate control and input processes. We used magnetoencephalography to investigate oscillatory dynamics during semantic decisions to pairs of words, when participants did or did not know the type of semantic relation between them. IFG showed early increases and decreases in oscillatory activity to prior task knowledge, while pMTG only showed positive effects of task knowledge at a later time window. Furthermore, both regions provided feedback to visual cortex when task goals were absent, while IFG also provided feedback when goals were known. This goal-dependent feedback coincided with an earlier onset of feedforward signalling from visual cortex to pMTG, indicating rapid retrieval of task-relevant features. Knowledge of task goals also enhanced simultaneous inputs to pMTG from both IFG and visual cortex, consistent with the view that pMTG integrates top-down control with bottom-up input. Our findings elucidate the separate roles of anterior and posterior components of the semantic control network and reveal the spectro-temporal cascade of interactions between semantic control and visual regions that underlie our ability to flexibly adapt cognition to the current goals.

Significance Statement

Using magnetoencephalography, we characterize the spectro-temporal dynamics that underlie our ability to flexibly adapt semantic cognition to the current context and goals. We find that semantic goals increase oscillatory activity first in IFG and later in pMTG, and ultimately facilitate visual processing. Effective connectivity analyses confirm the proposed direct modulation of visual cortex by semantic control regions both in the presence and absence of goals, resulting in rapid retrieval when semantic goals are known. Moreover, our findings suggest differential roles for the two semantic control regions: while IFGcontrolsearly goal-dependent retrieval, pMTGintegratestop-down information from IFG with bottom-up visual input later.
Assessing Aral Sea residual lake system: impact of fluctuating salinity on phytoplankton communities
Authors: Malashenkov Dmitry V. , Vörös Lajos , Duisen Aiym , Dashkova Veronika , Abilkas Aidyn , Vorobjev Ivan A. , Barteneva Natasha S.
Published: September 2024

The Aral Sea was once the fourth-largest inland water body in the world. However, the lake rapidly shrank over the past six decades, mainly due to the loss of inflow from one of its tributaries, the Amu Darya River. Lakes and reservoirs are traditionally characterized by static chemical and morphological parameters, leaving untouched a dynamic impact of phytoplankton changes. We used an integrated approach combining traditional microscopy and FlowCam-based imaging flow cytometry to study phytoplankton communities during the 2018 and 2019 expeditions in the Aral Sea remnant lakes system. The residual Aral Sea water bodies experienced different environmental conditions, forming hypersaline South Aral, North Aral Sea that is constantly getting freshwater, and brackish Chernyshev Bay and Tushchybas Lake with 2-8 times amplitude of salinity changes attributed to the variability in the precipitation and periodical influx of freshwater. The salinity fluctuations had an impact on the phytoplankton communities in Chernyshev Bay, making it similar to the phytoplankton of North Aral in 2018 while resembling the hypersaline South Aral phytoplankton assemblages in 2019. Multivariate analysis revealed that salinity, water temperature, ammonium, and nitrates were major contributors to explaining the variance in the sampling data. We conclude that drastic phytoplankton fluctuations occur in the two brackish water bodies in the middle of the former Aral Sea, reflecting changes in salinity.
Computing Stackelberg Equilibrium for Cancer Treatment
Authors: Ganzfried Sam
Published: September 2024

Recent work by Kleshnina et al. has presented a Stackelberg evolutionary game model in which the Stackelberg equilibrium strategy for the leading player corresponds to the optimal cancer treatment [4]. We present an approach that is able to quickly and accurately solve the model presented in that work.
3D Molecular Pretraining via Localized Geometric Generation
Authors: Sun Yuancheng , Chen Kai , Liu Kang , Ye Qiwei
Published: September 2024

Self-supervised learning on 3D molecular structures is gaining importance in data-driven scientific research and applications due to the high costs of annotating bio-chemical data. However, the strategic selection of semantic units for modeling 3D molecular structures remains underexplored, despite its crucial role in effective pre-training—a concept well-established in language processing and computer vision. We introduce Localized Geometric Generation (LEGO), a novel approach that treats tetrahedrons within 3D molecular structures as fundamental building blocks, leveraging their geometric simplicity and widespread presence across chemical functional patterns. Inspired by masked modeling, LEGO perturbs tetrahedral local structures and learns to reconstruct them in a self-supervised manner. Experimental results demonstrate LEGO consistently enhances molecular representations across biochemistry and quantum property prediction benchmarks. Additionally, the tetrahedral modeling and pretraining generalize from small molecules to larger molecular systems, validating by protein-ligand affinity prediction. Our results highlight the potential of selecting semantic units to build more expressive and interpretable neural networks for scientific AI applications.
Mesenchymal stem cell-derived extracellular vesicles alleviate imiquimod-induced psoriasis symptoms in a mouse disease model
Authors: Yi Yuan , Yan Yu , Liu Guowu , Cui Chuang , Zhai Yanhua , He Xinjun , Xu Ke
Published: September 2024

