bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel FABP4+C1q+ macrophages enhance antitumor immunity and associated with response to neoadjuvant pembrolizumab and chemotherapy in NSCLC via AMPK/JAK/STAT axis
Authors: Zhang Dong , Wang Min , Liu Gen , Li Xin , Yu Wenwen , Hui Zhenzhen , Ren Xiubao , Sun Qian 
Published: October 2024

Abstract
Immune checkpoint inhibitors (ICIs) immunotherapy facilitates new approaches to achieve precision cancer treatment. A growing number of patients with non-small cell lung cancer (NSCLC) have benefited from treatment with neoadjuvant ICIs combined with chemotherapy. However, the mechanisms and associations between the therapeutic efficacy of neoadjuvant pembrolizumab and chemotherapy (NAPC) and macrophage subsets are still unclear. We performed single-cell RNA sequencing (scRNA-seq) and identified a novel FABP4+C1q+ macrophage subtype, which exhibited stronger proinflammatory cytokine production and phagocytic ability. This subtype was found to be more abundant in tumor tissues and lymph nodes of major pathological response (MPR) patients compared to non-MPR patients, and was associated with a good efficacy of NAPC. Multiplex fluorescent immunohistochemical (mIHC) staining was subsequently used to verify our findings. Further mechanistic studies indicated that FABP4 and C1q regulate the expression of proinflammatory cytokines synergistically. In addition, FABP4 and C1q promote fatty acid synthesis, enhance anti-apoptosis ability and phagocytic ability of macrophage via the interaction of AMPK/JAK/STAT axis. This study provides novel insights into the underlying mechanisms and predictive biomarkers of NAPC. Our findings contribute to improving the prognosis of patients with NSCLC by potentially guiding more precise patient selection and treatment strategies.

Novelty & Impact Statements

We identified a group of macrophages (FABP4+C1q+ macrophages) related to the therapeutic efficacy of neoadjuvant chemoimmunotherapy. FABP4+C1q+ macrophages highly expressed proinflammatory cytokines-related genes and had a strong cytokine production and phagocytic ability. We believe that our study provides a novel insight into the synergistic mechanism of neoadjuvant ICI combined with chemotherapy and may lead to improved clinical outcomes in patients with NSCLC in the future.
STAT6/LINC01637 axis regulates tumor growth via autophagy and pharmacological targeting STAT6 as a novel strategy for uveal melanoma
Authors: Liu Bo , Yao Xueting , Huang Qinying , Fan Yichao , Yu Bo , Wang Jing , Wu Wencan , Dai Jinhui 
Published: October 2024

AbstractCompelling evidence has revealed a novel function of the STAT pathway in the pathophysiology of uveal melanoma (UM); however, its regulatory mechanisms remain unclear. Here, we analyzed the clinical prognostic value of STAT family genes in UM patients using bioinformatics approaches and found that high STAT6 expression is associated with poor prognosis. Furthermore, cellular experiments and a nude mouse model demonstrated that STAT6 promotes UM progression through the autophagy pathway both in vivo and in vitro. Next, RIP-PCR revealed that STAT6 protein binds to LINC01637 mRNA, which in turn regulates STAT6 expression to promote UM growth. Finally, molecular docking indicated that STAT6 is a target of Zoledronic Acid, which can delay UM tumorigenicity by inhibiting STAT6 expression. Taken together, our results indicate that the STAT6/LINC01637 axis promotes UM progression via autophagy and may serve as a potential therapeutic target for UM.
Structural basis for the rescue of hyperexcitable cells by the amyotrophic lateral sclerosis drug Riluzole
Authors: Hollingworth David , Thomas Frances , Page Dana A. , Fouda Mohamed A. , De Castro Raquel Lopez-Rios , Sula Altin , Mykhaylyk Vitaliy B. , Kelly Geoff , Ulmschneider Martin B. , Ruben Peter C. , Wallace B. A. 
Published: September 2024

