julilili42/papers huggingface dataset:
SARS-CoV-2 infection in pregnant women and incidence of thromboembolic disease – an analysis of the Covid-19 Related Obstetric and Neonatal Outcome Study (CRONOS) in Germany
2025-02-10

<title>Abstract</title> Purpose The aim of the present study was to quantify the rate of thromboembolic events (TE) in pregnant women with SARS-CoV-2 infection and to characterize risk factors to provide a basis for individualized recommendation on prophylactic measures. Methods CRONOS is a multicenter, prospective observational study conducted in Germany and Austria during the COVID-19 pandemic. Pregnant women with confirmed SARS-CoV-2 infection were enrolled. Data on demographics, medical history, COVID-19-related aspects, and pregnancy and birth outcomes were collected. TE was particularly queried and used as the primary outcome. A combination of “TE,” “maternal or fetal death,” or “severe postpartum hemorrhage” was defined as a secondary endpoint. Risk analyses were performed using univariate and multivariable logistic regression models. Results Data from 8033 pregnant patients showed 40 TEs (0.5% incidence). TE rates were 10% in ICU patients, 0.2–0.4% in those with moderate-to-mild COVID-19, and &lt; 0.1% in asymptomatic women. Pulmonary embolism occurred in 21 cases, deep vein thrombosis in 12, and 7 had atypical or arterial TE. Risk factors included advanced gestational age, COVID-19 symptoms, hospitalization or ICU admission, premature birth, cesarean section, delivery within 4 weeks of infection, higher weight gain, anemia, and chronic inflammatory bowel disease. COVID-19 vaccination reduced risk. The logistic risk model yielded an AUC of 0.87 (95% CI 0.81–0.94). Conclusion The TE rate in pregnant women is largely determined by the severity of the disease. In asymptomatic or mild cases, other factors outweigh TE risk, while severe COVID-19 requiring ICU admission poses a high TE risk despite prophylaxis.
Peripheral Immune Profiles in Individuals at Genetic Risk of Amyotrophic Lateral Sclerosis and Alzheimer’s Disease
2025-02-10

The immune system plays a crucial role in the pathogenesis of neurodegenerative diseases. Here, we explored whether blood immune cell profiles are already altered in healthy individuals with a genetic predisposition to amyotrophic lateral sclerosis (ALS) or Alzheimer’s disease (AD). Using multicolor flow cytometry, we analyzed 92 immune cell phenotypes in the blood of 448 healthy participants from the Berlin Aging Study II. We calculated polygenic risk scores (PGSs) using genome-wide significant SNPs from recent large genome-wide association studies on ALS and AD. Linear regression analyses were then performed of the immune cell types on the PGSs in both the overall sample and a subgroup of older participants (&gt;60 years). While we did not find any significant associations between immune cell subtypes and ALS and AD PGSs when controlling for the false discovery rate (FDR = 0.05), we observed several nominally significant results (p &lt; 0.05) with consistent effect directions across strata. The strongest association was observed with CD57+ CD8+ early-memory T cells and ALS risk (p = 0.006). Other immune cell subtypes associated with ALS risk included PD-1+ CD8+ and CD57+ CD4+ early-memory T cells, non-classical monocytes, and myeloid dendritic cells. For AD, naïve CD57+ CD8+ T cells and mature NKG2A+ natural killer cells showed nominally significant associations. We did not observe major immune cell changes in individuals at high genetic risk of ALS or AD, suggesting they may arise later in disease progression. Additional studies are required to validate our nominally significant findings.
Treatment, tolerability and outcomes of enfortumab vedotin plus pembrolizumab in advanced urothelial carcinoma: An analysis of the Austrian enfortumab registry.
2025-02-10

