julilili42/papers huggingface dataset:
Pre-interventional transesophageal echocardiography as a reliable predictor of residual shunt following patent foramen ovale closure
2025-07-24

Abstract Background Closure of a patent foramen ovale (PFO) is an effective strategy in the prevention of recurrent stroke after cryptogenic stroke. Residual shunt (RS) is a common issue following PFO closure and may affect safety and efficacy. Transesophageal echocardiography (TEE) is the key diagnostic tool, but standardized assessment of morphological parameters to prevent RS remains challenging. Aims In this study, we investigate the diagnostic value of different anatomical parameters assessed by TEE to predict RS after PFO closure. Methods We consecutively enrolled five-hundred and twenty-seven ( n = 527) patients undergoing PFO closure. We performed pre-interventional TEE, and after PFO closure, we then screened for RS by TEE at 6-month follow-up. Results Pre-interventional TEE measures of PFO morphology revealed significant differences in patients with RS in comparison to those with closed PFO. Incidence of RS was significantly more frequent in patients with atrial septum aneurysm ( p = 0.022) and increasing PFO size ( p = 0.025). In patients with RS, we found significantly increased length ( p = 0.005) of septum primum and PFO tunnel ( p = 0.036) as well as excursion ( p = 0.005) of septum primum. By training machine learning models on TEE parameters, stratification of PFO morphology resulted in high diagnostic accuracy to predict RS after PFO closure. Conclusions Our study elucidates that a baseline characterization of PFO morphology using TEE improves diagnostic precision to identify patients with RS after PFO closure. A standardized approach might thus enhance the efficacy and safety of transcatheter PFO closure. Prediction of complete closure might reduce complications and allow for a more refined patient selection and treatment. Graphical Abstract Prediction of peri-device leak in patients PFO and paradoxical embolism undergoing percutaneous PFO closure. Workflow of this study investigating the association of morphological determinants with an increased incidence of residual shunting assessed through transesophageal echocardiography.
Non-invasive physical plasma activates stimulator of interferon genes pathway in triple negative breast cancer and is associated with increased host immune response
2025-07-24

Triple-negative breast cancer (TNBC), characterized by the absence of ER, PR, and HER2 receptors, remains one of the most aggressive breast cancer subtypes, with limited therapeutic options and a high relapse rate. While immune checkpoint inhibitors (ICIs) have shown promise by leveraging TNBC’s immunogenic profile, their use is often accompanied by significant toxicity, necessitating the development of safer immunomodulatory strategies. Non-invasive physical plasma (NIPP), a novel low thermal plasma technology that can be generated using various gases, including argon, and producing reactive oxygen and nitrogen species (RONS), has emerged as a potential alternative. This study investigates the capacity of direct (argon plasma devitalization, APD) and indirect (plasma-treated solution, PTS) plasma modalities to induce cytotoxicity and activate immune signaling via the stimulator of interferon genes (STING) pathway in TNBC. Dose-dependent RONS generation by APD and PTS correlated with reduced viability and apoptosis induction in MDA-MB-231 TNBC cells. Both plasma modalities caused DNA damage and upregulated key proteins in the STING pathway, including γ-H2AX, p-STING, and p-TBK1, with sustained activation observed up to 24 hours post-treatment. Furthermore, STING-dependent transcription of IFN-β and interferon-stimulated genes (ISGs) confirmed the immunogenic potential of NIPP. Conditioned media from plasma-treated TNBC cells induced M1 polarization in THP-1-derived macrophages, an effect significantly reduced upon specific STING inhibition with H-151. The immunomodulatory effects of NIPP were validated in patient-derived TNBC organoids, where plasma treatment disrupted organoid structure, reduced viability, and promoted M1 macrophage polarization. Collectively, these findings highlight the dual cytotoxic and immunostimulatory potential of NIPP in TNBC through STING pathway activation, claiming it as a promising, low-toxicity component in combination with conventional immunotherapy.
Investigating the effects of transcranial direct current stimulation (tDCS) on working memory training in individuals with schizophrenia
2025-07-24

