julilili42/papers huggingface dataset:
Most prominent challenges in translational neuroscience and strategic solutions to bridge the gaps: Perspectives from an editorial board interrogation
2025-08-12

Recent progress in translational neuroscience has significantly advanced our understanding of neurological diseases. Research progress closely went in line with innovations in research methods, which have expanded our insights considerably beyond previous limits. However, despite the development of disease-modifying treatments, therapeutic options in brain diseases still lag behind fundamental discoveries in basic neuroscience. This perspective examines the factors that hinder clinical progress in translational neuroscience and provides solutions on how to overcome them. Editorial board members of Exploration of Neuroscience were interrogated about the most prominent challenges they see in translational neuroscience and about possible ways to overcome these issues. Key challenges were seen at the interface between experimental research and clinical studies by several members, both from the basic and applied neuroscience fields, which include the selection of appropriate study readouts and endpoints. The establishment of refined study endpoints, combined with biomarkers capable of predicting treatment responses in human patients, will be crucial for the successful clinical implementation of new therapies. Further obstacles were found in the standardization of experimental models, interventions, and assessments both in animals and humans, as well as in the development of personalized treatment strategies. These challenges can be addressed through more clearly defined experimental procedures that closely match clinical conditions and precision-based approaches that ensure efficient therapeutic responses. As a great opportunity, treatment options targeting pathophysiological processes in multiple brain diseases and disease processes in different organ systems were noted. Significant barriers remain in the funding of investigator-driven clinical trials through public research programs, as well as the education of translational and clinician scientists dedicated to clinical translation. Enhanced communication between experimental neuroscientists and clinicians, with a shared understanding and common language, will be essential for the success of future research endeavors.
Polar Fourier transform in practice: its efficiency and characteristics in reconstructing radially acquired MRI images
2025-08-12

Abstract Objective The Polar Fourier Transform (PFT) has been proposed as a direct alternative to gridding for reconstructing radially acquired MRI data. This study evaluates the feasibility of inline PFT implementation on a clinical MRI scanner and assesses its computational performance and image quality under acceleration. Materials and methods PFT was implemented as modular components within the Siemens Image Calculation Environment, using a recursive numerical Hankel transform. Phantom and in vivo brain datasets acquired with 2D radial trajectories were reconstructed using both PFT and vendor-supplied gridding. Reconstruction time, SNR, artifact behavior, and spatial resolution were assessed across multiple undersampling levels (up to 8 ×), using simulations and repeated scans. Results PFT was successfully integrated with a runtime of ~ 6–9 × acquisition time. It exhibited spatially variant behavior, concentrating resolution in central region while shifting undersampling-induced blurring outward. Compared to gridding, PFT reduced structured streaks and better preserved image quality under acceleration. Gradient delay artifacts were reduced by alternating spoke polarity. Notably, the pituitary gland and basilar artery remained visible at high acceleration, highlighting preserved central fidelity. Discussion PFT enables effective inline reconstruction for radial MRI and preserves image quality in small central regions of interest under aggressive undersampling—supporting dynamic and ROI-focused applications.
Successful School‐to‐Training Transitions—Can Individual Goal‐Striving Resources Compensate for Structural Obstacles in the Local Context?
2025-08-12

ABSTRACT Introduction While it is well‐established that structural obstacles such as low local employment opportunities negatively affect adolescents’ school‐to‐work transitions, the impact of individual agency in relation to these obstacles is understudied. Hence, we focus on the key research question of how adolescents’ goal‐striving resources—tenacious goal pursuit (TGP) and flexible goal adjustment (FGA)—affect successful transitions from secondary school to vocational education and training (VET) against the backdrop of structural obstacles in the local context. Methods We measured transition success in terms of a) the start of a VET position, b) concordance between attained and aspired VET position, c) deviance from the aspired position and d) satisfaction with the attained VET position. We examined our research questions in a longitudinal design, using data from the German National Educational Panel Study (NEPS). Our sample consisted of adolescents who graduated in 2012/2016 with the aspiration to start VET ( N = 3382; M Age = 16.77; n Females = 1524). We conducted multiple regression analyses to answer our research questions. Results We found interaction effects of TGP × FGA on three out of four indicators of transition success. Their direction did not only depend on the outcome variable under examination but also on the structure of the local context: High levels of both TGP and FGA are helpful in favorable contexts—that means when local unemployment is low—but maladaptive when structural obstacles are high. Conclusion We recommend that support programs for adolescents that aim to enhance goal‐striving resources should consider these complex interrelations.
Low dimensional latent structure underlying the choices of mice
2025-08-12