736 Background: The treatment of advanced urothelial carcinoma (UC) has dramatically changed with the introduction of antibody-drug conjugates and immunotherapy. Since the report of the EV-302 trial data in October 2023, enfortumab vedotin (EV) in combination with pembrolizumab (P) is the preferred standard of care in 1 st line therapy. Methods: Clinical data were derived from 17 clinics participating in the Austrian EV registry. Patients receiving 1 st line EV + P for advanced UC from 09/2023 to 09/2024 were included. The main objectives of the registry were to evaluate patient characteristics, including comorbidities, treatment duration, efficacy and safety in a real-world setting. Results: In total 103 patients were included, 24 females and 79 males with a median age of 71 years (range 32 - 92). The majority of patients (89.3%) had an eastern cooperative oncology group performance status (ECOG PS) of 0 to 1, 6.7 % patients had an ECOG PS of 2 and 3.8% had an ECOG PS of 3. Liver metastasis was present in 19.4% of patients. At the time of data cut-off, 81.6% of patients were alive. Therapy with either EV or P was ongoing in 67.0% of patients. First response evaluation was performed in 88 patients, of these the objective response rate (ORR) was 65.9% with 12.5% complete remissions. After a median follow up of 4.0 months, the median overall survival (OS) and progression free survival (PFS) was not reached. Adverse events occurred in 69.9% of patients, with ≥ grade 3 toxicities in 30.1% of patients. Therapy with either EV or P was discontinued due to toxicity in 20.4% of patients. Patients with a high (≥5) Charlson comorbidity index (CCI) had significantly worse outcomes in terms of ORR (p = 0.02), PFS (p = 0.02) and OS (p = 0.04) as compared to patients with a lower CCI (0-4). There was also a trend for more severe adverse events in patients with a high CCI (p = 0.07), however, the overall adverse event rate, dose reductions and treatment discontinuations were similar in both groups. Renal function, body mass index and known diabetes mellitus had no influence on efficacy or tolerability in our analysis. In patients with ECOG PS 2 the ORR was 71.4% which is numerically similar to patients with ECOG PS 0-1. Conclusions: These first Austrian real-world data evaluate the efficacy and tolerability of EV plus P in routine clinical practice. Our data confirm the ORR to the pivotal EV-302 phase III trial, however patients with significant comorbidities as reflected by a higher score in the CCI had significantly worse outcomes. Updated data with longer follow up will be presented at the meeting.
Small molecule treatment alleviates photoreceptor cilia defects in LCA5-deficient human retinal organoids
2025-02-11

Abstract Bialleleic pathogenic variants in LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report the use of gene editing to generate isogenic LCA5 knock-out (LCA5 KO) induced pluripotent stem cells (iPSC) and their differentiation to retinal organoids. The molecular and cellular phenotype of the LCA5 KO retinal organoids was studied in detail and compared to isogenic controls as well as patient-derived retinal organoids. The absence of LCA5 was confirmed in retinal organoids by immunohistochemistry and western blotting. There were no major changes in retinal organoid differentiation or ciliation, however, the localisation of CEP290 and IFT88 was significantly altered in LCA5 KO and patient photoreceptor cilia with extension along the axoneme. The LCA5-deficient organoids also had shorter outer segments and rhodopsin was mislocalised to the outer nuclear layer. We also identified transcriptomic and proteomic changes associated with the loss of LCA5. Importantly, treatment with the small molecules eupatilin, fasudil or a combination of both drugs reduced CEP290 and IFT88 accumulation along the cilia. The treatments also improved rhodopsin traffic to the outer segment and reduced mislocalisation of rhodopsin in the outer nuclear layer (ONL). The improvements in cilia-associated protein localisation and traffic were accompanied by significant changes in the transcriptome towards control gene expression levels in many of the differentially expressed genes. In summary, iPSC-derived retinal organoids are a powerful model for investigating the molecular and cellular changes associated with loss of LCA5 function and highlight the therapeutic potential of small molecules to treat retinal ciliopathies.
Role of Suspended Particulate Matter for the Transport and Risks of Organic Micropollutant Mixtures in Rivers: A Comparison between Baseflow and High Discharge Conditions
2025-02-11

