julilili42/papers huggingface dataset:
Enhanced basal melting in winter and spring: seasonal ice–ocean interactions at the Ekström Ice Shelf, East Antarctica
2025-08-05

Abstract. Basal melting of Antarctic ice shelves significantly contributes to ice sheet mass loss, with distinct regional disparities in melt rates driven by ocean properties. In Dronning Maud Land (DML), East Antarctica, cold water predominantly fills the ice shelf cavities, resulting in generally low annual melt rates. In this study, we present a 4-year record of basal melt rates at the Ekström Ice Shelf, measured using an autonomous phase-sensitive radio-echo sounder (ApRES). Observations reveal a low mean annual melt rate of 0.44 m a−1, with a seasonal variability. Enhanced melting occurs in winter and spring, peaking at over 1 m a−1, while rates are decreased in summer and autumn. We hypothesise that the dense water formed during sea-ice formation erodes the water column stratification during late winter and spring, leading to an increase in the buoyancy of the ice shelf water plume. An idealised plume model supports this hypothesis, indicating that the plume velocity is the primary driver of seasonal basal melt rate variability, while changes in ambient water temperature play a secondary role in the range of oceanographic conditions that are observed below the Ekström Ice Shelf. These findings offer new insights into the dynamics of ice–ocean interactions in East Antarctica, emphasising the need for further observations to refine our understanding of ocean variability within ice shelf cavities and improve assessments of ice shelf mass balance.
Sleep Neurophysiology in Depression
2025-08-05

Sleep disturbances are both a primary symptom of and risk factor for major depressive disorder (MDD). Sleep alterations in MDD include the presence of insomnia or hypersomnia and aberrations in sleep macro- and microstructure, including a reduced latency until and prolonged duration of the first rapid eye movement (REM) episode, decreased slow-wave sleep (SWS), disturbed sleep continuity, and decreased steepening of aperiodic neural activity. MDD sleep is also characterized by dysfunctional autonomic cardiac activity as reflected by decreased heart rate variability. Sedating and novel antidepressants may improve sleep continuity and SWS while activating antidepressants tend to suppress REM sleep. Cognitive processing during sleep may contribute to MDD symptomatology; however, empirical research in this direction is still inconclusive. The rapid effects of antidepressants on sleep structure and of acute sleep deprivation on MDD symptoms suggest an intimate association between sleep and MDD neuropathology; however, the underlying mechanisms still need to be elucidated. This narrative review aims to provide a comprehensive overview of our current understanding of the physiology of sleep alterations in MDD and to discuss how sleep may play a role in current therapeutic approaches while also identifying novel strategies for modulating sleep in the context of depression. It seeks to offer a well-rounded foundation of the current knowledge on sleep and depression to guide basic and clinical scientists in future investigations related to improving existing and developing novel sleep-based therapeutic interventions.
Attonewton Force Resolution Measurements with Silicon Nanospheres at the Thermal Noise Limit in Ambient-Temperature Liquids
2025-08-05

Precise force measurements are crucial for understanding fundamental physics or nanoscale interactions, such as those of molecular machines in biology. Optical tweezers are versatile force transducers for such measurements, enabling meticulous manipulation of small particles. However, achieving high-resolution, subfemtonewton force measurements under physiological conditions remains challenging due to thermal fluctuations and instrument noise. Here, we employed an ultrastable optical tweezers setup in an isolated environment with precise temperature control, which minimized instrumental noise and enabled prolonged, low-force measurements. We utilized water-suspended, high-refractive index silicon nanospheres for improved resolution and trapping stability. Our system achieved a force resolution of ≈60 aN, with a sensitivity of 2.7 fN Hz<sup>-0.5</sup>, allowing us to measure forces as low as 0.30 ± 0.06 fN. Our drag force measurements demonstrate the importance of optimized experimental conditions for low-force measurements, providing a robust framework for scientific investigations that require high-precision force characterization.
Long-term impact of the SARS-CoV-2 pandemic on respiratory viruses in Germany
2025-08-05

