julilili42/papers huggingface dataset:
Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a N2M2 umbrella trial
2025-09-05

Abstract Advances in molecular understanding and diagnostic precision of glioblastoma enable the identification of key genetic alterations in a timely manner and, in principle, allow treatments with targeted compounds based on molecular markers. Here we report the results of the phase 1/2 umbrella trial NCT Neuro Master Match (N 2 M 2 ), which evaluated targeted treatments in 228 patients with newly diagnosed glioblastoma without O6-methylguanine DNA-methyltransferase promoter hypermethylation. Stratification for treatment was conducted by a trial-specific molecular tumor board across five subtrials, each evaluating a targeted therapy—alectinib, idasanutlin, palbociclib, vismodegib or temsirolimus—selected according to the best-matching molecular alteration. Patients without matching alterations were randomized between subtrials without strong biomarkers using atezolizumab and asunercept, and the standard of care (SOC), temozolomide. All received radiotherapy. The primary endpoints were dose-limiting toxicities (phase 1) and progression-free survival at 6 months (PFS-6; phase 2). Secondary endpoints included safety and tolerability, as well as overall survival (OS). The subtrials for alectinib and vismodegib did not open as they did not have matching patients. The idasanutlin subtrial ( n = 9) was terminated early at the discretion of the manufacturing company. The temsirolimus subtrial ( n = 46) demonstrated a PFS-6 of 39.1% and median OS of 15.4 months in patients with activated mammalian target of rapamycin (mTOR) signaling compared to a PFS-6 at 18.5% in the SOC group ( n = 54), meeting the primary endpoint. The atezolizumab ( n = 42), asunercept ( n = 26) and palbociclib ( n = 41) subtrials did not meet the primary endpoint for efficacy. The safety signals of N 2 M 2 match prior experiences with the drugs in quality and quantity; no relevant negative interaction with the parallel radiotherapy was noted. The results of the N 2 M 2 trial support further investigation of temsirolimus in addition to radiotherapy in patients with newly diagnosed glioblastoma with activated mTOR signaling. ClinicalTrials.gov registration: NCT03158389 .
Studying therapy effects and disease outcomes in silico using artificial counterfactual tissue samples
2025-09-05

Understanding the interactions of different cell types inside the immune tumor microenvironment (iTME) is crucial for the development of immunotherapy treatments as well as for predicting their outcomes. Highly multiplexed tissue imaging (HMTI) technologies offer a tool which can capture cell properties of tissue samples by measuring expression of various proteins and storing them in separate image channels. HMTI technologies can be used to gain insights into the iTME and in particular how the iTME differs for different patient outcome groups of interest (e.g., treatment responders vs. non-responders). Understanding the systematic differences in the iTME of different patient outcome groups is crucial for developing better treatments and personalising existing treatments. However, such analyses are inherently limited by the fact that any two tissue samples vary due to a large number of factors unrelated to the outcome. Here, we present CF-HistoGAN, a machine learning framework that employs generative adversarial networks (GANs) to create artificial counterfactual tissue samples that resemble the original tissue samples as closely as possible but capture the characteristics of a different patient outcome group. Specifically, we learn to "translate" HMTI samples from one patient group to create artificial paired samples. We show that this approach allows to directly study the effects of different patient outcomes on the iTMEs of individual tissue samples. We demonstrate that CF-HistoGAN can be employed as an explorative tool for understanding iTME effects on the pixel level. Moreover, we show that our method can be used to identify statistically significant differences in the expression of different proteins between patient groups with greater sensitivity compared to conventional approaches.
Effect of Estrogen on Sirt1 Signaling in Human Macrophages
2025-09-05