Psoriasis is an immune mediated, chronic inflammatory skin disease. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have inherent immunomodulatory potency from their parental cells, the mesenchymal stem cells (MSCs). In this study, we revealed the application potential of MSC-EVs to alleviate psoriatic symptoms in imiquimod-induced psoriasis mouse model.
Spectral Changes in Motor Thalamus Field Potentials during Movement
Authors: Klassen Bryan T , Baker Matthew R , Jensen Michael A , Valencia Gabriela Ojeda , Miller Kai Joshua
Published: September 2024

The motor thalamus plays a crucial role in the integration and modulation of sensorimotor information and projects to the primary motor cortex. While voltage power spectral changes in the motor cortex with movement have been well-characterized, the corresponding activity in the motor thalamus, particularly broadband (sometimes referred to as high gamma) power, remains unclear. The present study aims to characterize spectral changes in the motor thalamus during hand movements of 15 subjects undergoing awake deep brain stimulation surgery targeting the ventral intermediate (VIM) nucleus of the thalamus for disabling tremor. We analyzed power changes in subject-specific low frequency oscillations (<30 Hz) and broadband power (captured in 65-115 Hz band) of serial field potential recordings. Consistent with previous studies, we found widespread decreases in low-frequency oscillations with movement. Importantly, in most subjects we also observed a significant increase in broadband power, primarily in the inferior recording sites corresponding with estimated VIM region. One subject also performed an imagined movement task during which low frequency oscillatory power was suppressed. These electrophysiologic changes may be leveraged as biomarkers for thalamic functional mapping, DBS targeting, and closed loop applications.
Evaluation of stress tolerance in IR64 rice near-isogenic lines carryingSUB1andDRO1genes
Authors: Soe Ibrahim , Thu Hang Nguyen Thi , Odama Emmanuel , Chepkoech Rael , Ookawa Taiichiro , Ismail Abdelbagi M , Sakagami Jun-Ichi
Published: September 2024

Flooding and drought significantly reduce rice yield in rainfed environments. Rice varieties that tolerate complete inundation for up to two weeks carry theSUB1Agene, while those enduring deeper water conditions for weeks or months have theSK1andSK2genes. Conversely, theDRO1gene, responsible for deep-rooting, helps in water acquisition under drought. In this study, we compared the growth of NIL-SUB1DRO1 a novel rice genotype with an IR64 background regarding its dual tolerance to submergence and drought. Additionally, we assessed its recovery capacity after exposure to stress. Sixteen and thirteen-days old seedlings of three genotypes (Experiment 1-1 and 2-1) and fourteen-days old seedlings of the two genotypes (Experiment 1-2 and 2-2) were tested under submergence and drought stress in a greenhouse experimental condition respectively. Seedlings were submerged for 10 and 7 days and then allowed to recover for 10 and 7 days respectively. In the drought experiment, seedlings underwent 29 days of drought (Experiment 2-1) and 18 days of drought, followed by 10 days of rewatering (Experiment 2-2). Growth parameters were measured before and after treatment, 4 days after submergence in experiment 1-1 and after the recovery periods. Submergence and drought adversely affected growth and performance. Shoot elongation in submerged plants was reduced by 29.2% for NIL-SUB1DRO1 compared to IR64. Accelerated shoot elongation of IR64 negatively affected its recovery. Chlorophyll content and maximum fluorescence of IR64 were significantly lower than other genotypes after 10 and 7 days of complete submergence. Ten days after recovery in experiment 1-1 the Chlorophyll content and maximum fluorescence of IR64 were not significantly different compared to other genotypes. Seven days after of recovery in experiment 1-2, NIL-SUB1DRO1 had significantly higher chlorophyll content and maximum fluorescence than IR64. After 29 days of drought the tiller number and leaf area of IR64 was lower than other genotypes (Experiment 2-1), while in Experiment 2-2 during drought treatment and recovery, NIL-SUB1DRO1 had greater relative water content, leaf water potential, leaf area, SPAD value, dry weights of shoots and roots, root length, surface area and volume compared to IR64. stomatal conductance of IR64 was higher than NIL-SUB1DRO1 during drought, leading to greater water loss and reduced growth during recovery. NIL-SUB1DRO1 absorbed and retained water more effectively under dry conditions. NIL-SUB1DRO1 and NIL-SUB1 is tolerant to submergence and NIL-SUB1DRO1 and NIL-DRO1 to drought, with no negative effects from combining these genes in modern rice varieties for rainfed lowlands.
Ndufs4 inactivation in glutamatergic neurons reveals swallow-breathing discoordination in a mouse model of Leigh Syndrome
Authors: Huff Alyssa , Oliveira Luiz Marcelo , Karlen-Amarante Marlusa , Ebiala Favour , Ramirez Jan Marino , Kalume Franck
Published: September 2024