Abstract Cognitive impairments in schizophrenia significantly impact daily functioning and quality of life, posing a major therapeutic challenge. While both cognitive training and transcranial direct current stimulation (tDCS) have shown promise in improving cognitive function, their combined effects remain underexplored. This double-blind, sham-controlled, randomized clinical trial investigated whether adaptive working memory training (aWMT) paired with anodal tDCS to the right dorsolateral prefrontal cortex (DLPFC) enhances cognitive outcomes in schizophrenia. Twenty-eight individuals with schizophrenia or schizoaffective disorder completed ten sessions of aWMT with concurrent 2 mA anodal or sham tDCS. Cognitive improvements were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, three days after training, and at follow-ups one month, and three months later. Clinical measures evaluated psychopathology, depression, and quality of life. Anodal tDCS significantly improved working memory performance during training, with gains partially sustained at follow-ups. Short-term transfer effects with large effect sizes were observed in the BACS, although clinical symptoms and quality of life remained unaffected. While preliminary, these findings indicate that tDCS could support cognitive training outcomes in schizophrenia. Larger randomized controlled trials are needed to confirm transfer effects and determine the long-term benefits of this approach. If proven effective, integrating tDCS into cognitive remediation therapies could represent an innovative strategy to address cognitive deficits in schizophrenia.
Rationally warranted promise: the virtue-economic account of pursuit-worthiness
2025-07-25

Abstract Pursuing a scientific idea is often justified by the promise associated with it. Philosophers of science have proposed various ways of unpacking this idea of promise, including more specific indicators. Economic models in particular emphasise the trade-off between an idea’s benefits and its costs. Taking up this Peirce-inspired idea, we spell out the metaphor of such a cost-benefit analysis for scientific ideas. It fruitfully urges a set of salient meta-methodological questions that accounts of scientific pursuit-worthiness ought to address. In line with such a meta-methodological framework, we also articulate and explore an appealing and auspicious concretisation—what we shall dub “the virtue-economic account of pursuit-worthiness”: cognitive benefits and costs of an idea, we suggest, should be characterised in terms of an idea’s theoretical virtues, such as empirical adequacy, explanatory power, or coherence. Assessments of pursuit-worthiness are deliberative judgements in which scientifically competent evaluators weigh and compare the prospects of such virtues, subject to certain rationality constraints that ensure historical and contemporary scientific circumspection, coherence and systematicity. The virtue-economic account, we show, sheds new light on the normativity of scientific pursuit, methodological pluralism in science, and the rationality of historical science.
Enhanced Separation of Intact Proteins and Proteoforms by CZE‐MS Using Sulfobetaine‐Modified Poly(α‐L‐lysine)‐Based Multilayer Coatings for EOF Adjustment
2025-07-25

ABSTRACT Mass spectrometry–based top‐down protein analysis requires efficient separation. In the context of proteoform analysis, capillary zone electrophoresis (CZE) is very valuable. The resolution of two peaks in CZE can be increased when the absolute mobility of the counter‐directed electroosmotic flow (EOF) is close to the effective mobility of the analytes, resulting in a low apparent mobility of the analytes. The mobility of the EOF of highly efficient sulfobetaine‐modified poly(α‐L‐lysine) (α‐PLL) coatings changes depending on the number of modified side chains. Here, such coatings are used to selectively increase the peak resolution of proteoforms of model proteins and analytes in a complex protein sample (intact yeast protein extract). Whereas a high EOF system allows for the separation of proteins of a wide mobility range (complete proteome), lower EOF systems allow for a much better separation of proteins and proteoforms of low mobility, including those containing acidic post‐translation modifications (PTMs). This leads to the identification of 2.5 times more proteoforms by MS/MS experiments in the lower mobility range of the yeast proteome. The sulfobetaine‐modified α‐PLL coatings presented here exhibit a toolbox for highly resolved separation of proteins and proteoforms in targeted or untargeted top‐down protein analysis. Summary Sample complexity is one of the main challenges when analyzing a proteome on the proteoform level. In the course of this, capillary electrophoresis–mass spectrometry turned out to be an excellent tool because of its high‐performing separation, particularly for large molecules. Here, we present a method enabling the best possible separation due to efficient and EOF‐tunable coatings, allowing for flexible and dedicated selection of a range of proteins and proteoforms to be analyzed under ideal separation conditions. The high performance is demonstrated by the separation of proteoforms of common PTM‐rich model proteins as well as complex proteome samples.
Indirect Zero-Field Nuclear Magnetic Resonance Spectroscopy
2025-07-25

