julilili42/papers huggingface dataset:
Abemaciclib Plus Fulvestrant in Patients With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Final Overall Survival Results From MONARCH 2
2025-08-01

PURPOSE The MONARCH 2 study demonstrated statistically significant benefit in final progression-free survival (PFS) and interim overall survival (OS) with abemaciclib plus fulvestrant for cyclin-dependent kinase 4/6 inhibitor–naïve hormone receptor–positive, human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) that progressed during endocrine therapy (ET). Here, we report final prespecified OS analyses and other secondary end points. METHODS Patients with hormone receptor–positive, HER2– ABC who had disease progression during ET were randomly assigned 2:1 to receive abemaciclib or placebo, plus fulvestrant. The primary end point was investigator-assessed PFS; key secondary end points included OS and safety, and chemotherapy-free survival was an exploratory end point. RESULTS With a median 80-month follow-up, a total of 440 OS events occurred (abemaciclib, 283; placebo, 157). Median OS was 45.8 and 37.3 months with abemaciclib and placebo, respectively (hazard ratio [HR], 0.784 [95% CI, 0.644 to 0.955]). Although OS benefit was generally consistent across subgroups, a notable numerical benefit was observed in subgroups with poorer prognosis: visceral disease (HR, 0.643 [95% CI, 0.499 to 0.829]), primary resistance to ET (HR, 0.634 [95% CI, 0.436 to 0.922]), and progesterone receptor–negative status (HR, 0.623 [95% CI, 0.405 to 0.959]). Abemaciclib also delayed subsequent chemotherapy initiation (HR, 0.674 [95% CI, 0.562 to 0.809]), with substantial difference in yearly chemotherapy-free survival rates (3-year, 42.0% v 29.3%; 4-year, 37% v 18.6%, 5-year, 32.4% v 14.7%). No new safety signals or cumulative toxicities were identified with prolonged abemaciclib exposure. CONCLUSION These results further validate the clinical benefit previously demonstrated in MONARCH 2, reinforcing abemaciclib plus fulvestrant as an effective treatment option for patients with hormone receptor–positive, HER2– ABC who progressed after previous ET.
Unveiling novel and legacy PFAS in human hair
2025-08-01

A recent approach for human biomonitoring of per- and polyfluoroalkyl substances (PFAS) is non-invasive human hair sampling. In this study, solid-phase extraction (SPE), liquid-chromatography and tandem mass spectrometry (UPLC-MS/MS) were used to measure an extended set of PFAS in human hair. 45 hair samples from German voluntary subjects (19 female, 26 male) were screened for 26 target compounds, including perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs), fluorotelomer sulfonic acids (FTSAs), fluorotelomer carboxylic acids (FTCAs), fluorotelomer unsaturated carboxylic acids (FTUCAs), polyfluoroalkyl phosphate diesters (diPAPs), perfluorooctanesulfonamide (FOSA), N-ethyl perfluorooctane sulfonamidoacetic acid (N-EtFOSAA) and bis(trifluoromethane)sulfonimide (NTf2). 22 out of 26 target analytes were detected with two to 16 PFAS per sample. The most frequently detected substances were 6:2 FTSA, PFOS, PFOA and 6:2 diPAP with detection frequencies (Df) of 93, 87, 84, and 78 %, respectively. The emerging ionic liquid ingredient NTf2 was found in 44 % of all samples, which points to its widespread occurrence. To the best of our knowledge, NTf2 has been detected for the first time in human hair. The PFAS sum concentrations per subject ranged from 121 pg/g to 10332 pg/g. Maximum concentrations were found for PFOS (3763 pg/g), 6:2 FTSA (3600 pg/g) and PFPeS (3154 pg/g). Young subjects <30 years showed significantly higher levels for the ∑<sub>PFAS</sub> (median 2231 pg/g) and the ∑<sub>PFSAs</sub> (median 735 pg/g) compared to subjects >30 years (median ∑<sub>PFAS</sub> 1196 pg/g, and for ∑<sub>PFSAs</sub> 453 pg/g). This study demonstrates that in addition to the generally monitored PFCAs and PFSAs further precursors like diPAPs, FTSAs, and their transformation products considerably contribute to the total PFAS pattern in hair. This reflects the PFAS exposure of humans, even if blood-hair transfer factors are not yet established for PFAS and subject selection was not representative for the whole German population.
Increased extracellular volume after aortic valve replacement: a footprint of reverse ventricular remodeling that does not affect conduction velocity
2025-08-01