Swallowing, both nutritive and non-nutritive, is highly dysfunctional in children with Leigh Syndrome (LS) and contributes to the need for both gastrostomy and tracheostomy tube placement. Without these interventions aspiration of food, liquid, and mucus occur resulting in repeated bouts of respiratory infection. No study has investigated whether mouse models of LS, a neurometabolic disorder, exhibit dysfunctions in neuromuscular activity of swallow and breathing integration. We used a genetic mouse model of LS in which the NDUFS4 gene is knocked out (KO) specifically in Vglut2 or Gad2 neurons. We found increased variability of the swallow motor pattern, disruption in breathing regeneration post swallow, and water-induced apneas only in Vglut2 KO mice. These physiological changes likely contribute to weight loss and premature death seen in this mouse model. Following chronic hypoxia (CH) exposure, swallow motor pattern, breathing regeneration, weight, and life expectancy were not changed in the Vglut2-Ndufs4-KO CH mice compared to control, indicating a rescue of phenotypes. These findings show that like patients with LS, Ndufs4 mouse models of LS exhibit swallow impairments as well as swallow-breathing dyscoordination alongside the other phenotypic traits described in previous studies. Understanding this aspect of LS will open roads for the development of future more efficacious therapeutic intervention for this illness.
High-content microscopy and machine learning characterize a cell morphology signature ofNF1genotype in Schwann cells
Authors: Tomkinson Jenna , Mattson Cameron , Mattson-Hoss Michelle , Sarnoff Herb , Bouley Stephanie J. , Walker James A. , Way Gregory P.
Published: September 2024

Neurofibromatosis type 1 (NF1) is a multi-system, autosomal dominant genetic disorder driven by the systemic loss of the NF1 protein neurofibromin. Loss of neurofibromin in Schwann cells is particularly detrimental, as the acquisition of a ‘second-hit’ (e.g., complete loss of NF1) can lead to the development of plexiform neurofibroma tumors. Plexiform neurofibromas are painful, disfiguring tumors with an approximately 1 in 5 chance of sarcoma transition. Selumetinib is currently the only medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of plexiform neurofibromas in a subset of patients. This motivates the need to develop new therapies, either derived to treatNF1haploinsufficiency or complete loss ofNF1function. To identify new therapies, we need to understand the impact neurofibromin has on Schwann cells. Here, we aimed to characterize differences in high-content microscopy imaging in neurofibromin-deficient Schwann cells. We applied a fluorescence microscopy assay (called Cell Painting) to two isogenic Schwann cell lines, one of wildtype genotype (NF1+/+) and one ofNF1null genotype (NF1-/-). We modified the canonical Cell Painting assay to mark four organelles/subcellular compartments: nuclei, endoplasmic reticulum, mitochondria, and F-actin. We utilized CellProfiler pipelines to perform quality control, illumination correction, segmentation, and cell morphology feature extraction. We segmented 22,585NF1wildtype and null cells, utilized 907 significant cell morphology features representing various organelle shapes and intensity patterns, and trained a logistic regression machine learning model to predict theNF1genotype of single Schwann cells. The machine learning model had high performance, with training and testing data yielding a balanced accuracy of 0.85 and 0.80, respectively. All of our data processing and analyses are freely available on GitHub. We look to improve upon this preliminary model in the future by applying it to large-scale drug screens of NF1 deficient cells to identify candidate drugs that return NF1 patient Schwann cells to phenocopy NF1 wildtype and healthier phenotype.
Impact of early postoperative ambulation on gait recovery after hip fracture surgery: A multicenter cohort study
Authors: Nakamura Keisuke , Kurobe Yasushi , Sue Keita , Sakurai Shinichi , Sasaki Tomohiro , Yamamoto Shuhei , Ushiyama Naoko , Taga Masahito , Momose Kimito
Published: September 2024

Objective

This study aimed to investigate the effect of early postoperative ambulation on gait recovery at the initial postoperative week and at discharge after hip fracture surgery in older patients.

Design

Multicenter prospective cohort study.

Setting and Participants

The study included 882 patients aged ≥65 years from 10 acute hospitals in Japan.

Methods

Patients were divided into two groups according to the interval between surgery and first ambulation: early-ambulation (EA) group (initiation of ambulation on postoperative day 1 or 2) and late-ambulation (LA) group (initiation of ambulation on postoperative day 3 or later). The Functional Independence Measure (FIM) was assessed 1 day postoperatively, 1 week postoperatively, and at discharge. Independent walking regardless of use of walking aids was defined as walking FIM ≥5. Confounding variables were age, mobility and cognitive function before injury, medical history, fracture type, and waiting days for surgery.

Multivariate logistic regression analysis was conducted to determine whether EA affected independent walking at 1 week postoperatively and at discharge.

