julilili42/papers huggingface dataset:
Klebsiella pneumoniae contributes to altered cytotoxicity of thiopurines in vitro: Possible implications of biotransformation and bacterial metabolism
2025-05-29

Abstract Background and purpose Thiopurines are used in paediatric inflammatory bowel disease (IBD), but some patients do not respond. Because the gut microbiota influences drug efficacy and IBD‐patient microbiota presents increased bacterial abundance, we investigated the impact of candidate Enterobacteriaceae on drug cytotoxicity, metabolism and efficacy. Experimental approach Thiopurines were exposed in vitro to bacteria for 4 h at 37°C and drug concentrations measured by UV spectrophotometry. Cytotoxic effects and drug metabolite concentrations on NALM6 and JURKAT cells were determined after treatment with thiopurines exposed or not to bacteria. Drugs were measured in Klebsiella pneumoniae lysates and bacterial conditioned media were used for metabolomic analyses. Shotgun metagenomic sequencing was performed on eight IBD‐patient faecal stools. Key results Incubation of thiopurines with K. pneumoniae , but not Escherichia coli and Salmonella enterica , reduced thiopurine concentrations and cytotoxicity on NALM6 and JURKAT cells. Thiopurine metabolites were lower in cells treated with drugs previously exposed to K. pneumoniae . Internalisation of drugs was demonstrated by their detection in lysates after bacterial incubation. Untargeted metabolomics revealed biotransformation of thiopurines by K. pneumoniae , as reactions of deconjugation, reduction, glycosylation, acetylation or conjugation with propionic acid. Incubation with thiopurines led to changes in the secretion of endogenous bacterial metabolites. K. pneumoniae faecal abundance was associated with lower thiopurine metabolite concentrations in erythrocytes of paediatric IBD‐patients. Conclusions and Implications K. pneumoniae decreases the cytotoxicity of thiopurines through internalisation of MP and TG. We revealed potential bacterial drug biotransformation, as well as negative correlations between bacterial abundance and drug metabolites.
Embryo-derived trypsin-induced calcium entry is inhibited by endometrial infertility factor, LEFTY2
2025-05-29

Introduction A transient window of uterine receptivity ensures that embryos implant in an optimal endometrial environment. Failure to establish or premature closure of the implantation window is thought to be a major cause of infertility, which affects many couples globally. Embryos release trypsin, which designates its developmental potential and plays a crucial role in implantation. Calcium (Ca 2+ ) signalling participates in receptivity and is thus a prerequisite for embryo implantation. Left-right determination factor 2 (LEFTY2) is a negative regulator of endometrial receptivity and is associated with unexplained infertility. We hypothesize that LEFTY2 impedes Ca 2+ entry induced by trypsin in endometrial cells. Methods In silico analysis was performed to investigate classical trypsin pathway genes in human embryos. Trypsin levels from single human embryo conditioned medium were subject to ELISA. To determine if trypsin signals can modulate calcium entry, intracellular calcium [Ca 2+ ] i was determined utilizing Fura-2 fluorescence in human endometrial epithelial cells (Ishikawa cells). Bioinformatic analysis on publicly available single cell sequencing data was used to investigate the expression of L-type calcium channel (CACNA1C) in endometrium. qRT-PCR and immunofluorescence were used to quantify L-type calcium channel abundance. Results We report that the trypsin machinery is established at the blastocyst stage and that high levels of trypsin are associated with a successful pregnancy. Treatment with LEFTY2 or combined treatment with LEFTY2 and trypsin blocked the increase of L-type Ca 2+ channel levels and activity. Treatment of endometrial cells with trypsin was followed by an increase of [Ca 2+ ] i , an effect that was significantly blunted by amiloride and LEFTY2. Further, the trypsin induced increase of [Ca 2+ ] i was significantly blunted by L-type calcium channel inhibitor nifedipine. In the presence of nifedipine, LEFTY2 did not further modify trypsin induced increase of [Ca 2+ ] i . LEFTY2 significantly decreased levels of L-type Ca 2+ channel. Discussion Taken together, we demonstrate that high trypsin levels are associated with a positive pregnancy outcome and that infertility factor LEFTY2 downregulates trypsin induced Ca 2+ increase due in part by interference with nifedipine sensitive Ca 2+ entry. These findings contribute further to our knowledge of unexplained infertility and failed assisted reproductive technologies.
Scoring German Alternate Uses Items Applying Large Language Models
2025-05-29