AbstractNeuronal hyperexcitability is a key element of many neurodegenerative disorders including the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), where it occurs associated with elevated late sodium current (INaL). INaL results from incomplete inactivation of voltage-gated sodium channels (VGSCs) after their opening and shapes physiological membrane excitability. However, dysfunctional increases can cause hyperexcitability-associated diseases. Here we reveal the atypical binding mechanism which explains how the neuroprotective ALS-treatment drug riluzole stabilises VGSCs in their inactivated state to cause the suppression of INaL that leads to reversed cellular overexcitability. Riluzole accumulates in the membrane and enters VGSCs through openings to their membrane-accessible fenestrations. Riluzole binds within these fenestrations to stabilise the inactivated channel state, allowing for the selective allosteric inhibition of INaL without the physical block of Na+ conduction associated with traditional channel pore binding VGSC drugs. We further demonstrate that riluzole can reproduce these effects on a disease variant of the non-neuronal VGSC isoform Nav1.4, where pathologically increased INaL is caused directly by mutation. Overall, we identify a model for VGSC inhibition that produces effects consistent with the inhibitory action of riluzole observed in models of ALS. Our findings will aid future drug design and supports research directed towards riluzole repurposing.
Caspase-1-dependent spatiality in triple-negative breast cancer and response to immunotherapy
Authors: Zheng Weiyue , Marini Wanda , Murakami Kiichi , Sotov Valentin , Butler Marcus , Gorrini Chiara , Ohashi Pamela S. , Reedijk Michael 
Published: October 2024

AbstractTumor immune microenvironment (TIME) spatial organization predicts outcome and therapy response in triple-negative breast cancer (TNBC). An immunosuppressive TIME containing elevated tumor-associated macrophages (TAM) and scarce CD8+ T cells is associated with poor outcome, but the regulatory mechanisms are poorly understood. Here we show that ETS1-driven caspase-1 expression, required for IL1β processing and TAM recruitment, is negatively regulated by estrogen receptors alpha (ERα) and a defining feature of TNBC. Elevated tumoral caspase-1 is associated with a distinct TIME characterized by increased pro-tumoral TAMs and CD8+ T cell exclusion from tumor nests. Mouse models prove the functional importance of ERα, ETS1, caspase-1 and IL1β in TIME conformation. Caspase-1 inhibition induces an immunoreactive TIME and reverses resistance to immune checkpoint blockade, identifying a therapeutically targetable mechanism that governs TNBC spatial organization.
Temporal asymmetries in inferring unobserved past and future events
Authors: Xu Xinming , Zhu Ziyan , Zheng Xueyao , Manning Jeremy R. 
Published: October 2024

AbstractUnlike temporally symmetric inferences about simple sequences, inferences about our own lives are asymmetric: we are better able to infer the past than the future, since we remember our past but not our future. Here we explore whether there are asymmetries in inferences about the unobserved pasts and futures of other people’s lives. In two experiments (analyses of the replication experiment were pre-registered), our participants view segments of two character-driven television dramas and write out what they think happens just before or after each just-watched segment. Participants are better at inferring unseen past (versus future) events. This asymmetry is driven by participants’ reliance on characters’ conversational references in the narrative, which tend to favor the past. This tendency is also replicated in a large-scale analysis of conversational references in natural conversations. Our work reveals a temporal asymmetry in how observations of other people’s behaviors can inform inferences about the past and future.
Cellular location shapes quaternary structure of enzymes
Authors: Abrusán György , Zelezniak Aleksej 
Published: October 2024

AbstractThe main forces driving protein complex evolution are currently not well understood, especially in homomers, where quaternary structure might frequently evolve neutrally. Here we examine the factors determining oligomerisation by analysing the evolution of enzymes in circumstances where homomers rarely evolve. We show that 1) In extracellular environments, most enzymes with known structure are monomers, while in the cytoplasm homomers, indicating that the evolution of oligomers is cellular environment dependent; 2) The evolution of quaternary structure within protein orthogroups is more consistent with the predictions of constructive neutral evolution than an adaptive process: quaternary structure is gained easier than it is lost, and most extracellular monomers evolved from proteins that were monomers also in their ancestral state, without the loss of interfaces. Our results indicate that oligomerisation is context-dependent, and even when adaptive, in many cases it is probably not driven by the intrinsic properties of enzymes, like their biochemical function, but rather the properties of the environment where the enzyme is active. These factors might be macromolecular crowding and excluded volume effects facilitating the evolution of interfaces, and the maintenance of cellular homeostasis through shaping cytoplasm fluidity, protein degradation, or diffusion rates.
Reduced subthalamic and subthalamic-cortical coherences associated with the therapeutic carryover effect of coordinated reset deep brain stimulation
Authors: Zheng Lvpiao , Luo Ziling , Mohanty Biswaranjan , Amoozegar Sana , Johnson Luke A. , Vitek Jerrold L. , Wang Jing 
Published: September 2024

