Lavandula species are one of the most popular aromatic plants in the world and have a high content of high-quality essential oil (EO). Although there are many species in this genus, only lavandin (Lavandula intermedia Emeric ex Loisel.) and lavender (L. angustifolia Mill.)  are highly valued worldwide. The quality and yield of lavandin and lavender depend on genetic factors, environmental conditions and cultivation methods. Therefore, the aim of this paper is to research the effects of the application of biostimulant on the inflorescence yield and the quality of lavandin and lavender. The treatments used in this research consisted of a combination of different species (lavandin and lavender) and biostimulant (applied and unapplied). The research results show that all the research traits significantly depended on the used species and the applied biostimulant. The inflorescence yield, the content of total flavonoids, and the content of EO were higher in the lavandin species (477.3 g plant-1, 17.21 mg CAE g-1, 8.57 mL 100 g-1, respectively) than in the lavender species (180.5 g plant-1, 13.41 mg CAE g-1, and 3.69 mL 100 g-1, respectively). EOs of lavandin and lavender were rich in linalool and linalyl acetate. The use of biostimulators had a positive effect on the inflorescence yield and the content of essential oil. Furthermore, the applied biostimulant increased the linalool content in the essential oil of both researched species, i.e. it positively affected its quality.

Atrial cardiomyopathy is closely associated with atrial fibrillation (AF), and some patients exhibit no dysfunction at rest but demonstrate evident changes in left atrial (LA) function and LA volume during exercise. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF). A prospective cohort of 1055 patients in SR was enrolled across 12 centers. The main study cohort was divided into two groups: the modeling group (n = 513) and the verification group (n = 542). All patients underwent ESE, which included B-lines, LA volume index (LAVi), and LA strain of the reservoir phase (LASr). Age, resting and stress LAVi and LASr, and B-lines were identified as a combination of detectors for PAF in both groups. In the entire cohort, aside from resting and stress LAVi and LASr, additional parameters differentiating PAF and non-PAF patients were the presence of systemic hypertension, exercise E/e’ > 7, worse right ventricle (RV) contraction during exercise (∆ tricuspid annular plane systolic excursion < 5 mm), a lower left ventricular contractile reserve (< 1.6), and a reduced chronotropic reserve (heart rate reserve < 1.64). The composite score, summing all 9 items, yielded a score of > 4 as the best sensitivity (79%) and specificity (65%). ESE can complement rest echocardiography in the identification of previous PAF in patients with SR through the evaluation of LA functional reservoir and volume reserve, LV chronotropic, diastolic, and systolic reserve, and RV contractile reserve. A scoring system predicting the probability of PAF. The score was computed using the cutoff values as in the illustration. The score >4 demonstrated a sensitivity of 79% and a specificity of 65% of PAF.

Spherically symmetric Einstein-{\ae}ther (E{\AE}) theory with a Maxwell-like kinetic term is revisited. We consider a general choice of the metric and the \ae{}ther field, finding that:~(i) there is a gauge freedom allowing one always to use a diagonal metric; and~(ii) the nature of the Maxwell equation forces the \ae{}ther field to be time-like in the coordinate basis. We derive the vacuum solution and confirm that the innermost stable circular orbit (ISCO) and photon ring are enlarged relative to general relativity (GR). Buchdahl's theorem in E\AE{} theory is derived. For a uniform physical density, we find that the upper bound on compactness is always lower than in GR. Additionally, we observe that the Newtonian and E\AE{} radial acceleration relations run parallel in the low pressure limit. Our analysis of E\AE{} theory may offer novel insights into its interesting phenomenological generalization: \AE{}ther--scalar--tensor theory ({\AE}ST).