Results

The number of patients in the EA and LA groups was 292 (33.1%) and 590 (66.9%), respectively. The number of patients walking independently 1 week postoperatively and at discharge was 156 (17.7%) and 292 (33.1%), respectively. Multivariate logistic regression analysis revealed that EA was associated with independent walking at 1 week postoperatively (odds ratio [OR], 3.27; 95% confidence interval [CI], 2.17-4.94;P< .0001) and at discharge after adjusting for confounders (OR, 3.33; 95% CI, 2.38-4.69;P< .0001). EA was associated with the recovery to pre-injury walking status at discharge after adjusting for confounders (OR, 3.05; 95% CI, 1.59–5.93;P=.0009).

Conclusion and Implications

Early ambulation after hip fracture surgery has an impact on independent walking and recovery of pre-injury walking status at 1 week postoperatively and at discharge from acute hospitals in older patients.
Technology-Supported Self-Triage Decision Making: A Mixed-Methods Study
Authors: Kopka Marvin , Wang Sonja Mei , Kunz Samira , Schmid Christine , Feufel Markus A.
Published: September 2024

Symptom-Assessment Application (SAAs) and Large Language Models (LLMs) are increasingly used by laypeople to navigate care options. Although humans ultimately make a final decision when using these systems, previous research has typically examined the performance of humans and SAAs/LLMs separately. Thus, it is unclear how decision-making unfolds in such hybrid human-technology teams and if SAAs/LLMs can improve laypeople's decisions. To address this gap, we conducted a convergent parallel mixed-methods study with semi-structured interviews and a randomized controlled trial. Our interview data revealed that in human-technology teams, decision-making is influenced by factors before, during, and after interaction. Users tend to rely on technology for information gathering and analysis but remain responsible for information integration and the final decision. Based on these results, we developed a model for technology-assisted self-triage decision-making. Our quantitative results indicate that when using a high-performing SAA, laypeople's decision accuracy improved from 53.2% to 64.5% (OR = 2.52, p < .001). In contrast, decision accuracy remained unchanged when using a LLM (54.8% before vs. 54.2% after usage, p = .79). These findings highlight the importance of studying SAAs/LLMs with humans in the loop, as opposed to analyzing them in isolation.
Patterns and functional consequences of antibody speciation in maternal-fetal transfer of coronavirus-specific humoral immunity
Authors: Hederman Andrew P. , Brookes Hannah M. , Natarajan Harini , Heyndrickx Leo , Ariën Kevin K. , Weiner Joshua A. , Rottenstreich Amihai , Zarbiv Gila , Wolf Dana , Goetghebuer Tessa , Marchant Arnaud , Ackerman Margaret E.
Published: September 2024

Maternal antibodies serve as a temporary form of inherited immunity, providing humoral protection to vulnerable neonates. Whereas IgG is actively transferred up a concentration gradient via the neonatal Fc Receptor (FcRn), maternal IgA and IgM are typically excluded from fetal circulation. Further, not all IgG molecules exhibit the same transfer efficiency, being influenced by subclass, Fab and Fc domain glycosylation, antigen-specificity, and the temporal dynamics of maternal antibody responses. Here, we investigate the phenotypes and functions of maternal and cord blood antibodies induced by SARS-CoV-2 infection and compare them to those induced by mRNA vaccination, focusing on breadth of antigen recognition and antiviral functions including neutralization and effector function. While cord blood coronavirus-specific antibody functional breadth and potency appeared to be more compromised than binding breadth and potency in both groups, vaccination induced substantially greater function and breadth in cord blood than did natural infection. These functional phenotypes were associated with speciation of the maternal serum repertoires, as some IgG subpopulations were enriched while others were relatively depleted. Relevant to the continued protection of vulnerable populations in the context of a diversifying pathogen, greater breadth was observed for antibody effector functions than for neutralization, and these activities were associated with greater affinity for antigen. This work provides insights into the functional breadth of maternal-fetal antibody responses in the context of novel mRNA vaccines and a recently emerged pathogen that is likely to be a public health burden for the foreseeable future.
Enhancing NADPH to Restore Redox Homeostasis and Lysosomal Function in G6PD-Deficient Microglia
Authors: Mondal Abir , Mukherjee Soumyadeep , Upadhyay Prince , Saxena Isha , Pati Soumya , Singh Shailja
Published: September 2024