AbstractCoordinated reset deep brain stimulation (CR DBS), a promising treatment for Parkinson’s disease (PD), is hypothesized to desynchronize neuronal populations. However, little in vivo data probes this hypothesis. In a parkinsonian nonhuman primate, we found that subthalamic CR DBS suppressed subthalamic and cortical-subthalamic coherences in the beta band, correlating with motor improvements. Our results support the desynchronizing mechanism of CR DBS and propose potential biomarkers for closed-loop CR DBS.
Empirical modelling of 2205 DSS flow curves using strain-compensated Arrhenius rate-type constitutive model
Authors: Gonya Elvis M. , Siyasiya Charles W. , Makhatha Mamookho E. 
Published: September 2024

AbstractThis work predicts, hot flow curves of 2205 DSS using strain-compensated Arrhenius rate-type constitutive model. Twenty-five (25) × Ø10 diameter × 15 mm height cylindrical samples were hot compressed at a temperature between 850 and 1050 °C at an interval of 50 °C and strain rates between 0.001 and 5 s−1, using Gleeble 1500D. After the tests, corrected flow curves were plotted followed by computation of deformations constants at various deformation conditions using steady state stress. The values of the constants were (α = 0.009708, Q = 445 kJ/mol and n = 3.7) and seemed comparable to the previous studies of DSS. Steady state predictive model was then constructed using the calculated constants and showed a reasonably good accuracy with low value of MARE = 7.78%. Furthermore, calculated strain compensated Arrhenius rate type model was used to predict flow curves at various deformation. The model had a good estimation of flow curves of flow curves at 900–1050 °C across all strain rates as reflected by MARE = 5.47%. A notable discrepancy between predicted and experimental flow stress was observed at 850 °C and across all the strain rates. A model refinement using generalised reduced gradient improved the accuracy of the model by 34.7% despite deformation conditions at 850 °C and low strain rates (0.01/ 0.1) s−1 showing minimum improvement. Further modification of Z-parameter by compensating for the strain rate improved the accuracy of the model at 850 °C/0.01 s−1/0.1 s−1. Lastly, a comparison of the current model with the other non-linear model showed that the latter was more accurate in estimation of flow curves since it relied on characteristics flow stress points controlled by underlying active deformation mechanisms.
Optimal parameter identification of solid oxide fuel cell using modified fire Hawk algorithm
Authors: Khajuria Rahul , Bukya Mahipal , Lamba Ravita , Kumar Rajesh 
Published: September 2024

AbstractAn accurate and efficient approach is required to identify the unknown parameters of solid oxide fuel cell (SOFC) mathematical model for a robust design of any energy system considering SOFC. This research study proposes a modified fire hawk algorithm (MFHA) to determine the values of SOFC model parameters. The performance evaluation of MFHA is tested on two case studies. Firstly, the performance of MFHA is tested on commercially available cylindrical cell developed by Siemens at four temperatures. Results reveal that the least value of sum of squared error (SSE) is 1.04E−05, 2.30E−05, 1.03E−05, and 1.60E−05 at 1073 K, 1173 K, 1213 K, and 1273 K respectively. Results obtained using MFHA have been compared with original fire hawk algorithm (FHA) and other well established and recent algorithms. Secondly, MFHA is implemented for estimating unknown parameters of a 5 kW dynamic tabular stack of 96 cells at various pressures and temperatures. The obtained value of SSE at different temperatures of 873 K, 923 K, 973 K, 1023 K and 1073 K is 1.18E−03, 6.12E−03, 2.21E−02, 5.18E−02, and 6.00E−02, respectively whereas, SSE at different pressures of 1 atm, 2 atm, 3 atm, 4 atm, and 5 atm is 6.05E−02, 6.11E−02, 5.53E−02, 5.11E−02, and 6.64E−02 respectively.
Lack of optimistic bias during social evaluation learning reflects reduced positive self-beliefs in depression and social anxiety, but via distinct mechanisms
Authors: Hoffmann Janina A. , Hobbs Catherine , Moutoussis Michael , Button Katherine S. 
Published: September 2024

