julilili42/papers huggingface dataset:
Grammaticalization of sentence adverbs and modal particles revisited
2025-03-20

Abstract This paper investigates the development of sentence adverbs (SAdvs) and modal particles (MPs) by especially focusing on the German language. By exploring their common grammaticalization paths, we claim that these are much more restricted than previously assumed. In particular, we argue that two pathways seem to play a major — if not exclusive — role, namely one starting from lower adverbs and one from parenthetical clauses, and that syntactic ambiguity in the middle field plays a fundamental role in this process. In addition, we show that there is no evidence of secondary grammaticalization occurring within the class of sentence adverbs and modal particles.
IgE autoantibodies to nuclear antigens in patients with different connective tissue diseases: re-evaluation and novel findings
2025-03-20

Introduction Connective tissue diseases (CTD) are characterised by the overproduction of multiple autoantibodies, especially antinuclear antibodies (ANA) of the IgG type. Meanwhile, also IgE autoantibodies have been described. The aim was therefore, to establish an ELISA for the demonstration of IgE autoantibodies to SSA/Ro, SSB/La, RNP proteins and dsDNA in sera from patients with systemic lupus erythematosus (SLE), Sjoegren’s syndrome (SS), and mixed connective tissue disease (MCTD) to investigate their frequency and clinical relevance. Methods Serum samples from 110 patients with SLE, 118 patients with SS, 41 patients with MCTD, and 73 controls were analysed by ELISA for IgE autoantibodies against dsDNA, SSA/Ro52, and SSA/Ro60, SSB/La, and RNP proteins using recombinant antigens. Patients were assessed for different clinical manifestations. Results In SLE and SS, IgE anti-SSA/Ro52-, -SSA/Ro60- and -SSB/La-antibodies showed a significantly higher reactivity than in controls. IgE anti-dsDNA-antibodies were present in 66% of SLE patients. In SLE, there was a correlation of IgE anti-dsDNA- and -anti-SSA/Ro52-antibodies with disease activity and cutaneous manifestation. Neither IgE anti-SSA/Ro- nor -anti-SSB/La-antibodies were associated with distinct clinical manifestations in SS. Also, anti-RNP-antibodies were found to be of the IgE type (up to 90% in MCTD and 70% in SLE). In MCTD, IgE anti-Sm/RNPB- and -anti-RNP68-antibodies correlated with pulmonary manifestations. IgE anti-dsDNA- but not the other IgE autoantibodies decreased under immunosuppressive therapy. Conclusion IgE anti-SSA/Ro-, -SSB/La-, -RNP-, and -dsDNA antibodies show a high frequency and specificity for the prevailing CTD. We confirmed an association of anti-dsDNA and anti-SSA/Ro52 antibodies with disease activity in SLE. In MCTD, there was an association of anti-Sm/RNP B and -RNP68 antibodies with pulmonary disorder.
Subglacial landscape formation and sediment discharge: relating basal conditions to bedform dimensions and properties at Rutford Ice Stream, West Antarctica
2025-03-20

Basal conditions that facilitate fast ice flow are still poorly understood and their parameterization in ice‐flow models results in high uncertainties in ice‐flow and consequent sea‐level rise projections. Direct observations of basal conditions beneath modern ice streams are limited due to the inaccessibility of the bed. One approach to understanding basal conditions is through investigating the basal landscape of ice streams and glaciers, which has been shaped by ice flow over the underlying substrate. Bedform variation together with observations of ice‐flow properties can reveal glaciological and geological conditions present during bedform formation. Here we map the subglacial landscape and identify basal conditions of Rutford Ice Stream (West Antarctica) using different visualization techniques on novel high‐resolution 3D radar data. This novel approach highlights small‐scale features and details of bedforms that would otherwise be invisible in conventional radar grids. Our data reveal bedforms of &lt;300 m in length, surrounded by bedforms of &gt;10 km in length. We correlate variations in bedform dimensions and spacing to different glaciological and geological factors. We find no significant correlation between local (&lt;3 × 3 km) variations in bedform dimensions and variations in ice‐flow speed and (surface or basal) topography. We present a new model of subglacial sediment discharge, which proposes that variations in bedform dimensions are primarily driven by spatial variation in sediment properties and effective pressure. This work highlights the small‐scale spatial variability of basal conditions and its implications for basal slip. This is critical for more reliable parameterization of basal friction of ice streams in numerical models.
A Randomized Crossover Trial to Evaluate the Effect of Positioning on Obstructive Sleep Apnea in Infants with Robin Sequence
2025-03-20

