julilili42/papers huggingface dataset:
Intravenous thrombolysis before endovascular treatment in acute vertebrobasilar occlusions: Pooled analysis of the French and German Stroke Registries
2025-04-16

Introduction: Whether intravenous thrombolysis (IVT) provides additional benefit in eligible patients with acute vertebrobasilar occlusion who undergo endovascular treatment (EVT) remains an open question. Patients and methods: We conducted a pooled analysis using data from two national stroke registries, the ETIS registry in France and GSR-ET registry in Germany. Patients who underwent EVT for vertebral and/or basilar artery occlusions from January 2015 to December 2023 were included. The primary efficacy outcome was a favorable shift toward better functional outcomes on modified Rankin Scale (mRS) scores at 90 days. Safety outcomes included 90-days mortality and symptomatic haemorrhagic transformation (sICH). Comparisons between IVT + EVT and direct EVT groups were made combining inverse propensity score matching, probability of treatment weighting (IPTW) and regression models. Results: Among 2028 patients treated during the study period, 797 (39.2%) received IVT before EVT, while 1231 (60.7%) had EVT alone. After IPTW matching, we compared 211 patients treated with IVT + EVT to 260 direct EVT patients. Patients in the IVT + EVT group had a favorable shift across the 90-day mRS distribution (common aOR 1.43 per 1-point mRS improvement, 95% CI 1.01–2.04; p = 0.046), higher odds of 90-day favorable functional outcome (aOR 1.56, 95% CI 1.00–2.44; p = 0.049) and lower odds of 90-day mortality (aOR 0.62, 95% CI 0.39–0.99; p = 0.045). IVT was not associated with increased risk of sICH (aOR 1.65, 95% CI 0.62–4.35; p = 0.313). Discussion: This registry-based study suggests a potential benefit of IVT before EVT in eligible patients with vertebrobasilar occlusions. Conclusion: Randomized clinical trials are necessary to confirm these findings and to validate the benefits of IVT in this clinical context.
Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy
2025-04-16

Abstract Partial phenotypic overlap has been suggested between multiple system atrophy and spinocerebellar ataxia 27B, the autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. In this study, we investigated the frequency of FGF14 GAA•TTC repeat expansion in clinically diagnosed and pathologically confirmed multiple system atrophy cases. We screened 657 multiple system atrophy cases (193 clinically diagnosed and 464 pathologically confirmed) and 1003 controls. The FGF14 repeat locus was genotyped using long-range PCR and bidirectional repeat-primed PCRs, and expansions were confirmed with targeted long-read Oxford Nanopore Technologies sequencing. We identified 19 multiple system atrophy cases carrying an FGF14 GAA≥250 expansion (2.89%, n = 19/657), a significantly higher frequency than in controls (1.40%, n = 12/1003) (P = 0.04). Long-read Oxford Nanopore Technologies sequencing confirmed repeat sizes and polymorphisms detected by PCR, with high concordance (Pearson's r = 0.99, P &amp;lt; 0.0001). Seven multiple system atrophy patients had a pathogenic FGF14 GAA≥300 expansion (five pathologically confirmed and two clinically diagnosed), and 12 had intermediate GAA250–299 expansion (six pathologically confirmed and six clinically diagnosed). A similar proportion of cerebellar-predominant and parkinsonism-predominant multiple system atrophy cases had FGF14 expansions. Multiple system atrophy patients carrying an FGF14 GAA≥250 expansion exhibited severe gait ataxia, autonomic dysfunction and parkinsonism, in keeping with a multiple system atrophy phenotype, with a faster progression to falls (P = 0.03) and regular wheelchair use (P = 0.02) in comparison to the multiple system atrophy cases without FGF14 GAA expansion. The length of the GAA•TTC repeat expansion lengths was inversely correlated with survival in multiple system atrophy patients (r = −0.67; P = 0.02) but not with age of onset. Therefore, screening for FGF14 GAA•TTC repeat expansion should be considered for multiple system atrophy patients with rapid loss of mobility and for complete diagnostic accuracy at inclusion in disease-modifying multiple system atrophy drug trials.
Motor and cognitive function after unipolar depressive episodes: a 6 years longitudinal observational study
2025-04-16