This study develops the two-field correlation spectroscopy (COSY) in zero to ultralow field (ZULF) liquid state nuclear magnetic resonance (NMR). We demonstrated the successful integration of signal amplification by reversible exchange (SABRE) hyperpolarization with two-dimensional (2D) NMR spectroscopy, enabling the detection of ZULF COSY spectra with increased sensitivity. Field cycling allowed the acquisition of two-field COSY spectra at varying magnetic field strengths, including zero-field conditions. This enabled insight into both <i>J</i>-coupling and Zeeman-dominated regimes, benefiting from ultralow field observation sensitivity and mitigating the low-frequency noise by conducting readout at higher fields (>5 μT). Our study explores the effects of polarization transfer, apodization techniques, and the potential for further application of ZULF NMR in chemical analysis exemplified for three X-nuclei and three corresponding molecules: [1-<sup>13</sup>C]pyruvate, [<sup>15</sup>N]acetonitrile, and [3-<sup>19</sup>F]pyridine. These findings pave the way for more sensitive and cost-effective NMR spectroscopy in low-field regimes.
Actual and Perceived Risk of Colorectal Neoplasia in First-Degree Relatives of Patients with Colorectal Cancer
2025-07-25

INTRODUCTION: Individuals with a family history (FH) of colorectal cancer (CRC) are at increased risk of CRC. We aimed to assess the objective role and subjective perception of risk factors of colorectal neoplasia within this high-risk group. METHODS: Questionnaire and screening colonoscopy results were obtained from individuals aged 40–54 years with a reported FH of CRC in a first-degree relative in a multicenter cross-sectional study in Germany. Descriptive statistics characterized the cohort and distribution of risk factors. Multivariable logistic regression was used to derive adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) to evaluate factors associated with colorectal neoplasia and with subjectively perceived increased CRC-risk. RESULTS: Among 922 participants, 220 (23.9%) were diagnosed with colorectal neoplasia, 63 (6.8%) of these being advanced lesions. Strong associations with advanced neoplasia were observed for obesity (aOR 2.44, 95% CI 1.12–5.22), smoking (aOR 1.47, 95% CI 1.14–1.88 per 10-pack-years) and physical activity &lt;45 minutes per day (aOR 2.51, 95% CI 1.11–5.25). For smoking and physical activity, but not for obesity, similar associations were also seen with any colorectal neoplasia. No associations were seen with number and age at diagnosis of affected family members. By contrast, the latter factors, but none of the behavioral factors were strongly associated with subjectively perceived CRC-risk. DISCUSSION: Within a cohort of individuals aged 40–54 years with a FH of CRC, obesity, smoking, and lack of physical activity represented the most prominent modifiable risk factors for the development of advanced colorectal neoplasia but did not significantly impact risk perception in these high-risk participants.
Examination of speech processing in noise reveals cognitive deficits in early Huntington's disease
2025-07-25

Processing speech amongst noise requires sensory and cognitive abilities that are often affected by Huntington's Disease. However, their impact on daily communication remains unclear. We examined the effects of Huntington's Disease on speech-in-noise processing using everyday sentences and words in noise contexts and conditions that mimic different daily life scenarios. In Premanifest (n = 16) and Manifest Huntington's Disease (n = 12) and Control (n = 26) participants, we examined speech discrimination amongst non-demanding and attentionally demanding noise. We also examined how Huntington's Disease affected the ability to use spatial separation cues to disambiguate speech from noise in single-voice masker or multi-talker backgrounds. Finally, we administered a validated questionnaire where participants rated auditory processing difficulties during daily life activities. Sentence-in-noise discrimination was impaired in individuals with Manifest Huntington's Disease in almost all signal-to-noise ratio conditions with the attentionally-demanding masker and amongst the non-demanding noise masker with the most difficult signal-to-noise ratio. Premanifest Huntington's Disease participants had difficulty perceiving speech in some attentionally demanding noise conditions. Spatial cues provided situational benefits to speech processing under attentionally-demanding conditions for participants at all stages of Huntington's Disease, except for the Manifest Huntington's Disease group when stimuli included a single competing speaker. A logistic regression model using speech processing performance as a predictor successfully distinguished healthy control and Premanifest groups with 87.5% accuracy. Stage-dependent impairments in speech processing were observed under naturalistic noise conditions. These results further our understanding and contextualization of communication difficulties experienced by people with Huntington's Disease.
Youngest Toba Tuff (YTT) beds as a Late Pleistocene isochron in the Indian subcontinent? New geochronological and sedimentological insights
2025-07-25