Background: The prone position is one of the most frequently used treatment options for infants with Robin sequence (RS), but its effect and its safety regarding the increased risk of sudden infant death syndrome are controversial. Methods: In a prospective randomized crossover study, we investigated the effects of the prone versus supine position on obstructive sleep apnea (OSA) using polygraphy. Infants with RS admitted to the University Hospital Tuebingen between 4/2021 and 5/2023 were analyzed for their obstructive apnea index (OAI), oxygen desaturation index &lt; 80%, minimum and basal oxygen saturation, basal and highest transcutaneous carbon dioxide level, and respiratory and heart rate in both sleep positions. Results: A total of 29 children were analyzed. A total of 21/29 children were measured in both positions, while 6/29 children were only measured in the supine position and 2/29 only in the prone position. We found no significant difference in the OAI for the supine versus prone position in main effects analyses. In unadjusted linear model analysis, infants in the supine position had an OAI of 9.9 (95% CI, −2.4, 22.3) events/h higher than those in the prone position. A total of 13/21 infants benefitted from the prone position, whilst 8/21 had a worsening of their OSA. We found no evidence of a significant interaction between sleeping position and syndromic status. Conclusions: Prone positioning improves, but does not eliminate, OSA symptoms in infants with RS, and severe OSA may often persist. There are infants in whom a change to the prone position leads to a worsening of their OSA.
Validation of the Coach and Athlete Versions of the German CART-Q
2025-03-20

Abstract: The coach−athlete relationship that develops over an athletic career is fundamental to athletic performance. This study examined the psychometric properties of the German version of the Coach−Athlete Relationship Questionnaire (CART-Q) from the perspective of coaches and athletes. 229 coaches and 515 athletes from numerous sports and competitive levels participated. The CART-Q shows good internal consistency. A confirmatory factor analysis replicated the factorial structure of the original English CART-Q for the German coach (CFI = .929, TLI = .902, RMSEA = .095, SRMR = .052) and athlete versions (CFI = .950, TLI = .934, RMSEA = .093, SRMR = .043). The CART-Q’s construct validity appeared in associations with relationship satisfaction and perceived coach leadership behaviors. Furthermore, concurrent correlations with leadership behavior indicated criterion validity. The results suggest that the German CART-Q is a reliable and valid instrument for research and applied settings.
Efficacy of laser-assisted caries removal and hard tissue preparation: A meta-analysis
2025-03-20

Laser-assisted caries removal reduces the need for anesthesia and minimizes patient discomfort compared to conventional rotary instruments, while restoration survival and pulp vitality are not affected. However, excavation speed remains significantly slower. Furthermore, results should be interpreted with caution considering the low level of the evidence.
Soft Focused Shock Wave Treatment of Solid Tumors. Part I: Physico-mechanical Preconditions, Parametric Simulation and Technical Applicator Design
2025-03-20

<title>Abstract</title> Purpose To explore the feasibility of targeted impairment of malignant tumors by application of soft focused shock wave treatment, the physico-mechanical preconditions are investigated. This innovative “soft” approach is different from the FDA-approved high intensity focused ultrasound (HIFU)-based histotripsy. Methods Atomic force microscopy investigation for cell mechanics, multiple parametric simulations (DICOM/FEM analysis, MATLAB conversion to PZFLEX/ONSCALE). Results Individual tumor cell evaluation of physical properties as basis for multiple parametric simulations determine the optimal treatment parameters (total energy required, energy flux density, shock wave frequency) and applicator positions; design flexibility of applicator devices for extra- and intracorporeal treatment. Conclusion The fundamental feasibility and reliability of our approach were proven in tumor cells providing a reliable basis for the translation into clinical applications.
Deafness Progressing to Cochlear Implant Eligibility Is Eight Times More Likely in the Hypoplastic Than the Degenerative Endotype of Menière's Disease
2025-03-20