Cardiovascular diseases are the leading cause of human death worldwide. The role of the female hormone estrogen (E2) in this context is subject of debate. E2 might counteract inflammation by acting on macrophages; however, the underlying cellular mechanisms remain poorly understood. In the current study, we used primary human macrophages to investigate the effects of E2 on the NAD+-dependent deacetylase Sirt1, protein acetylation, and pro-inflammatory phenotype. Male and female primary monocytes from healthy adult individuals were polarized into pro-inflammatory M1 macrophages via treatment with LPS and IFN-γ followed by treatment with E2 for 24 h. While E2 treatment had no effect on the Sirt1 protein expression, it significantly increased the acetylation state of nuclear proteins p53 and Ku70. In addition, E2 increased NFκB-p65 expression exclusively in male M1 macrophages, while TNF-α was reduced in female M1 macrophages following E2 treatment. In male monocyte-like cells, E2 significantly reduced nuclear Sirt1 expression and increased Ku70 acetylation. The current study demonstrated that E2 treatment of human M1 macrophages leads to downregulation of nuclear Sirt1 and hyperacetylation of corresponding nuclear proteins. These molecular changes are associated with an enhancement of the pro-inflammatory phenotype in male primary macrophages, while an attenuation of inflammation was observed in female cells.
From meaning to sound: how word learning shapes non-native speech perception
2025-09-05

Introduction Adult learners often struggle to perceive and acquire unfamiliar speech sounds in a second language, especially at the initial stages of learning. Traditional perceptual training methods, such as discrimination tasks, tend to be less effective with beginners, as they rely on low-level acoustic judgments and lack meaningful context. This study investigates whether training with cross-situational word learning (CSWL), a meaning-based learning paradigm, can improve the perceptual discrimination of non-native vowel contrasts. Methods Thirty-seven native speakers of Hungarian were trained on eight European Portuguese pseudowords through a single CSWL session involving alternating passive and active learning blocks, feedback, and exposure to multiple native voices. Participants completed identification and discrimination tasks before and after training. Non-native word learning and vowel discrimination were measured before and after training, by means of identification and discrimination tasks, respectively. Results Learners achieved above-chance word identification, indicating successful lexical learning. However, improvement in vowel discrimination was contrast-specific: participants improved in three of six contrasts, while performance remained low for the most difficult contrast. Learners also showed lower identification accuracy for pseudowords containing this contrast, and individual discrimination ability was associated with word learning success. Discussion These findings highlight that while meaning-based training through CSWL can support early lexical and phonological learning, perceptual challenges remain for difficult contrasts. The study advances our understanding of how word learning and sound perception interact during second language acquisition and demonstrates the potential of lexically grounded approaches for perceptual training at the onset of learning.
Total-Arterial Revascularization Is Superior in Heart Failure Patients with Reduced Ejection Fraction—A Propensity Score Matched Retrospective Multicenter Analysis
2025-09-05

Background: Total arterial revascularization (TAR) may improve outcomes in patients with ischemic cardiomyopathy and heart failure with reduced ejection fraction (HFrEF). Methods: We retrospectively screened 574 adults with HFrEF (LVEF &lt; 40%) undergoing isolated CABG across four German centers (2017–2023). After 1:1 propensity score matching, 240 patients were analyzed (120 TAR vs. 120 NTAR). The primary endpoint was in-hospital MACCE (death, MI, stroke). Key secondary endpoints included ICU/hospital length-of-stay, ventilation time, delirium, transfusion requirements, and acute kidney injury. Results: MACCE occurred in 4.1% (TAR) vs. 14.2% (NTAR) (p = 0.007). TAR was associated with shorter ICU stay (median 44.5 h vs. 90 h, p &lt; 0.001), shorter hospital stay (10 d vs. 12 d, p = 0.002), reduced ventilation time (8 h vs. 12 h, p &lt; 0.001), lower delirium (5.0% vs. 14.2%, p = 0.016), and fewer RBC transfusions intra-operatively (0.13 ± 0.45 vs. 0.31 ± 0.58 units, p = 0.028) and during the entire stay (0.70 ± 1.33 vs. 1.77 ± 2.91 units, p &lt; 0.001). Conclusions: In this multicenter propensity-matched cohort, TAR was associated with lower in-hospital MACCE and more favorable perioperative outcomes compared with NTAR. Prospective studies are warranted to confirm causality and long-term benefits.
Multimodal Image Guidance in Subthalamic Deep Brain Stimulation for Parkinson’s Disease
2025-09-05