Numerous studies suggest that common genetic and epigenetic factors such as p53, histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), the (Ataxia Telangiectasia mutated) ATM gene, cyclin-dependent kinase 5 (CDK5), glycogen synthase kinase 3 (GSK3) and altered expression of microRNA (miRNA) play a crucial role in cancer and neurodegeneration. As there is growing evidence that epigenetic aberrations in cancer and neurological diseases lead to complex pathophysiological changes, the simultaneous targeting of epigenetic and other related pathways by dual-target inhibitors may contribute to the discovery of more effective and personalized therapeutic options. Computer-Aided Drug Design (CADD) provides comprehensive bioinformatic, chemoinformatic, and chemometric approaches for the design of novel chemotypes of epigenetic dual-target inhibitors, enabling efficient discovery of new drug candidates for innovative treatments of these multifactorial diseases. The detailed anticancer mechanisms by which the epigenetic dual-target inhibitors alter metastatic and tumorigenic properties, influence the tumor microenvironment, or regulate the immune response are also presented and discussed in the review. To improve our understanding of the pathogenesis of cancer and neurodegeneration, this review discusses novel therapeutic agents targeting different molecular mechanisms involved in these multifactorial diseases.

Biomarkers associated with the progression from gastric intestinal metaplasia (GIM) to gastric adenocarcinoma (GA), i.e., GA-related GIM, could provide valuable insights into identifying patients with increased risk for GA. The aim of this study was to utilize multi-bioinformatics to reveal potential biomarkers for the GA-related GIM and predict potential drug repurposing for GA prevention in patients. The multi-bioinformatics included gene expression matrix (GEM) by microarray gene expression (MGE), ScType (a fully automated and ultra-fast cell-type identification based solely on a given scRNA-seq data), Ingenuity Pathway Analysis, PageRank centrality, GO and MSigDB enrichments, Cytoscape, Human Protein Atlas and molecular docking analysis in combination with immunohistochemistry. To identify GA-related GIM, paired surgical biopsies were collected from 16 GIM-GA patients who underwent gastrectomy, yielding 64 samples (4 biopsies per stomach x 16 patients) for MGE. Co-analysis was performed by including scRNAseq and immunohistochemistry datasets of endoscopic biopsies of 37 patients. The results of the present study showed potential biomarkers for GA-related GIM, including GEM of individual patients, individual genes (such as RBP2 and CD44), signaling pathways, network of molecules, and network of signaling pathways with key topological nodes. Accordingly, potential treatment targets with repurposed drugs were identified including epidermal growth factor receptor, proto-oncogene tyrosine-protein kinase Src, paxillin, transcription factor Jun, breast cancer type 1 susceptibility protein, cellular tumor antigen p53, mouse double minute 2, and CD44.

Leveraging recent advancements in machine learning-based flavor tagging, we develop an optimal analysis for measuring the hadronic cross-section ratios R_bRb, R_cRc, and R_sRs at the FCC-ee during its WWWW, ZhZh, and t\bar{t}tt‾ runs. Our results indicate up to a two-order-of-magnitude improvement in precision, providing an unprecedented test of the SM. Using these observables, along with R_\ellRℓ and R_tRt, we project sensitivity to flavor non-universal four-fermion (4F) interactions within the SMEFT, contributing both at the tree-level and through the renormalization group (RG). We highlight a subtle complementarity with RG-induced effects at the FCC-ee’s ZZ-pole. Our analysis demonstrates significant improvements over the current LEP-II and LHC bounds in probing flavor-conserving 4F operators involving heavy quark flavors and all lepton flavors. As an application, we explore simplified models addressing current BB-meson anomalies, demonstrating that FCC-ee can effectively probe the relevant parameter space. Finally, we design optimized search strategies for quark flavor-violating 4F interactions.

Quantization is a powerful tool for accelerating large language model (LLM) inference, but the accuracy-performance trade-offs across different formats remain unclear. In this paper, we conduct the most comprehensive empirical study to date, evaluating FP8, INT8, and INT4 quantization across academic benchmarks and real-world tasks on the entire Llama-3.1 model family. Through over 500,000 evaluations, our investigation yields several key findings: (1) FP8 (W8A8-FP) is effectively lossless across all model scales, (2) well-tuned INT8 (W8A8-INT) achieves surprisingly low (1-3\%) accuracy degradation, and (3) INT4 weight-only (W4A16-INT) is more competitive than expected, rivaling 8-bit quantization. Further, we investigate the optimal quantization format for different deployments by analyzing inference performance through the popular vLLM framework. Our analysis provides clear deployment recommendations: W4A16 is the most cost-efficient for synchronous setups, while W8A8 dominates in asynchronous continuous batching. For mixed workloads, the optimal choice depends on the specific use case. Our findings offer practical, data-driven guidelines for deploying quantized LLMs at scale -- ensuring the best balance between speed, efficiency, and accuracy.

