julilili42/papers huggingface dataset:
SMAS: Structural MRI-based AD Score using Bayesian supervised VAE
2025-08-18

This study introduces the Structural MRI-based Alzheimer's Disease Score (SMAS), a novel index intended to quantify Alzheimer's Disease (AD)-related morphometric patterns using a deep learning Bayesian-supervised Variational Autoencoder (Bayesian-SVAE). The SMAS index was constructed using baseline structural MRI data from the DELCODE study and evaluated longitudinally in two independent cohorts: DELCODE (n=415) and ADNI (n=190). Our findings indicate that SMAS has strong associations with cognitive performance (DELCODE: r=-0.83; ADNI: r=-0.62), age (DELCODE: r=0.50; ADNI: r=0.28), hippocampal volume (DELCODE: r=-0.44; ADNI: r=-0.66), and total gray matter volume (DELCODE: r=-0.42; ADNI: r=-0.47), suggesting its potential as a biomarker for AD-related brain atrophy. Moreover, our longitudinal studies indicated that SMAS may be useful for the early identification and tracking of AD. The model demonstrated significant predictive accuracy in distinguishing cognitively healthy individuals from those with AD (DELCODE: AUC=0.971 at baseline, 0.833 at 36 months; ADNI: AUC=0.817 at baseline, improving to 0.903 at 24 months). Notably, over 36 months, the SMAS index outperformed existing measures such as SPARE-AD and hippocampal volume. The relevance map analysis revealed significant morphological changes in key AD-related brain regions, including the hippocampus, posterior cingulate cortex, precuneus, and lateral parietal cortex, highlighting that SMAS is a sensitive and interpretable biomarker of brain atrophy, suitable for early AD detection and longitudinal monitoring of disease progression.
Safety and vision outcomes of subretinal gene supplementation therapy in PDE6A-associated retinitis pigmentosa: a non-randomised controlled trial
2025-08-18

Purpose PDE6A -associated retinitis pigmentosa (RP) is a rare inherited retinal disease leading to severe vision loss and blindness, with no available treatment. This study assessed the safety and vision outcomes of a gene therapy using an adeno-associated virus (AAV) vector encoding PDE6A (AAV8.hPDE6A). Methods In an open-label, non-randomised controlled phase I/IIa trial, nine patients with biallelic PDE6A variants received a single subretinal injection of AAV8.hPDE6A. Doses were either 1.0×1010 (n=6) or 5.0×1010 (n=3) total vector genomes. Safety was the primary endpoint, assessed via clinical examinations, laboratory analyses and optical coherence tomography imaging. Secondary outcomes included changes in visual function, such as best corrected visual acuity (BCVA), contrast sensitivity, colour perception, dark adaptation thresholds, visual fields, patient-reported outcomes and chromatic pupil campimetry over 1 year. Results The mean patient age was 40.1 years, with baseline BCVA ranging from 40 to 82 letters (0.9–0.1 logMAR). No systemic adverse events occurred, and most ocular events resolved without treatment. Persistent adverse events included small peripheral atrophic areas (n=2), disturbed colour discrimination (n=3), cataract (n=1), slight central retinal thinning (n=5) and moderate visual acuity loss (n=2, 1 in each dose group). BCVA, full-field stimulus thresholds and other visual function measures showed statistically non-significant changes, with a trend towards worsening of retinal sensitivity in the treated eyes. Conclusion Subretinal gene therapy with AAV8.hPDE6A did not improve visual function over 1 year and posed risks, including central retinal thinning and visual acuity decline. This is in contrast to the safety and efficacy profile established in preclinical models.
Interactome Profiling of a Lysine Deacetylase Trapping Probe Library Uncovers Crosstalk Between HDAC6 and NF‐κB Signaling
2025-08-18