The alternate uses task (AUT) is the most popular measure when it comes to the assessment of creative potential. Since their implementation, AUT responses have been rated by humans, which is a laborious task and requires considerable resources. Large language models (LLMs) have shown promising performance in automatically scoring AUT responses in English as well as in other languages, but it is not clear which method works best for German data. Therefore, we investigated the performance of different LLMs for the automated scoring of German AUT responses. We compiled German data across five research groups including ~50,000 responses for 15 different alternate uses objects from eight lab and online survey studies (including ~2300 participants) to examine generalizability across datasets and assessment conditions. Following a pre-registered analysis plan, we compared the performance of two fine-tuned, multilingual LLM-based approaches [Cross-Lingual Alternate Uses Scoring (CLAUS) and the Open Creativity Scoring with Artificial Intelligence (OCSAI)] with the Generative Pre-trained Transformer (GPT-4) in scoring (a) the original German AUT responses and (b) the responses translated to English. We found that the LLM-based scorings were substantially correlated with human ratings, with higher relationships for OCSAI followed by GPT-4 and CLAUS. Response translation, however, had no consistent positive effect. We discuss the generalizability of the results across different items and studies and derive recommendations and future directions.
Degradable film mulching increases soil carbon sequestration in major Chinese dryland agroecosystems
2025-05-30

Plastic film mulching (PM), which contributes to nearly half of the increased crop yields in dryland agroecosystems, exacerbates environmental burdens due to its non-degradable nature. Globally, there is a growing demand to replace non-degradable PM with degradable film mulching (DM), yet its impacts on soil organic carbon (SOC) in dryland agroecosystems remains unknown. Here, using multi-field studies and mesocosm experiments, we found that DM strongly increased but PM reduced SOC storage (0-1 m). This difference is likely attributable to the higher microbial C use efficiency in soil under DM, leading to increased microbial-derived C compared to PM. Under the high roading scenario for 2100, DM could reduce the decomposition of SOC (0-1 m) in China's drylands by 9.0 ± 1.0 Mg ha<sup>-1</sup> year<sup>-1</sup> (one standard error) compared with PM. Our findings highlight that DM is a promising alternative to PM for sequestrating SOC and alleviating C loss under climate change in dryland agroecosystems.
The effectiveness of e-learning in focused cardiac ultrasound training: a prospective controlled study
2025-05-30

Abstract Introduction Focused Cardiac Ultrasound (FOCUS) is an essential tool for rapid cardiac assessment across various clinical subspecialties. Consequently, teaching foundational FOCUS skills is of critical importance. This study investigates the effectiveness of e-learning in imparting FOCUS skills. Materials and methods This prospective, controlled study assessed competency development among medical students attending a FOCUS workshop (study group) at two time points: T1 (pre-training) and T2 (post-training, after completing e-learning). The competence gain of the group was compared to a reference group (control group) of physicians who had also used the e-learning in preparation for a certified FOCUS workshop. Objective competencies were measured at both time points using short-answer and multiple-choice theory tests. Subjective self-assessments of competencies and opinions of the e-learning were investigated through evaluation forms at T2 using a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). Demographic information was collected at T1, and user behaviour during e-learning was assessed at T2. Primary endpoints were the increase in theoretical competencies (study group) and the comparison of subjective and objective competency levels (study vs. reference). Results A total of 104 participants (study group = 48; reference group = 56) were included. The study group exhibited a significant ( p &lt; 0.001) increase in theoretical competencies. However, at T2 the reference group achieved significantly higher theoretical test scores ( p &lt; 0.001). One influencing factor was previous practical experience ( p = 0.02), which was significantly higher in the reference group ( p &lt; 0.001). Both groups estimated their competency at the end of preparation to be at similar levels (4.3 ± 0.9 scalepoints [SP] versus 4.3 ± 1.0 SP; p = 0.94). Evaluation results of the e-learning were positive in both groups (5.8 ± 0.9 SP versus 6.2 ± 0.7 SP; p = 0.04), with results in the reference group being significantly higher. Conclusion Both the improvement in competencies and the positive reception of digital learning media should encourage the increased implementation of e-learning formats. This study shows that such formats in ultrasound training can effectively complement face-to-face workshops and should be included in certified training curricula.
High-affinity PQQ import is widespread in Gram-negative bacteria
2025-05-30

Pyrroloquinoline quinone (PQQ) is a soluble redox cofactor used by diverse bacteria. Many Gram-negative bacteria that encode PQQ-dependent enzymes do not produce it and instead obtain it from the environment. To achieve this, Escherichia coli uses the TonB-dependent transporter PqqU as a high-affinity PQQ importer. Here, we show that PqqU binds PQQ with high affinity and determine the high-resolution structure of the PqqU-PQQ complex, revealing that PqqU undergoes conformational changes in PQQ binding to capture the cofactor in an internal cavity. We show that these conformational changes preclude the binding of a bacteriophage, which targets PqqU as a cell surface receptor. Guided by the PqqU-PQQ structure, we identify amino acids essential for PQQ import and leverage this information to map the presence of PqqU across Gram-negative bacteria. This reveals that PqqU is encoded by Gram-negative bacteria from at least 22 phyla occupying diverse habitats, indicating that PQQ is an important cofactor for bacteria that adopt diverse lifestyles and metabolic strategies.
The Association of Lipoprotein(a) and Stroke Recurrence: A Systematic Review and Meta-Analysis
2025-05-30