Objective To investigate whether one of the two recently described MD endotypes—defined by either endolymphatic sac degeneration (MD-dg patients) or hypoplasia (MD-hp patients)—is associated with an increased likelihood of undergoing CI. Study Design Retrospective multicenter cross-sectional study. Setting Five tertiary referral centers. Patients CI cohort: 115 adult MD patients with a history of uni- or bilateral CI. Non-CI cohort: 72 MD patients with no CI history. All included patients matched current diagnostic criteria for definite MD. Intervention Cochlear implantation. Main Outcome Measures Endotype distribution (MD-dg versus MD-hp) between the CI cohort and the non-CI cohort. The endotype was determined using high-resolution CT data based on the angular trajectory of the vestibular aqueduct, following established protocols. Secondary outcomes included disease laterality, age at MD diagnosis, duration of MD, and pre-CI hearing thresholds. Results The CI cohort included significantly more MD-hp patients than the non-CI cohort (72% versus 24%, p &lt; 0.0001). The odds ratio of CI for an MD-hp patient relative to an MD-dg patient was 8.4 (95% confidence interval, 4.3–16.1). Pre-CI audiometric data showed no significant differences in hearing thresholds between endotypes, neither in the implanted nor in the non-implanted ear. Conclusions The MD-hp endotype, frequently associated with bilateral disease and early-age disease onset, is strongly linked to a higher likelihood of CI. Endotyping of MD patients based on endolymphatic sac pathology can effectively stratify their risk of severe hearing loss, guiding personalized audiological follow-up and clinical decisions regarding potential CI.
CD38-mediated metabolic reprogramming promotes the stability and suppressive function of regulatory T cells in tumor
2025-03-21

In the tumor microenvironment (TME), regulatory T cells (T regs ) adapt their metabolism to thrive in low-glucose, high-lactate conditions, but the mechanisms remain unclear. Our study identifies CD38 as a key regulator of this adaptation by depleting nicotinamide adenine dinucleotide (oxidized form) (NAD + ), redirecting lactate-derived pyruvate toward phosphoenolpyruvate and bypassing the tricarboxylic acid (TCA) cycle. This prevents accumulation of α-ketoglutarate, which destabilizes T regs by inducing hypermethylation at the Foxp3 locus. Restoring NAD + with nicotinamide mononucleotide reverses this adaptation, pushing T regs back to the TCA cycle and reducing their suppressive function. In YUMM1.7 melanoma-bearing mice, small-molecule CD38 inhibition selectively destabilizes intratumoral T regs , sparking robust antitumor immunity. These findings reveal that targeting the CD38-NAD + axis disrupts T regs metabolic adaptation and offers a strategy to enhance antitumor responses.
Cytosolic Peroxiredoxin TSA1 Influences Acetic Acid Metabolism and pH Homeostasis in Wine Yeasts
2025-03-22

Acetic acid is a key metabolite in yeast fermentation, influencing wine quality through its role in volatile acidity. In <i>Saccharomyces cerevisiae</i>, acetic acid production involves aldehyde dehydrogenases, primarily Ald6p during fermentation and Ald4p under respiratory conditions. However, the regulatory mechanisms of these enzymes throughout fermentation and how they differ in commonly used strains remain partially unclear. This study explores cytosolic peroxiredoxin Tsa1p as a novel regulator of acetic acid metabolism. <i>TSA1</i> gene deletion revealed strain-dependent effects on acetic acid metabolism and tolerance, showing reduced production and enhanced consumption in the laboratory media. Under respiration, Ald4p-driven acetic acid production, which raises extracellular pH, was mitigated by the absence of Tsa1p. During wine fermentation, <i>TSA1</i> deletion decreased the initial acetic acid surge by downregulating the <i>ALD6</i> transcription and enzymatic activity. These findings establish Tsa1p as a metabolic regulator and a potential target for modulating acetic acid levels to manage volatile acidity and improve wine quality.
Altered IgG4 serum levels in VEXAS syndrome – a retrospective monocentric cohort study
2025-03-22

