bluuebunny/crossref_metadata_2025 huggingface dataset:
Families of Children/Youth with Complex Needs Before, During, and After COVID-19 Pandemic Restrictions
Authors: Arbeau Kim , Atallah Serena , St. Pierre Jeff
Published: January 2025

During the COVID-19 pandemic, families with children who had complex special needs faced many obstacles and had less resources available to them. Little published research has described post-lockdown family functioning in clinical samples. The current study investigated caregiver well-being, family functioning, and child/youth symptomatology in three Canadian samples of families with children/youth who had pre-existing, complex, emotional, behavioural, developmental, and mental health needs pre-pandemic (clinic intake within 1 year prior to March 2020), COVID pandemic (clinic intake 1 year during societal lockdowns), and post-restrictions (clinic intake between summer 2022 and summer 2023). Cross-sectional archival data (n > 300 in each cohort) were compared from assessments completed by families as standard of care at a tertiary children’s service agency. As predicted, the pandemic intake sample reported significantly more parental mental health challenges, stress, conflicts, and went on fewer recreational outings than the pre-pandemic sample. While parent stress levels and family outing rates in the post-restriction sample resembled the pre-pandemic sample, post-lockdown parental mental health symptoms, family conflict, and family respite levels indicate that families are still recovering. Child symptom levels were high in all three samples, likely a result of intake criteria at this tertiary mental health agency. Research recommendations are offered. Clinical agencies should be mindful that some families of children with complex needs may still be impacted by the COVID-19 pandemic changes and consider using a family oriented, trauma-informed care approach to assess the effect of the pandemic.
Comments on a paper published by Ali Shabani et al. 2024.: how accurate is the SALTMED model in simulating rapeseed yield and growth under different irrigation and salinity levels? Modeling earth systems and environment. Published on line 03 February 2024
Authors: Ragab Ragab
Published: January 2025

The SALTMED model employs the well-known physically based equations. It is a comprehensive integrated management tool for water, crops, farmland and fertilizers. The model was initially developed in 2002 under the SALTMED EU Funded Project and has been subjected to further developments over four EU funded Projects until 2019. In 2020, Wiley dedicated a special issue to SALTMED, compiling 17 papers on SALTMED applications worldwide, as acknowledgement and testimony to SALTMED’s valuable contribution to improve water productivity (Ragab 2020). SALTMED users, and they are many across the world, reported good model results, and currently the model is adopted by many organizations across the world as a reliable management tool. This paper is focused on the only case of wrong application of the SALTMED model in Iran based on the misunderstanding of the model processes. This paper aims to clarify where the authors incorrectly applied the model and how it should have been applied.
A survey on deep learning for polyp segmentation: techniques, challenges and future trends
Authors: Mei Jiaxin , Zhou Tao , Huang Kaiwen , Zhang Yizhe , Zhou Yi , Wu Ye , Fu Huazhu
Published: January 2025

Early detection and assessment of polyps play a crucial role in the prevention and treatment of colorectal cancer (CRC). Polyp segmentation provides an effective solution to assist clinicians in accurately locating and segmenting polyp regions. In the past, people often relied on manually extracted lower-level features such as color, texture, and shape, which often had problems capturing global context and lacked robustness to complex scenarios. With the advent of deep learning, more and more medical image segmentation algorithms based on deep learning networks have emerged, making significant progress in the field. This paper provides a comprehensive review of polyp segmentation algorithms. We first review some traditional algorithms based on manually extracted features and deep segmentation algorithms, and then describe benchmark datasets related to the topic. Specifically, we carry out a comprehensive evaluation of recent deep learning models and results based on polyp size, taking into account the focus of research topics and differences in network structures. Finally, we discuss the challenges of polyp segmentation and future trends in the field.
Epidemiological and Clinical Characteristics of Mpox in Jakarta, Indonesia During October 2023 to February 2024
Authors: Purnama Tri Bayu , Wagatsuma Keita , Supriadi Supriadi , Salamah Qonita Nur , Tang Julian W. , Saito Reiko
Published: January 2025

Objective

Mpox, a zoonotic disease, has emerged as a significant international public health concern due to an increase in the number of cases diagnosed in non-endemic countries. To support public health response efforts to interrupt Mpox transmission in the community, this study aims to identify epidemiological and clinical aspects of Mpox in Jakarta, Indonesia.

Methods

The study collected Mpox data from the Provincial Health Department in Jakarta, Indonesia, from October 2023 to February 2024. This included the symptom characteristics and demographics of polymerase chain reaction (PCR)-confirmed and PCR-negative Mpox cases, which were then compared using the χ2 test.

Results

Of the PCR-confirmed total of 58 Mpox cases, most were males (96.6%, 56/58). Of these, 67.2% (39/58) reported recent sexual activity within the 21 days prior to the disease onset date, with 41.4% (24/58) reporting only 1 sexual partner during that period. Among PCR-confirmed Mpox cases, common symptoms included fever (81.1%, 47/58), rash (63.8%, 37/58), and lesions (93.1%, 54/58).

