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ContextAdipose steroid metabolism modifies body fat development in polycystic ovary syndrome (PCOS).ObjectiveTo determine whether subcutaneous (SC) abdominal adipose aldo-keto reductase 1C3 (AKR1C3; a marker of testosterone generation) is increased in normal-weight women with PCOS vs age- and body mass index (BMI)-matched normoandrogenic ovulatory women (controls) and is related to SC abdominal adipose activator protein-1 (AP-1; a marker of adipocyte differentiation) and/or androgen receptor (AR) protein expression in predicting fat accretion.DesignProspective cohort study.SettingAcademic center.PatientsEighteen normal-weight PCOS women; 17 age- and BMI-matched controls.InterventionsCirculating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy, immunohistochemistry.Main outcome measuresClinical characteristics, hormonal concentrations, body fat distribution, SC adipose AKR1C3, AR, and AP-1 protein expression.ResultsWomen with PCOS had significantly higher serum androgen levels and greater android/gynoid fat mass ratios than controls. SC adipose AKR1C3, AR, and AP-1 protein expressions were comparable between the study groups, but groups differed in correlations. In PCOS women vs controls, SC adipose AKR1C3 protein expression correlated positively with android and gynoid fat masses and negatively with SC adipose AP-1 protein expression. SC adipose AR protein expression correlated negatively with fasting serum free fatty acid and high-density lipoprotein levels. In both study groups, SC adipose AKR1C3 protein expression negatively correlated with serum cortisol levels.ConclusionIn normal-weight PCOS women, SC abdominal adipose AKR1C3 protein expression, in combination with intra-adipose AP-1 and AR-dependent events, predicts fat accretion in the presence of physiological cortisol levels.

The low bioavailability of most phytochemicals limits their anticancer effects in humans. The present study was designed to test whether combining arctigenin (Arc), a lignan mainly from the seed of Arctium lappa, with green tea (GT) and quercetin (Q) enhances the chemopreventive effect on prostate cancer. We performed in vitro proliferation studies on different cell lines. We observed a strong synergistic anti-proliferative effect of GT+Q+Arc in exposing androgen-sensitive human prostate cancer LNCaP cells. The pre-malignant WPE1-NA22 cell line was more sensitive to this combination. No cytotoxicity was observed in normal prostate epithelial PrEC cells. For an in vivo study, 3-week-old, prostate-specific PTEN (phosphatase and tensin homolog) knockout mice were treated with GT+Q, Arc, GT+Q+Arc, or the control daily until 16 weeks of age. In vivo imaging using prostate-specific membrane antigen (PSMA) probes demonstrated that the prostate tumorigenesis was significantly inhibited by 40% (GT+Q), 60% (Arc at 30 mg/kg bw), and 90% (GT+Q+Arc) compared to the control. A pathological examination showed that all control mice developed invasive prostate adenocarcinoma. In contrast, the primary lesion in the GT+Q and Arc alone groups was high-grade prostatic intraepithelial neoplasia (PIN), with low-grade PIN in the GT+Q+Arc group. The combined effect of GT+Q+Arc was associated with an increased inhibition of the androgen receptor, the PI3K/Akt pathway, Ki67 expression, and angiogenesis. This study demonstrates that combining Arc with GT and Q was highly effective in prostate cancer chemoprevention. These results warrant clinical trials to confirm the efficacy of this combination in humans.

Abstract Background Sex- and gender-based medicine (SGBM) addresses differences between males/men and females/women with regard to clinical manifestation, diagnostics, treatment and outcomes of diseases. The implementation of SGBM in the medical curriculum varies, and data on the knowledge of lecturers and students about SGBM is scarce. This study aims to evaluate the perceived importance and knowledge of SGBM among lecturers and students. Methods This cross-sectional observational survey was conducted using a questionnaire, including ranked with a Likert Scale. Statistical analysis was performed with the Chi-squared test. All lecturers and students at the Bern University Medical School in Switzerland were invited to voluntarily participate. Results 114 (34.1%) lecturers and 903 (41.4%) students participated in the survey. Women perceived education of SGBM to be of greater importance than men in lecturer and student subgroups respectively (lecturers women vs. men median 6.0 vs. 5.0, P = 0.011; students 6.0 vs. 5.0, P

he effectiveness of knowledge transfer activities in a large organization, such as a university or research institute, can be significantly improved by paying attention to a few key factors. One such factor could be the so-called scouting activity. The knowledge transfer process does not necessarily start with the submission of the invention disclosure. Scouting is the activity of identifying those elements of knowledge within the institution that can be used to start a new knowledge transfer process. Another factor could be to broaden the scope of knowledge elements, i.e. to focus not only on technologies but also on non-technological innovations or know-how-type intellectual properties. All this can significantly broaden the range of knowledge that can be transferred, generating more and better potential outcomes for the institution. In this article, we explore the possible applications of these types of factors and activities.