Background and Purpose Lipoprotein(a) [Lp(a)] is a lipoprotein structurally similar to low-density lipoprotein and is considered a genetically determined risk factor for cardiovascular disease. Although Lp(a) has been linked to ischemic stroke, its role in secondary stroke prevention, particularly in stroke recurrence, remains unclear.Methods A systematic search of MEDLINE and Scopus databases was conducted to identify randomized controlled trials (RCTs) and observational studies reporting Lp(a) levels in patients with ischemic stroke or transient ischemic attack. The primary outcome was stroke recurrence, and secondary outcomes included poor functional outcome, all-cause mortality, and recurrent vascular events. Pooled odds ratios (ORs) were calculated using a random-effects model.Results A total of 12 studies, including one RCT post hoc analysis and 11 observational studies, comprising 17,903 patients (mean age 63 years, 38% female), were included. Elevated Lp(a) levels were significantly associated with increased stroke recurrence (OR: 1.69; 95% confidence interval [CI]: 1.09–2.63; P=0.020) and poor functional outcome (OR: 2.09; 95% CI: 1.40–3.11; P&lt;0.001). No significant associations were found between Lp(a) levels and all-cause mortality (OR: 2.20; 95% CI: 0.89–5.43; P=0.088) or recurrent vascular events (OR: 2.66; 95% CI: 0.95–7.44; P=0.063).Conclusion Elevated Lp(a) levels are linked to increased stroke recurrence and poor functional outcome in stroke patients. Lp(a) may represent a novel therapeutic target in secondary stroke prevention in addition to a promising biomarker.
Antiplatelet Use Prior to Anticoagulant Initiation in Patients With Atrial Fibrillation-Related Ischemic Stroke: An ELAN Trial Analysis
2025-05-30

Background and Purpose Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach.Methods A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets.Results Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66–1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65–1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30–1.08], HRweighted 0.57 [0.30–1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56–6.63], HRweighted 1.88 [0.56–6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1.Conclusion Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.
Hemolysis in a Novel Centrifugal Blood Pump With Low Priming Volume: In Vitro Comparative Study Using Human Blood and Numerical Analysis
2025-05-30

Extracorporeal circulation (ECC) procedures, including extracorporeal membrane oxygenation (ECMO), provide essential support for critically ill patients, but complications such as hemolysis and thromboembolic events remain significant concerns. This study evaluates the hemocompatibility of the CBM LifeMotion centrifugal ECMO pump, designed with a low priming volume and shrouded impeller, comparing its performance to three commercially available pumps (Maquet, Sorin, and Novalung). Human blood was used in a simulated ECC model, following American Society for Testing and Materials (ASTM) testing protocols, to evaluate hemolysis and white blood cell damage. The CBM pump demonstrated hemolysis levels similar to the Maquet and Sorin pumps, all of which exhibited low hemolysis compared to the Novalung pump, which showed the highest hemolysis. A numerical analysis further assessed the CBM pump’s performance under low-flow conditions, revealing reduced fluid shear stress due to the lower rotor speed, whereas the blood’s exposure time to this shear stress increased. Despite these differences, the overall hemolytic potential under low-flow conditions was comparable to ASTM conditions. These results suggest that the CBM LifeMotion pump, with its reduced priming volume and favorable hemocompatibility, shows promise for ECMO applications. Further clinical research is required to validate these findings in real-world settings.
Eye makeup in Northwestern Iran at the time of the Assyrian Empire: a new kohl recipe based on manganese and graphite from Kani Koter (Iron Age III)
2025-05-31

Abstract Kohl was ubiquitous in ancient Egypt and the Middle East, and routinely included among the toiletries deposited in burials. For Egypt, kohl recipes are increasingly well‐studied and known to use a range of inorganic and organic ingredients. Although these are often lead‐based, manganese‐ and silicon‐rich compounds are also attested. For the Middle East, our still limited knowledge is now augmented by analysis of a new kohl sample from a burial in the Iron Age cemetery of Kani Koter in Northwestern Iran. Our integrated multidisciplinary approach shows that the black colouration was most likely obtained by mixing manganese oxides with natural graphite.
Assessing limits of sustainable seed harvest in wild plant populations
2025-05-31