Abstract Lysine or histone deacetylases (HDACs) remove acetyl groups from lysine residues of numerous proteins, thereby regulating their function and activity. HDAC6 is involved in multiple cellular processes, yet its protein interaction network remains poorly understood. To uncover novel HDAC6 substrates, we performed an acetylome analysis of HDAC6 knockdown cells, which served as a basis for the design of an HDAC6‐trapping peptide library containing hydroxamic acids. Most probes enriched HDAC6 from cell lysates stronger than HDAC1. Proteomic profiling of the trapping probes revealed a preferential enrichment of HDAC6 and resulted in the identification of novel putative HDAC6 interaction partners. Among those were several components of the pro‐inflammatory transcription factor NF‐κB that were independently confirmed as HDAC6 binders. Mechanistically, HDAC6 counteracted NF‐κB activity induced upon p300‐catalyzed acetylation of NF‐κB p50. These findings indicate a potential anti‐inflammatory function of HDAC6 in NF‐κB signaling.
Very Young Children Learning German Notice the Incorrect Syllable Stress of Words
2025-08-18

Syllable stress can help to quickly identify words in a language with variable stress placement like German. Here, we asked at what age incorrect syllable stress impairs language learners’ attempts to assign meaning to familiar words. We recorded the looking times of young children learning German aged from 4 to 15 months (infants, N69) and 2 to 4 years (toddlers, N28). Participants saw displays of two pictures (e.g., a car and a baby); one of both objects (the target) was named. The disyllabic name of the target was either correctly stressed on the first syllable (“BA.by”) or it was incorrectly stressed on the second syllable (“ba.BY”). On average, all children looked more at the target when they heard its correctly stressed name (compared to the incorrectly stressed name). Furthermore, the analyses of growth curves for all children showed a steeper increase in looking time at the target picture when children heard the correctly stressed target’s name compared to the incorrectly stressed name. These results thus suggest that even very young German-learning children use syllable stress for incremental word-meaning mapping. However, separate post hoc analyses revealed robust differences in overall target fixations only in toddlers but not in infants. The stronger effects in toddlers compared to infants could be related either to the growing vocabulary or the increasing sensitivity to word stress with increasing age.
Malaria amidst the COVID-19 pandemic in Gabon: an application of autoregressive integrated moving average (ARIMA) models within an interrupted time series (ITS) framework to hospital-based data
2025-08-18

Abstract Background Coinciding with the SARS-CoV-2 pandemic, malaria cases and malaria-related deaths increased globally between 2020 and 2022. However, evidence linking the pandemic to increased malaria burden remains ambiguous. We assessed the extent to which an observed malaria resurgence in Lambaréné, Gabon, can be associated with pandemic-related disruptions in malaria control programmes. Methods Using observational data from two tertiary referral hospitals, spanning 2018 to early 2023, we applied autoregressive integrated moving average (ARIMA) models in an interrupted time series (ITS) framework to test for changes in trends and levels following the onset of the pandemic. The primary outcome is the monthly malaria diagnosis rate (per 1000 all-cause hospital diagnoses). As a sub-analysis, we focused on monthly maternal malaria incidence. Results Following an initial drop (–47.32, P = 0.031), potentially due to risk-averse behaviours, the malaria diagnosis rate gradually and concavely increased (linear term: 7.32, P = 0.001; squared term: –0.19, P = 0.001) to a peak above pre-pandemic levels. Additional analyses suggest that this resurgence was likely driven by disruptions to malaria control activities and a waning efficacy of malaria control tools administered pre-pandemic. Conversely, a resurgence in maternal malaria incidence was not estimated. Conclusion Findings align with several national and global descriptive reports, but add a more detailed understanding of underlying dynamics, therefore reinforcing the importance of maintaining malaria control in the general population. The absence of a meaningful increase in maternal malaria provides some reassurance that malaria in pregnancy-specific control remained unchanged during the SARS-CoV-2 pandemic. However, observed peaks in post-pandemic maternal malaria incidence should raise concerns given the risks that malaria poses to this group.
A comparison of 27 Arabidopsis thaliana genomes and the path toward an unbiased characterization of genetic polymorphism
2025-08-19