Introduction Unipolar depression is a frequent psychiatric disorder and associated with cognitive and motor deficits. It is also a prodromal or risk marker for various neurodegenerative diseases. Little research has been done on the extent to which motor and cognitive deficits persist in remitted depressive episode, and to what extent these deficits can be progressive. Methods A total of 401 healthy subjects of the Tübingen TREND study aged between 50 and 80 years were examined over 6 years at intervals of 2 years. Of those, 81 had a positive history of unipolar depression (Dep+) and 320 had not (Dep-). We ruled out currently depressive participants. Mini-Mental-State Examination (MMSE), Consortium to Establish a Registry for Alzheimer’s disease (CERAD), the motor part of the Movement disorder society-revised version of the Unified Parkinson disease rating scale (MDS-UPDRS III), gait speed, and dual tasking parameters were compared between groups. Results Dep+ had lower gait velocity than Dep-. No significant change in parameters was found over the observed time. Discussion Reduced gait speed in Dep+ may have potential as a diagnostic and prognostic marker for Dep- if confirmed in further studies. The lack of progression of all studied parameters over 6 years specifically in Dep+ argues against a relevant potential of this approach to define prodromal neurodegenerative cohorts by history of depression.
Go for Gold: Development of a Scalable Synthesis of [1‐(Ethoxycarbonyl)cyclopropyl] Triphenylphosphonium Tetrafluoroborate, a Key Reagent to Explore Covalent Monopolar Spindle 1 Inhibitors
2025-04-16

Covalent approaches have resurged in drug discovery and chemical biology during the last decade. So‐called targeted covalent inhibitors typically show a strong and persistent drug–target interaction as well as a high degree of selectivity. In our research group, RMS‐07 (8) , a First‐in‐Class covalent inhibitor of the protein kinase threonine tyrosine kinase (TTK)/monopolar spindle 1, which shows promising results in a variety of different solid cancer cell types and will be further optimized in terms of covalent binding kinetics, has recently been developed. However, synthetic accessibility is restricted by a high price and limited availability of [1‐(ethoxycarbonyl)cyclopropyl] triphenylphosphonium tetrafluoroborate ( 10 ), a key reagent required to assemble the tricyclic core scaffold in a Wittig‐type cyclization reaction. This reagent is also described as a valuable synthon for the synthesis of a range of ring systems with interesting applications in medicinal chemistry. However, reliable procedures for its large‐scale synthesis are scarce. Only one prior report describes the synthesis of reagent 10 , and it contains limited experimental details, making it challenging to reproduce and scale up. Herein, a concise and reproducible decigram‐scale synthetic protocol for accessing key reagent 10 is described.
Long‐term hydrologic connectivity on the Australian dryland margins: Evidence from the Willandra Lakes World Heritage Area over the last 60 ky
2025-04-16

ABSTRACT The semi‐arid Australian continental inland is increasingly subject to climatic extremes such as drought and flooding. Combined with the exceptionally low topographic relief characteristic of this region, hydroclimatic extremes can have an enormous impact on the land surface. Nevertheless our understanding of dryland hydrologic connectivity and earth‐surface response remains poorly understood and largely unquantified. Here we investigate the impact of past hydroclimate on the semi‐arid Willandra Lakes over the last 60 ky, integrating sediment‐based chronologies for filling and drying of multiple basins with water‐flux modelling and reconstruction of palaeoclimate parameters. We quantify the threshold inflow volume required to fill the lake system to 2 km 3 . We establish that prior to 25 ka, permanent lakes persisted for protracted periods of time in response to increased catchment precipitation, consistent with regional geomorphic indicators for wetter conditions. By contrast, the Last Glacial Maximum (LGM) oversaw rapid couplets of lake filling and drying despite lower precipitation, temperature, and increasing evaporation. We propose that seasonal snow melt from the highland headwaters during this cold phase, coupled with increased effective runoff due to reduced vegetation cover, was responsible for the large quantities of water entering the system at this time.
Marco Polo and the Political Economy of the Yuan Empire: Realities and Ideologies
2025-04-16