An impressive wealth of cognitive neuroscience tasks involves combining perceptual information with an estimate of the latent state of the environment to make a decision. Such tasks have driven the development of theoretically motivated cognitive models which offer compactly parameterised, and thereby insightful, accounts of the internal processes by which this might happen. However, the very large amounts of data that can now be collected present a challenge and an opportunity for this framework. The challenge is that these models can be shown to underfit the data systematically (Nassar &amp; Frank, 2016; Palminteri, Wyart, &amp; Koechlin, 2017; Wilson &amp; Collins, 2019), particularly in how they characterise the effect of the latent state estimate. But this opens up the opportunity to extend the framework and employ richer, more highly parameterised and flexible models, in a data-driven manner (Dezfouli, Griffiths, Ramos, Dayan, &amp; Balleine, 2019). Unfortunately, it is tremendously difficult to interpret these models, precisely because of their flexibility. Here, we follow a recent approach (Eckstein, Summerfield, Daw, &amp; Miller, 2024), in which components of compact models are progressively replaced with more flexible homologues, but, where possible, the resulting insights are mapped back into theoretically-transparent forms. We prove the effectiveness of our scheme by applying it to one of the largest available decision-making data sets for mice, more than 300,000 choices from 139 subjects studied by the International Brain Lab (The International Brain Laboratory et al., 2021). We found widely generalisable phenomena such as notable effects of continual fluctuations in task engagement and systematic differences between learning and forgetting of chosen and unchosen options in determining the subjective state estimate. Our results show that combining theory-driven and data-driven methods can reveal cognitive processes that would have been difficult to discover using either method on its own.
Sometimes They Come Back: Pulsations in A 0538–66 at 69 ms Rediscovered with NICER
2025-08-12

Abstract We report on Neutron Star Interior Composition Explorer (NICER) X-ray observations of the Be X-ray binary A 0538–66 located in the Large Magellanic Cloud. Fast pulsations (69 ms) in this source were discovered in 1980 during a bright outburst in which it reached a luminosity of ∼8 × 10 38 erg s −1 but were never reobserved since then. We clearly detected the pulsations at P = 69.3055 ± 0.0005 ms with a pulsed fraction of ∼20% during a short time interval (∼11 minutes) on 2023 January 9, when A 0538–66 had a luminosity of ∼8 × 10 36 erg s −1 (0.3–10 keV). The pulsations were not detected in other NICER observations (total exposure ∼162.7 ks), during which A 0538–66 had a similar or lower luminosity. On 2023 February 8–9 the source exhibited a strong variability, with short flares reaching ∼10 38 erg s −1 , but no periodic pulsations were detected. Assuming the magnetospheric radius lies within the corotation radius during pulsations, we estimate the neutron star magnetic field is below ∼2.7 × 10 10 G. This would make A 0538–66 the high-mass X-ray binary with the weakest known magnetic field. We discuss implications for magnetic field evolution in accreting pulsars and propose that, alternatively, A 0538–66 has a stronger magnetic field, and during the NICER detection, a centrifugal barrier may have been active while part of the plasma accumulated at the magnetosphere sporadically leaked through it via an instability mechanism, allowing accretion onto the polar caps.
Adjuvant anti-PD-1 therapy improves melanoma-specific survival in stage IIIC-IV melanoma patients with high tumor mutation burden and BRAF V600 mutation
2025-08-12