Abstract Making sense of whole-genome polymorphism data is challenging, but it is essential for overcoming the biases in SNP data. Here we analyze 27 genomes of Arabidopsis thaliana to illustrate these issues. Genome size variation is mostly due to tandem repeat regions that are difficult to assemble. However, while the rest of the genome varies little in length, it is full of structural variants, mostly due to transposon insertions. Because of this, the pangenome coordinate system grows rapidly with sample size and ultimately becomes 70% larger than the size of any single genome, even for n = 27. Finally, we show how short-read data are biased by read mapping. SNP calling is biased by the choice of reference genome, and both transcriptome and methylome profiling results are affected by mapping reads to a reference genome rather than to the genome of the assayed individual.
Physiotherapeutic management of patients with SMA: A questionnaire-based online survey among physiotherapists within the SMArtCARE network
2025-08-19

Background and objectives: Disease-modifying treatments (DMT) have dramatically changed phenotypes in patients with spinal muscular atrophy (SMA). Because publications regarding standards of care were published before DMTs emerged, detailed recommendations and guidelines for physiotherapeutic management are still lacking. The objective of this study was to map the physiotherapeutic management of patients with SMA within the SMArtCARE network, a disease-specific registry for patients with 5q-SMA with 83 participating centers in Germany, Switzerland, and Austria. Methods: An online survey using a modified Delphi approach was conducted among physiotherapists with two questionnaire rounds between June 2022 and June 2023. Seven physiotherapeutic experts developed and revised the questionnaires focusing on the main topics of stretching, positioning, mobility and exercise, and chest physiotherapy. The second questionnaire was based on eight different case studies. Results: The second questionnaire was sent to 148 participants with a response rate of 28%. Most of the physiotherapists were well experienced in treating SMA patients. There was a strong consensus that home-based stretching should be used in pediatric patients with contractures regardless of their motor function. Muscle strengthening training was considered to be essential for all sitters and for walkers with moderate motor function restriction by a strong consensus. For all patients with respiratory involvement there was a consensus for prophylactic respiratory therapy. Conclusion: Our results describe the current physiotherapeutic management and recommendations within the SMArtCARE network. These findings highlight the need for an individualized approach, and the necessity of developing and adjusting existing guidelines.
Multiscale Diffusion, Dynamic Cluster Formation, and Intermolecular Interactions in Pharmaceutically Relevant Monoclonal Antibody Formulations
2025-08-19

Due to their specificity and versatility, monoclonal antibodies (mAbs) are the most popular class of biopharmaceuticals typically administered via intravenous injection. One of the current pharmaceutical challenges concerns mAb formulations for subcutaneous (SC) injection, which is gaining importance as an alternative administration route offering convenience to patients by allowing self-administration compared to other parenteral delivery methods. With volumes lower than 1-2 mL being better tolerated in the subcutaneous space, highly concentrated mAb formulations are needed to achieve significant therapeutic effects, potentially increasing the solution viscosity and altering drug injectability. The main challenge is to maintain the solution viscosity below the SC injectability threshold (15-20 mPa·s) while preserving solution stability. Since the understanding of macroscopic viscosity requires in-depth knowledge on protein multiscale diffusion, mutual interactions, and aggregation, we employ two complementary neutron scattering techniques to investigate 9 different mAbs of IgG1/IgG4 subtypes in aqueous solution as a function of protein concentration and temperature. The synergy between neutron spin-echo (NSE), a spectroscopy technique providing dynamic information, and small-angle neutron scattering (SANS), a time-averaged static technique, enables us to probe the short-time collective diffusion of different mAbs, explore their self-association into small transient clusters, their intermolecular interactions, and ultimately access their internal dynamics. This study builds on previous neutron backscattering (NBS) findings, bridging a critical gap between the time scales probed by NBS and viscometry. It also confirms that the formation of short-lived clusters comprising more than two monomers is a key factor driving high solution viscosity, phase separation, and opalescence.
GAA ‐ FGF14 Expansions and CACNA1A Variants: Phenotypic Overlap and Diagnostic Implications
2025-08-19