Despite the popularity of large language model (LLM) quantization for inference acceleration, significant uncertainty remains regarding the accuracy-performance trade-offs associated with various quantization formats. We present a comprehensive empirical study of quantized accuracy, evaluating popular quantization formats (FP8, INT8, INT4) across academic benchmarks and real-world tasks, on the entire Llama-3.1 model family. Additionally, our study examines the difference in text generated by quantized models versus their uncompressed counterparts. Beyond benchmarks, we also present a couple of quantization improvements which allowed us to obtain state-of-the-art accuracy recovery results. Our investigation, encompassing over 500,000 individual evaluations, yields several key findings: (1) FP8 weight and activation quantization (W8A8-FP) is lossless across all model scales, (2) INT8 weight and activation quantization (W8A8-INT), when properly tuned, incurs surprisingly low 1-3% accuracy degradation, and (3) INT4 weight-only quantization (W4A16-INT) is competitive with 8-bit integer weight and activation quantization. To address the question of the"best"format for a given deployment environment, we conduct inference performance analysis using the popular open-source vLLM framework on various GPU architectures. We find that W4A16 offers the best cost-efficiency for synchronous deployments, and for asynchronous deployment on mid-tier GPUs. At the same time, W8A8 formats excel in asynchronous"continuous batching"deployment of mid- and large-size models on high-end GPUs. Our results provide a set of practical guidelines for deploying quantized LLMs across scales and performance requirements.

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease’s burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), “lower is better for longer”, and recent data have strongly emphasised the need for also “the earlier the better”. In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of “extremely high-risk” individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy’s effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.

Spherically symmetric Einstein-{\ae}ther (E{\AE}) theory with a Maxwell-like kinetic term is revisited. We consider a general choice of the metric and the \ae{}ther field, finding that:~(i) there is a gauge freedom allowing one always to use a diagonal metric; and~(ii) the nature of the Maxwell equation forces the \ae{}ther field to be time-like in the coordinate basis. We derive the vacuum solution and confirm that the innermost stable circular orbit (ISCO) and photon ring are enlarged relative to general relativity (GR). Buchdahl's theorem in E\AE{} theory is derived. For a uniform physical density, we find that the upper bound on compactness is always lower than in GR. Additionally, we observe that the Newtonian and E\AE{} radial acceleration relations run parallel in the low pressure limit. Our analysis of E\AE{} theory may offer novel insights into its interesting phenomenological generalization: \AE{}ther--scalar--tensor theory ({\AE}ST).

(1) Background: This case study analyzed the successful performances of female gymnasts in the finals of the 39th and 40th World Cup in Maribor (SLO). The aim was to identify variations in their execution of the Clear Hip Circle to Handstand (CHCH) on uneven bars based on kinematic parameters. (2) Methods: This study involved elite female gymnasts from the 39th (n = 5, age: 17 ± 6 months) and 40th (n = 8, age: 17.5 ± 6 months) World Cups, totaling 13 gymnasts. Kinematic analysis was performed on 15 successful routines using the Ariel Performance Analysis System (Ariel Dynamics Inc., San Diego, CA). The analysis focused on 16 anthropometric reference points and 8 body segments, including the body mass center of gravity (CG). The main reference points analyzed were the hip joint, the shoulder joint, and the CG along the xy-axes. Trajectory, velocity, angle, and angular velocity of the hips and shoulders were calculated. Pearson correlation analysis was employed to assess the relationships between the kinematic variables. (3) Results: High intercorrelations between the reference points along the xy-axes (0.81–0.99) and optimal movement velocity were found. Dispersed results were observed for kinematic parameters of angle (0.10–0.16) and angular velocity of the hip joints (0.60–1.00), with similar dispersions for shoulder joints (0.51–1.00). Three distinct techniques were identified: (1) stretched body with minimal hip joint flexion throughout; (2) extended body with a short, quick hip joint extension during shoulder movement; and (3) hyperextension in the hip joint. (4) Conclusions: The kinematic analysis revealed three different performance styles of the CHCH among finalists. These variations in technique do not affect the success of the performance. This research contributes to a better understanding of the technique but does not prefer one style over another.