The partition dynamics of organic micropollutants between water and suspended particulate matter (SPM) in riverine ecosystems differs between dry and wet weather, as demonstrated at two sites at the Ammer River, Germany. One site was impacted by a wastewater treatment plant (WWTP) and the other by runoff of a mixed agricultural/urban area. Liquid and gas chromatography coupled to high-resolution mass spectrometry were used to quantify 415 organic chemicals, and their mixture effects were characterized with three in vitro bioassays indicative of the activation of the aryl hydrocarbon (AhR) and peroxisome proliferator-activated (PPARγ) receptors and the oxidative stress response. During wet weather, the total chemical concentrations and bioactivities in the water increased, but the concentrations in SPM did not change. As SPM levels increased, the SPM-bound chemicals contributed 6-16% to the overall concentrations in the water column during wet weather but only 0.1-0.9% during dry weather. The mixture effects were more strongly associated with SPM under wet conditions, particularly for AhR activity, where SPM accounted for over 90% of the observed effects. The AhR activity may therefore serve as an indicator for assessing the risks of SPM-related pollution in rivers. The high SPM-bound mixtures' activation of AhR and oxidative stress response during rain were primarily caused by polycyclic aromatic hydrocarbons, indicating a major contribution of road runoff.
Development and validation of a novel metabolic health-related nomogram to improve predictive performance of cardiovascular disease risk in patients with prediabetes
2025-02-11

This study developed a reliable nomogram for predicting CVD risk in patients with prediabetes. The model demonstrated robust performance and offered a simple yet individualized approach for predicting the CVD risk in patients with prediabetes.
Preferred Working Time Models and Equal Opportunities in Gynecology and Obstetrics: Results of the Systematic Trinational FARBEN Survey
2025-02-11

Abstract The trinational survey project conducted by the Young Forums of the German, Austrian, and Swiss Societies for Gynecology and Obstetrics aims to assess the preferences of prospective and practicing gynecologists regarding various work-time models, the compatibility of family and career, as well as parental leave. Between October 2023 and May 2024, a total of 1364 participants took part in the survey. The questionnaire consisted of 62 questions covering topics such as the workplace in general, work-time models, training priorities, team compositions, and professional goals. Participation was voluntary and anonymous. Of the 1364 participants, 75.3% were employed in Germany, 12.9% in Austria, and 11.8% in Switzerland. Men were significantly more likely to aspire to a chief physician position compared to women (26.5% vs. 3.6%; p &lt; 0.001). Only 12.5% of participants overall preferred full-time employment, although 63.0% of residents worked full-time. Additionally, 65.4% of respondents stated that their workplace did not provide childcare with flexible hours. At the same time, 76.0% valued workplace-proximate childcare as an important factor in choosing an employer. The results highlight heterogeneous and individual needs and priorities among all (prospective) gynecologists. At a time when individuality and equality are becoming increasingly significant, it is essential to promote work environments that meet the demands and needs of all physicians. The results should therefore be critically discussed to implement potential adjustments and improvements in practice.
Design, construction, and deployment of a multi-locus transcranial magnetic stimulation system for clinical use
2025-02-11

<title>Abstract</title> <bold>Background:</bold>Transcranial magnetic stimulation (TMS) is an established method for noninvasive brain stimulation, used for investigating and treating brain disorders. Recently, multi-locus TMS (mTMS) has expanded the capabilities of TMS by employing an array of overlapping stimulation coils, enabling delivery of stimulation pulses at different cortical locations without physical coil movement. We aimed to design, construct, and deploy an mTMS device and a five-coil array for clinical environment, emphasizing safety of the system. <bold>Methods:</bold> Our mTMS device is controlled by a field-programmable gate array (FPGA). The power electronics comprises five stimulation channels, each consisting of a high-voltage capacitor connected to a pulse circuit, controlling a single coil in the array. The device contains custom-designed circuit boards, with functions such as monitoring the system state, reporting errors, and delivering pulses. Our design utilizes redundancy in both hardware and firmware to ensure robust operation and safety. We performed an automated motor mapping test to verify the electronic targeting capabilities of the device. <bold>Results:</bold> We constructed the mTMS device and deployed it to the Hertie Institute for Clinical Brain Research (Tübingen, Germany). Compared to our earlier prototype, the new design improves patient and operator safety. The motor mapping test confirmed that our device can accurately target stimulation pulses in the cortex. <bold>Significance:</bold>mTMS or other similar technologies are currently not available for hospital use. The present device and its installation are major steps toward establishing multicoil TMS as an accessible clinical tool for investigation and treatment of the brain.
A hyper-acute immune hemolytic anemia induced by contrast medium was successfully treated with eculizumab: a case report
2025-02-11