Abstract VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory disorder characterized by somatic mutations in the UBA1 gene in hematopoietic stem cells and associated with diffuse inflammation and myelodysplastic changes amongst others. Due to unspecific symptoms the diagnosis is challenging, and there is an unmet need for clinical markers to select patients for genetic examination. Sera of 9 patients with confirmed VEXAS syndrome were analyzed for immunoglobulin (Ig)G4 levels. Disease parameters and clinical response to therapy were correlated with IgG4 levels. A histopathological examination was performed on the available samples to exclude IgG4-related autoimmune diseases. In this cohort, 44% of our patients showed markedly elevated serum IgG4 levels. We observed a general trend toward a positive correlation between IgG4 levels and inflammatory markers as well as a correlation with clinical response in one patient. Histopathological analysis showed no evidence of IgG4 related disease. IgG4 levels seem to be elevated in a relevant fraction of patients with VEXAS syndrome. In some cases, this might be misinterpreted as IgG4-related disease, a pitfall clinicians should be aware of. Furthermore, our results warrant the further evaluation of a potential correlation of IgG4 levels with disease activity and severity of inflammation. IgG4 serum levels might be useful in the evaluation of the disease course.
Understanding the Optoelectronic Processes in Colloidal 2D Multi‐Layered MAPbBr3 Perovskite Nanosheets: Funneling, Recombination and Self‐Trapped Excitons
2025-03-22

Abstract Colloidal chemistry methods have made quasi 2D perovskites readily accessible. Ultrathin perovskites exhibit charge transport properties which are beneficial for solar cells and the combination of layers with different thicknesses directs charge carriers toward thicker layers with a smaller bandgap. However, detailed knowledge about the mechanisms by which excitons and charge carriers funnel and recombine in these structures is lacking. Here, colloidal 2D methylammonium lead bromide (MAPbBr 3 ) Ruddlesden‐Popper perovskites with a broad combination of layers ( n = 3 to 10, and bulk fractions with n &gt; 10) is characterized by femtosecond transient absorption spectroscopy and time‐resolved photoluminescence. It is found that second‐ and third‐order processes dominate in MAPbBr 3 nanosheets, indicating exciton‐exciton annihilation (EEA) and Auger recombination. Long‐lived excitons in thin layers (e.g., n = 5, E b = 136 meV) funnel into high n within 10–50 ps, which decreases their exciton binding energy below k B T and leads to radiative recombination. Parallel and consecutive funneling compete with trapping processes, making funneling an excellent tool to overcome exciton self‐trapping when high‐quality n ‐ n interfaces are present. Free charge carriers in high‐ n regions on the other hand facilitate radiative recombination and EEA is bypassed, which is desirable for LED and lasing applications.
Managing discordance between HbA 1c and glucose management indicator
2025-03-23

Abstract Aims The assessment of haemoglobin A1c (HbA 1c ) continues to play an essential role in diabetes care; however, major advances in new technologies widen the armament available to clinicians to further refine treatment for their patients. Whilst HbA 1c remains a critical glycaemic marker, advances in technologies such as Continuous Glucose Monitoring (CGM) now offer real‐time glucose monitoring, allowing a more instant assessment of glycaemic control. Discrepancies between laboratory‐measured HbA 1c and Glucose Management Indicator (GMI) values are a significant clinical issue. In this article, we present a checklist of potential sources of error for both GMI and HbA 1c values and provide suggestions to mitigate these sources in order to continue to improve diabetes care. Methods We identified key literature pertaining to GMI measurement, HbA 1c measurement, and potential factors of discordance between the two. Using these sources, we explore the potential factors leading to discordance and how to mitigate these when found. Results We have constructed a quick reference checklist covering the main sources of discordance between HbA 1c and GMI, with accompanying narrative text for more detailed discussion. Discordance can arise due to various factors, including CGM accuracy, sensor calibration, red blood cell turnover and other physiological conditions. Conclusions GMI will likely continue to be used in the upcoming years by both persons with diabetes and their health care providers, and so it is important for users of CGM devices to be equipped with the knowledge to understand the potential causes of discordance between GMI and HbA 1c values.
A patent review of CXCR7 modulators (2019-present)
2025-03-23

ACKR3 agonists gained traction as a treatment for cardiovascular and pain conditions. WW-12, which was derived from the chemical modifications of conolidine, became a novel small-molecule pain modulator by activating ACKR3, which in turn boosted endogenous opioid peptides for the classical opioid receptors.ACKR3 antagonist ACT-1004-1239 from Idorsia Pharmaceuticals Ltd. has demonstrated the ability to treat cancer, acute lung injury/ARDS, and autoimmune diseases, including multiple sclerosis. The outcomes of these clinical trials will direct the development and indications of future ACKR3 modulators.
Biochemostratigraphy of the Eger floodplain (Southern Germany) – Detection and quantification of heavy metal contamination and paleoenvironmental conditions: The basic dataset
2025-03-23