Conclusions

The predominance of male Mpox cases indicates transmission within men who have sex with men (MSM) networks, while higher prevalence among individuals with HIV or syphilis is due to shared behaviors, highlighting the need for surveillance, contact tracing, and targeted public health interventions.
Experiences and needs of unaccompanied irregular migrant minors who arrive in Spain on small boats: A qualitative study
Authors: Berthe-Kone Ousmane , Granero Molina José , Fernández-Sola Cayetano , Jiménez-Lasserrotte María del Mar , Robles-Bello Maria Auxiliadora
Published: January 2025

The European Union receives thousands of unaccompanied irregular migrant minors every year, but little is known about their life experiences during the migration process. The aim of this study is to describe their experiences as minors when they arrived in Spain in small boats, which will help to understand their psychosocial and health needs. A descriptive qualitative study was undertaken. In-depth interviews were conducted with 18 unaccompanied irregular migrants (15 men and 3 women) from different African countries with a mean age of 20.05 years (SD = 2.77). Thematic analysis was used to analyse the data. Three main themes emerged such as (1) unaccompanied irregular migrant minors: risking it all for a better life; (2) redefining your identity as a means of adaptation and (3) obtaining legal status to avoid deportation. Unaccompanied migrant minors risk their lives on the migration journey, but do not always find better conditions in the destination country. The unaccompanied irregular migrant minors are forced to rebuild their lives at a high cost; they experience rejection from the host society and their culture of origin, which has a negative impact on their physical and psychological health over time.
Impacts of herbicides used for control of invasive Pinus contorta on the potential for reinvasion and germination of restoration species
Authors: Rolando Carol A. , Fields Fiona , Scott Matthew B. , Sapsford Sarah , Paul Thomas S.
Published: January 2025

Herbicides that persist in the forest litter and soil following their use for managing invasive plant species may negatively affect restoration efforts as well as minimize reinvasion via their residual phytotoxic activity. This study determined the impact of an herbicide mixture comprising triclopyr, dicamba, picloram, and aminopyralid (TDPA) for the control of dense infestations of a woody invader, Pinus contorta Douglas ex Loudon, on the germination of reinvading P. contorta and three New Zealand native species (Chionochloa rubra Zotov, Nothofagus cliffortiodes (Hook. f.) Oerst., and Leptospermum scoparium J.R. Forst. & G. Forst.) used in restoration. Given the essential role of ectomycorrhizal fungi in facilitating conifer reinvasion, the impact of residual herbicides present in mineral soil on the ectomycorrhizal infection of P. contorta seedling roots was also examined. Germination trials were conducted using intact forest litter–soil cores collected at 27, 112 and 480 d (after herbicide spraying) from sprayed and adjacent unsprayed dense P. contorta infestations. At the same time, mineral soil was also collected for the ectomycorrhizal infection study. Post-spray herbicide residue bound in the litter significantly decreased survival, germination rate, root and shoot growth, and also caused malformation of P. contorta seedlings. Similar results were recorded for native species’ germination; however, overall viability of native seed was poor, resulting in low germination rates. There was no difference in levels of ectomycorrhizal infection rates of P. contorta between treatments. Results indicate residual levels of TDPA herbicide in forest floor litter negatively affect P. contorta reinvasion, native recruitment, and active restoration management. Ectomycorrhizal fungi, however, are unaffected by this herbicide mixture and therefore remain a risk to facilitating reinvasion as residual herbicide declines.
An intermittency based Reynolds-averaged transition model for mixing flows induced by interfacial instabilities
Authors: Xie Hansong , Qi Han , Xiao Mengjuan , Zhang Yousheng , Zhao Yaomin
Published: January 2025

The evolutionary process of mixing induced by Rayleigh–Taylor (RT) and Richtmyer–Meshkov (RM) instabilities typically progresses through three stages: initial instability growth, subsequent mixing transition and ultimate turbulent mixing. Accurate prediction of this entire process is crucial for both scientific research and engineering applications. For engineering applications, Reynolds-averaged Navier–Stokes (RANS) simulation stands as the most viable method currently. However, it is noteworthy that existing RANS mixing models are primarily tailored for the fully developed turbulent mixing stage, rendering them ineffective in predicting the crucial mixing transition. To address that, the present study proposes a RANS mixing transition model. Specifically, we extend the idea of the intermittent factor, which has been widely employed to integrate with turbulence models for predicting boundary layer transition, to mixing problems. Based on a high-fidelity simulation of a RT case, the intermittent factor defined based on enstrophy is extracted and then applied to RANS calculations, showing that it is possible to accurately predict mixing transition by introducing the intermittent factor to the turbulence production from the baseline K-L turbulence mixing model. Furthermore, to facilitate practical predictions, a transport equation has been established to model the spatio-temporal evolution of the intermittent factor. Coupled with the K-L model, the intermittent factor provided by the transport equation is applied to modify the Reynolds stress in RANS calculations. Thereafter, the present transition model has been validated in a series of tests, demonstrating its accuracy and robustness in the capturing mixing process in different types and stages of interfacial mixing flows.
Robust Inference for Generalized Linear Mixed Models: A “Two-Stage Summary Statistics” Approach Based on Score Sign Flipping
Authors: Andreella Angela , Goeman Jelle , Hemerik Jesse , Finos Livio
Published: January 2025