Abstract Background Accurate electrode placement and individual stimulation parameters influence the outcomes of subthalamic deep brain stimulation in Parkinson’s disease. Neuroimaging-based models can help evaluate how electrode placement impacts improvement, aiming to reduce the burden of DBS programming. However, most existing models have been developed to explain differences between patients rather than differences between contacts within the same patient, leaving the clinical relevance of image-guided programming unclear. Methods We analyzed data from patients with Parkinson’s disease treated with subthalamic deep brain stimulation to develop and validate a neuroimaging-informed model of motor improvement measured by the Unified Parkinson’s Disease Rating Scale. Five approaches were tested: active contact coordinates, electric fields, tract activations, as well as structural and functional networks. All approaches were integrated into a combined ridge regression model and validated using two hold-out datasets. Results The sample included 236 patients (604 stimulation sites), divided into a training cohort (N = 129), a retrospective validation cohort (N = 89), and a prospectively acquired validation cohort (N = 21 electrodes). Consistent with expectations, our model explained approximately 11% of the variance in unseen group-level data ( R 2 = 0.11, p = 0.001). At the individual level, the model identified the optimal clinical contact or its neighboring contact in all but one case (mixed-effects R 2 = 0.32, p = 1 x 10 -16 ). Conclusion The imaging-informed model explained the expected variance at the group level and demonstrated potential for guiding stimulation programming, suggesting that image-guided approaches may improve clinical decision-making while reducing the need for lengthy postoperative testing.
Large-Scale Color Biases in the Retinotopic Functional Architecture Are Region Specific and Shared across Human Brains
2025-09-08

Despite the functional specialization in visual cortex, there is growing evidence that the processing of chromatic and spatial visual features is intertwined. While past studies focused on visual field biases in retina and behavior, large-scale dependencies between coding of color and retinotopic space are largely unexplored in the cortex. Using a sample of male and female volunteers, we asked whether spatial color biases are shared across different human observers and whether they are idiosyncratic for distinct areas. We tested this by predicting the color a person was seeing using a linear classifier that has never been trained on chromatic responses from that same brain, solely by taking into account: (1) the chromatic responses in other individuals’ brains and (2) commonalities between the spatial coding in brains used for training and the test brain. We were able to predict the color (and luminance) of stimuli seen by an observer based on other subjects’ activity patterns in areas V1–V3, hV4, and LO1. In addition, we found that different colors elicited systematic, large-scale retinotopic biases that were idiosyncratic for distinct areas and common across brains. The area-specific spatial color codes and their conservation across individuals suggest functional or evolutionary organization pressures that remain to be elucidated.
Structure–Activity Relationships of 3-Hydroxypropanamidines (HPAs) with Potent In Vivo Antimalarial Activity
2025-09-08

New treatment strategies are required to combat the spread of drug-resistant <i>Plasmodium falciparum</i> malaria. The synthesis and preclinical evaluation of novel 3-hydroxy-propanamidines (HPAs), with modifications of the phenanthrene and the 4-fluorobenzamidine moieties, has yielded several analogs exhibiting excellent in vitro growth inhibition of drug-sensitive or resistant <i>P. falciparum</i> fresh clinical isolates and culture-adapted strains. No cytotoxicity in the human HepG2 cell line was observed, demonstrating notable parasite selectivity. The most active HPA <b>7d</b>, which features a 4-bromobenzamidine moiety, inhibited the formation of synthetic hemozoin (β-hematin) with IC<sub>50</sub> values lower than chloroquine and the lead compound <b>TKK130</b>. Additionally, <b>7d</b> showed a killing rate comparable to chloroquine. In initial in vivo pharmacokinetics, <b>7d</b> displayed a favorable pharmacokinetic profile, with a fast onset and slow elimination phase. In vivo, <b>7d</b> demonstrated dose-dependent curative activity after oral administration in the <i>Plasmodium berghei</i> mouse model, without apparent signs of toxicity.
Anterior Cruciate Ligament Pathology as a Predisposing Factor for Bucket Handle Meniscal Tear
2025-09-08