Departing from a Yuan perspective of political economy, it will be shown that we can find a substantial number of descriptions in the Devisement dou monde on the Mongol state’s involvement in, and influence on, the Chinese economy. Apart from these explicit references, the Venetian’s account contains numerous implicit indications of important sectors of the economy that, at least indirectly, can be linked to economic measures during Qubilai’s reign. An idealistic tone frequently permeates Polo’s narration concerning the Mongol emperor’s economic policies, but relevant positive evaluations are also present in late Yuan and early Ming sources.
BRAVO – a workflow for improving rating reliability in behavioural research
2025-04-16

Reliability assessments are a quality control protocol commonly employed in fields of research that deal with video-recorded behavioural data. During these assessments, the same sample of videos is coded (at least) twice by the same researcher (intrarater reliability), or - more often - by two different researchers independently (interrater reliability). Next, levels of agreement are quantified to assess how reliable the behavioural classification is. In this manuscript, we concentrate on interrater reliability, though our points hold generally true for both cases. Despite the importance of interrater reliability assessments to ensure research quality, to the best of our knowledge there is no guideline to date specifying how they should be conducted to avoid potentially detrimental effects of ‘coders’ degrees of freedom’ (CDF) and ‘questionable coder practices’ (QCP). For instance, there is no consensus regarding how large the sample of behaviours evaluated should be, the sample composition, the inclusion of negative controls or what statistical measures should be used to compare the raters’ classifications. To begin to fill this methodological gap, we provide a list of best practices to conduct reliability tests, which we term the BRAVO (Balanced Reliability Assessment of Video Observations) workflow. We complement these recommendations with a series of simulations highlighting the properties of BRAVO and its use-cases. BRAVO represents the first step in creating a methodological gold-standard that researchers can use to perform valid reliability assessments. Given the widespread use of behavioural data across fields, we hope that the BRAVO workflow will be implemented by researchers from a variety of disciplines such as psychology, ethology, behavioural economics, and anthropology to increase quality control and scientific transparency.
Universality in the Near-Side Energy-Energy Correlator
2025-04-17

We investigate the energy-energy correlator (EEC) of hadrons produced on the same side in <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:mrow><a:msup><a:mrow><a:mi>e</a:mi></a:mrow><a:mrow><a:mo>+</a:mo></a:mrow></a:msup><a:msup><a:mrow><a:mi>e</a:mi></a:mrow><a:mrow><a:mo>−</a:mo></a:mrow></a:msup></a:mrow></a:math> annihilation or in leading jets in <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" display="inline"><c:mrow><c:mi>p</c:mi><c:mi>p</c:mi></c:mrow></c:math> collisions. We observe a remarkable universality of the correlator. Using a nonperturbative transverse momentum dependent (TMD) fragmentation function to model the transition from the “free-hadron” region to the perturbative collinear region, we are able to describe the near-side shapes and peaks over a wide range of energy for both the <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" display="inline"><e:msup><e:mi>e</e:mi><e:mo>+</e:mo></e:msup><e:msup><e:mi>e</e:mi><e:mo>−</e:mo></e:msup></e:math> annihilation and the <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" display="inline"><g:mi>p</g:mi><g:mi>p</g:mi></g:math> jet substructure measurements in terms of just two parameters. We present further predictions for the ratio of the projected three-point energy correlator to the EEC. The excellent agreement between our calculations and the experimental data may provide new insights into the role of nonperturbative physics for EECs, and suggests the possibility of exploring nonperturbative TMDs using theoretical tools developed for the energy correlators.
Otitis Media With Effusion (OME) and Eustachian Tube Dysfunction: The Role of Allergy and Immunity—An EAACI Position Paper
2025-04-17