Abstract Background Respiratory viral diseases are one of the greatest challenges facing our healthcare system, with them being one of the main causes of death. This has been demonstrated once again by the impact of the SARS-CoV-2 pandemic in recent years. We study the impact of the SARS-CoV-2 pandemic on the prevalence of respiratory viruses by analysing a subset of the Clinical Virology network database, covering 2,216,198 samples tested for 18 different viral pathogens in the time span from 2010 to 2024. Methods We calculated the prevalence of 17 respiratory viruses before and after onset of the SARS-CoV-2 pandemic and compared the degree of seasonality shift with a newly developed a metric dubbed seasonal disruption index. In addition, we compared coinfection statistics prior to and after the pandemic onset, and also studied the correlation of infection counts with non-pharmaceutical interventions in the time frame from early 2020 to end of 2022. Results We found that the viral pathogens show a varying degree of seasonality disruption. It is largest among those that are known to show a highly seasonal behavior, namely Influenza and RSV, the latter having the highest seasonal disruption index. Most perennial viruses continued to appear throughout the year. Coinfections occurred before and after the pandemic; patterns before and after pandemic onset are surprisingly similar. The occurrence of most viruses is nonlinearly correlated with the degree of non-pharmaceutical interventions. Conclusion The SARS-CoV-2 pandemic had a considerable impact on the occurrence and seasonality of other respiratory viruses. While nearly all seasonality patterns were initially disrupted due to the heavy non-pharmaceutical interventions, viruses are regaining their pre-pandemic seasonality.
Prioritization of epileptogenic-associated genes through comparative transcriptome analyses
2025-08-05

<title>Abstract</title> Background: Gene expression in the context of epilepsy syndromes has been studied in a variety of animal epilepsy models and in human patient samples. Joint analyses of this diverse range of data and the integration of transcriptomics with genetic data may identify genes involved across syndromes. These shared genes and processes present the opportunity to classify a core set of molecular pathways relevant to epileptogenesis. Methods: Here we performed a comparative analyses of organismal models covering major induction mechanisms, sequencing technologies and animal systems to identify genes common to the two principal syndrome categories of generalized and focal epilepsies, which represent distinct pathophysiological mechanisms of seizure initiation and development. We integrated the differentially expressed genes with genome-wide association studies to identify representative models, deregulated genes across epilepsy models and associations with other diseases. Results: Models for generalised epilepsies show fewer genes are differentially expressed than those for focal epilepsies. We found no overlap across all models but a group of 25 genes were detected across all focal models. Of these <italic>LRRC8B</italic>encodes a gliotransmitter previously not implicated in epileptogenesis. Integration with human genetic data highlights two models to be particularly representative for genetic generalised epilepsy. We also demonstrate the previously recognized relation with cancers across the majority of the focal models in contrast to the generalised models. Conclusions: We suggest <italic>LRRC8B</italic> as a new gene involved in the epileptogenesis of focal seizures. Our analyses highlights pathways of particular relevance in the molecular biology of epilepsy and underscores the need for further development of generalised models.
Prognostic impact of the choice of chemotherapy after first-line CDK4/6 inhibitor therapy in patients with metastatic hormone receptor-positive, HER2-negative breast cancer
2025-08-05

Although the choice of chemotherapy post-CDK4/6i did not significantly affect PFS or OS, combinations with bevacizumab may have some benefit. Nevertheless, considering side effects may be most important when choosing the type of second-line chemotherapy.
Batchwise data analysis with inter-batch feature alignment in large scale platelet lipidomics study using UHPLC-ESI-QTOF-MS/MS by data-independent SWATH acquisition
2025-08-05