Abstract The dataset presents a 43 year-long reanalysis of pollen seasons for three major allergenic genera of trees in Europe: alder (Alnus), birch (Betula), and olive (Olea). Driven by the meteorological reanalysis ERA5, the atmospheric composition model SILAM predicted the flowering period and calculated the Europe-wide dispersion pattern of pollen for the years 1980–2022. The model applied an extended 4-dimensional variational data assimilation of in-situ observations of aerobiological networks in 34 European countries to reproduce the inter-annual variability and trends of pollen production and distribution. The control variable of the assimilation procedure was the total pollen release during each flowering season, implemented as an annual correction factor to the mean pollen production. The dataset was designed as an input to studies on climate-induced and anthropogenically driven changes in the European vegetation, biodiversity monitoring, bioaerosol modelling and assessment, as well as, in combination with intra-seasonal observations, for health-related applications.

We present Golden Gate, an FPGA-based simulation tool that decouples the timing of an FPGA host platform from that of the target RTL design. In contrast to previous work in static time-multiplexing of FPGA resources, Golden Gate employs the Latency-Insensitive Bounded Dataflow Network (LI-BDN) formalism to decompose the simulator into subcomponents, each of which may be independently and automatically optimized. This structure allows Golden Gate to support a broad class of optimizations that improve resource utilization by implementing FPGA-hostile structures over multiple cycles, while the LI-BDN formalism ensures that the simulator still produces bit- and cycle-exact results. To verify that these optimizations are implemented correctly, we also present LIME, a model-checking tool that provides a push-button flow for checking whether optimized subcomponents adhere to an associated correctness specification, while also guaranteeing forward progress. Finally, we use Golden Gate to generate a cycle-exact simulator of a multi-core SoC, where we reduce LUT utilization by up to 26% by coercing multi-ported, combinationally read memories into simulation models backed by time-multiplexed block RAMs, enabling us to simulate 50% more cores on a single FPGA.

Abstract Ornithopod dinosaurs evolved numerous craniodental innovations related to herbivory. Nonetheless, the relationship between occlusion, tooth wear rate, and tooth replacement rate has been neglected. Here, we reconstruct tooth wear rates by measuring tooth replacement rates and tooth wear volumes, and document their dental microwear. We demonstrate that total tooth volume and rates of tooth wear increased steadily during ornithopod evolution, with deeply-nested taxa wearing up to 3360 mm3 of tooth volume/day. Increased wear resulted in asymmetric tooth crown formation with uneven von Ebner line increment width by the Late Jurassic, and in faster tooth replacement rates in multiple lineages by the mid-Cretaceous. Microwear displays a contrasting pattern, with decreasing complexity and pit percentages in deeply-nested and later-occurring taxa. We hypothesize that early ornithopods were browsers and/or frugivores but deeply nested iguanodontians were bulk-feeders, eating tougher, less nutritious plants; these trends correlate with increasing body mass and longer gut passage times.

Purpose Bilateral cleft lip and palate (BCLP) are severe congenital anomalies. The cleft interferes with the normal growth of the maxilla, leading to deficient midfacial development. The aim of the present study was to evaluate the short-term influence of preoperative nasoalveolar moulding (NAM) therapy on maxillary arch dimensions in patients with BLCP.Materials and methods 18 newborns (male: 12; female: 6) were recruited who underwent NAM therapy before cheiloplasty. The pre- (T0) and post-NAM (T1) plaster casts of the maxilla were scanned using a laboratory scanner. The measured parameters on the digital casts included premaxilla width, right and left alveolar cleft width, right and left molar region length, anterior interalveolar-, intercanine-, intermolar-, intertuberosity width, palatal length and anterior basal angle.Results Both left (p = 0.047) and right (p = 0.019) alveolar clefts significantly reduced in size at T1. A significant expansion in premaxilla width was detected (p = 0.037). Anterior basal angle showed a significant increase too. Except for the intermolar width (p = 0.045), no significant changes were identified in the transversal dimensions.Conclusion NAM therapy could potentially serve as an effective tool in mitigating the severity of bilateral cleft deformities at a short-term interval without interfering with maxillary growth. However, long-term studies are required to confirm the effectiveness of the therapy.

Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.

This paper discusses the regimes of Jarosław Kaczyński in Poland (2015–) and Viktor Orbán in Hungary (2010–) from the perspective of a curious paradox: they are very different in functioning but adhere to right-wing ideological frames that are very similar. First, we argue for a dual-level approach to understanding the formal and informal nature of these regimes, and we identify Poland as a conservative autocratic attempt and Hungary as an established patronal autocracy. After a comparative analysis of the two systems, we analyze the regimes’ common ideological frames and explain how legitimacy panels fit the purposes of an ideology-driven regime (Poland) and an ideology-applying one (Hungary). Finally, the analysis is used to explain the divergent responses of the Polish and the Hungarian regimes to the 2022 Russian invasion of Ukraine, which also brought the mutual relations of the two de-democratizing countries in the European Union to a breaking point.

The aims of the study were (1) to develop a domain-general computer-based assessment tool for inductive reasoning and to empirically test the theoretical models of Klauer and Christou and Papageorgiou; and (2) to develop an online game to foster inductive reasoning through mathematical content and to investigate its effectiveness. The sample was drawn from fifth-grade students for the assessment (N = 267) along with the intervention study (N = 122). The online figurative test consisted of 54 items: nine items were developed for each of the six inductive reasoning processes. The digital game-based training program included 120 learning tasks embedded in mathematical content with differential feedback and instructional support. The test had good psychometric properties regarding reliabilities, means, and standard deviations. Confirmatory factor analyses revealed that the six processes of inductive reasoning and the three latent factors of Similarity, Dissimilarity, and Integration could be empirically confirmed. The training program was effective in general (corrected effect size = 0.38); however, the process of cross-classification was not developed significantly. Findings could contribute to a more detailed understanding of the structure and the modifiability of inductive reasoning processes and could reveal further insights into the nature of fluid intelligence.

Study region: Pannonian Basin, Hungary, Maros fluvial fan. Study focus: This paper presents a novel approach to characterise a distal lobe of a fluvial fan, demonstrating how a combined interpretation of high-resolution geophysical methods like electrical resistivity tomography and geophysical cone penetration tests together with log-correlation, hydrogeochemical, isotope and noble gas data provides a sound basis for aquifer characterisation. This multidisciplinary investigative approach is applicable to any fluvial fan to support water management. New hydrological insights for the region: (1) The studied fluvial fan forms a hydraulically interconnected aquifer system, with three channel belts and six hydrostratigraphic units. (2) Mean groundwater residence times are distinct in the aquifers studied. Holocene infiltration, with apparent residence time younger than 20–22 years is characteristic in the uppermost channel belt and forms part of local groundwater flow systems. The deeper aquifers host groundwater infiltrated during the Pleistocene, as part of the intermediate flow system. (3) Where the silty-clayey floodplain sediments have been replaced by sandy deposits, and groundwater abstraction is present, groundwater can communicate between the upper and lower channel belts, therefore fresh infiltration passes into the deeper channel belts, resulting mostly in mean residence times younger than 100 years. However, Pleistocene infiltration was detected at about 30 m below surface in the second channel belt, where the unconfined aquifer is missing and silty-clayey sediments are on the surface.

Erythrina stricta Roxb., an underutilized legume species native to the Indian subcontinent, is traditionally employed in various medicinal applications. This study systematically examines the nutritional quality, encompassing proximate and mineral composition of E. stricta seeds, with a focus on characterizing the seed oil. The seeds exhibit commendable proximate composition, with 26.81% protein and 18.71% fibre. Noteworthy mineral elements include 5.0 mg/g DW of calcium and 787.0, 32.7, 36.8 and 497.0 µg/g of iron, copper, boron and zinc, respectively. The seeds yield 13.43% oil, with oleic, palmitic, linoleic and stearic acids as prominent fatty acids, constituting 48.82%, 20.63%, 20.27% and 6.47%, respectively. Antinutrients such as oxalate and phytate are present in concentrations of 26.85 and 16.04 mg/g FW, respectively. In conclusion, this study underscores E. stricta seeds as a robust source of both nutrients and oil, warranting further exploration and consideration for potential applications.