Despite the versatility of generalized linear mixed models in handling complex experimental designs, they often suffer from misspecification and convergence problems. This makes inference on the values of coefficients problematic. In addition, the researcher’s choice of random and fixed effects directly affects statistical inference correctness. To address these challenges, we propose a robust extension of the “two-stage summary statistics” approach using sign-flipping transformations of the score statistic in the second stage. Our approach efficiently handles within-variance structure and heteroscedasticity, ensuring accurate regression coefficient testing for 2-level hierarchical data structures. The approach is illustrated by analyzing the reduction of health issues over time for newly adopted children. The model is characterized by a binomial response with unbalanced frequencies and several categorical and continuous predictors. The proposed approach efficiently deals with critical problems related to longitudinal nonlinear models, surpassing common statistical approaches such as generalized estimating equations and generalized linear mixed models.
From high to low: Simulating nondeterminism and state with state
Authors: TANG WENHAO , SCHRIJVERS TOM
Published: January 2025

Some effects are considered to be higher level than others. High-level effects provide expressive and succinct abstraction of programming concepts, while low-level effects allow more fine-grained control over program execution and resources. Yet, often it is desirable to write programs using the convenient abstraction offered by high-level effects, and meanwhile still benefit from the optimizations enabled by low-level effects. One solution is to translate high-level effects to low-level ones.

This paper studies how algebraic effects and handlers allow us to simulate high-level effects in terms of low-level effects. In particular, we focus on the interaction between state and nondeterminism known as the local state, as provided by Prolog. We map this high-level semantics in successive steps onto a low-level composite state effect, similar to that managed by Prolog’s Warren Abstract Machine. We first give a translation from the high-level local-state semantics to the low-level global-state semantics, by explicitly restoring state updates on backtracking. Next, we eliminate nondeterminism altogether in favour of a lower-level state containing a choicepoint stack. Then we avoid copying the state by restricting ourselves to incremental, reversible state updates. We show how these updates can be stored on a trail stack with another state effect. We prove the correctness of all our steps using program calculation where the fusion laws of effect handlers play a central role.
Carnivorous Plants and Man-Eating Women: Vegetal (New) Womanhood and the Botanical Gothic
Authors: Reid Daisy
Published: January 2025

This paper explores the genre of the botanical gothic, a derivative of the fin de siècle adventure novel in which (generally male) British explorers engage in combat with fictitious killer vegetation from the colonial periphery. I argue that the carnivorous plant of the botanical gothic is intimately entangled with another “man-eating” figure: that of the New Woman. Through a reading of H. G. Wells's “The Flowering of the Strange Orchid” (1894), Algernon Blackwood's “The Man Whom the Trees Loved” (1912), and Beatrice Grimshaw's “The Tale of the Scarlet Butterflies” (1908), I demonstrate the extent to which the monstrous plant is implicitly gendered as threateningly female and depicted as a sort of exoticized vegetal femme fatale that lures weak-minded men to their demise. This, I argue, builds upon contemporaneous anxieties surrounding feminine sexual independence and the destabilization of gender roles in order to create an excessively sensualized feminine plant “rival” to supplant—and indeed queer—the normatively gendered dynamic of the local, domestic space. Male subjects in such narratives are emasculated under the threateningly penetrative agencies of the carnivorous plant that becomes a vegetal stand-in, I suggest, for the deviant and “man-eating” sexuality attributed to the New Woman figure herself.
The Pickwick Papers and “Sam Weller's Scrap Sheet”: The Making of a Print-Neutral Public
Authors: Shand Elizabeth
Published: January 2025

The unprecedented popularity of Charles Dickens's first serial novel, The Posthumous Papers of the Pickwick Club (1836–37), among all classes of readers helped shape Britain's mass reading public. The irrevocable change that Dickens effected on Victorian print culture is well established, but there is little discussion of how his early works interpreted the print culture in which they first circulated. I approach Pickwick according to the perspective of a little-known contemporary response, “Sam Weller's Scrap Sheet (1837),” printed by John Cleave. “Sam Weller's Scrap Sheet” cleverly reproduces the narrative, form, and material of Pickwick according to the perspective of a laboring-class reader. Its attention to print material and class identity informs a new reading of Pickwick: in order to unify disparate reading and writing cultures, I argue, Pickwick fictively binds together materials sourced from a variety of print cultures and redefines them unanimously as “paper.” As the “Scrap Sheet” makes clear, this effaces the productive agency of the “papers’” originating contexts. Tying together discussions from Pickwick’s reception history, print history, and media studies, this paper more broadly examines the tensions that accompanied shifting relationships to material print in early-industrial England.
Scaling Dialogue for Democracy: Can Automated Deliberation Create More Deliberative Voters?
Authors: Fishkin James , Bolotnyy Valentin , Lerner Joshua , Siu Alice , Bradburn Norman
Published: January 2025