Microglia, the residential immune cells in the central nervous system (CNS) exhibited in multiple states from resting to activated, play a significant role in neurogenesis, myelination, synaptic transmission, immune surveillance, and neuroinflammation. The aggravated inflammatory response by microglia triggers the generation of superoxide, which often causes the degeneration of neurons, leading to the development of Parkinson's and Alzheimer's. The oxidative stress is key to many neurological disorders, often regulated by many genes. The terminal neutralization of oxidative stress is mediated by NADPH and glutathione. The cytosolic NADPH level is majorly contributed by a key enzyme called glucose-6-phosphate dehydrogenase (G6PD). The deficiency of G6PD is associated with hemolytic anemia, diabetes, cardiovascular, autoimmune, and neurological disorders. Our recent study indicated that G6PD deficiency decreases cytosolic NADPH levels and alters redox homeostasis and lysosomal function in microglia. Therefore, replenishment of NADPH is crucial for targeting G6PD deficiency-mediated microglial dysfunctions. This research promotes alternate metabolic pathways by targeting the expression and activity of enzymes such as isocitrate dehydrogenase 1 (IDH1) and malic enzyme 1 (ME1), which are responsible for cytoplasmic NADPH production. Metabolites like citric and malic acid supplementation promote NADPH production and reduce microglial oxidative stress. Additionally, using another group of small molecule metabolites, such as dieckol and resveratrol, enhances the expression of IDH1 and ME1 enzymes to resolve potential tissue heterogeneity. Finally, combining these metabolites supplementation increased NADPH production and restored redox homeostasis and lysosomal function in G6PD deficient microglia, indicating their further use as potential therapeutics against G6PD deficiency disorders.
Repetitive magnetic stimuli over the motor cortex impair consolidation of a balance task by suppressing up-regulation of intracortical inhibition
Authors: Egger Sven , Wälchli Michael , Meyer Samuel , Taube Wolfgang
Published: September 2024

Low-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) was shown to impair short-term consolidation of a balance task, emphasizing the importance of M1 in balance skill consolidation. However, the disruptive mechanisms of rTMS on neural consolidation processes and their persistence across multiple balance acquisition sessions remain unclear. GABAergic processes are crucial for motor consolidation and, at the same time, are up-regulated when learning balance skills. Therefore, this study investigated the impact of rTMS on GABA-mediated short-interval intracortical inhibition (SICI) and consolidation of balance performance. Participants (n=31) underwent six balance acquisition sessions on a rocker board, each followed by rTMS (n=15) or sham-rTMS (n=16). In the PRE-measurement, SICI was assessed at baseline and after balance acquisition with subsequent rTMS/sham-rTMS. In the POST-measurement, this procedure was repeated to assess the influence of motor memory reactivation on SICI. In addition, SICI-PRE and SICI-POST were compared to assess long-term processes. Both groups achieved similar improvements within the balance acquisition sessions. However, they did not consolidate equally well indicated by significant declines in performance for the rTMS group (p= 0.006) in the subsequent sessions. Both short-(p= 0.014) and long-term (p= 0.038) adaptations in SICI were affected by rTMS: while the sham-rTMS group up-regulated SICI, rTMS led to reductions in inhibition. The interfering effect of rTMS on both balance consolidation and up-regulation of SICI suggests that increased intracortical inhibition is an important factor to protect and consolidate the newly acquired motor memory.
Different behaviourally relevant stimuli evoke different forms of adaptation in the olfactory system
Authors: Birkett Elliot , Nikolaev Anton
Published: September 2024

Sensory neurons are continuously exposed to a large diversity of stimuli and adjust their response according to the recent stimulation history, in a process called adaptation. Recent studies have demonstrated that many sensory neurons not only depress (decrease their response to repetitive sensory stimulation) but some neurons exhibit facilitation: a small initial response followed by increase in response amplitude. Adaptation has been mainly studied with neutral stimuli and it is not known whether different behaviourally relevant stimuli evoke adaptation with similar or different properties. Here we used ethologically relevant stimuli to study adaptation in the zebrafish olfactory system. We found that repetitive presentation of food odour caused a variety of adaptations ranging from very strong depression to facilitation, but depression was the predominant dynamic. On the other hand, a different behaviourally-relevant stimulus, alarm substance, evoked much stronger facilitation and also decreased the amplitude of responses to food presentation. Other sensory modalities, aversive mechanosensory and attractive visual stimuli, also caused adaptation with different properties in the same brain area. Different forms of adaptation may therefore be used for processing sensory stimuli evoking different behavioural reactions.

Graphical abstract

Highlights

Food odour evokes a diversity of adaptations ranging from extreme depression to facilitation

Alarm substance evokes much stronger facilitation than food odour

Alarm substance inhibits responses to food odour

Mechanosensory stimulation evokes both depression and facilitation

Visual stimuli evoke responses in the olfactory bulbs that strongly and quickly depress
Human NLRP3 inflammasome activation leads to formation of condensate at the microtubule organizing center
Authors: Wang Jue , Wu Man , Magupalli Venkat G. , Dahlberg Peter D. , Wu Hao , Jensen Grant J.
Published: September 2024