AbstractProcessing social feedback optimistically may maintain positive self-beliefs and stable social relationships. Conversely, a lack of this optimistic bias in depression and social anxiety may perpetuate negative self-beliefs and maintain symptoms. Research investigating this mechanism is scarce, however, and the mechanisms by which depressed and socially anxious individuals respond to social evaluation may also differ. Using a range of computational approaches in two large datasets (mega-analysis of previous studies, n = 450; pre-registered replication study, n = 807), we investigated how depression (PHQ-9) and social anxiety (BFNE) symptoms related to social evaluation learning in a computerized task. Optimistic bias (better learning of positive relative to negative evaluations) was found to be negatively associated with depression and social anxiety. Structural equation models suggested this reflected a heightened sensitivity to negative social feedback in social anxiety, whereas in depression it co-existed with a blunted response to positive social feedback. Computational belief-based learning models further suggested that reduced optimism was driven by less positive trait-like self-beliefs in both depression and social anxiety, with some evidence for a general blunting in belief updating in depression. Recognizing such transdiagnostic similarities and differences in social evaluation learning across disorders may inform approaches to personalizing treatment.
Experimental study on the parameters affecting the performance of spiral tube pump
Authors: Meseret Million , Wami Dawit , Nallamothu Ramesh Babu 
Published: September 2024

AbstractThis experimental study delves into the critical parameters influencing the performance of spiral tube pumps—a centuries-old technology attributed to H.A. Wirtz in 1746. The Spiral Tube Pump system, constructed using a transparent flexible tube wound spirally on a waterwheel, harnesses the kinetic energy of a river, offering a simple, cost-effective, and emission-free irrigation solution using locally available materials. Operating on the principles of a manometer, water and air plugs are pushed into the pipe alternately by the pump. Key factors crucial to enhancing the performance of this technology are investigated, focusing on submergence ratio, rotational speed, outer diameter, and the number of turns of the spiral tube. The experimental setup involves a prototype featuring a 4-meter-long, ¾-inch diameter transparent flexible tube spirally wound on a 1.5-meter-wide water wheel, achieving a maximum output of approximately 30 L per minute discharge and a 3.3-meter head. Through a series of rigorous experimental procedures, it becomes evident that wheel speed and submergence ratio significantly impact the pump’s discharge. For 600% increase in wheel speed, up to about 500% discharge increase was observed. Also for 300% increase in submergence ratio, up to about 275% increase in discharge was observed. The number of spiral turns predominantly influences the pump’s head. For 100% increase in spiral turn, up to about 33% increment in head was observed. And the outer diameter affects both discharge and head. For 87% increase in outer diameter, up to about 80% of increase in discharge and up to about 163% increase in head was observed. These findings underscore the adaptability of the Spiral Tube Pump design to specific irrigation field conditions. For instance, in scenarios where the irrigation field is elevated relative to the river, incorporating a greater number of spiral tube turns can enhance the pump’s efficiency in transporting water to the desired location.
Assessing and correcting neighborhood socioeconomic spatial sampling biases in citizen science mosquito data collection
Authors: Padilla-Pozo Álvaro , Bartumeus Frederic , Montalvo Tomás , Sanpera-Calbet Isis , Valsecchi Andrea , Palmer John R. B. 
Published: September 2024