Abstract Seed harvesting from wild plant populations is key for ecological restoration, but it may threaten the persistence of the source populations. Consequently, several countries have set guidelines limiting the proportions of harvestable seeds. However, these guidelines are inconsistent and lack a solid empirical basis. We used matrix population models based on 280 wild plant species, stored in he COMPADRE Plant Matrix Database, to model the demographic consequences of seed harvesting. Current guidelines do not protect populations of annuals and short‐lived perennials because maximal allowed harvest drew all annual species included in our study to extinction. In contrast, current guidelines are overly restrictive for long‐lived plants because these plants could tolerate even higher seed removal than currently allowed. The maximum possible fraction of seed production that can be harvested without compromising the long‐term persistence of populations was strongly related to generation time of the target species. When harvesting seeds every year, the fraction of seeds that was safe to harvest (safe seed fraction) ranged from 80% in long‐lived species to 2% in most annuals. Less frequent seed harvesting substantially increased the safe seed fraction. In the most vulnerable annual species, it was safe to harvest 5%, 10%, or 30% of a population's seed production when harvesting every 2, 5, or 10 years, respectively. Our results provide a quantitative basis for seed harvesting legislation, based on the generation times of species and harvesting regime.
Subjective, behavioural and physiological correlates of stress in women using hormonal contraceptives
2025-06-01

Background Stress, a major risk factor for mental health problems, is influenced by hormonal fluctuations from the menstrual cycle and hormonal oral contraceptives (OC). Despite widespread use, the impact of hormonal intrauterine devices (IUDs) on stress is limited to one study. Aims This study examines psychoendocrine stress responses in women using IUDs, OCs and women with a natural, regular menstrual cycle (NC) to better understand how endogenous and exogenous hormones influence stress. Method Using a repeated-measures design, we investigated stress responses in IUD and OC users and NC women. The Maastricht Acute Stress Task and its control task were applied twice within 4 months to assess subjective, endocrine and physiological stress correlates. Detailed endogenous and exogenous hormonal profiles were obtained, and women completed a 7-day diary (via ecological momentary assessment) after each appointment. Results Based on subjective, physiological and cortisol responses, stress induction was successful in all groups. IUD users reported higher subjective stress, negative affect and anxiety and lower positive affect compared to NC women. OC users exhibited a blunted cortisol response and higher heart rate but reported less acute stress and negative emotions than the other groups in the 7-day diary. Oestradiol and progesterone were suppressed in OC and IUD users compared with NC women. Progesterone, testosterone and oestradiol were differently associated with skin conductance, socio-emotional stress and negative affect. Conclusions IUD and OC use distinctly affect stress response, possibly because of their diverging metabolic pathways and hormone levels. IUD users showed higher emotional reactivity to stress in both lab and daily life, while OCs influenced physiological correlates. These findings highlight that exogenous hormone administration, previously thought to have limited systemic effects, affects women’s psychological well-being, underscoring the need for further research into stress-related disorders among women using hormonal contraceptives.
Exploring the social dimensions of AI integration in healthcare: a qualitative study of stakeholder views on challenges and opportunities
2025-06-01

Objectives This study aimed to investigate the opportunities and challenges associated with integrating artificial intelligence (AI) in healthcare by exploring the perspectives of various stakeholders. The objective was to provide a nuanced understanding of stakeholder views to address concerns and promote the acceptance and successful integration of AI technologies in medical practice. Design This exploratory qualitative study used semi-structured interviews. Data were analysed using a combination of deductive and inductive coding, followed by content analysis to identify and develop categories. Setting This study was conducted in Tübingen, Germany, within the framework of the TüKITZMed project (Tübingen AI Training Center for Medicine), between August 2022 and March 2023. Participants A total of 38 stakeholders participated, including 6 lecturers, 9 clinicians, 10 healthcare students, 6 AI experts and 7 institutional stakeholders. Inclusion criteria included professionals involved in or affected by AI in healthcare, while exclusion criteria comprised individuals without relevant experience. Interventions Not applicable. Outcome measures The main outcome was the identification of thematic categories capturing stakeholders’ perceptions, expectations and concerns regarding the integration of AI in healthcare. Results The analysis identified two main thematic categories: two main categories encompassing a total of 14 subcategories: (1) perceived opportunities of AI in medicine, including aspects of increased efficiency, reduced workload and improved patient safety and (2) perceived challenges of AI in medicine, such as its impact on medical decision-making and concerns about dependence on technology. These themes reflect diverse perspectives and insights across stakeholder groups. Conclusions Diverse stakeholder perspectives offer valuable insights into the anticipated effects of AI in healthcare. Understanding these perspectives can support decision-makers in designing context-sensitive AI strategies and identifying areas for further professional and institutional development. Future research should monitor how these attitudes evolve in response to technological progress and real-world implementation.