The theory and practice of what has come to be called “deliberative democracy” have been revived for the modern era with a focus on deliberative microcosms selected through random sampling or “sortition.” But might it be possible to spread some of the benefits of deliberation beyond mini-publics to the broader society? Can technology assist with scaling an organized deliberative process? In particular, would those who experience such a process become more deliberative voters? Would their considered judgments from deliberation influence their voting? We draw on a larger than usual experiment with public deliberation and a one-year follow-up in the mid-term U.S. elections to suggest answers to these questions. It has implications for whether spreading an organized deliberative process could, in theory, be used to create more deliberative elections.
Integrated Analysis of Seismic Sources and Structures: Understanding Earthquake Clustering During Hydraulic Fracturing
Authors: Zhang Fangxue , Chen Yunfeng , Wang Ruijia , Yu Hongyu , Chen Hanlin , Liu Fushen , Shi Xuhua
Published: January 2025

The distribution of hydraulic‐fracturing‐related seismicity is largely controlled by subsurface structures, yet the physical process that governs the redistribution of injected fluids and stress heterogeneity remains underexplored due to a lack of observational constraints. In this study, we monitored an active hydraulic fracturing (HF) well for two months with a surface nodal array of 60 three‐component stations. We built a high‐resolution catalog comprised of 1369 events (; Mc = −0.2). Their associated seismogenic structures are resolved by seismic reflection data and a 3D velocity model obtained from ambient noise imaging. Earthquakes concentrate near the transition zone between high and low‐velocity structures, with the majority occurring on the high‐velocity side, accompanied by abrupt variations in seismic attributes from reflection data. Particularly, relatively large ( 1.0) earthquakes terminate near the edge of the high‐velocity zone. This distinct interface may represent a geological boundary or strong material property contrast that acts as a physical barrier to rupture propagation and migration of seismic sequence. Locally, two key nearby clusters exhibit distinct characteristics in spatial concentration, focal mechanisms and statistical features. We suggest that variations of structural dimension (i.e., fractures vs. faults) within a complex fault system can dominate the clustering behaviors. Overall, our integrated analysis provides new constraints on mechanical interactions among seismicity, local geological structure, and fluid migration during HF operations.
Impact of Solar Wind Density and Velocity Variations on the Martian Magnetosphere and Ion Escape Process
Authors: Song Yihui , Lu Haoyu , Cao Jinbin , Li Shibang , Wu Xiaoshu , Wang Jianxuan , Chen Nihan , Zhang Xiaoxin , Cao Yuchen , Zhao Jianing
Published: January 2025

The dynamic pressure of solar wind, which is determined by both solar wind density and velocity, is a crucial factor influencing the Martian plasma environment. In this study, we employ a multifluid magnetohydrodynamic (MHD) model to investigate the distinct effects of variations in solar wind velocity and density on boundary layers and the ion escape process. The simulation results indicate that, when the solar wind dynamic pressure is held constant, an increase in solar wind density leads to a significant expansion of the bow shock (BS) and a slight contraction of the magnetic pile‐up boundary. Under conditions of elevated solar wind density, the electric fields that typically inhibit solar wind penetration weaken, allowing a greater number of solar wind protons to traverse the BS. This results in enhanced energy inputs, leading to increased thermal and magnetic pressures. Consequently, the tailward ion escape flux rises substantially due to the increased planetary ion density associated with the higher solar wind proton density. Furthermore, under these conditions, the magnetic field lines exhibit greater piling‐up, with the interplanetary magnetic field penetrating to lower altitudes within the ionosphere, thereby creating additional tailward transport channels for planetary ions. Additionally, as solar wind density increases, the current sheet shifts toward the dawn side, resulting in a more pronounced asymmetry structure.
The Friction Behavior of Rock‐Ice Avalanches in Relation to Rock‐Ice Segregation: Insights From Flume Physical Experiments
Authors: Fan Xuanmei , Feng Zetao , Ni Tao , Deng Yu , Zhang Jing , Dai Lanxin
Published: January 2025

Rock‐ice avalanches in cold‐high mountainous regions exhibit remarkably high mobility, frequently resulting in catastrophic consequences. However, the systematic influence of ice on the mobility of rock‐ice avalanches remains poorly understood. This paper addresses this gap by conducting a comprehensive flume experiment in a temperature‐controlled room at −10°C, simulating rock‐ice avalanches and considering variations in rock‐ice particle size ratios and ice contents. Overall mobility and segregation patterns are quantified by analyzing deposition characteristics, while high‐speed cameras capture velocity and segregation features during motion. Our investigation reveals a notable rock‐ice segregation phenomenon that significantly impacts the mobility of the mixture. Building on insights from prior numerical experiments conducted under nearly‐no‐base‐slip conditions (Feng et al., 2023, https://doi.org/10.1029/2023jf007115), our results underscore that the particle segregation simultaneously inﬂuences both internal (bulk) and basal frictions, thereby producing diﬀerent nonlinear impacts on the mobility of the rock‐ice flow. Additionally, an empirical formula is proposed to describe the evolution of the friction coefficient in cases with different rock‐ice particle size ratios and ice contents. These findings have significant implications for predicting runout and assessing the risk of rock‐ice avalanches.
From light sensing to adaptive learning: hafnium diselenide reconfigurable memcapacitive devices in neuromorphic computing
Authors: Alqahtani Bashayr , Li Hanrui , Syed Abdul Momin , El-Atab Nazek
Published: January 2025