Abstract Background An intronic (GAA)•(TTC) repeat expansion in FGF14 was recently identified as the cause of spinocerebellar ataxia 27B (SCA27B), a disorder presenting with both chronic cerebellar ataxia and episodic symptoms. The phenotype of SCA27B overlaps with that of CACNA1A spectrum disorders. Objective The objective of this work was to investigate the prevalence of GAA‐ FGF14 repeat expansions in patients with ataxia so far considered to be related to underlying CACNA1A variants. Methods This is a cross‐sectional multicenter study. Results GAA‐ FGF14 testing showed pathogenic expansions (≥250 repeats) in 6/67 (9%) patients carrying CACNA1A variants. All patients with a pathogenic GAA‐ FGF14 expansion had a disease onset &gt;40 years and carried variants of uncertain significance (VUSs) in CACNA1A . Genetic reevaluation led to the reclassification of CACNA1A VUSs as likely benign in four of six patients, who were ultimately diagnosed with SCA27B. Conclusions Late‐onset ataxia cases previously considered as CACNA1A ‐related disorder should be reevaluated and tested for SCA27B, particularly if related to a VUS in CACNA1A . © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
New Arabic Records From Cairo on Supernovae 1181 and 1006
2025-08-19

ABSTRACT The remnant of the historical supernova SN 1181 is under discussion: While the previously suggested G130.7+3.1 (3C58) appears too old (3000–5000 year), the unusual star IRAS00500+6713 with a surrounding nebula (Pa‐30) has an expansion age not inconsistent with a SN Iax explosion in ad 1181 under the assumption that neither acceleration nor deceleration occurred. Previously, only reports from China and Japan were known, pointing to an event near the northern circumpolar region. Any further reports from other cultures can therefore be highly relevant. We present here an Arabic poem in praise of Saladin by the contemporaneous author Ibn Sanā' al‐Mulk (Cairo, Egypt). We re‐date its composition to between Dec 1181 and May 1182. It contains a new bright star, which can be identified as SN 1181. The poem also provides new and independent information on the object type (called ‘najm’ for ‘star’), location on sky in or near the Arabic constellation al‐Kaff al‐Khaḍīb (lit. the henna‐dyed hand, five bright stars in Cassiopeia), and brightness (brighter than Cas, 2.25 mag). In addition, we present another Arabic text on SN 1006, also from Cairo, by the historian al‐Maqrīzī, probably based on the contemporaneous al‐Musabbiḥī.
PUMA-induced apoptosis drives bone marrow failure and genomic instability in telomerase-deficient mice
2025-08-19

Abstract Bone marrow failure is a severe complication of human telomere biology disorders and predisposes individuals to secondary leukemia. A deeper understanding of this process could offer significant clinical benefits. Using a preclinical mouse model deficient in the RNA component of the telomerase (mTerc), we demonstrate that bone marrow failure results from excessive apoptosis, predominantly mediated by the pro-apoptotic p53 target PUMA. Genetic ablation of Puma alleviates hematological phenotypes and reduces the risk of lethal bone marrow failure while preserving genomic stability. Mechanistically, PUMA deficiency decreases the sensitivity of hematopoietic cells to lethal stressors, including critically short telomeres. As a consequence, reduced compensatory turnover of hematopoietic progenitors slows down telomere shortening at the population level, delays stem cell exhaustion, and diminishes the acquisition of somatic mutations - ultimately preventing neoplastic transformation. Elevated expression of both p53 and PUMA is also observed in the bone marrow from patients with telomere biology disorders. While apoptosis resistance is traditionally associated with malignant transformation, our findings provide evidence that selective inhibition of PUMA-mediated apoptosis may represent a viable therapeutic strategy to prevent or delay leukemic transformation in this patient population.
Biofilm formation of Yersinia enterocolitica and its response against GRAS compounds in meat juice
2025-08-19

Abstract Yersinia enterocolitica is a food-borne pathogen that causes yersiniosis, and its primary sources are animal-originated foods. This work aimed to analyze the effect of fresh pork meat juice (MJ) on planktonic and biofilm growth of Y. enterocolitica strains and to investigate the activity of some generally recognized as safe (GRAS) food preservatives. Twenty-eight Y. enterocolitica strains were used to test growth and biofilm formation in MJ, trypticase soy broth supplemented with 0.25% of glucose (TSBG) alone and in combination with 50% MJ (TSBG:MJ). All strains grew in MJ but most of them to lesser extent than in TSBG. Although TSBG:MJ was the most favorable medium for biofilm formation, many strains were able to form biofilm in MJ. To determine GRAS compounds activity, one B1A and one B1B Y. enterocolitica strain were selected. In nutrient broth with MJ, acetic acid was the most effective compound with MIC of 0.78 mg ml−1, MBC of 3.14 mg ml−1, and BIC of 1.57 mg ml−1 for both strains; for B1A strain, BBC was 12.56 mg ml−1 and for B1B strain, it was 25.12 mg ml−1. Although not all strains exhibited the same ability to form biofilms in MJ, it reduces the susceptibility of Y. enterocolitica to GRAS compounds.
An event generator for neutrino-induced deep inelastic scattering and applications to neutrino astronomy
2025-08-20