ABSTRACT The ~75 ka Young Toba super‐eruption was a catastrophic extreme event that spewed vast quantities of volcanic ash and aerosols and is argued to have caused a drastic volcanic winter, climatic upheaval, and a human genetic bottleneck. The global and regional impacts of the eruption on climate dynamics and past hominin populations are strongly contested due to conflicting global climatic records and archeological datasets. The Indian subcontinent is a key place for Toba research due to its proximity to Mt. Toba (Indonesia). Most of central and peninsular India is estimated to have been covered by a ~5 cm ash layer, with deposits found in different fluvial systems across the subcontinent. For a long time, many of these Youngest Toba Tuff (YTT) deposits, occurring in both archeological and non‐archeological contexts, were believed to be primary tephra deposits dating to ~75 ka. However, the use of YTT as a Late Pleistocene chronological marker is surrounded by many uncertainties, primarily due to the complex and varying nature of the depositional and sedimentary contexts of YTT and chronological irregularities. Recent sedimentological and geochronological data indicate that most of the YTT deposits in India are secondary deposits, resulting from later erosion and redeposition occurring thousands of years after the eruption. This highlights the unreliability of YTT as an isochron and raises questions about the credibility of paleoclimate (terrestrial and marine) and archeological datasets that use YTT as a chronological marker. Our study contributes to this debate and reveals the complex redepositional history of YTT deposits in the Indian subcontinent through geochronological and geoarchaeological analyses of YTT‐bearing sequences from Motravulapadu, Andhra Pradesh, India. Our findings suggest that the final burial of YTT occurred around 30 ka, highlighting a temporal gap of more than 40 000 years after the eruption. Notably, the redeposited tephra horizon appears visually uniform and compositionally pure, despite its secondary context, adding complexity to its stratigraphic interpretation. Our multiproxy sedimentological approach demonstrates the importance of integrating detailed stratigraphic, magnetic, granulometric, and chronological analyses to resolve such depositional ambiguities; it underscores the need for similar frameworks in future studies of YTT‐bearing sequences. We suggest that YTT in India cannot be used as a reliable chronological marker without independent age estimations of its deposition. However, it has significant potential for identifying regional geological events.
Terrestrial Gastropod Traces on Medieval Human Remains: Taphonomic Evidence from Nysa in Western Anatolia
2025-07-25

<title>Abstract</title> This study investigates mollusc-induced taphonomic modifications on human skeletal remains unearthed from 11th–12th century burials at the ancient city of Nysa (Aydın, western Turkey). Taphonomic alterations—such as pitting, linear grooves, and superficial abrasions—were identified on cranial, tibial, rib, and scapular bones. These modifications were evaluated in connection with three terrestrial gastropod species found in situ: <italic>Cornu aspersum</italic> (= <italic>Helix aspersa</italic>), <italic>Oxychilus camelinus</italic>, and <italic>Caracollina lenticula</italic>. Macroscopic and stereomicroscopic observations revealed distinct morphological patterns consistent with biological activity, particularly the gnawing and burrowing behavior typical of <italic>Cornu aspersum</italic>. Endocranial and ectocranial surfaces of cranial bones exhibited small perforations (1–2 mm), while the tibiae showed linear, sequential cavities (2–3 mm), indicating prolonged and directed contact. The spatial association of gastropod shells and modified bones, especially the scapula, strengthens the hypothesis of direct biological interaction. Furthermore, ecological traits and seasonal activity cycles of the gastropods support the inference that the burials may have occurred during spring or autumn, when gastropod activity peaks. This study documents a rarely addressed taphonomic phenomenon and emphasizes the interpretive potential of gastropod-bone interactions for reconstructing burial conditions, microenvironmental dynamics, and seasonality. By integrating malacological, archaeological, and taphonomic evidence, the research contributes to a more nuanced understanding of inhumation processes and highlights the need to consider invertebrate activity as a significant factor in post-mortem bone alteration.
Enhancing tandem mass spectrometry-based metabolite annotation with online chemical labeling
2025-07-26