Advancements in neuromorphic computing have given an impetus to the development of systems with adaptive behavior, dynamic responses, and energy efficiency characteristics. Although charge-based or emerging memory technologies such as memristors have been developed to emulate synaptic plasticity, replicating the key functionality of neurons—integrating diverse presynaptic inputs to fire electrical impulses—has remained challenging. In this study, we developed reconfigurable metal-oxide-semiconductor capacitors (MOSCaps) based on hafnium diselenide (HfSe2). The proposed devices exhibit (1) optoelectronic synaptic features and perform separate stimulus-associated learning, indicating considerable adaptive neuron emulation, (2) dual light-enabled charge-trapping and memcapacitive behavior within the same MOSCap device, whose threshold voltage and capacitance vary based on the light intensity across the visible spectrum, (3) memcapacitor volatility tuning based on the biasing conditions, enabling the transition from volatile light sensing to non-volatile optical data retention. The reconfigurability and multifunctionality of MOSCap were used to integrate the device into a leaky integrate-and-fire neuron model within a spiking neural network to dynamically adjust firing patterns based on light stimuli and detect exoplanets through variations in light intensity.
Impact of lymph node metastasis on immune microenvironment and prognosis in colorectal cancer liver metastasis: insights from multiomics profiling
Authors: Zhang Yueyang , Wu Deng , Zhang Zhen , Ma Jian , Jiao Shuai , Ma Xiaolong , Li Jiangtao , Meng Yongsheng , Zhao Zhixun , Chen Haipeng , Jiang Zheng , Wang Guiyu , Liu Haiyi , Xi Yanfeng , Zhou Haitao , Wang Xishan , Guan Xu
Published: January 2025

Background

This study aimed to investigate the prognostic impact of lymph node metastasis (LNM) on patients with colorectal cancer liver metastasis (CRLM) and elucidate the underlying immune mechanisms using multiomics profiling.

Methods

We enrolled patients with CRLM from the US Surveillance, Epidemiology, and End Results (SEER) cohort and a multicenter Chinese cohort, integrating bulk RNA sequencing, single-cell RNA sequencing and proteomics data. The cancer-specific survival (CSS) and immune profiles of the tumor-draining lymph nodes (TDLNs), primary tumors and liver metastasis were compared between patients with and without LNM. Pathological evaluations were used to assess immune cell infiltration and histological features.

Results

The CRLM patients with LNM had significantly shorter CSS than patients without LNM in two large cohorts. Our results showed that nonmetastatic TDLNs exhibited a greater abundance of immune cells, including CD4+ T cells, CD8+ T cells, and CD19+ B cells, whereas metastatic TDLNs were enriched with fibroblasts, endothelial cells, and macrophages. Immunohistochemical analysis confirmed elevated levels of CD3+ T cells, CD8+ T cells, and CD19+ B cells in nonmetastatic TDLNs. The presence of nonmetastatic TDLNs was associated with enhanced antitumor immune responses in primary tumors, characterized by a higher Klintrup–Makinen (KM) grade and the presence of tertiary lymphoid structures. Furthermore, liver metastasis in patients with nonmetastatic TDLNs were predominantly of the desmoplastic growth pattern (dHGP), while those with metastatic TDLNs were predominantly of the replacement growth pattern (rHGP).

Conclusions

This research highlights the adverse prognostic impact of LNM on patients with CRLM and reveals potential related mechanisms through multiomics analysis. Our research paves the way for further refinement of the AJCC TNM staging system for CRLM in clinical practice.
Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction
Authors: Hansen Cathrin E. , Vacondio Davide , van der Molen Lennart , Jüttner Annika A. , Fung Wing Ka , Karsten Manon , van het Hof Bert , Fontijn Ruud D. , Kooij Gijs , Witte Maarten E. , Roks Anton J. M. , de Vries Helga E. , Mulder Inge , de Wit Nienke M.
Published: January 2025

Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model. In vitro, ERCC1-deficient brain ECs displayed increased senescence-associated secretory phenotype expression, reduced BBB integrity, and higher sprouting capacities due to an underlying dysregulation of the Dll4-Notch pathway. In line, EC-KO mice showed more P21+ cells, augmented expression of angiogenic markers, and a concomitant increase in the number of brain ECs and pericytes. Moreover, EC-KO mice displayed BBB leakage and enhanced cell adhesion molecule expression accompanied by peripheral immune cell infiltration into the brain. These findings were confined to the white matter, suggesting a regional susceptibility. Collectively, our results underline the role of endothelial aging as a driver of impaired BBB function, endothelial sprouting, and increased immune cell migration into the brain, thereby contributing to impaired brain homeostasis as observed during the aging process.
Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism
Authors: Fu Wei , Lai Yuanting , Li Kexin , Yang Yue , Guo Xiao , Gong Qifan , Zhou Xiaofeng , Zhou Liying , Liu Cenxi , Zhang Zhi , So Jisun , Zhang Yufeng , Huang Lin , Lu Guangxing , Yi Chuanyou , Wang Qichu , Fan Chenyu , Liu Chao , Wang Jiaxing , Yu Haiyi , Zhao Yimin , Huang Tao , Roh Hyun Cheol , Liu Tiemin , Tang Huiru , Qi Jianping , Xu Ming , Zheng Yan , Huang He , Li Jin
Published: January 2025