ABSTRACT IgE‐mediated allergies play a significant role in respiratory diseases. Given the similar mucosal epithelium of the upper and lower respiratory tracts and their shared (patho)physiological immune responses, the “unified airways” concept views these tracts as a single system. Recently, this model has been extended to include the middle ear, with studies confirming that the Eustachian tube and middle ear are both anatomically and functionally part of the upper airways. However, the relationship between allergies and middle ear disorders remains controversial, with conflicting findings regarding pathogenesis and treatment. The increasing prevalence of allergies highlights the importance of further research. In Germany, the current sensitization rate to aeroallergens is 33.6%, with similar trends across Europe, where rates commonly range up to 30%. This widespread increase underscores the urgent need for a deeper understanding of the correlation between allergies and middle ear disorders across diverse European populations. Ineffective pharmacotherapy or possibly harmful medication for acute and chronic OME, such as systemic steroids, is most likely used globally in an uninformed way, due to a lack of evidence on the connection between allergic inflammation and eustachian tube dysfunction. Further research is essential to clarify the mechanisms linking IgE‐mediated allergies to middle ear pathologies and to develop effective treatment strategies. Addressing these knowledge gaps is critical for improving patient outcomes and managing the rising burden of allergic diseases.
Elevated Cholinesterase Activity and the Metabolic Syndrome—Dissecting Fatty Liver, Insulin Resistance and Dysglycaemia
2025-04-17

ABSTRACT Background and Aims While low plasma butyrylcholinesterase (BChE) is a well‐established marker of reduced liver synthesis capacity, the clinical significance of elevated BChE is unclear. In small studies, high BChE has long been suspected in hepatic steatosis and metabolic syndrome. We aimed to clarify the relation between BChE, liver fat and glucose metabolism in deeply phenotyped cohorts. Methods Plasma BChE activity was measured in 844 humans (554 women) of the cross‐sectional Tübingen Diabetes Family Study, with a wide BMI range (17.7–55.1 kg/m 2 ). It was furthermore measured before and after two independent lifestyle intervention studies in 215 and 116 participants. Liver fat was quantified with 1 H‐MR‐spectroscopy, and metabolism was assessed by oral glucose tolerance tests. Results BChE was positively associated with liver fat, independent of sex, age and BMI. BChE was higher in participants with metabolic syndrome. BChE was positively associated with fasting and 2‐h glycaemia, independent of sex, age and BMI. BChE was negatively associated with insulin sensitivity, independent of sex, age, BMI and liver fat. The reduction of liver fat and improvement in insulin sensitivity during lifestyle interventions are associated with the reduction in BChE, independent of body weight loss. Conclusions Higher plasma BChE activity is linked to liver fat accumulation, as well as impaired glucose tolerance and insulin resistance, independent of liver fat. This suggests that BChE could be a marker for processes in hepatocytes that contribute to impaired glucose metabolism. Further investigations are needed to clarify the mechanistic contribution and potential diagnostic value of elevated BChE in hepatic steatosis and metabolic diseases.
Pension Reform Effects in Times of Technological Change and Shifting Task Composition
2025-04-17

Abstract We study heterogeneity in the effects of a pension reform in Germany: the introduction of the old-age pension for the very long-term insured, which lowered the threshold for full pension receipt from age 65 to 63. Using a regression discontinuity design (RDD) and rich administrative pension data, we estimate the effects of the reform on eligible workers who differ in a number of occupational characteristics. Transitions into the new early retirement scheme occurred more frequently from jobs involving mainly manual and routine tasks, which contributed to the changing composition of tasks in the workforce. While the introduction of new technologies, materials and machines in an industry was associated with more workers claiming early retirement, workers affected by frequent PC use and new PC programmes were less likely to use the early retirement scheme.
“Anyone who weighs up risks doesn’t belong here”: how do elite handball players manage physical health risk throughout their professional careers?
2025-04-17

Objectives Elite athletes frequently encounter physical health risks, such as an injury, illness or pain, which are accompanied by sociocultural norms, individual perceptions, and situational pressures. While research has explored risk management in sports, limited attention has been given to the subjective experiences of athletes managing these risks across their careers. This study addresses this gap by examining how elite handball players manage physical health risks, focusing on the role of risk perception, evaluation, and coping. Methods Using a constructivist lens, 11 handball players from the German national teams (5 females, 6 males) participated in biographical mapping interviews, providing insights into their career-long management of physical health risks. Results Using reflexive thematic analysis, we generated four themes: (1) Externalizing risks and refraining from proactivity, (2) Relinquishing control under medical uncertainty, (3) Fluctuating prioritization of health or success, and (4) Calculated health-risk taking to achieve success. The findings illustrate that athletes’ risk management strategies vary based on career stage, injury experiences, situational priorities, and social pressures. The insights contribute to a deeper understanding of the dynamics of physical health risk management in high-performance sports and their sociocultural underpinnings. The study highlights the need for interventions that foster proactive risk management, emphasize personal agency, and balance performance with long-term health.
Variants in CFAP410 cause a range of retinal and skeletal phenotypes
2025-04-17