Contrast medium is frequently associated with allergic reactions and kidney dysfunction. However, contrast media can induce hemolytic anemia with a broad spectrum of hemolytic manifestations. We report a 38-year-old patient with very severe immune hemolytic anemia after the application of iomeprol due to a CT of the thorax/abdomen. In this case report, we illustrate the diagnostics and treatment of life-threatening hemolytic anemia induced by a contrast medium that was successfully treated with eculizumab.
Evidence for an evaluative effect of stimulus co-occurrence may be inflated by evaluative differences between assimilative and contrastive relations
2025-02-11

Recent research on relational evaluative conditioning (relational EC) suggests that stimulus co-occurrence can have a direct effect on evaluations over and above the particular relation between the co-occurring stimuli. This research is based on a process dissociation approach where co-occurrence effects are demonstrated via attenuated evaluative learning for co-occurring stimuli that are connected by contrastive in comparison to assimilative relations. Instead of attributing such attenuations to an orthogonal influence of stimulus co-occurrence, we investigated whether (a) contrastive relations tend to produce weaker evaluations than their assimilative counterparts and (b) such evaluative differences can inflate evidence for co-occurrence effects on continuous as well as on categorical evaluation measures. A pilot study (<i>N</i> = 85) confirmed notion (a), while a first experiment (<i>N</i> = 42) produced preliminary evidence for notion (b) in the context of multinomial processing tree (MPT) modelling. In a second, high-powered experiment (<i>N</i> = 229), sub-sample MPT analyses (including only CSs with correct memory for the CS-US proposition) demonstrated that evidence for co-occurrence effects can be inflated by evaluative differences between assimilative vs. contrastive relations. The theoretical and methodological implications of these findings are discussed.
Quadratically enriched tropical intersections
2025-02-11

Abstract Using tropical geometry, one can translate problems in enumerative geometry to combinatorial problems. Thus, tropical geometry is a powerful tool in enumerative geometry over the complex and real numbers. Results from <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:msup> <m:mi mathvariant="double-struck">A</m:mi> <m:mn>1</m:mn> </m:msup> </m:math> \\mathbb{A}^{1} -homotopy theory allow to enrich classical enumerative geometry questions and get answers over an arbitrary field. In the resulting area, <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:msup> <m:mi mathvariant="double-struck">A</m:mi> <m:mn>1</m:mn> </m:msup> </m:math> \\mathbb{A}^{1} -enumerative geometry, the answer to these questions lives in the Grothendieck–Witt ring of the base field k. In this paper, we use tropical methods in this enriched set up by showing Bézout’s theorem and a generalization, namely the Bernstein–Kushnirenko theorem, for tropical hypersurfaces enriched in <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"> <m:mrow> <m:mi>GW</m:mi> <m:mo>⁡</m:mo> <m:mrow> <m:mo stretchy="false">(</m:mo> <m:mi>k</m:mi> <m:mo stretchy="false">)</m:mo> </m:mrow> </m:mrow> </m:math> \\operatorname{GW}(k) .
Jet Definition and Transverse-Momentum–Dependent Factorization in Semi-inclusive Deep-Inelastic Scattering
2025-02-12