Neurotensin (NTS) is a secretory peptide produced by lymphatic endothelial cells. Our previous study revealed that NTS suppressed the activity of brown adipose tissue via interactions with NTSR2. In the current study, we found that the depletion of Ntsr2 in white adipocytes upregulated food intake, while the local treatment of NTS suppressed food intake. Our mechanistic study revealed that suppression of NTS-NTSR2 signaling enhanced the phosphorylation of ceramide synthetase 2, increased the abundance of its products ceramides C20–C24, and downregulated the production of GDF15 in white adipose tissues, which was responsible for the elevation of food intake. We discovered a potential causal and positive correlation between serum C20–C24 ceramide levels and human food intake in four populations with different ages and ethnic backgrounds. Together, our study shows that NTS-NTSR2 signaling in white adipocytes can regulate food intake via its direct control of lipid metabolism and production of GDF15. The ceramides C20–C24 are key factors regulating food intake in mammals.
Modern biology of extrachromosomal DNA: A decade-long voyage of discovery
Authors: Yang Qing-Lin , Xie Yipeng , Qiao Kailiang , Lim Jun Yi Stanley , Wu Sihan
Published: January 2025

Genomic instability is a hallmark of cancer and is a major driving force of tumorigenesis. A key manifestation of genomic instability is the formation of extrachromosomal DNAs (ecDNAs) — acentric, circular DNA molecules ranging from 50 kb to 5 Mb in size, distinct from chromosomes. Ontological studies have revealed that ecDNA serves as a carrier of oncogenes, immunoregulatory genes, and enhancers, capable of driving elevated transcription of its cargo genes and cancer heterogeneity, leading to rapid tumor evolution and therapy resistance. Although ecDNA was documented over half a century ago, the past decade has witnessed a surge in breakthrough discoveries about its biological functions. Here, we systematically review the modern biology of ecDNA uncovered over the last ten years, focusing on how discoveries during this pioneering stage have illuminated our understanding of ecDNA-driven transcription, heterogeneity, and cancer progression. Furthermore, we discuss ongoing efforts to target ecDNA as a novel approach to cancer therapy. This burgeoning field is entering a new phase, poised to reshape our knowledge of cancer biology and therapeutic strategies.
Globally scalable glacier mapping by deep learning matches expert delineation accuracy
Authors: Maslov Konstantin A. , Persello Claudio , Schellenberger Thomas , Stein Alfred
Published: January 2025

Accurate global glacier mapping is critical for understanding climate change impacts. Despite its importance, automated glacier mapping at a global scale remains largely unexplored. Here we address this gap and propose Glacier-VisionTransformer-U-Net (GlaViTU), a convolutional-transformer deep learning model, and five strategies for multitemporal global-scale glacier mapping using open satellite imagery. Assessing the spatial, temporal and cross-sensor generalisation shows that our best strategy achieves intersection over union  >0.85 on previously unobserved images in most cases, which drops to  >0.75 for debris-rich areas such as High-Mountain Asia and increases to  >0.90 for regions dominated by clean ice. A comparative validation against human expert uncertainties in terms of area and distance deviations underscores GlaViTU performance, approaching or matching expert-level delineation. Adding synthetic aperture radar data, namely, backscatter and interferometric coherence, increases the accuracy in all regions where available. The calibrated confidence for glacier extents is reported making the predictions more reliable and interpretable. We also release a benchmark dataset that covers 9% of glaciers worldwide. Our results support efforts towards automated multitemporal and global glacier mapping.
Parameters for one health genomic surveillance of Escherichia coli from Australia
Authors: Watt Anne E. , Cummins Max L. , Donato Celeste M. , Wirth Wytamma , Porter Ashleigh F. , Andersson Patiyan , Donner Erica ,   Australian Pathogen Genomics One Health Working Group, Sintchenko Vitali , Arnott Alicia , Zahedi Alireza , Bull Rowena , Webb Jessica R. , Ingle Danielle , Horan Kristy , Hoang Tuyet , Ferdinand Angeline , Zulfiqar Tehzeeb , Thompson Craig , Leong Lex E. X. , Hoye Bethany , Browning Glenn F. , Wille Michelle , Wright Rose , Donald Angela , Bartlett Zoe , Levy Avram , Bareja Christina , Gonzales Tatiana , Minney-Smith Cara , Flynn Erin , Phabmixay Aruna , Huynh Thy , Jennison Amy V. , Seemann Torsten , Djordjevic Steven P. , Howden Benjamin P.
Published: January 2025

