Miracle-dz/UniFAR-FTUs huggingface dataset:
Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer

Background Cryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated the local and systemic immunological effects of cryoablation and the potential of combining cryoablation with programmed cell death protein 1 (PD-1) blockade to boost immunotherapy efficacy in NSCLC. Methods We first investigated systemic immunological effects induced by cryoablation in patients with early-stage NSCLC. Subsequently, we explored cryoablation-induced antitumor immunity and the underlying biological mechanisms using KP (Kras G12D/+, Tp53 −/−) mutant lung cancer cell allograft mouse models. Moreover, the synergistic efficacy of cryoablation and PD-1 blockade was explored in both mouse models and patients with unresectable NSCLC. Results We found that cryoablation significantly increased circulating CD8+ T cell subpopulations and proinflammatory cytokines in patients with early-stage NSCLC. In lung cancer cell allograft mouse models, we demonstrated that cryoablation resulted in abscopal growth inhibition of contralateral, non-ablated tumors. Integrated analysis of bulk, single-cell RNA and T cell receptor (TCR) sequencing data revealed that cryoablation reprogrammed the intratumoral immune microenvironment and increased CD8+ T cell infiltration with higher effector signature, interferon (IFN) response, and cytolytic activity. Mechanistically, cryoablation promoted antitumor effect through the STING-dependent type I IFN signaling pathway, and type I IFN signaling blockade attenuated this antitumor effect. We also found that the combination of PD-1 blockade with cryoablation further inhibited tumor growth compared with either treatment alone in an allograft mouse model. Moreover, the combination therapy induced notable tumor suppression and CD8+ T cell infiltration in patients with unresectable NSCLC. Conclusions Our results provide mechanistic insights into how cryoablation triggers the antitumor immune effect in lung cancer, thereby potentiating programmed cell death ligand 1 (PD-L1)/PD-1 blockade efficacy in the clinical treatment of NSCLC.
How to achieve green development? A study on spatiotemporal differentiation and influence factors of green development efficiency in China

For a long time, China ’s extensive economic development model has produced a large amount of emissions, which has brought indelible damage to the environment. Green development is of vital importance for China to achieve high-quality development, and it is the core of alleviating environmental problems and promoting sustainable development. How to achieve China ’s green development requires us to evaluate the level of green development in China ’s provinces and analyze the reasons. In this study, an evaluation index system including undesired output of green development efficiency is constructed, and then the Supe-SBM model is used to assess the green development efficiency of 30 Chinese provinces. This paper also discusses the spatial and temporal differences as well as the factors affecting green development efficiency of green development efficiency among provinces. The findings demonstrate: (1) The green development efficiency in the eastern region is the highest, followed by the western region, while the central region has the lowest, but they all show a downward trend. (2) The spatial characteristics of green development efficiency are remarkable, according to the Global Moran’s I index. However, the results of local spatial agglomeration demonstrate "small agglomeration and large dispersion," with the majority of provinces exhibiting L-L agglomeration. (3) Technological Progress, Opening Up, Urbanization Level are positively correlated with the green development efficiency. Industrial Structure, Financial Development, Energy Structure and green development efficiency are significantly negatively correlated, while Environmental Regulation shows no significant impact.
Norepinephrine induces anoikis resistance in high-grade serous ovarian cancer precursor cells

High-grade serous carcinoma (HGSC) is the most lethal gynecological malignancy in the United States. Late diagnosis and the emergence of chemoresistance have prompted studies into how the tumor microenvironment, and more recently tumor innervation, may be leveraged for HGSC prevention and interception. In addition to stess-induced sources, concentrations of the sympathetic neurotransmitter norepinephrine (NE) in the ovary increase during ovulation and after menopause. Importantly, NE exacerbates advanced HGSC progression. However, little is known about the role of NE in early disease pathogenesis. Here, we investigated the role of NE in instigating anchorage independence and micrometastasis of preneoplastic lesions from the fallopian tube epithelium (FTE) to the ovary, an essential step in HGSC onset. We found that in the presence of NE, FTE cell lines were able to survive in ultra-low-attachment (ULA) culture in a β-adrenergic receptor–dependent (β-AR–dependent) manner. Importantly, spheroid formation and cell viability conferred by treatment with physiological sources of NE were abrogated using the β-AR blocker propranolol. We have also identified that NE-mediated anoikis resistance may be attributable to downregulation of colony-stimulating factor 2. These findings provide mechanistic insight and identify targets that may be regulated by ovary-derived NE in early HGSC.
Bodily maps of musical sensations across cultures