Increased ECV 3 months after AVR in patients with no LGE scar and with normal ventricular conduction appears to be a footprint of reverse ventricular remodeling that does not necessarily translate into changes in myocardial CV.
Design, Synthesis, and Molecular Evaluation of SNAr‐Reactive N‐(6‐Fluoro‐3‐Nitropyridin‐2‐yl)Isoquinolin‐3‐Amines as Covalent USP7 Inhibitors Reveals an Unconventional Binding Mode
2025-08-01

ABSTRACT The cysteine protease ubiquitin‐specific protease 7 (USP7), also known as herpes‐associated ubiquitin‐specific protease (HAUSP), has gained increasing attention in recent years due to its proven overexpression in several cancer types and its role in tumorigenesis. Herein, after a design based on molecular docking experiments, we report the synthesis of a series of mildly electrophilic compounds that covalently modify the catalytic cysteine 223 in USP7 through a nucleophilic aromatic substitution (S N Ar) reaction. The compounds were first evaluated using differential scanning fluorimetry (DSF) to describe their influence on the melting temperature of native and mutant USP7 variants. Furthermore, the possible formation of a covalent bond was analyzed using intact protein mass spectrometry (MS). For promising derivatives, IC 50 values were determined in an enzyme activity assay to confirm an inhibitory effect on USP7. Finally, a co‐crystal structure revealed that the prototype compound ( 7a ) arylates the catalytic cysteine in the apo form of USP7 via an unconventional binding mode near the catalytic triad. The synthesis and biological evaluation of this compound series provides valuable structure–activity relationships (SAR) and reveals an interesting and unprecedented binding mode, thus providing a basis for improving USP7 inhibitors.
Exploration of Fluorinated Peptoid‐Based Histone Deacetylase Inhibitors as Dual‐Stage Antiplasmodial Agents
2025-08-01

ABSTRACT The antiplasmodial properties of a series of fluorinated peptoid‐capped histone deacetylase inhibitors (HDACi) were investigated against asexual blood stages of the drug‐sensitive 3D7 and drug‐resistant Dd2 strains of Plasmodium falciparum , as well as the exo‐erythrocytic liver stages and mature gametocytes. Among the series, compound 1h emerged as the most potent derivative, showing strong activity against both P. falciparum strains ( Pf 3D7 and Dd2 IC 50 : 0.010 μM) and Plasmodium berghei liver stages ( Pb EEF IC 50 : 0.74 μM), while lacking activity against mature gametocytes. Compound 1b was identified as a second hit compound with slightly lower activity against asexual blood and liver stages ( Pf 3D7 IC 50 : 0.019 μM; Pf Dd2 IC 50 : 0.023 μM; Pb EEF IC 50 : 2.25 μM) but showed excellent parasite selectivity (SI HepG2/3D7 : 2389; SI HepG2/Dd2 : 1973) and low single‐digit micromolar activity against mature gametocytes (IC 50 : 1.70 μM). Compared to our previous hit compound MAHA‐022, both 1b and 1h exhibited improved activity against asexual blood stages and enhanced parasite selectivity, albeit with reduced activity against liver stage parasites. Taken together, compounds 1b and 1h represent promising multi‐stage antiplasmodial HDACi scaffolds for further development and optimization.
MMAP-09 EFFICACY OF IPILIMUMAB-NIVOLUMAB IN PATIENTS WITH MULTIPLE MELANOMA BRAIN METASTASES
2025-08-01