Immune checkpoint inhibitors (ICI) have significantly improved melanoma-specific survival (MSS), particularly in patients with tumors with a high tumor mutational burden (TMB) or BRAF mutation. In the adjuvant setting, ICIs significantly improve relapse-free survival (RFS), but data on MSS are still lacking. Tissue samples from 83 patients with stage IIIC/D/IV melanoma who started adjuvant ICI between March 2018 and September 2019 were examined using a 700 gene panel. TMB and BRAF V600E/K mutation status were analyzed to determine their potential influence on RFS and MSS. TMB levels ≥ 20 Var/Mb were classified as TMB high, corresponding to the top 20% TMB levels in the cohort. RFS and MSS were significantly improved in patients whose tumors had high TMB levels and BRAF V600E/K mutation (p&amp;lt;0.001 and p=0.002, respectively). Patients with BRAF -mutated tumors and high TMB seem to benefit particularly from adjuvant ICI.
Bacterial infections and pathogenic situations: The case of Staphylococcus lugdunensis
2025-08-13

Traditionally, researchers have viewed different species and strains of bacteria as pathogens or as commensals. Different bacterial species and strains may be placed on a spectrum of pathogenicity or virulence, with highly pathogenic bacteria at one end, and minimally pathogenic bacteria at the other. It has also been recognized that a species or strain of bacteria can behave sometimes as a pathogen, and at other times as a commensal. Consequently, researchers have proposed that a spectrum of less pathogenic to more pathogenic bacteriological <i>behavior</i> be produced, in contrast to the spectrum of less pathogenic to more pathogenic bacteriological <i>species</i>. I propose that a third spectrum of pathogenicity should be developed: a spectrum of <i>pathogenic situations</i>. This is illustrated using the example of <i>Staphylococcus lugdunensis</i>. Some researchers consider <i>S. lugdunensis</i> to be a commensal that might be used to eradicate the dangerous pathogen <i>S. aureus</i> from a patient's nose, whereas other researchers consider <i>S. lugdunensis</i> to be a dangerous pathogen in its own right. Inoculating <i>S. lugdunensis</i> into the nose of a patient might be understood as inoculating them with a dangerous pathogen. However, thinking in terms of pathogenic situations, this same intervention could be understood as reducing the pathogenicity of the situation. As knowledge of the situations in which <i>S. lugdunensis</i> is dangerous is incomplete, this review of concepts of pathogenicity should not be used to justify challenge experiments, but rather to illustrate a different way of thinking about pathogenicity.
Best Oculomotor Endpoints for Clinical Trials in Hereditary Ataxias: A Systematic Review and Consensus by the Ataxia Global Initiative Working Group on Digital‑Motor Biomarkers
2025-08-13

Abstract Oculomotor deficits are common in hereditary cerebellar ataxias (HCAs) and their quantitative assessment offers a sensitive and reliable manner to capture disease-severity and progression. As a group of experts of the Ataxia Global Initiative to support trial readiness, we previously established harmonized methodology for quantitative oculomotor assessments in HCAs. Here, we aimed to identify to most promising oculomotor/vestibular outcomes as endpoints for future trials. Through a systematic MEDLINE search we identified 130 articles reporting oculomotor/vestibular recordings in patients with HCAs. A total of 2,018 subjects were included: 1,776 with genetically-confirmed and 242 with clinically-defined HCAs. Studied diseases included spinocerebellar ataxias (SCA) 1/2/3/6/7/27B, episodic ataxia type 2, Friedreich ataxia, RFC1-related ataxia, fragile X-associated tremor/ataxia syndrome, cerebrotendinous xanthomatosis, ataxia-telangiectasia, ataxia with oculomotor apraxia types 1&amp;2, and Niemann-Pick disease type C. We identified up to four oculomotor/vestibular outcomes per diagnostic entity, based on their ability to robustly discriminate patients from controls, correlate with disease-severity, detect longitudinal change, and represent different disease stages. For each parameter we provide recommendations for recordings. While the implementation of quantitative assessments into clinical trials offers a unique opportunity to track dysfunction of oculomotor/vestibular networks and to assess the impact of interventions, in some HCAs, endpoint qualification of available outcomes requires further validation to characterize their reliability, sensitivity to change, and minimally important change to patients. For all HCAs for which quantitative data are scarce or lacking, there is an urgent need for prospective studies covering a broader range of oculomotor/vestibular domains as approaching new treatments require harmonized and reliable endpoints.
Activation of the HPV16 late promoter by viral E2 and cellular BRD4 and ZC3H4 proteins
2025-08-13