The NLRP3 inflammasome is a multi-protein molecular machine that mediates inflammatory responses in innate immunity. Its dysregulation has been linked to a large number of human diseases. Using cryogenic fluorescence-guided focused-ion-beam (cryo-FIB) milling and electron cryo-tomography (cryo-ET), we obtained 3-D images of the NLRP3 inflammasomein situat various stages of its activation at macromolecular resolution. The cryo-tomograms unexpectedly reveal dense condensates of the human macrophage NLRP3 inflammasome that form within and around the microtubule organizing center (MTOC). We also find that following activation, the trans-Golgi network disperses and 50-nm NLRP3-associated vesicles appear which likely ferry NLRP3 to the MTOC. At later time points after activation, the electron-dense condensates progressively solidify and the cells undergo pyroptosis with widespread damaged mitochondria and autophagasomal structures.
Evaluating the Effectiveness of Nirsevimab in Reducing Pediatric RSV Hospitalizations in Spain
Authors: Jimeno S. , Peláez A. , Labourt A. , Acuña F. , Linares L. , Llana Martín I. , Calle A , Natalini Martínez S.
Published: September 2024

Background and objective

Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Nirsevimab has demonstrated to be a promise tool for preventing severe RSV disease. Although clinical trials have demonstrated the efficacy of Nirsevimab in preventing severe RSV disease, evidence regarding its performance in real-world clinical settings is still limited due to its recent introduction. This study aims to fill this knowledge gap by evaluating the impact of Nirsevimab in a cohort of infants and determining its effectiveness in reducing the burden of RSV disease.

Methods

Retrospective study of RSV hospitalizations in children under six months of age, between October 1stand March 31st, across four seasons: pre-COVID (2018-2019), COVID (2019-2020), post-COVID pre-Nirsevimab (2022-2023), and Nirsevimab season (2023-2024).

Results

Nirsevimab has demonstrated significant efficacy in reducing RSV-related hospitalizations in infants under six months of age. During the 2023/24 season, following the introduction of Nirsevimab, there was a substantial reduction in RSV-related lower respiratory tract infection (LRTI) hospitalizations. Among infants under 3 months of age, hospitalizations decreased by 79.3% (IRR: 0.21, 95% CI: 0.12–0.34). In infants aged 3 to 6 months, there was a 66.9% reduction (IRR: 0.33, 95% CI: 0.15– 0.64). Additionally, Nirsevimab decreased the severity of RSV cases with LRTI who required support of equipment for sanitary use further reducing overall healthcare burden.

Conclusion

These results underscore Nirsevimab’s vital role in preventing severe RSV infections and hospitalizations, especially among the most vulnerable infants, positioning it as a critical advancement in pediatric respiratory care.
Longitudinal changes in epigenetic clocks predict survival in the InCHIANTI cohort
Authors: Kuo Pei-Lun , Moore Ann Zenobia , Tanaka Toshiko , Belsky Daniel W , Lu Ake Tzu-Hui , Horvath Steve , Bandinelli Stefania , Ferrucci Luigi
Published: September 2024

Abstracts

Importance

Cross-sectional assessment of epigenetic clocks provides information on the pace of aging. Whether longitudinal acceleration or deceleration of epigenetic clocks over time provides additional mortality prediction is unknown.

Objective

To test the independent associations of baseline levels and longitudinal changes in epigenetic clocks with mortality

Design

Longitudinal study

Setting

InCHIANTI, a population-based study of community dwelling individuals in Tuscany, Italy.

Participants

699 InCHIANTI study participants aged 21-95 years at baseline with longitudinal measurements of DNA methylation.

Exposure

Baseline levels and longitudinal changes in seven epigenetic clocks, including two first-generation clocks developed using chronological age for reference (Hannum Clock, Horvath Clock), three second-generation clocks developed using time-to-death for references (DNAmPhenoAge, DNAmGrimAge, DNAmGrimAge Version 2), and two third-generation clocks developed using longitudinal rate of change of multiple phenotypes for reference (DunedinPOAm_38, DunedinPACE).

Main Outcomes and Measures

Mortality was the primary outcome. Cox regression was used to estimate independent associations of baseline and longitudinal changes in epigenetic clocks with mortality.

Results

Adjusting for age, sex, study sites, and epigenetic clock at the baseline, longitudinal changes of the following epigenetic clocks were associated with mortality: Hannum clock (aHR = 1.14, 95% CI:[1.03, 1.26]), DNAmPhenoAge (aHR = 1.23, 95% CI: [1.10,1.37]), DNAmGrimAge (aHR = 1.13, 95% CI: [1.02,1.26]), DNAmGrimAge Version 2 (aHR = 1.18, 95% CI:[1.06,1.31]), and DunedinPOAm_38 (aHR = 1.15, 95%CI: [1.01,1.30]).

Conclusions and Relevance

Our findings confirm that epigenetic clocks capture a dimension of health that is predictive of mortality and add the notion that time changes of epigenetic age reflect changes in health that additionally and independently contribute to mortality prediction. Future studies should test whether interventions that slow down the rate of epigenetic aging are associated with longer healthspan and lifespan.