Untargeted lipidomics by ultra-high-performance liquid chromatography (UHPLC) hyphenated with tandem mass spectrometry using data-independent acquisition (DIA) is a technique with increasing popularity for generating new hypotheses in support of clinical research. Its strength is its data comprehensiveness on both MS and MS/MS level. However, especially when applying SWATH acquisition for large-scale analysis, e.g. clinical studies with over 1000 s to 10,000 s of samples, simultaneous processing of acquired data in multiple batches over longer period of time may be challenging due to retention time and mass shifts as well as huge bulk of data, particularly when computer power is limited. This problem can be alleviated by a batchwise data processing strategy by inter-batch feature alignment of separately processed sample batches. After batchwise automated data processing in MS-DIAL, feature lists can be combined by aligning identical features from different batches attributed to similarity in precursor m/z and retention time, with the intention to generate a representative reference peak list for targeted data extraction. The workflow was established with detected features from three batches of platelet lipid extracts of coronary artery disease (CAD) patients (n = 120) and then applied on a clinical cohort with 1057 CAD patients measured in 22 batches. As a result, the lipidome coverage was significantly increased when several batches were used to create the target feature list compared to a single batch and the increase of annotated features levelled off with 7-8 batches. Further, the lipid identification was improved in terms of number of structurally annotated features.
A Pharmacometrics‐Informed Trial Simulation Framework for Optimizing Study Designs for Disease‐Modifying Treatments in Rare Neurological Disorders
2025-08-05

ABSTRACT The development of new treatments for rare neurological diseases (RNDs) may be very challenging due to limited natural history data, lack of relevant biomarkers and clinical endpoints, small and heterogeneous patient populations, and other complexities. A systematic approach is needed for comparing various design and analysis strategies to identify “optimal” approaches for a clinical trial in a chosen RND with the given resource constraints. For this purpose, we propose a pharmacometrics‐informed clinical scenario evaluation framework (CSE‐PMx), which includes some important research hallmarks relevant to RND clinical trials: a disease progression model for simulating individual longitudinal outcomes, the choice of a suitable randomization method for trial design, and an option to perform subsequent statistical analysis with randomization tests. We illustrate the utility of CSE‐PMx for an exemplary randomized trial to compare the disease‐modifying effect of an experimental treatment versus control in patients with Autosomal‐Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS). In the considered example, our simulation evidence suggests that a nonlinear mixed‐effects model (NLMEM) with a population‐based likelihood ratio test analysis is valid, robust, and more powerful than some conventional methods such as two‐sample t ‐test, analysis of covariance (ANCOVA), or a mixed model with repeated measurements (MMRM). Our proposed framework is very flexible and generalizable to clinical research in other rare disease indications.
Multiple Resumptions and Local Mutable State, Directly
2025-08-05

While enabling use cases such as backtracking search and probabilistic programming, multiple resumptions have the reputation of being incompatible with efficient implementation techniques, such as stack switching. This paper sets out to resolve this conflict and thus bridge the gap between expressiveness and performance. To this end, we present a compilation strategy and runtime system for lexical effect handlers with support for multiple resumptions and stack-allocated mutable state. By building on garbage-free reference counting and associating stacks with stable prompts, our approach enables constant-time continuation capture and resumption when resumed exactly once, as well as constant-time state access. Nevertheless, we also support multiple resumptions by copying stacks when necessary. We practically evaluate our approach by implementing an LLVM backend for the Effekt language. A performance comparison with state-of-the-art systems, including dynamic and lexical effect handler implementations, suggests that our approach achieves competitive performance and the increased expressiveness only comes with limited overhead.
Geometric principles determining the morphology of oligodendrocyte precursor cells in brain white matter
2025-08-05