AbstractClimatic, ecological, and socioeconomic factors are facilitating the spread of mosquito-borne diseases, heightening the importance of vector surveillance and control. Citizen science is proving to be an effective tool to track mosquito populations, but methods are needed to detect and account for small scale sampling biases in citizen science surveillance. In this article we combine two types of traditional mosquito surveillance records with data from the Mosquito Alert citizen science system to explore the ways in which the socioeconomic characteristics of urban neighborhoods result in sampling biases in citizen scientists’ mosquito reports, while also shaping the spatial distribution of mosquito populations themselves. We use Barcelona, Spain, as an example, and focus on Aedes albopictus, an invasive vector species of concern worldwide. Our results suggest citizen scientists’ sampling effort is focused more in Barcelona’s lower and middle income census tracts than in its higher income ones, whereas Ae. albopictus populations are concentrated in the city’s upper-middle income tracts. High resolution estimates of the spatial distribution of Ae. albopictus risk can be improved by controlling for citizen scientists’ sampling effort, making it possible to provide better insights for efficiently targeting control efforts. Our methodology can be replicated in other cities faced with vector mosquitoes to improve public health responses to mosquito-borne diseases, which impose massive burdens on communities worldwide.
Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to pneumococcal vaccination
Authors: Morgan Duncan M. , Zhang Yiming J. , Kim Jin-Hwan , Murillo MaryAnn , Singh Suddham , Loschko Jakob , Surendran Naveen , Sekulovic Ognjen , Feng Ellie , Shi Shuting , Irvine Darrell J. , Patil Sarita U. , Kanevsky Isis , Chorro Laurent , Christopher Love J. 
Published: September 2024

AbstractSingle-cell RNA sequencing (scRNA-seq) can resolve transcriptional features from individual cells, but scRNA-seq techniques capable of resolving the variable regions of B cell receptors (BCRs) remain limited, especially from widely-used 3′-barcoded libraries. Here, we report a method that can recover paired, full-length variable region sequences of BCRs from 3′-barcoded scRNA-seq libraries. We first verify this method (B3E-seq) can produce accurate, full-length BCR sequences. We then apply this method to profile B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in five infant rhesus macaques. We identify BCR features associated with specificity for the ST3 antigen which are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and profile antigen-specific responses elicited by vaccination.
Nitric oxide induces the distinct invisibility phenotype of Mycobacterium tuberculosis
Authors: Gap-Gaupool Brindha , Glenn Sarah M. , Milburn Emily , Turapov Obolbek , Crosatti Marialuisa , Hincks Jennifer , Stewart Bradley , Bacon Joanna , Kendall Sharon L. , Voskuil Martin I. , Riabova Olga , Monakhova Natalia , Green Jeffrey , Waddell Simon J. , Makarov Vadim A. , Mukamolova Galina V. 
Published: September 2024

AbstractDuring infection Mycobacterium tuberculosis (Mtb) forms physiologically distinct subpopulations that are recalcitrant to treatment and undetectable using standard diagnostics. These difficult to culture or differentially culturable (DC) Mtb are revealed in liquid media, their revival is often stimulated by resuscitation-promoting factors (Rpf) and prevented by Rpf inhibitors. Here, we investigated the role of nitric oxide (NO) in promoting the DC phenotype. Rpf-dependent DC Mtb were detected following infection of interferon-γ-induced macrophages capable of producing NO, but not when inducible NO synthase was inactivated. After exposure of Mtb to a new donor for sustained NO release (named NOD), the majority of viable cells were Rpf-dependent and undetectable on solid media. Gene expression analyses revealed a broad transcriptional response to NOD, including down-regulation of all five rpf genes. The DC phenotype was partially reverted by over-expression of Rpfs which promoted peptidoglycan remodelling. Thus, NO plays a central role in the generation of Rpf-dependent Mtb, with implications for improving tuberculosis diagnostics and treatments.
Nitrogen deposition contributed to a global increase in nitrous oxide emissions from forest soils
Authors: Cen Xiaoyu , Müller Christoph , Kang Xiaoyan , Zhou Xuhui , Zhang Jinbo , Yu Guirui , He Nianpeng 
Published: September 2024

AbstractNitrous oxide is a potent greenhouse gas. Anthropogenically enhanced nitrogen deposition causes natural forest soils to release more nitrous oxide, exacerbating global warming. We used data from nitrogen addition experiments conducted in forests worldwide to quantify the spatially varying sensitivity of soil nitrous oxide emission to nitrogen deposition, thereby inferring soil nitrous oxide emission dynamics from nitrogen deposition data. From 1985 to 2015, nitrous oxide emitted from global forest soils increased from 3.55 to 3.85 teragrams of nitrogen per year. Nitrogen deposition contributed directly to 9.0% of global forest soil nitrous oxide emissions. The derived country-specific sensitivities of soil nitrous oxide emission to nitrogen deposition could be employed as localized emission factors for forestland nitrous oxide emission inventories. This study sheds light on a process-augmented data-driven approach to estimating global nitrous oxide emissions by synthesizing experimental and observational data.