Key Points

Question: Is the rate of change in epigenetic clock associated with differential mortality?

Findings: In 699 adults with followed for up to 24 years, faster longitudinal changes in epigenetic clocks (Hannum clock, DNAmPhenoAge, DNAmGrimAge, DNAmGrimAge version 2, DunedinPOAm_38, DunedinPACE) were significantly associated with higher mortality, independent of baseline epigenetic age and other confounders.

Meaning: Independent of chronological age, epigenetic clock and change over time of epigenetic clock independently predicted the risk of death. Interventions that slow down the pace of epigenetic aging may enhance healthy longevity.
Accuracy of Online Symptom-Assessment Applications, Large Language Models, and Laypeople for Self-Triage Decisions: A Systematic Review
Authors: Kopka Marvin , von Kalckreuth Niklas , Feufel Markus A.
Published: September 2024

Symptom-Assessment Application (SAAs, e.g., NHS 111 online) that assist medical laypeople in deciding if and where to seek care (self-triage) are gaining popularity and their accuracy has been examined in numerous studies. With the public release of Large Language Models (LLMs, e.g., ChatGPT), their use in such decision-making processes is growing as well. However, there is currently no comprehensive evidence synthesis for LLMs, and no review has contextualized the accuracy of SAAs and LLMs relative to the accuracy of their users. Thus, this systematic review evaluates the self-triage accuracy of both SAAs and LLMs and compares them to the accuracy of medical laypeople. A total of 1549 studies were screened, with 19 included in the final analysis. The self-triage accuracy of SAAs was found to be moderate but highly variable (11.5 – 90.0%), while the accuracy of LLMs (57.8 – 76.0%) and laypeople (47.3 – 62.4%) was moderate with low variability. Despite some published recommendations to standardize evaluation methodologies, there remains considerable heterogeneity among studies. The use of SAAs should not be universally recommended or discouraged; rather, their utility should be assessed based on the specific use case and tool under consideration.
Parasitic and Commensal interactions among Mimiviruses, Sputnik-like virophages, and Transpovirons: A theoretical and dynamical systems approach
Authors: Ortega-Atehortúa Emmanuel , Rivera Parra Nicole , Rodríguez Boris A. , Machado-Rodríguez Gloria , Arboleda Rivera Juan Camilo
Published: September 2024

Giant viruses have been in the scope of virologists since 2003 when they were isolated fromAcanthamoebaspp. Giant viruses, in turn, get infected by another virus named virophage and a third biological entity that corresponds to a transpoviron which can be found in the capsids of giant and virophage viruses. So far, transpovirons seem to behave as commensal entities while some virophages exhibit commensal behavior under laboratory conditions. To study the system’s behavior, we used a theoretical approximation and developed an ordinary differential equation model. The dynamical analysis showed that the system exhibits an oscillatory robust behavior leading to a hyperparasitic Lotka-Volterra dynamic. But the biological mechanism that underlines the transpoviron persistence over time remains unclear and its status as a commensal entity needs further assessment. Also, the ecological interaction that leads to the overall coexistence of the three viral entities needs to be further studied.
Magnetic Protein Aggregates Generated by Supramolecular Assembly of Ferritin Cages - A Modular Strategy for the Immobilization of Enzymes
Authors: Ölçücü Gizem , Wollenhaupt Bastian , Kohlheyer Dietrich , Jaeger Karl-Erich , Krauss Ulrich
Published: September 2024

Efficient and cost-effective immobilization methods are crucial for advancing the utilization of enzymes in industrial biocatalysis. To this end,in vivoimmobilization methods relying on the completely biological production of immobilizates represent an interesting alternative to conventional carrier-based immobilization methods. In this contribution, we present a novel immobilization strategy utilizingin vivoproduced, magnetic protein aggregates (MPAs). MPA production is facilitated by the expression of gene fusions consisting of genes encoding for the yellow fluorescent protein variant citrine and variants of the iron storage protein ferritin, including a magnetically enhanced ferritin mutant fromEscherichia coli.Expression of the gene fusions allows supramolecular assembly of the fusion proteinsin vivo, which is driven by citrine-dependent dimerization of ferritin cages. Upon cell lysis, the assemblies coalesce in solution to form MPAs. The fusion of the mutantE. coliferritin to citrine yields fluorescent, insoluble protein aggregates that display magnetic properties, verified by their attraction to neodymium magnets. We further demonstrate that these novel, fullyin vivoproduced protein aggregates can be magnetically purified without the need forex vivoiron-loading. Utilizing a bait/prey strategy, MPAs were functionalized by the post-translational attachment of an alcohol dehydrogenase to the MPA particles to enable proof-of-concept for enzyme immobilization, giving rise to catalytically-active magnetic protein aggregates (CatMPAs). The resulting (Cat)MPAs could easily be obtained from crude cell extracts via centrifugation, or purified using magnetic columns, and exhibited superior stability. The strategy presented here therefore represents a highly modular method to produce magnetic enzyme immobilizates which can be obtained with high purity.
TheDrosophilaEstrogen-Related Receptor promotes triglyceride storage within the larval fat body
Authors: Fasteen Tess D. , Hernandez Melody R. , Policastro Robert A. , Sterrett Maria C. , Zenter Gabriel E. , Tennessen Jason M.
Published: September 2024