We used transgenic mice expressing membrane-tagged green fluorescence protein in the oligodendrocyte precursor cells (OPCs), high-resolution imaging, and detailed quantitative morphometric analysis to investigate the geometrical principles that govern structural organization of OPCs in the mouse corpus callosum. Our major findings are: (1) During the first two months of postnatal life in mice, total length of all OPCs processes increases via elaboration of new branches from the existing processes rather than via the appearance of new processes; (2) New branches are preferentially added to more distal sites of OPCs processes; (3) The processes of OPCs show stronger preferential alignment with the posterior-anterior brain axis rather than with the lateral-medial or dorsal-ventral brain axes; at the same time, the processes of OPCs show stronger preferential alignment with the lateral-medial than with the dorsal-ventral brain axis. Our study is the first detailed comprehensive analysis of OPCs morphology comparable to those available for neurons. It helps understanding the geometrical principles that govern structural organization of OPCs. These principles are important when taking into account that OPCs receive synaptic input from neurons and are capable of synaptic integration. Arborization and structural organization of OPCs processes is expected to influence the travel of synaptic input from the processes (where synapses are located) to the cell soma (where synaptic inputs are integrated), in analogy to how it occurs in neurons. Hence, the integrated synaptic signal at the OPCs cell soma which is likely to influence development and behavior of OPCs will depend on the cell morphology.
Steering the Chain-Elongating Microbiome to C8 or C6 Production with Ethanol and Lactate as Coelectron Donors
2025-08-06

Microbial chain elongation is a sustainable process to convert organic residues into valuable biochemicals <i>via</i> anaerobic fermentation. The operating conditions for the bioreactor and the ecological interactions among functional populations are crucial in controlling this process, but they have not been completely ascertained. Here, we studied two operating conditions (<i>i.e.</i>, environmental factors): (1) the substrate ratio of ethanol and lactate as coelectron donors, and (2) the temperature, which affected both the product specificity (<i>i.e.</i>, function) and microbial dynamics of chain-elongating microbiomes in a continuously fed bioreactor with product extraction that is the third pertinent operating condition. Specifically, we found that the increase in the substrate ratio of ethanol to lactate shifted the microbiomes toward <i>n</i>-caprylate (C8) production, while the slightly higher operating temperatures of 37 or 42 °C were advantageous to <i>n</i>-caproate (C6) production. We detected a core microbiome that was similar for all operating conditions and the two bioreactors, consisting of populations from <i>Sphaerochaeta</i> spp., <i>Caproiciproducens</i> spp., and Oscillospiraceae. Besides the core microbiome, we observed positive correlations between Erysipelaclostridiaceae UCG-004, <i>Bacteroides</i> spp., Oscillospiraceae NK4A214, Rikenellaceae RC9, and <i>Pseudoclavibacter</i> spp. with <i>n</i>-caprylate production in a dormant microbiome. Similar populations compared to the core microbiome were positively correlated with <i>n</i>-caproate production for both bioreactors, because <i>n</i>-caproate must first be produced before conversion into <i>n</i>-caprylate. The results showed that we can steer microbiomes toward a high specificity of certain medium-chain carboxylates.
Top-down and bottom-up bilingual speech production: The effects of language context on inhibitory control
2025-08-06

Abstract Language-switching sometimes causes delayed responses, especially when switching from the later-acquired languages (here, L2) to the dominant native language (L1). It is well-established that language proficiency plays a role in production, but what about language context (i.e., the ratio of L1 and L2)? We investigated language context within two language production processes: “top-down” (naming pictures) and “bottom-up” (reading words aloud). We suggest that switch cost asymmetry was not only affected by language context, but also by production modality. In picture naming, the degree of inhibition relies largely on the activation level of the predominant language in the language context, whereby affects the asymmetry. However, the asymmetry disappears when language processing only requires reading aloud words with orthographically unique and constrained to one language. We provide evidence with dynamics of inhibition in different language contexts, suggesting that future study should continue to explore the flexibility of production processes in bilingual speakers.
Improved pathogen identification in sepsis or septic shock by clinical metagenomic sequencing
2025-08-06

The integration of NGS-based pathogen diagnostics in sepsis has the potential to improve patients ́ outcomes as compared to a treatment strategy based on standard-of-care microbiological diagnostics alone.
EnsembleAge: enhancing epigenetic age assessment with a multi-clock framework
2025-08-06