Objective. To test if the presence of anterior cruciate ligament pathology is a predisposing factor for the occurrence of a bucket handle tear of the meniscus. Materials and methods. In a retrospective double-center setting, 3340 consecutive knee MRI examinations dated between October 2018 and March 2021 with various 1.5 and 3T MRI machines have been reviewed. All cases with bucket-handle tear of the meniscus have been sought. From the bucket handle cases, only those with available previous MRI examinations showing unremarkable meniscus were included. Results. From the evaluated 3340 knee MRI-scans, 36 cases with bucket handle tears were identified (30 and 6 cases involving the medial and lateral meniscus, respectively). Nine out of 36 cases had previous MRI-scan with a non-tear status of the involved meniscus. Interestingly, all these nine cases showed a clear anterior cruciate ligament abnormality prior to the occurrence of bucket handle tear. The nature of the associated anterior cruciate ligament pathology ranged from complete and previous reconstruction in tear in 3 and 6 cases, respectively. Conclusion. A significant association between underlying anterior cruciate ligament pathology and later development of bucket handle tears of the meniscus could be shown. This result highlights the importance of the proprioceptive role of the anterior cruciate ligament in maintaining knee stabilization which can results in further structural meniscal injuries and therefore underlining the necessity of addressing the menisci during its anterior cruciate reconstruction and the importance of their clinical and radiological follow-up
An Integrated Paleoenvironmental Reconstruction of the Early Pleistocene Hominin-Bearing Site of Dursunlu (Türkiye)
2025-09-08

The fossiliferous Dursunlu Lignite Quarry (DLQ) is highlighted prominently in the archeological and paleontological literature because of the study of Pleistocene fauna and lithic artifacts, being considered the oldest Paleolithic site in Türkiye. Although the fauna and flora assemblage from DLQ are reasonably well known, taxonomic studies devoted to some groups, such as ostracods, mollusks, reptiles, and amphibians, have never been carried out. Here, we describe, illustrate, and study the taxonomic composition and ecological implications of the unpublished material of said groups, together with the aquatic plants and fish, recovered from six samples taken from the palustrine and peat bog facies of the sedimentary sequence. In addition, the recovered charophytes and cyprinids refine our taxonomical knowledge of both aquatic plants and fish. Our results concur with previous paleoenvironmental inferences based on flora and fauna composition—with DLQ representing a very shallow eutrophic lake with a dense palustrine vegetation belt during the cold (glacial) stage of the late Early Pleistocene—as well as highlight the study of all available groups as pivotal for better understanding the paleolake biota. We further conclude that the wetland areas of Dursunlu and surrounding steppe areas appear to have been an excellent environment for sporadic settlement of hominins during the Early Pleistocene, given the availability of food resources and easy access to water.
Isolated spinal aneurysms with spontaneous regression
2025-09-08

Abstract Purpose To share our clinical experience with conservative management of isolated spinal arterial aneurysms (ISAs) and to identify clinical scenarios where conservative management may be appropriate, in the context of a literature review. Methods We performed a retrospective review of spinal angiograms from two German neuroradiology centers and conducted a systematic literature review of reported ISA cases. We analyzed demographics, clinical presentation, imaging findings, treatments, and outcomes. Results We identified seven patients (mean age 48; 4 women) with nine ISAs, eight of which were managed conservatively. Five of them had excellent short-term outcomes, and spontaneous regression was documented in four cases. With our cases, 208 ISAs have been reported in the literature in 164 patients (mean age 51; 52% female). They most commonly present with subarachnoid hemorrhage (90%) and back pain (69%). Most are located in the thoracic (51%) or cervical spine (40%) and involve the anterior spinal circulation (63%). They may be treated by surgical intervention (47%) or conservatively (37%), less commonly by endovascular therapy (16%). 78% of patients have favorable outcomes (mRS 0–3), similar across all treatment approaches. In 52% of conservatively managed cases, spontaneous regression was documented by imaging. Clinical deterioration was primarily associated with respiratory complications and spinal cord infarction, with a documented rebleeding rate of 8% and a mortality rate of 12%. Conclusions ISAs are a rare and potentially underrecognized cause of cerebral and spinal subarachnoid hemorrhage. In select cases, particularly small ISAs of the anterior spinal or a radiculomedullary artery and with transient neurological symptoms, conservative management appears to be a reasonable approach, supported by increasing evidence of the possibility of spontaneous regression.
Learning morphology from cross-situational statistics
2025-09-08