Abstract Immunotherapy with ipilimumab (ipi) and nivolumab (nivo) has shown impressive response rates in patients with melanoma brain metastases (MBM) with a clinical outcome comparable to patients without MBM. However, within clinical trials most patients had only single brain metastases and data in patients with multiple lesions is lacking. We retrospectively analyzed clinical outcome including response rates, progression-free and overall survival in patients with at least 5 MBM who received ipi-nivo +/- radiotherapy (RT). Collection of data is ongoing; in an interim analysis 74 patients were included: Patients had a median age of 58 (range 26-83), 50 (68%) male, 56 (76%) patients with multiple (&amp;gt; 10) MBM at therapy start. 29 (39%) had symptomatic MBM controlled with a median of 12mg dexamethasone (range 4-24mg). At start of ipi-nivo 29 (39%) patients received WBRT and 17 (23%) SRS. In patients without RT 11/28 (39%) responded to ipi-nivo, 2 of them received 4 and 12mg dexamethasone. In patients with combined RT 4/17 (24%, SRS of up to 10 MBM) and 6/29 (21%, WBRT) responded. 6 or 12 weeks after the initiation of ipi-nivo another 4 patients received SRS and 8 patients WBRT as salvage RT. Overall survival did not significantly differ in patients with 5-9 or multiple MBM or dependent on the addition of RT, no matter if SRS or WBRT was applied.To conclude, ipi-nivo demonstrated efficacy independent from added RT in patients with multiple MBM.
Learned Insignificance of Credibility Signs
2025-08-01

Abstract A large part of how people learn about their shared world is via social information. However, in complex modern information ecosystems, it can be challenging to identify deception or filter out misinformation. This challenge is exacerbated by the existence of a dual‐learning problem whereby: (1) people draw inferences about the world, given new social information; and simultaneously (2), they draw inferences about how credible various sources of information are, given social cues and previous knowledge. In this context, we investigate how social influence and individual cognitive processing interact to explain how one might lose the ability to reliably assess information. Crucially, we show how this happens even when individuals engage in rational belief updating and have access to objective cues of deception. Using an agent‐based model, the Reputation Game Simulation, we show that mere misinformation is not the problem: The dual‐learning problem can be solved successfully with limited Bayesian reasoning, even in the presence of deceit. However, when certain agents consistently engage in fully deceptive behavior, intentionally distorting information to serve nonepistemic goals, this can lead nearby agents to unlearn or discount objective cues of credibility. This is an emergent delusion‐like state, wherein false beliefs resist correction by true incoming information. Further, we show how such delusion‐like states can be rehabilitated when agents who had previously lost the ability to discern cues of credibility are put into new, healthy—though not necessarily honest—environments. Altogether, this suggests that correcting misinformation is not the optimal solution to epistemically toxic environments. Though difficult, socially induced cognitive biases can be repaired in healthy environments, ones where cues of credibility can be relearned in the absence of nonepistemic communication motives.
Mitral Annular Disjunction in Marfan Syndrome: A Multicenter Cardiovascular Magnetic Resonance Study
2025-08-01

The high prevalence, large extent, and predominantly pan-annular distribution of MAD suggest a systemic annular pathology in MFS. Overall presence of MAD was not associated with changes to left heart parameters, aortic dimensions, and cardiovascular events. However, MAD, taking into account its extent and affected insertion sites, could serve as a potential marker of disease progression given the shown association of localizations and distance with LV dysfunction and remodeling as well as aortic enlargement and the formation of MVP.
Deciphering Pleistocene Fault Activity in the Eastern Alps: Dating Fault Gouges With Electron Spin Resonance and Optically Stimulated Luminescence
2025-08-01

Abstract The Eastern Alps have been influenced by post‐collisional indentation tectonics since the Miocene. Currently, Adria‐Europe convergence, albeit slow, is accommodated and distributed across several faults. The seismogenic potential of some of these faults is unclear. We applied optically stimulated luminescence (OSL) and electron spin resonance (ESR) dating to fault gouges to constrain which portions of the Periadriatic Fault (PAF) System, Lavanttal Fault, and Šoštanj Fault experienced surface‐rupturing earthquakes during the Quaternary. The saturation level of the quartz ESR Al center signal was used as a metric of seismic activity to compare between the faults. Our results showed that the Lavanttal Fault experienced the least Quaternary seismic activity, followed by the PAF, while the Šoštanj Fault exhibits the most recent seismic events. The Lavanttal Fault samples showed ESR saturation levels of approximately 97%, and minimum ages ranging 863 ± 41–2,151 ± 323 ka, indicating that if earthquakes occurred, they did so before this period. The PAF was seismically active during the Pleistocene, with maximum ESR ages ranging 899 ± 67–305 ± 25 ka and minimum K‐feldspar OSL ages ranging 179 ± 13 to 62 ± 4 ka (pIRIR 225 ). Despite a spread in ESR ages, the saturation level was consistent between samples, averaging 66 ± 4%. The Šoštanj Fault yielded an ESR age of 644 ± 30 ka and OSL of 30 ± 4 ka. The age difference lies in the dating range of both systems, but the results still suggest a shorter recurrence interval than the other two faults. Overall, our results show the utility of ESR and OSL dating in identifying periods of fault activity and complementing other approaches to fill temporal gaps.
Molecular mimicry as a driver of T cell-mediated tumour immunity
2025-08-01