Significance Music is inherently linked with the body. Here, we investigated how music's emotional and structural aspects influence bodily sensations and whether these sensations are consistent across cultures. Bodily sensations evoked by music varied depending on its emotional qualities, and the music-induced bodily sensations and emotions were consistent across the tested cultures. Musical features also influenced the emotional experiences and bodily sensations consistently across cultures. These findings show that bodily feelings contribute to the elicitation and differentiation of music-induced emotions and suggest similar embodiment of music-induced emotions in geographically distant cultures. Music-induced emotions may transcend cultural boundaries due to cross-culturally shared links between musical features, bodily sensations, and emotions.
Worldwide Distribution and Extracutaneous Manifestations of Henoch-Schönlein Purpura in Adults: Narrative Review

Background Henoch-Schönlein purpura (HSP), a leukocytoclastic small vessel vasculitis, exhibits both cutaneous and systemic manifestations. While predominantly observed in childhood, it may manifest in adults with more pronounced systemic involvement. Furthermore, HSP is a global phenomenon showcasing epidemiological and systemic variances. Objective This study aims to scrutinize extracutaneous manifestations in adults with HSP, discerning distinctions according to geographical regions on a worldwide scale. Methods A comprehensive search encompassing PubMed, Embase, Cochrane Library, and Web of Science was executed, covering papers published from January 1, 1970, to December 1, 2019. Keywords used included “Henoch-Schönlein purpura,” “henoch schonlein purpura+adult,” “IgA vasculitis+adult,” “HSP+adult,” and “IgAV. ” A total of 995 publications were identified, from which 42 studies encompassing 4064 patients were selected, with a predominant focus on cases reported in Asia, Europe, and the Americas. Results Among adults afflicted with HSP, European patients exhibited a higher propensity for male predominance (P<.001), gastrointestinal involvement (P<.001), and musculoskeletal complications (P<.001). Conversely, patients from the Americas were least likely to experience genitourinary involvement (P<.001). Conclusions HSP demonstrates a variance in distribution and extracutaneous manifestations within distinct geographical boundaries. In the adult population, European patients exhibited a higher prevalence of male gender and gastrointestinal and musculoskeletal involvement. Asian patients were more predisposed to genitourinary involvement when compared to their American counterparts. The establishment of prospective studies using standardized reporting measures is imperative to validate the relationships unveiled in this investigation.
Multisensory strategies for postural compensation after lateral line loss

To control elevation underwater, aquatic vertebrates integrate multisensory information (e.g., vestibular, visual, proprioceptive) to guide posture and swim kinematics. Here we characterized how larval zebrafish changed posture and locomotive strategies after imposed instability (decreased buoyancy) in the presence and absence of visual cues. We discovered that larvae sank more after acute loss of lateral line (flow-sensing) hair cells. In response, larvae engaged different compensatory strategies, depending on whether they were in the light or dark. In the dark, larvae swam more frequently, engaging their trunk to steer their nose up and climb more effectively. However, in the light, larvae climbed more often, engaging both pectoral fins and trunk to elevate. We conclude that larvae sense instability and use vestibular and visual information as available to control posture and trajectory. Our work is a step towards understanding the multisensory neural computations responsible for control strategies that allow orientation and navigation in depth.
Chaperone quality control in liquid-phase separated organelles

Molecular chaperones, central to the cellular proteostasis network, play an essential role in preventing the formation and proliferation of harmful aggregates associated with neurodegenerative diseases. Notably, for many intrinsically disordered proteins (IDPs), which are prone to form such damaging deposits, the formation of nano-clusters and phase separation into organelles prior to aggregation have been observed. The impact of molecular chaperones on such assemblies, remains unclear. In our study, we concentrated on the family of small heat shock proteins (sHsps), which are typically dynamic and form large oligomeric structures. While sHsps are mainly structured/folded proteins, they can undergo transient multivalent interactions, like many IDPs. Thus, sHsps might be a suitable regulator for vital and ubiquitous formation of membrane-less organelles in eukaryotic cells rich in IDPs and to inhibit aberrant aggregation. Here we show, using microfluidic diffusional sizing, that the formation of nano-clusters of FUS, associated with neurodegenerative diseases can be inhibited by the presence of sHsps. Furthermore, we identify that, depending on their assembly state, sHsps are capable of targeting specifically the interface between the dense droplet phase and the dilute phase not only of FUS but also of TDP-43, likely because the interface is the primary starting point for fibril formation or protein aggregation in general. Our findings emphasise the impact of molecular chaperones on maintaining the homeostasis of IDPs in the dilute and condensed phase. This could help to understand how chaperone dysregulation can influence aberrant protein association.
edgeR 4.0: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets

edgeR is an R/Bioconductor software package for differential analyses of sequencing data in the form of read counts for genes or genomic features. Over the past 15 years, edgeR has been a popular choice for statistical analysis of data from sequencing technologies such as RNA-seq or ChIP-seq. edgeR pioneered the use of the negative binomial distribution to model read count data with replicates and the use of generalized linear models to analyse complex experimental designs. edgeR implements empirical Bayes moderation methods to allow reliable inference when the number of replicates is small. This article announces edgeR version 4, which includes new developments across a range of application areas. Infrastructure improvements include support for fractional counts, implementation of model fitting in C++, and a new statistical treatment of the quasi-likelihood pipeline that improves accuracy for small counts. The revised package has new functionality for differential methylation analysis, differential transcript expression, differential transcript and exon usage, testing relative to a fold-change threshold and pathway analysis. This article reviews the statistical framework and computational implementation of edgeR, briefly summarizing all the existing features and functionalities but with special attention to new features and those that have not been described previously.
Development of an irrigation scheduling recommendation for pomegranate trees (Punica granatum)

Pomegranate culture in Spain is concentrated in the south east, where water available is scarce. There is a need for providing growers with some irrigation recommendations for improving water use efficiency. For this purpose, information from indicators of the continuous soil-plant-atmosphere is being used in a commercial drip irrigated pomegranate orchard, for delivering to growers a weekly irrigation recommendation, taking into account the reference evapotranspiration, plant water status determined via stem water potential measurements and the soil water available to plant obtained from capacitance probes that measured soil water content at different depths. Watering recommendations are calculated in order to fulfil crop water requirements and also avoid water percolation. The average annual water application has been around 425 mm. The information obtained has been transferred by means of an experimental crop coefficient (Kc) integrated in a dissemination tool for calculating water crops requirements. Experimental Kc values increased from 0.32 in March to 0.74 in July, decreasing to 0.42 in November.
Standardised Measurements for Monitoring and Comparing Multiphoton Microscope Systems

The goal of this protocol is to enable better characterisation of multiphoton microscopy hardware across a large user base. The scope of this protocol is purposefully limited to focus on hardware, touching on software and data analysis routines only where relevant. The intended audiences are scientists using and building multiphoton microscopes in their laboratories. The goal is that any scientist, not only those with optical expertise, can test whether their multiphoton microscope is performing well and producing consistent data over the lifetime of their system.
Use of microhabitat and substratum types by sympatric snakes in a mediterranean area of central Italy

La distribution ecologique de trois especes de serpents (Vipera aspis, Coluber viridiflavus, Elaphe longissima) en relation avec les caracteristiques du micro-habitat et du substrat a ete etudiee dans une situation mediterraneenne cotiere d'Italie centrale (foret de Castel Fusano, province de Rome), composee de dunes sableuses face a la mer et de pinedes internes. Les densites de serpents varient considerablement d'une station a l'autre et presentent des valeurs moyennes de 0,2 individus par ha pour Vipera aspis, 3,5 individus par ha pour Coluber viridiflavus et 1,5 individu par ha pour Elaphe longissima. Les frequences d'observation de chaque espece varient significativement en fonction du micro-habitat. En general, Vipera aspis et Coluber viridiflavus presentent des preferences similaires en terme de micro-habitat. Cependant, d'importantes variation saisonnieres dans la frequence d'utilisation des differents micro-habitats ont pu etre mises en evidence. Les trois especes se rechauffent preferentiellement sur des litieres de feuilles, bien que de legeres differences interspecifiques et saisonnieres aient pu etre relevees. Coluber viridiflavus et Elaphe longissima s'averent relativement proches quant au choix preferentiel du substrat. Cependant, les trois especes ont tendance a thermoreguler sur un type de substrat donne, de facon independante de sa disponibilite dans l'environnement. Coluber viridiflavus s'est averee l'espece la plus generaliste a la fois du point de vue de l'utilisation de chaque type de substrat et de micro-habitat, tandis que Elaphe longissima est apparue comme l'espece la plus specialisee. Les raisons ecologiques impliquees dans ces differences interspecifiques sont discutees a la lueur des autres travaux disponibles sur ce theme.
BaYaka mothers balance childcare and subsistence tasks during collaborative foraging in Congo Basin

Across cultures, mothers face trade-offs between childcare and other labor. In hunter-gatherer societies, mothers face this choice on a daily basis when deciding either to take infants on foraging trips or to leave them with caregivers in the village. Yet, it remains unclear how the presence of infants in foraging groups constrains mothers’ mobility during foraging. Here, we present GPS, energy expenditure and food returns data of 359 foraging trips of 23 BaYaka mothers in the Republic of the Congo. We find that mothers spent more time on out-of-village foraging activities when they took infants along, compared to when they left infants behind. However, infant presence in foraging groups does not affect mothers’ travel distance, travel range, energy expenditure or food returns. Regardless of infant presence, women travel longer and further in a larger area when foraging in groups, compared to when foraging alone, especially in groups with more adults, females and both kin and non-kin. Our results suggest that BaYaka mothers develop ways to accommodate childcare with foraging activities by combining individual-level and group-level behavioural strategies. Our study highlights that group foraging may allow mothers with infants to maintain high mobility, which may have been a key to human range expansion.
ARYANA-BS: Context-Aware Alignment of Bisulfite-Sequencing Reads