Abstract Metabolite identification in non-targeted mass spectrometry-based metabolomics remains a major challenge due to limited spectral library coverage and difficulties in predicting metabolite fragmentation patterns. Here, we introduce Multiplexed Chemical Metabolomics (MCheM), which employs orthogonal post-column derivatization reactions integrated into a unified mass spectrometry data framework. MCheM generates orthogonal structural information that substantially improves metabolite annotation through in silico spectrum matching and open-modification searches, offering a powerful new toolbox for the structure elucidation of unknown metabolites at scale.
Monolayer-Defined Flat Colloidal PbSe Quantum Dots in Extreme Confinement
2025-07-28

Colloidal 2D PbX (X = S, Se, Te) nanocrystals are innovative materials pushing the boundaries of quantum confinement by combining crystal thicknesses down to a monolayer with additional confinement in the lateral dimension. These flat PbSe quantum dots (fQDs) exhibit telecommunication band photoluminescence (1.43-0.83 eV), which is highly interesting for fiber optic information processing. With scanning tunneling microscopy/spectroscopy (STM/STS), we probe single-layer-defined fQD populations down to one monolayer, showing an in-gap state free QD-like density of states in excellent agreement with theoretical tight-binding (TB) calculations. Cryogenic ensemble spectra match STS/STM and TB calculations and exhibit the contribution of mono-, bi-, and trilayers to the photoluminescence. Comparing the electronic band gaps with the optical ones, we derive exciton binding energies as high as 600 meV for PbSe monolayers. Our results allow for a target-oriented synthesis of a <b>new class</b> of QDs with record binding energies and precisely tailored optical properties at technologically relevant wavelengths.
Targeting CD276 with Adapter-CAR T-cells provides a novel therapeutic strategy in small cell lung cancer and prevents CD276-dependent fratricide
2025-07-28

Abstract Background Survival rates in Small Cell Lung Cancer (SCLC) remain dismal, posing a huge medical need for novel therapies. T-cells, engineered to express chimeric antigen receptors (CAR-T) have demonstrated clinical activity against a variety of haematological malignancies. Yet, efficacy against solid tumour entities remains limited. Methods In this study, we investigated the expression of CD276 (B7-H3), an immune checkpoint molecule and promising target antigen for CAR-T therapy in SCLC, at the RNA and protein level. We further developed novel Fab-based adapter molecules (AM) targeting CD276 and optimized our previously established modular Adapter CAR-T (AdCAR-T) platform as well as AM dosing schemes. Results CD276 is broadly expressed across SCLC subtypes, representing a promising target for CAR-T therapy. We describe that T-cell activation and CAR-signalling induces CD276-expression on CAR-T, resulting in CD276-dependent fratricide, limiting anti-CD276-CAR-T expansion and activity. The AdCAR-T platform allows CAR-T expansion in absence of CD276 targeting. Novel CD276 targeted AMs demonstrate potent in vitro and in vivo activity against SCLC. Intermittent AM-dosing allows functional persistence of AdCAR-T in vivo in contrast to CD276-targeted conventional CAR-T. AdCAR-T in vivo expansion and activity is further promoted by introducing activation-induced, AM remote controlled, IL-18 secretion into the AdCAR-T design. Conclusion We identified CD276 as a promising target antigen, uniformly expressed in SCLC and demonstrate the therapeutic potential of novel anti-CD276 Fab-based AM in combination with optimized, IL-18 armoured AdCAR-T.