This paper introduces a control system for Doubly Fed Induction Generator (DFIG) based on a Disturbance Observer (DOB) for island mode operation. The proposed control system is validated through experiments, confirming its effectiveness in maintaining stable operation during island mode. The system responded efficiently to variations in wind speed and load conditions, demonstrating the efficacy of the implemented control scheme. The proposed control system unifies the design approach for both the inner and outer loops of the cascaded control system structure, simplifying implementation and parameter tuning.

Despite recent advances in endovascular therapy, up to half of acute ischemic stroke patients experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction, eTICI<3) after intervention. However, many of these patients will achieve complete delayed reperfusion at the 24h follow‐up, which is linked to good clinical outcome and minimal new infarct development. We aimed to systematically review literature and perform a meta‐analysis on the natural evolution of incomplete reperfusion after endovascular therapy. We conducted a systematic review of MEDLINE, Embase and PubMed up until March 1, 2024 using a predefined search strategy. Only full‐text English written articles reporting rates of either favorable (i.e. delayed reperfusion) or unfavorable progression (i.e. persistent perfusion deficit) of incompletely reperfused tissue were included. Primary outcome was the rates of delayed reperfusion 24h post‐intervention and its association with functional independence (modified Rankin Scale, mRS 0‐2) at 90 days post‐intervention. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random‐effects model. Publication bias was assessed using funnel plots and the Luis Furuya‐Kanamori (LFK) index. Six studies involving 950 patients (50.7% female; median age 71, IQR 60 ‐ 79) were included. Four studies assessed the evolution of incomplete reperfusion on MRI perfusion imaging, while two studies used DWI and NCCT imaging, where new infarct was used to denote unfavorable progression. Complete delayed reperfusion, or absence of new infarct, occurred in 41% (inter‐quartile range, IQR 33% ‐ 51%) of cases 24h post‐intervention. Achieving delayed reperfusion was associated with higher likelihood of functional independence at 90 days (OR 2.53, 95%CI 1.88 ‐ 3.42). No evidence of publication bias was found (LFK=0.2). Nearly half of patients with incomplete reperfusion achieve complete delayed reperfusion, leading to favorable clinical outcomes. This subgroup of eTICI<3 patients may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (e.g. intra‐arterial lytics or secondary distal thrombectomy). Accurately predicting the progression of incomplete reperfusion could optimize patient selection for adjunctive reperfusion attempts at the end of an intervention.

Background/Objectives: The importance of fixed-dose combinations (FDCs) for the treatment of hypertension is well established. However, from a stability perspective, FDCs present a challenge since the degradation of one active pharmaceutical ingredient (API) can be affected by the presence of another API. The aim of this study was to compare the degradation behaviors and evaluate the degradation kinetics of three antihypertensive drugs, perindopril tert-butylamine (PER), amlodipine besylate (AML), and indapamide (IND). Methods: The degradation processes were studied using the previously developed reverse phase high-performance liquid chromatographic (RP-HPLC) method after exposing each drug individually, as well as the combinations of two/three drugs, to different stress factors, such as light, oxidation, acidic, basic, or neutral pH values at different temperatures. Results: The results show that PER is most unstable under basic conditions and that AML displays a negative, while IND displays a positive effect, on PER stability when combined. AML is most affected by basic conditions and oxidation, and its stability is affected by both drugs positively; IND undergoes extreme photolysis, which is positively affected by AML but negatively by PER. Conclusions: Great care must be taken when formulating FDCs with these three drugs, as well as solutions or oral suspensions adjusted for geriatric or pediatric populations, since the stability of all three drugs is greatly affected by pH conditions, as well as light or oxidation factors and their interactions.