Ciliopathies are associated with a range of phenotypes including retinal degeneration and skeletal abnormalities. We present a retrospective study of 49 patients with variants in Cilia and Flagella Associated Protein 410 (CFAP410) from multiple ophthalmic centers across the world. Common clinical features included early-onset reduced visual acuity, photophobia, and delayed light-to-dark adaptation. A cone-rod dystrophy pattern was observed roughly two times more commonly than rod-cone dystrophy. A minority of patients (22.4%) presented with skeletal abnormalities consistent with axial spondylometaphyseal dysplasia (SMDAX). Patients with the most severe ophthalmic and skeletal phenotypes had disease-associated variants within conserved leucine-rich regions of CFAP410, and the structural effects of these variants were modelled using ChimeraX. This report furthers our understanding of CFAP410-associated clinical phenotypes such as retinal dystrophy and skeletal dysplasia.
First Search for Dark Photon Dark Matter with a madmax Prototype
2025-04-18

We report the first result from a dark photon dark matter search in the mass range from 78.62 to <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:mrow><a:mn>83.95</a:mn><a:mtext> </a:mtext><a:mtext> </a:mtext><a:mi mathvariant="normal">μ</a:mi><a:mi>eV</a:mi><a:mo>/</a:mo><a:msup><a:mi>c</a:mi><a:mn>2</a:mn></a:msup></a:mrow></a:math> with a dielectric haloscope prototype for (Magnetized Disc and Mirror Axion eXperiment). Putative dark photons would convert to detectable photons within a stack consisting of three sapphire disks and a mirror. The emitted power of this system is received by an antenna and successively digitized using a low-noise receiver. No significant signal attributable to dark photons has been observed above the expected background. Assuming unpolarized dark photon dark matter with a local density of <d:math xmlns:d="http://www.w3.org/1998/Math/MathML" display="inline"><d:mrow><d:msub><d:mrow><d:mi>ρ</d:mi></d:mrow><d:mrow><d:mi>χ</d:mi></d:mrow></d:msub><d:mo>=</d:mo><d:mn>0.3</d:mn><d:mtext> </d:mtext><d:mtext> </d:mtext><d:mrow><d:mi mathvariant="normal">G</d:mi><d:mi>eV</d:mi><d:mtext> </d:mtext><d:msup><d:mrow><d:mi>cm</d:mi></d:mrow><d:mrow><d:mn>3</d:mn></d:mrow></d:msup></d:mrow></d:mrow></d:math> we exclude a dark photon to photon mixing parameter <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" display="inline"><g:mi>χ</g:mi><g:mo>&gt;</g:mo><g:mn>2.7</g:mn><g:mo>×</g:mo><g:msup><g:mn>10</g:mn><g:mrow><g:mo>−</g:mo><g:mn>12</g:mn></g:mrow></g:msup></g:math> over the full mass range and <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" display="inline"><i:mi>χ</i:mi><i:mo>&gt;</i:mo><i:mn>1.1</i:mn><i:mo>×</i:mo><i:msup><i:mn>10</i:mn><i:mrow><i:mo>−</i:mo><i:mn>13</i:mn></i:mrow></i:msup></i:math> at a mass of <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" display="inline"><k:mn>80.57</k:mn><k:mtext> </k:mtext><k:mtext> </k:mtext><k:mrow><k:mi mathvariant="normal">μ</k:mi><k:mi>eV</k:mi><k:mo>/</k:mo><k:msup><k:mi>c</k:mi><k:mn>2</k:mn></k:msup></k:mrow></k:math> with a 95% confidence level. This is the first physics result from a prototype and exceeds previous constraints on <n:math xmlns:n="http://www.w3.org/1998/Math/MathML" display="inline"><n:mi>χ</n:mi></n:math> in this mass range by up to almost three orders of magnitude.