Motivation DNA methylation plays a crucial role in biological processes, including imprinting, development, inflammation, and several disorders, such as cancer. Bisulfite sequencing (BS) is the gold standard for single-base resolution in measuring DNA methylation. This process involves treating genomic DNA with sodium bisulfite, followed by polymerase chain reaction (PCR), converting unmethylated cytosines to thymines (C to T) and guanines to adenines (G to A). However, aligning reads obtained through next-generation sequencing (NGS) of the converted DNA is challenging due to the high number of mismatches caused by these conversions. Various BS aligners aim to simplify BS read alignment to conventional DNA alignment by modifying the reference genome and/or reads. Methods include three-letter alignment and wild-card alignment, each with its limitations. This work introduces a novel BS aligner, ARYANA-BS, which departs from conventional DNA aligners by considering base alterations in BS reads within its alignment engine. Leveraging well-established DNA methylation patterns in different genomic contexts, ARYANA-BS generates five indexes from the reference, aligns each read to all indexes, and selects the hit with the minimum penalty. To further enhance alignment accuracy, an optional EM step has been developed, incorporating methylation probability information in the decision-making process for the index with the minimum penalty for each read. The presented approach seeks to improve the accuracy of BS read alignment by accounting for the intricacies of DNA methylation patterns in diverse genomic contexts. Results Our experimental results, based on both simulated and real data, demonstrate that ARYANA-BS achieves state-of-the-art accuracy while maintaining competitive speed and memory usage. Availability The source code of ARYANA and ARYANA-BS, the read simulator for both normal and bisulfite-treated reads, SAM file analyzer which is used for post processing of the alignment penalties, and test procedures for benchmarking different aligners using simulated and real data, are publicly available in https://github.com/hnikaein/aryana. Contact sharifi@sharif.edu Supplementary information Supplementary data are available at Journal Name online.
Temporal Dynamics of Brain Mediation in Predictive Cue-induced Pain Modulation

Pain is not a mere reflection of noxious input. Rather, it is constructed through the dynamic integration of prior predictions with incoming sensory input. However, the temporal dynamics of the behavioral and neural processes underpinning this integration remain elusive. Here, we identified a series of brain mediators that integrated cue-induced expectations with noxious inputs into ongoing pain predictions using a semicircular scale designed to capture rating trajectories. Temporal mediation analysis revealed that during the early-to-mid stages of integration, the frontoparietal and dorsal attention network regions, such as the lateral prefrontal, premotor, and parietal cortex, mediated the cue effects. Conversely, during the mid-to-late stages of integration, the somatomotor network regions mediated the effects of stimulus intensity, suggesting that the integration occurs along the cortical hierarchy from transmodal to unimodal brain systems. Our findings advance the understanding of how the brain integrates prior and sensory information into pain experience over time.
Evaluating the Effects of Environmental Disturbances and Pesticide Mixtures on Soil Microbial Endpoints

Pesticides are widely used in conventional agriculture, either applied separately or in combination during the culture cycle. Due to their occurrence and persistence in soils, pesticide residues may have an impact on soil microbial communities and on supported ecosystem services. In this regard, the EFSA (European Food Safety Authority) recently published a scientific opinion inciting to change pesticide risk assessment to better protect soil microbe-mediated processes. Climate change is another major concern for all living organisms including soil microbial community stability. Extreme climatic events, such as heat waves or heavy rainfalls, are becoming more and more frequent and their impact on soil microbial diversity and functions have already been demonstrated. The objectives of this study were to evaluate the effects of temperature and humidity disturbances and pesticide active ingredients exposure on soil microbial community structure and functions. To this end, 250 soil microcosms were exposed to either a heat disturbance, a high humidity to mimic heavy rain, or no environmental disturbance. After three days of recovery, soil microcosms were treated with different active ingredients: clopyralid (herbicide), cypermethrin (insecticide) and pyraclostrobin (fungicide). The treatments were applied alone or in combination at 1x or 10x of the agronomical dose. We then evaluated the effects of the disturbances and the active ingredients on various microbial endpoints related to the diversity and the structure of soil microbial communities, and with a specific focus on microbial guilds involved in nitrification. Overall, we demonstrated that the impact of environmental disturbances applied to soil microcosms, especially heat, on microbial endpoints was stronger than that of the active ingredients applied alone or in combinations. Compounded effects of environmental disturbances and active ingredients were detected, but sparsely and were of small scale for the chosen pesticides.