Recently, a large pool of antigens derived from viral and bacterial microorganisms showing molecular mimicry with tumour-cell-expressed antigens was identified. These antigens can be presented by MHC molecules and elicit T cells that are crossreactive with microbial antigens and tumour-cell-associated antigens. In the setting of metastatic melanoma, such T cells can contribute to the response induced by immune checkpoint blockade therapy. Here, the current understanding of molecular mimicry in T cell-mediated tumour immunity and how this might be exploited for developing new preventive and therapeutic approaches for cancer is described. In particular, the literature on the concept and evidence of molecular mimicry in cancer is reviewed, covering the whole translational spectrum, from the antigen discovery strategy to the clinical evaluation.
Unravelling the difference in craniofacial morphology of Yucatan miniature and standard pigs during postnatal ontogeny
2025-08-01

The Yucatan miniature pig has become a preferred model for craniofacial research due to its anatomical and physiological similarities to humans. However, the factors driving midfacial hypoplasia in Yucatans during postnatal ontogeny remain unclear. This study characterized postnatal skull growth and development, and morphological variations in Yucatan and standard (domestic) pigs, with a focus on the role of joint maturation in resulting craniofacial dysmorphology. Forty available head specimens (Yucatan: n = 20, 0–12 months; standard: n = 20, 0–8 months) were analysed using multidimensional craniometric measurements and geometric morphometrics. Results show that both breeds follow an allometric growth trajectory, largely driven by the expansion of craniofacial organs and capsules. At birth, skull morphology was similar between breeds; however, Yucatans developed a shorter face and more compact neurocranium, while maintaining a nearly identical mandibular shape to standard pigs. Over the first three months, Yucatans exhibit delayed calvarial suture fusion compared with standard pigs, while skull base synchondroses remain patent in both breeds. These findings reflect the scaling relations between breeds and highlight differential growth patterns of the midface, neurocranium and mandible in Yucatans, emphasizing their interactions with organ development, cavity expansion and joint maturation, offering insights into the mechanisms driving craniofacial diversification in pig models.
Reduced Platelet Aggregation and Plasma Cytokine Levels Mitigate Progressive Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
2025-08-01

Reduced platelet aggregation is associated with attenuation of MASLD features. Antiplatelet therapy correlates with decreased pro-inflammatory and pro-fibrotic chemokine signaling linked to the morphological characteristics of MASLD. Assessment of platelet reactivity and specific chemokines may enhance understanding of MASLD pathophysiology and support the development of novel therapeutic strategies.
A receptor antagonist counterbalances multiple systemin phytocytokines in tomato
2025-08-01

Tight regulation of immune activation is crucial for plant health. How plants control the actions of their immunostimulatory phytocytokines is largely unknown. Here, we identify antiSYS as a natural inhibitor of the tomato cytokine systemin. AntiSYS is a systemin-like peptide encoded in a gene cluster with four additional paralogs, three of which comprise newly identified agonistic systemins. AntiSYS is a potent and specific antagonist of the systemin receptor. Tomato mutants lacking antiSYS show aberrant growth and reduced reproductive fitness. These symptoms of antiSYS deficiency are not observed in plants lacking functional systemin receptors, suggesting a role of antiSYS in counterbalancing agonistic systemins. Thus, reminiscent of antagonistic interleukins controlling immune homeostasis in animals, antiSYS serves a crucial role in the regulation of phytocytokine activity in tomato plants.
A Deep Learning Earth System Model for Efficient Simulation of the Observed Climate
2025-08-01