Genomics is a cornerstone of modern pathogen epidemiology yet demonstrating transmission in a One Health context is challenging, as strains circulate and evolve within and between diverse hosts and environments. To identify phylogenetic linkages and better define relevant measures of genomic relatedness in a One Health context, we collated 5471 Escherichia coli genome sequences from Australia originating from humans (n = 2996), wild animals (n = 870), livestock (n = 649), companion animals (n = 375), environmental sources (n = 292) and food (n = 289) spanning over 36 years. Of the 827 multi-locus sequence types (STs) identified, 10 STs were commonly associated with cross-source genomic clusters, including the highly clonal ST131, pandemic zoonotic lineages such as ST95, and emerging human ExPEC ST1193. Here, we show that assessing genomic relationships at ≤ 100 SNP threshold enabled detection of cross-source linkage otherwise obscured when applying typical outbreak-oriented relatedness thresholds ( ≤ 20 SNPs) and should be considered in interrogation of One Health genomic datasets.
Quantum-limited stochastic optical neural networks operating at a few quanta per activation
Authors: Ma Shi-Yuan , Wang Tianyu , Laydevant Jérémie , Wright Logan G. , McMahon Peter L.
Published: January 2025

Energy efficiency in computation is ultimately limited by noise, with quantum limits setting the fundamental noise floor. Analog physical neural networks hold promise for improved energy efficiency compared to digital electronic neural networks. However, they are typically operated in a relatively high-power regime so that the signal-to-noise ratio (SNR) is large (>10), and the noise can be treated as a perturbation. We study optical neural networks where all layers except the last are operated in the limit that each neuron can be activated by just a single photon, and as a result the noise on neuron activations is no longer merely perturbative. We show that by using a physics-based probabilistic model of the neuron activations in training, it is possible to perform accurate machine-learning inference in spite of the extremely high shot noise (SNR  ~ 1). We experimentally demonstrated MNIST handwritten-digit classification with a test accuracy of 98% using an optical neural network with a hidden layer operating in the single-photon regime; the optical energy used to perform the classification corresponds to just 0.038 photons per multiply-accumulate (MAC) operation. Our physics-aware stochastic training approach might also prove useful with non-optical ultra-low-power hardware.
Heterodyne analysis of high-order partial waves in attosecond photoionization of helium
Authors: Jiang Wenyu , Roantree Luke , Han Lulu , Ji Jiabao , Xu Yidan , Zuo Zitan , Wörner Hans Jakob , Ueda Kiyoshi , Brown Andrew C. , van der Hart Hugo W. , Gong Xiaochun , Wu Jian
Published: January 2025

Partial wave analysis is key to interpretation of the photoionization of atoms and molecules on the attosecond timescale. Here we propose a heterodyne analysis approach, based on the delay-resolved anisotropy parameters to reveal the role played by high-order partial waves during photoionization. This extends the Reconstruction of Attosecond Beating By Interference of Two-photon Transitions technique into the few-photon regime. We demonstrate that even for moderate ( ~ 1TW/cm2) intensities, near-infrared-assisted photoionization of helium through Rydberg states results in a tiny contribution from the g0 wave, which has a significant impact on the photoelectron angular distributions via interference with the s- and d0-waves. This modulation also causes a substantial deviation in the angular distribution of the recovered spectral phase shift. Our analysis provides an efficient method to resolve isolated partial wave contributions beyond the perturbative regime, and paves the way towards understanding resonance-enhancement of partial waves.
Probing SARS-CoV-2 membrane binding peptide via single-molecule AFM-based force spectroscopy
Authors: Zhang Qingrong , Rosa Raissa S. L. , Ray Ankita , Durlet Kimberley , Dorrazehi Gol Mohammad , Bernardi Rafael C. , Alsteens David
Published: January 2025

The SARS-CoV-2 spike protein’s membrane-binding domain bridges the viral and host cell membrane, a critical step in triggering membrane fusion. Here, we investigate how the SARS-CoV-2 spike protein interacts with host cell membranes, focusing on a membrane-binding peptide (MBP) located near the TMPRSS2 cleavage site. Through in vitro and computational studies, we examine both primed (TMPRSS2-cleaved) and unprimed versions of the MBP, as well as the influence of its conserved disulfide bridge on membrane binding. Our results show that the MBP preferentially associates with cholesterol-rich membranes, and we find that cholesterol depletion significantly reduces viral infectivity. Furthermore, we observe that the disulfide bridge stabilizes the MBP’s interaction with the membrane, suggesting a structural role in viral entry. Together, these findings highlight the importance of membrane composition and peptide structure in SARS-CoV-2 infectivity and suggest that targeting the disulfide bridge could provide a therapeutic strategy against infection.
Evidence for saddle point-driven charge density wave on the surface of heavily hole-doped iron arsenide superconductors
Authors: Hu Quanxin , Zheng Yu , Xu Hanxiang , Deng Junze , Liang Chenhao , Yang Fazhi , Wang Zhijun , Grinenko Vadim , Lv Baiqing , Ding Hong , Yim Chi Ming
Published: January 2025