The Estrogen-Related Receptor (ERR) family of nuclear receptors (NRs) serve key roles in coordinating triglyceride (TAG) accumulation with juvenile growth and development. In both insects and mammals, ERR activity promotes TAG storage during the post-embryonic growth phase, with loss-of-function mutations in mouseEsrraandDrosophila melanogaster dERRinducing a lean phenotype. However, the role of insect ERRs in controlling TAG accumulation within adipose tissue remains poorly understood, as previous transcriptomic and metabolomic studies relied on whole animal analyses. Here we address this shortcoming by using tissue-specific approaches to examine the role of dERR in regulating lipid metabolism within theDrosophilalarval fat body. We find that dERR autonomously promotes TAG accumulation within fat body cells and regulates expression of genes involved in glycolysis, β-oxidation, and mevalonate metabolism. As an extension of these results, we not only discovered thatdERRmutant fat bodies exhibit decreased expression of known dHNF4 target genes but also found that dHNF4 activity is decreased indERRmutants. Overall, our findings indicate that dERR plays a multifaceted role in the larval fat body to coordinate lipid storage with developmental growth and hint at a conserved mechanism by which ERR and HNF4 homologs coordinately regulate metabolic gene expression.
Early intrinsic plasticity of ACC engram neurons defines memory formation and precision
Authors: Hadzibegovic Senka , Zhu Liangying , Ginger Melanie , De Sa Rafael , Le Corf Katy , Costa Maria JG , Le Feuvre Yves , Nicole Olivier , Bontempi Bruno , Frick Andreas
Published: September 2024

Neocortical memory engrams are thought to stabilize and mature via enhanced interconnectivity during the so-called systems-consolidation process. While synaptic plasticity of these engram connections is considered an important mechanism for storing memories, it cannot fully account for the dynamic vividness of remote, cortically-based memories. Indeed, cell-intrinsic plasticity has been touted as the crucial early priming mechanism that renders nascent engram neurons susceptible to ongoing plastic processes while providing flexibility for later encoding events. Here, we reveal that learning-related neuron-wide intrinsic excitability (IE) plasticity of nascent cortical engram neurons is a permissive mechanism for the formation and specificity of remote associative memories. Using a c-fos-dependent genetic and viral system for the targeted labeling of engram neurons in the anterior cingulate cortex (ACC) combined with ex vivo electrophysiology, we found that contextual fear learning triggered a time-dependent increase in their IE signature expressed over days during the early, but not late, phase of memory formation. Remarkably, chemogenetically hyperpolarizing engram neurons during this early plastic phase enhanced their maturation, increasing the strength and context-precision of consolidated memories and preventing memory disturbance caused by an interference event. Altogether, our findings identify cell-intrinsic plasticity within nascent ACC engram neurons as an essential tagging mechanism whose features determine the fate and dynamic content of remote memories.
Lower perceived stress enhances neural synchrony in perceptual and attentional cortices during naturalistic processing
Authors: Craig J. , Matisz C. , Klamer K. , Haines C. , Sullivan K. , Ekstrand C.
Published: September 2024

Perceived stress is the subjective appraisal of the level of stress experienced by an individual in response to external or internal demands. Recent research on perceived stress has highlighted its role in influencing cognition, leading to a disruption in cognitive processes, such as emotional processing, attention, and perception. However, most neuroimaging studies examining stress have used static stimuli (e.g., still images) that do not encapsulate real-life multimodal processing in the brain. The current research uses data from the Naturalistic Neuroimaging Database (v2.0; Aliko et al., 2020) to examine differences in neural synchrony (as measured by intersubject correlations; ISCs) associated with perceived stress using functional magnetic resonance imaging (fMRI). We evaluated how self-reported perceived stress levels influence neural synchrony patterns in response to different naturalistic stimuli by examining the differences in neural synchrony between individuals with low and high perceived stress levels. We determined that lower perceived stress was observed with greater neural synchrony areas associated with perceptual and attention processing, including the lateral occipital cortex, superior temporal gyrus, superior parietal lobule, orbital frontal cortex, and the occipital pole. These results indicate that high levels of perceived stress heavily alter neural processing of complex audiovisual stimuli. Together, these results provide evidence that perceived stress influences cognitive processing in everyday life.