Abstract A key challenge for computationally intensive state‐of‐the‐art Earth System models is to distinguish global warming signals from interannual variability. Here we introduce Deep Learning Earth System Model (DL ESy M), a parsimonious deep learning model that accurately simulates the Earth's current climate over 1000‐year periods with minimal smoothing and no drift. DL ESy M simulations equal or exceed key metrics of seasonal and interannual variability—such as tropical cyclogenesis over the range of observed intensities, the cycle of the Indian Summer monsoon, and the climatology of mid‐latitude blocking events—when compared to historical simulations from four leading models from the sixth Climate Model Intercomparison Project. DL ESy M, trained on both historical reanalysis data and satellite observations, is an accurate, highly efficient model of the coupled Earth system, empowering long‐range sub‐seasonal and seasonal forecasts while using a fraction of the energy and computational time required by traditional models.
Psychometric properties of the German Stroke and Aphasia Quality of Life Scale 39 generic version
2025-08-01

The German SAQOL-39g is an easy-to-administer and -score patient-reported scale that can be used in rehabilitation settings to measure health-related quality of life and support patient-centered goal setting in people with chronic post-stroke aphasia of different ages, stroke durations, severity and type of aphasia.
HLA Ligand Atlas DIA: extending the benign immunopeptidomics resource with increased sensitivity through data-independent acquisition mass spectrometry
2025-08-01

The human leukocyte antigen (HLA)-presented peptide repertoire, termed immunopeptidome, plays a crucial role for T-cell mediated immune reactions. Previously, the human immunopeptidome of non-malignant tissues has been mapped in a large-scale study, the HLA Ligand Atlas, via high-resolution data-dependent acquisition (DDA) mass spectrometry. This publicly available and user-friendly web interface ( https://hla-ligand-atlas.org ) is frequently used as a benign tissue reference in antigen discovery, especially for immunotherapy of cancer. Here, we extend the HLA Ligand Atlas resource with paired data-independent acquisition (DIA) runs for all tissue-subject combinations. This novel dataset comprises 946 DIA HLA class I and II immunopeptidomic runs from 242 non-malignant human samples across 18 subjects and 29 distinct tissues. Together with the published DDA runs, this extends the range and depth of analyses performed on the HLA Ligand Atlas dataset. In a concise analysis, we showcase advantages of DIA over DDA concerning spectral sampling and sensitivity. These findings are attributed to the increased dynamic range in DIA, enabling the identification of peptide transitions with low signal intensities. Moreover, we demonstrate the superior sensitivity by applying an HLA-A*02:01 allotype-specific spectral library search to identify and quantify HLA-presented peptides. We encourage reanalysis of the provided DDA and DIA data in combination as a reference for future research concerning human immunology.
Treatment Regimens with Ranibizumab in Neovascular Age-Related Macular Degeneration: Real-World Results from the PACIFIC Study Author List
2025-08-01

Over 2-year observational period, the treat and extend regimen emerged as a highly effective approach, particularly for those newly diagnosed, with a low risk of undertreatment. Despite its benefits, an unconscious shift to a observe-and-extend or "monitor-and-extend" approach occurred early in treatment, highlighting the need for tailored approaches to optimize patient outcomes in clinical practice.
Benchmarking the Structure-Based Virtual Screening Performance of Wild-Type and Resistant PfDHFR Using Docking and Machine Learning Re-Scoring
2025-08-01

The findings demonstrate that re-scoring with CNN-Score consistently augments the SBVS performance and enriches diverse and high-affinity binders for both <i>Pf</i>DHFR variants, offering important endorsements for improving malaria drug discovery, especially against the highly resistant Q variant.
Democratize MATCH_RECOGNIZE!
2025-08-01

Row pattern matching in terms of the MATCH_RECOGNIZE clause is a powerful and relatively recent feature in SQL that allows users to define regular patterns over ordered rows in a table. As of today, few database systems offer support for match recognize , making it unaccessible to a wide range of users. We demonstrate the implementation of a transpiler that translates match recognize into a plain SQL query executable by any database system that supports window functions and recursive common table expressions—no changes to the underlying database systems are required. We evaluate the performance of this approach on the running example to show that the transpiler generates code competitive with contemporary database systems that implement row pattern matching natively. The on-site demonstration is based on DuckDB.