ABSTRACT High-risk human papillomaviruses (HPV), particularly HPV16, are major causes of anogenital and oropharyngeal cancers. The HPV late promoter, P670 in the case of HPV16, is activated upon host cell differentiation and drives the expression of viral capsid proteins. While differentiation-specific host transcription factors have been implicated in regulating this promoter, the mechanism remains incompletely understood. HPV E2 proteins activate transcription by interacting with the host protein BRD4 (Bromodomain-containing protein 4). A biotin proximity ligation screen identified several novel E2 interactors, of which many overlap with the BRD4 interactome, suggesting BRD4 mediates a large fraction of these interactions. One such interactor, ZC3H4 (Zinc finger CCCH domain-containing protein 4), is known to restrict the expression of long non-coding RNAs, including enhancer and promoter upstream antisense RNAs (uaRNAs). E2 recruits ZC3H4 in a BRD4-dependent manner to specifically activate the P670 promoter in reporter assays. Supporting this, E2 and ZC3H4 co-localize in cells with high P670 activity. ZC3H4 is upregulated during differentiation, and its knockdown in differentiated HPV16- or HPV31-positive cells reduces late viral transcripts in an E2-BRD4-dependent manner. Interestingly, knockdown of ZC3H4 does not increase viral uaRNAs, suggesting that ZC3H4 does not enhance HPV late transcription by regulating viral antisense transcription. IMPORTANCE High-risk human papillomaviruses (HPVs), particularly HPV16, can cause anogenital and oropharyngeal cancers. HPV16 relies on the differentiation-dependent activation of its late promoter, P670, to produce capsid proteins. While host transcription factors contribute to this regulation, the mechanisms remain incompletely defined. Our findings reveal that the viral E2 protein collaborates with the host protein BRD4—a critical transcriptional regulator—to recruit other cellular partners, such as ZC3H4. Normally, ZC3H4 suppresses non-coding RNAs in cells, but HPV16 repurposes it via BRD4 to activate P670. This interaction intensifies in differentiated cells, where ZC3H4 levels rise, and disrupting ZC3H4 specifically blocks late viral gene expression without affecting antisense viral transcription. This highlights a unique, differentiation-dependent strategy HPV16 uses to hijack host machinery for its replication.
Predicting Drug Response with Multi-Task Gradient-Boosted Trees in Epilepsy
2025-08-13

Abstract Motivation Despite the availability of numerous anti-seizure medications (ASMs), drug resistance remains a major issue for people with epilepsy. The probability of achieving seizure freedom diminishes with each unsuccessful drug trial, and the impact of genetic and clinical markers on ASM response remains unclear. To address this issue, we used state-of-the-art machine learning (ML) methods to predict the response of people with epilepsy to individual ASMs based on their clinical and genomic information. Results To overcome data sparsity for less common drugs, we implement a multi-task (MT) learning approach for gradient-boosted trees (GBTs), assuming that predicting responses to different ASMs involves similar tasks. This strategy allows models for less prevalent drugs to leverage the more abundant data available for other drugs during training. The proposed model outperforms individual and combined drug-response predictions for most drugs. Our findings identify key genomic and clinical features influencing drug response, enhancing understanding of individual drug responses in people with epilepsy, and aiding clinicians in making informed treatment decisions. Availability and Implementation Due to privacy reasons data is not publically available. The code will be made available upon acceptance under https://github.com/pfeiferAI/MT-GBT
Decoding movie content from neuronal population activity in the human medial temporal lobe
2025-08-13