Abstract We extend the recently presented, fully exclusive, next-to-leading-order accurate event generator for the simulation of massless neutral- and charged-current deep inelastic scattering (DIS) to the case of incoming neutrinos. The generator can be used to study neutrino-nucleon interactions at (ultra) high energies, and is relevant for a range of fixed-target collider experiments and large-volume neutrino detectors, investigating atmospheric and astrophysical neutrinos. The matching with multi-purpose event generators such as is performed with the method, and accounts for parton showering and non-perturbative effects such as hadronization. This makes it possible to investigate higher-order perturbative corrections to realistic observables, such as the distribution of charged particles. To illustrate the capabilities of the code we provide predictions for several differential distributions in fixed-target collisions for neutrino energies up to <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>1</mml:mn> <mml:mspace/> <mml:mtext>PeV</mml:mtext> </mml:mrow> </mml:math> .
Early Thrombolysis and Outcomes in Central Retinal Artery Occlusion: An Individual Participant Data Meta-Analysis
2025-08-20

BACKGROUND: This individual participant data meta-analysis aimed to determine whether time to treatment influences the effect of intraarterial thrombolysis (IAT), intravenous thrombolysis, and conservative standard therapy on visual outcomes in nonarteritic central retinal artery occlusion. METHODS: We searched MEDLINE, CENTRAL, and Embase up to June 2023 for studies reporting treatment modality and peri-treatment best-corrected visual acuity (BCVA) for ≥5 participants, excluding patients with nonsevere vision loss (BCVA &lt;1.0 logarithm of the minimum angle of resolution [logMAR]) or treated after 24 hours of symptom onset. The primary outcome was recovery from severe vision loss (final BCVA &lt;1.0 logMAR). We used mixed-effect models and local polynomial regression to investigate nonlinear relationships between time to treatment and recovery from severe vision loss. RESULTS: Of 4074 screened studies, individual participant data were sought from 52, with 35 contributing individual participant data for 1038 participants. In total, 783 patients met inclusion criteria (age, 64.8±13.3 years; 35.5% female; baseline BCVA, 2.3±0.5 logMAR). For every hour decrease in time to treatment, thrombolysis was associated with greater improvement in BCVA (intraarterial, 0.02 logMAR [95% CI, 0–0.04]; intravenous, 0.04 logMAR [95% CI, 0.00–0.07]) than conservative standard therapy (0.01 logMAR [95% CI, 0–0.02]). A nonlinear relationship was detected for intraarterial thrombolysis with a changepoint at 8 hours (95% CI, 6.7–9.4). Thrombolysis was associated with increased recovery from severe vision loss compared with conservative standard therapy (intraarterial within 6 hours: odds ratio, 2.72 [95% CI, 1.02–7.28], 27.2% versus 12.0%; intravenous within 4.5 hours: odds ratio, 3.32 [95% CI, 1.24–8.92], 28.8% versus 11.1%). Findings were consistent in subgroup analysis restricted to patients receiving recombinant tissue-type plasminogen activator. Monte-Carlo simulations showed that a randomized controlled trial would require 95 participants per group to achieve 80% power to detect an odds ratio of 3.0 for recovery from severe vision loss. CONCLUSIONS: Early intervention in nonarteritic central retinal artery occlusion is associated with improvement in visual recovery, with intraarterial thrombolysis and intravenous thrombolysis outperforming nonthrombolytic treatments. These findings warrant confirmation in sufficiently powered randomized controlled trials.