The current state of floodplains - their morphology, sedimentation regimes and rates, biochemistry and ecosystem health - highlights the interconnectedness of human activities and natural ecosystems. Over the centuries, floodplains have been used for and transformed by many anthropogenic purposes including agriculture, industry and urban development. These activities have resulted in the accumulation of pollutants in highly vulnerable floodplains, yet we understand little about the historical evolution of Fluvial Anthropospheres. The Eger floodplain study site is located 2 km downstream of the mediaeval city walls of Nördlingen in southern Germany. In the Middle Ages, the city became an important and prosperous urban trade and craft centre due to its location at the crossroads of two major trade routes (Frankfurt-Würzburg-Augsburg and Nürnberg-Ulm). This data manuscript documents four alluvial soil-sediment profiles, NEP 1 to NEP 4, that were excavated and investigated in the floodplain section. The dataset includes grain-size data, element-specific X-ray Fluorescence (XRF) data, anthracological data, quantitative data of mollusc and microfossil assemblages from the sand-sized sediment fraction, pedological field parameters, biogeochemical soil properties and numerical data relating to radiocarbon and luminescence dating. These data provide the basis for reconstructing the Late Holocene biochemostratigraphy of the Eger River floodplain with respect to anthropogenic impacts and paleoenvironmental history.
Uncovering α-Selectivity for Liver X Receptor Agonists for Lipotoxic Cancer Therapies
2025-03-24

Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related deaths worldwide. We recently showed that pharmacologically induced lipotoxicity represents a promising therapeutic strategy for the treatment of HCC. Synthetic LXRα agonists induce the production of toxic saturated fatty acids in tumor cells. When combined with DFG-out Raf inhibitors, which block fatty acid desaturation by inducing proteasomal degradation of stearoyl-CoA desaturase (SCD1), LXRα activation can trigger lipotoxicity-induced cancer cell death. However, the clinical translation of this therapeutic strategy is limited by the lack of specific LXRα agonists for clinical use. Here, we have developed a series of promising maleimide LXR agonists with increased potency for LXRα and enhanced specificity. Our agonist frontrunner <b>40</b> shows high selectivity for LXRα and strong therapeutic efficacy in HCC organoids, therefore illustrating a strong potential for advancing this lipotoxic treatment strategy to clinical application.
Smartphone Application for Spastic Ataxias: Cross-Sectional Validation of a Newly Developed Smartphone App for Remote Monitoring in Spastic Ataxias
2025-03-24

Abstract Effective trial-planning in Spastic ataxias (SPAX) is impeded by the absence of validated outcome measures for detecting longitudinal changes. Digital outcome measures show promise, demonstrating sensitivity to disease severity changes in ataxia and strong correlations with clinical scales. The objective of this study was to develop a smartphone application for SPAX (SPAX-app) to obtain valid digital outcome measures for use in clinical trials. The app contains four tasks assessing gait, standing balance (stance), and finger and hand movements. We carried out a validation study in 22 SPAX patients and 10 controls. Subjects performed the tasks three times during one visit. In parallel, we performed Ambulatory Parkinson’s Disease Monitoring (APDM) sensor recordings, Q-motor upper limb assessment, and the Scale for the Assessment and Rating of Ataxia (SARA). Significant correlations were found between the SPAX-app and APDM or Q-motor for step time ( r = 0.91), all measures of stance ( r = 0.51–0.87) and duration of hand alternation ( r = 0.64). No significant correlations were found for variability measures (e.g. standard deviation of step time). All tasks of the SPAX-app, except for stance, can discriminate SPAX from controls and show moderate to high test-retest reliability (ICC 0.67–0.97). Significant correlations were found between SARA and step time ( r = 0.70), inter-onset interval in finger tapping ( r = 0.57), and duration of hand alternation ( r = 0.65). The stance task did not show significant correlations with SARA. With the SPAX-app, we present a set of digital outcome measures for potential use in clinical trials. Longitudinal studies are needed to evaluate whether these measures can track disease progression.