Abstract The human medial temporal lobe (MTL), a region implicated in memory and high-level cognition, contains neurons that respond selectively to stimuli belonging to specific categories, such as individual people, landmarks, or objects. However, these neurons have been largely studied via static, isolated presentations of stimuli. Therefore, it is unclear how neurons in the MTL respond to rich stimuli such as movies, and which dynamical stimulus features can be retrieved from neuronal population spiking activity. We studied single-unit responses from 2286 neurons recorded from the amygdala, hippocampus, entorhinal cortex, and parahippocampal cortex of 29 intracranially implanted patients during the presentation of an 83-minute movie. We found only a few individual neurons that exhibited a classic selective response to semantic features. However, we successfully decoded the presence of characters, settings, and visual transitions from neuronal population activity. The information relevant for decoding varies across regions depending on the feature category, as visual transitions could be decoded from subsets of neurons with selective responses, whereas character and location features relied on distributed representations. Our results demonstrate an approach for reliably decoding movie features in the human MTL, and suggest that the brain uses a population code when representing character and location features.
New temporal dimensions of the Linearbandkeramik cemetery horizon in Schwetzingen (Germany)
2025-08-13

Cemeteries of the Early Neolithic Linearbandkeramik culture (LBK, 5500–4900 BC) evoke a sense of emerging permanence of place as agricultural subsistence spread westward through Central Europe. Yet assumptions about the sequence of senescence and longevity of cemetery use are based on limited data. Here, the authors challenge the view that cemetery burial was a long-lasting Neolithic practice, modelling 50 new radiocarbon dates from the cemetery of Schwetzingen alongside published dates from eight other LBK mortuary contexts. The results, they argue, indicate a short-lived, largely contemporaneous cemetery horizon across Central Europe, forcing a re-evaluation of Early Neolithic social history.
B7-H3: a consistent marker in metastatic colorectal cancer with potential for targeted treatment
2025-08-13

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Despite advances in various treatment approaches, outcomes for patients with metastatic CRC (mCRC) remain poor, and treatment-associated side effects significantly impact quality of life. While immunotherapy has shown promise in certain malignancies, its efficacy in CRC is limited to a minority of patients, highlighting the urgent need for novel therapeutic targets to improve treatment efficacy while minimizing off-target effects. B7-H3 (CD276) has emerged as a promising immunotherapeutic target due to its selective expression on tumor cells and neovasculature, with minimal presence in healthy tissues. A novel IgG-based bispecific antibody targeting B7-H3 and CD3, CC-3, has demonstrated strong preclinical efficacy in stimulating T cell-mediated antitumor responses and is currently being evaluated in a first-in-human trial including patients with mCRC (NCT05999396). In this study, we investigated B7-H3 expression in a cohort of n = 55 mCRC patients and assessed its correlation with demographic, pathological, and molecular factors, as well as clinical outcomes. Additionally, to evaluate the stability of B7-H3 expression over time, we analyzed sequential biopsies from metastatic lesions from n = 7 patients at subsequent time points. Our findings demonstrate that B7-H3 is consistently overexpressed in mCRC, independent of demographic factors, primary tumor localization (right vs. left colon), common molecular and genetic alterations (HER2, MSI, KRAS, NRAS, BRAF, PIK3CA, p53), and serum tumor markers. Longitudinal analysis showed that B7-H3 expression was comparable or increased over time in sequential metastatic specimens. No significant association was observed between B7-H3 expression and overall survival or progression-free survival, and prior chemotherapy treatment did not influence B7-H3 expression levels. In conclusion, B7-H3 is stably and ubiquitously expressed in mCRC, reinforcing its potential as a robust target for immunotherapeutic strategies, including bispecific antibodies. The lack of variability across patient subgroups suggests that routine pre-treatment assessment of B7-H3 may not be necessary. These findings provide a strong rationale for the continued clinical evaluation of B7-H3-targeted therapies, such as CC-3 (NCT05999396), in mCRC patients.