Abstract Several widely used epigenetic clocks have been developed for mice and other species, but a persistent challenge remains: different mouse clocks often yield inconsistent results. To address this limitation in robustness, we present EnsembleAge, a suite of ensemble-based epigenetic clocks. Leveraging data from over 200 perturbation experiments across multiple tissues, EnsembleAge integrates predictions from multiple penalized models. Empirical evaluations demonstrate that EnsembleAge outperforms existing clocks in detecting both pro-aging and rejuvenating interventions. Furthermore, we introduce EnsembleAge HumanMouse, an extension that enables cross-species analyses, facilitating translational research between mouse models and human studies. Together, these advances underscore the potential of EnsembleAge as a robust tool for identifying and validating interventions that modulate biological aging.
Flavoprotein Fluorescence Imaging in Stargardt Disease: Linking Metabolic Stress to Structural Damage
2025-08-06

This study demonstrates that FPF imaging is a promising tool for detecting early metabolic changes in Stargardt disease, potentially serving as a non-invasive biomarker for monitoring disease progression and treatment response. However, current FPF imaging technology is insufficient to discern true FPF signals from lipofuscin-derived fluorescence, making location-specific and FAF comparative analyses imperative and highlighting the need for longitudinal studies.
Circulating epigenetic signatures classifying brain insulin resistance in humans
2025-08-06

Brain insulin action plays an important role in metabolic and cognitive health, but there is no biomarker available to assess brain insulin resistance in humans. Here, we developed a machine learning framework based on blood DNA methylation profiles of participants who did not have type 2 diabetes with and without brain insulin resistance and detailed metabolic phenotyping. We identified 540 DNA methylation sites (CpGs) as classifiers of brain insulin resistance in a discovery cohort ( n = 167), results that were validated in two replication cohorts ( n = 33 and 24) with high accuracy (83 to 94%). All 540 CpGs were differentially methylated and annotated to 445 genes mapping to neuronal development and axonogenesis processes. Methylation patterns of 98 of 540 CpGs exhibited a strong and significant ( P &lt; 0.05) blood-brain correlation, indicating that blood cells are a reliable proxy to capture brain-specific DNA methylation changes. These blood-based epigenetic signatures could potentially serve in the future for the early detection of individuals with brain insulin resistance in a broad clinical setting.
Aristotle on Misperceiving
2025-08-06

Suppose Socrates is looking at a bright red apple in good viewing conditions, so that it looks to him the colour it is. Schematically, Aristotle’s explanation of this “Good Case” is that the apple looks bright red to Socrates because he has taken on the perceptual form of bright red without the matter. But what happens if Socrates misperceives the apple instead and it looks purple? It is not at all clear how to apply Aristotle’s account of perception to such a “Bad Case.” Does Socrates still take on the perceptual form of the actual—bright red—colour of the apple in the Bad Case? Of purple? Neither? I argue that applying Aristotle’s account of perception to this sort of Bad Case requires that there are different ways of being in perceptual contact with perceptible qualities like the colour of an apple, depending on how that perceptual contact is mediated by changes in the sense organs and perceptual medium.
Metabolic state shapes cortisol reactivity to acute stress: A systematic review and meta-analysis of metabolic and hormonal modulators
2025-08-06

Abstract Individual variability in cortisol stress responses is shaped by multiple physiological factors. Yet the interaction with metabolic and hormonal states remains poorly understood. Therefore, we conducted a systematic review and meta-analysis to examine how metabolic factors (particularly glucose) and sex hormone levels (progesterone and estradiol) influence cortisol reactivity to acute stress. We identified 21 studies ( N = 1216 participants) and conducted random-effects meta-analyses for metabolic and hormonal states. Across studies, glucose administration was associated with a significant increase in cortisol responses to acute stress compared to fasting or non-glucose control conditions ( d = 0.30, 95% CI = [0.05, 0.60], BF 10 = 2.42, NNT = 10.63). In contrast, the effects of sex hormones on cortisol responses were smaller and more variable, with both progesterone and estradiol showing weak and inconsistent associations. Our results highlight a robust modulatory role of metabolic state, specifically glucose availability, on HPA axis reactivity, while evidence for sex hormone effects remains inconclusive. Future research should focus on better harmonization of designs concerning sex hormones and systematically examine interactions between metabolic and hormonal states to better explain sex differences in the prevalences of metabolic and stress-related disorders.