Unconventional superconductivity is known for its intertwining with other correlated states, making exploration of the intertwined orders important for understanding its pairing mechanism. In particular, spin and nematic orders are widely observed in iron-based superconductors; however, the presence of charge order is uncommon. Using scanning tunnelling microscopy, and through expanding the phase diagram of iron-arsenide superconductor Ba1−xKxFe2As2 to the hole-doping regime beyond KFe2As2 by surface doping, we demonstrate the formation of a charge density wave (CDW) on the arsenide surface of heavily hole-doped Ba1−xKxFe2As2. Its emergence suppresses superconductivity completely, indicating their direct competition. Notably, the CDW emerges when the saddle points approach the Fermi level, where its wavevector matches with those linking the saddle points, suggesting saddle-point nesting as its most probable formation mechanism. Our findings offer insights into superconductivity and intertwined orders, and a platform for studying them in iron-based superconductors close to the half-filled configuration.
Blobby is a synaptic active zone assembly protein required for memory in Drosophila
Authors: Lützkendorf J. , Matkovic-Rachid T. , Liu S. , Götz T. , Gao L. , Turrel O. , Maglione M. , Grieger M. , Putignano S. , Ramesh N. , Ghelani T. , Neumann A. , Gimber N. , Schmoranzer J. , Stawrakakis A. , Brence B. , Baum D. , Ludwig Kai , Heine M. , Mielke T. , Liu F. , Walter A. M. , Wahl M. C. , Sigrist S. J.
Published: January 2025

At presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify an additional Drosophila AZ protein, “Blobby”, essential for proper AZ nano-organization. Blobby biochemically associates with the ELKS family AZ scaffold protein Bruchpilot (BRP) and integrates into newly forming AZs. Loss of Blobby results in fewer AZs forming, ectopic AZ scaffold protein accumulations (“blobs”) and disrupts nanoscale architecture of the BRP-AZ scaffold. Functionally, blobby mutants show diminished evoked synaptic currents due to reduced synaptic vesicle release probability and fewer functional release sites. Blobby is also present in adult brain synapses, and post-developmental knockdown of Blobby in the mushroom body impairs olfactory aversive memory consolidation. Thus, our analysis identifies an additional layer of AZ regulation critical for developmental AZ assembly but also for AZ-mediated plasticity controlling behavior.
Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling
Authors: Kim David , Vanderbilt Chad M. , Yang Soo-Ryum , Nandakumar Subhiksha , Nafa Khedoudja , Feratovic Rusmir , Rekhtman Natasha , Rijo Ivelise , Casanova Jacklyn , Yun Anita , Brannon A. Rose , Berger Michael F. , Ladanyi Marc , Lin Oscar , Arcila Maria E.
Published: January 2025

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls. We highlight the impact of several optimization strategies to maximize performance with 4,871 prospectively sequenced clinical cytology samples tested by MSK-IMPACTTM. Special emphasis is given to the use of residual supernatant cell-free DNA (ScfDNA) as a valuable source of tumor DNA. Overall, cytology samples are similar in performance to surgical samples in identifying clinically relevant genomic alterations, achieving success rates up to 93% with full optimization. While cell block (CB) samples have excellent performance overall, low-level cross-contamination is identified in a small proportion of cases (4.7%), a common pitfall intrinsic to the processing of paraffin blocks, suggesting that more stringent precautions and processing modifications should be considered in quality control initiatives. By contrast ScfDNA samples have negligible contamination. Finally, ScfDNA testing exclusively used as a rescue strategy, delivered successful results in 71% of cases where tumor tissue from CB was depleted.
Local correlations necessitate waterfalls as a connection between quasiparticle band and developing Hubbard bands
Authors: Krsnik Juraj , Held Karsten
Published: January 2025

Waterfalls are anomalies in the angle-resolved photoemission spectrum where the energy-momentum dispersion is almost vertical, and the spectrum strongly smeared out. These anomalies are observed at relatively high energies, among others, in superconducting cuprates and nickelates. The prevalent understanding is that they originate from the coupling to some boson, with spin fluctuations and phonons being the usual suspects. Here, we show that waterfalls occur naturally in the process where a Hubbard band develops and splits off from the quasiparticle band. Our results for the Hubbard model with ab initio determined parameters well agree with waterfalls in cuprates and nickelates, providing a natural explanation for these spectral anomalies observed in correlated materials.
Reduced ATP turnover during hibernation in relaxed skeletal muscle
Authors: De Napoli Cosimo , Schmidt Luisa , Montesel Mauro , Cussonneau Laura , Sanniti Samuele , Marcucci Lorenzo , Germinario Elena , Kindberg Jonas , Evans Alina Lynn , Gauquelin-Koch Guillemette , Narici Marco , Bertile Fabrice , Lefai Etienne , Krüger Marcus , Nogara Leonardo , Blaauw Bert
Published: January 2025

Hibernating brown bears, due to a drastic reduction in metabolic rate, show only moderate muscle wasting. Here, we evaluate if ATPase activity of resting skeletal muscle myosin can contribute to this energy sparing. By analyzing single muscle fibers taken from the same bears, either during hibernation or in summer, we find that fibers from hibernating bears have a mild decline in force production and a significant reduction in ATPase activity. Single fiber proteomics, western blotting, and immunohistochemical analyses reveal major remodeling of the mitochondrial proteome during hibernation. Furthermore, using bioinformatical approaches and western blotting we find that phosphorylated myosin light chain, a known stimulator of basal myosin ATPase activity, is decreased in hibernating and disused muscles. These results suggest that skeletal muscle limits energy loss by reducing myosin ATPase activity, indicating a possible role for myosin ATPase activity modulation in multiple muscle wasting conditions.