Using the color dipole picture of deep inelastic scattering (DIS) and the color glass condensate effective theory, we study semi-inclusive jet production in DIS at small <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:mrow><a:mi>x</a:mi></a:mrow></a:math> in the limit where the photon virtuality <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" display="inline"><c:mrow><c:msup><c:mrow><c:mi>Q</c:mi></c:mrow><c:mrow><c:mn>2</c:mn></c:mrow></c:msup></c:mrow></c:math> is much larger than the transverse momentum squared <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" display="inline"><e:mrow><e:msubsup><e:mrow><e:mi>P</e:mi></e:mrow><e:mrow><e:mo>⊥</e:mo></e:mrow><e:mrow><e:mn>2</e:mn></e:mrow></e:msubsup></e:mrow></e:math> of the produced jet. In this limit, the cross section is dominated by aligned jet configurations, that is, quark–antiquark pairs in which one of the fermions—the would-be struck quark in the Breit frame—carries most of the longitudinal momentum of the virtual photon. We show that physically meaningful jet definitions in DIS are such that the effective axis of the jet sourced by the struck quark is controlled by its virtuality rather than by its transverse momentum. For such jet definitions, we show that the next-to-leading order cross section admits factorization in terms of the (sea) quark transverse momentum dependent distribution, which in turn satisfies a universal Dokshitzer-Gribov-Lipatov-Altarelli-Parisi and Sudakov evolution.
Guiding AI in radiology: ESR’s recommendations for effective implementation of the European AI Act
2025-02-13

Abstract This statement has been produced within the European Society of Radiology AI Working Group and identifies the key policies of the EU AI Act as they pertain to medical imaging. It offers specific recommendations to policymakers and the professional community for the effective implementation of the legislation, addressing potential gaps and uncertainties. Key areas include AI literacy, classification rules for high-risk AI systems, data governance, transparency, human oversight, quality management, deployer obligations, regulatory sandboxes, post-market monitoring, information sharing, and market surveillance. By proposing actionable solutions, the statement highlights ESR’s readiness in supporting appropriate application of the AI Act in the field, promoting clarity and the effective integration of AI technologies to ensure their impactful and safe use for the benefit of Europe’s patients. Critical relevance statement With the impending arrival of the EU AI Act, it is critical for stakeholders to provide timely input on its key areas. This statement offers expert feedback on the aspects of the EU AI Act that will affect medical imaging. Key Points The AI Act will significantly impact the field of medical imaging, shaping how AI technologies are used and regulated. The ESR is committed to develop guidelines and best practices, collaborating on the implementation process. This statement offers expert feedback on the aspects of the framework that will affect medical imaging. Graphical Abstract
Exploring Alternative Zinc-Binding Groups in Histone Deacetylase (HDAC) Inhibitors Uncovers DS-103 as a Potent Ethylhydrazide-Based HDAC Inhibitor with Chemosensitizing Properties
2025-02-13

In this work, we synthesized a series of peptoid-based histone deacetylase (HDAC) inhibitors with variations in the linker region and zinc-binding groups. All compounds were investigated for their HDAC inhibition, antiplasmodial activity, and cytotoxicity against native and cisplatin-resistant carcinoma cell lines. The ethylhydrazide <b>20</b> (<b>DS-103</b>) proved to be the most effective compound in these primary screenings. <b>DS-103</b> showed nanomolar inhibition of class I HDACs and of HDAC6 (class IIb). To further investigate the binding mode of <b>DS-103</b>, a crystal structure of <b>DS-103</b> in complex with HDAC6 was obtained, which represents the first reported crystal structure of an alkylhydrazide in complex with an HDAC enzyme. Importantly, <b>DS-103</b> completely reversed cisplatin resistance in two different platinum-resistant solid cancer cell lines and demonstrated strong synergism with cisplatin. The synergistic anticancer effects are mediated by increased DNA damage and p21 expression, resulting in caspase-mediated apoptosis and cell death.
Tracking spatial patterns and daily modulation of behavior in a natural population of the pulse-type weakly electric fish, Gymnotus omarorum
2025-02-13

Tracking individual spatial and activity-rest patterns in natural populations is challenging because it is seldom possible to monitor individual-specific traits continuously. The continuous emission of electric signals (EODs) by weakly electric fish provides a unique opportunity to do this. We present a cutting-edge technique, arrays of electrodes connected to low-cost amplifiers and tracking algorithm, to provide the individual identification of pulse-type weakly electric fish in the wild. Based only on EOD recordings of individuals of <i>Gymnotus omarorum</i>, we show that (1) there are more fish in core than in edge zones; (2) transitions into and out of the recording sites were more frequent at night, and (3) resident fish show robust nocturnal increases of EOD rate likely associated with daily variations of water temperature. This experimental approach can be extended to other species to improve our understanding of the behavior, ecology, and well-being of electric fish in natural environments.