Abstract Non-native languages tend to be acquired through a combination of explicit and implicit learning, where implicit learning requires coordination of language information with referents in the environment. In this study, we examined how learners use both language input and environmental cues to acquire vocabulary and morphology in a novel language and how their language background influences this process. We trained 105 adults with native languages (L1s) varying in morphological richness (English, German, Mandarin) on an artificial language comprising nouns and verbs with morphological features (number, tense, and subject-verb [SV] agreement) appearing alongside referential visual scenes. Participants were able to learn both word stems and morphological features from cross-situational statistical correspondences between language and the environment, without any instruction. German-speakers learned SV agreement worse than other morphological features, which were acquired equally effectively by English or Mandarin speakers, indicating the subtle and varied influence of L1 morphological richness on implicit non-native language learning.
Arithmetic fact retrieval deficits in chronic stroke – A deficit of relearning?
2025-09-08

In acute stroke patients, arithmetic fact retrieval deficits have been observed due to disrupted white matter connections within a left-hemispheric network centered around the angular gyrus and middle temporal gyrus (Smaczny et al., 2023). However, it remains unclear which specific structural disconnections also hinder successful remediation in the chronic stage of stroke. In this study, 92 patients were examined to determine which impairments continue to affect multiplication performance even in the chronic phase after a first-time unilateral left-hemispheric stroke. Our results revealed a strong association between impaired multiplication performance and the disconnection of left long-term memory (para)hippocampal areas from left frontal and right parietal regions. Thus, unlike previous findings in the acute stroke phase, our results in the chronic phase emphasize the importance of (para)hippocampal regions for successful multiplication performance. We suggest that the affected areas and connections in chronic patients with persistent multiplication problems not only indicate areas that are crucial for the relearning of arithmetic facts, but also those crucial for the learning of arithmetic facts in general. More generally, we suggest that the acquisition of arithmetic facts depends on structural integrity of a network centered around the left (para)hippocampus, while the retrieval of consolidated arithmetic facts from memory relies on the integrity of a left-hemispheric network involving angular gyrus and middle temporal gyrus.
Looking at people looking at art: observations of art interactions in an everyday urban environment
2025-09-08

Introduction Placing art in urban spaces can make urban public environments more attractive and colorful by offering beautiful and restorative environments. This may invite people to spend time in the area and create opportunities for social engagement, and community development. In this observational study we collaborated with “Keine Galerie” (translating to “not a gallery”), a small window gallery in the city of Vienna (Austria) to address the following questions: Does the presence of publicly available art influence people's behavior (in terms of type, frequency, and duration) in an urban space? Does it enhance peoples' social interactions, such as the amount of conversations in a group? Methods To capture the impact of presence of art, we collected data during two exhibitions by two different artists at Keine Galerie (i.e., art conditions) as well as between exhibitions when no art was visible (i.e., control condition). We used observational methods to unobtrusively assess how pedestrians who were passing through the study area interact with their environment either with or without art. Results Our results showed that art being present invites passers-by to interact with the space more than when no art is present (no art vs. art conditions) but also that the type of art may matter (Ex.1 vs. Ex. 2), which influenced not just the amount of interactions but also which interactions took place. Discussion We discuss these quantitative and qualitative differences, also with regard to potential confounding factors (e.g., weather), and propose avenues for further research into the impact of art in public space.