Milewski

Severe radiation-induced lymphopenia occurs in 40% of patients treated for primary brain tumors and is an independent risk factor of poor survival outcomes. We developed an in-silico framework that estimates the radiation doses received by lymphocytes during VMAT brain irradiation. 
Approach: We implemented a simulation consisting of two interconnected compartmental models describing the slow recirculation of lymphocytes between lymphoid organs (M_1) and the bloodstream (M_2). We used dosimetry data from 33 patients treated with chemo-radiation for glioblastoma to compare three cases of the model, corresponding to different physical and biological scenarios: H1) lymphocytes circulation only in the bloodstream i...

BACKGROUND: Lupus nephritis (LN) manifests systemic lupus erythematosus (SLE) and is characterized by various clinical and laboratory features. This study aimed to comprehensively evaluate the characteristics of LN patients according to the time of LN diagnosis: early-onset (LN diagnosed within one year from SLE diagnosis) vs. delayed-onset (LN diagnosed more than one year after SLE diagnosis). METHODS: We conducted a retrospective analysis of medical records from all SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022...

BACKGROUND: The rate of concomitant meniscal procedures performed in conjunction with anterior cruciate ligament (ACL) reconstruction is increasing. Few studies have examined these procedures in high-risk pediatric cohorts. HYPOTHESES: That (1) the rates of meniscal repair compared with meniscectomy would increase throughout the study period and (2) patient-related factors would be able to predict the type of meniscal operation, which would differ according to age...

No abstract text is available yet for this article.

Pill aspiration is a significant source of foreign body aspiration in the United States and can occur without swallowing dysfunction or illness. Consequences depend on various factors, such as the pill's chemical composition, size, and diagnostic delay. Aspiration of iron tablets poses a higher risk because of hydroxyl radical formation and subsequent caustic burns, inflammation, obstruction, and/or necrosis. We present a case of a middle-aged obese woman who died 3 weeks after aspirating an iron tablet. Autopsy revealed morbid obesity, a necrotic focus in the right middle lobe of the lung, bronchiolar granulation tissue with iron staining foreign matter, extending into an adjacent arteriole, and mural perforation of the hilar right middle lobe...

To investigate the association between area deprivation index (ADI) and aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Patients aged 40-95 years with severe AS confirmed by echocardiography were included. The 9-digit zip code of patient residence address was used to identify the ADI ranking, based on which patients were divided into 5 groups (with Group E being most deprived). The rates of AV intervention were compared among 5 groups using competing risks analysis, with death as a competing event...

Power-to-Gas (P2G) is considered as a promising energy storage technology in a long-time horizon. The rapid growth in the share of intermittent renewables in the energy mix is driving forward research and development in large-scale energy storage. This paper presents a feasibility analysis of a power-to-gas system in terms of various operating points and capacities. The analysis was performed using a system model, which features a solid oxide electrolyzer (SOE), a CO2 separation unit, and a methanation reactor as the key components...

Optical coherence microscopy (OCM) visualizes nuclei in live, unlabeled cells. As most cells are uninucleated, the number of nuclei in embryos may serve as a proxy of the cell number, providing important information on developmental status of the embryo. Importantly, no other non-invasive method currently allows for the cell number count in compacted embryos. We addressed the question of whether OCM, by providing the number of nuclei in compacted mouse embryos, may help evaluate embryo quality. We subjected compacted embryonic day 3 (E3...

Fusion-positive rhabdomyosarcoma (FP-RMS) is an aggressive pediatric sarcoma driven primarily by the PAX3-FOXO1 fusion oncogene, for which therapies targeting PAX3-FOXO1 are lacking. Here, we screen 62,643 compounds using an engineered cell line that monitors PAX3-FOXO1 transcriptional activity identifying a hitherto uncharacterized compound, P3FI-63. RNA-seq, ATAC-seq, and docking analyses implicate histone lysine demethylases (KDMs) as its targets. Enzymatic assays confirm the inhibition of multiple KDMs with the highest selectivity for KDM3B...

The proper development of embryos strongly depends on the quality of oocytes, so the evaluation of oocytes may be a useful initial step in in vitro fertilization procedures. Additionally, it enables embryologists to make more informed decisions regarding the treatments chosen for the patients and better manage patients' expectations. Optical coherence microscopy (OCM) allows for non-invasive 3D visualization of intracellular structures, such as spindles or nuclei, which have been linked to the success of embryonic development...

Invited for the cover of this issue are the groups and colleagues of Anne-Marie Caminade at the CNRS and University of Toulouse, Evamarie Hey-Hawkins at Leipzig University, and Agustí Lledós from the Autonomous University of Barcelona. The image depicts birds crowned by a carborane competing for access to food, to illustrate the steric hindrance encountered when grafting carboranes to dendrimers (artwork by Dr. Christoph Selg). Read the full text of the article at 10.1002/chem.202303867.

Combining the results of base models to create a meta-model is one of the ensemble approaches known as stacking. In this study, stacking of five base learners, including eXtreme gradient boosting, random forest, feed-forward neural networks, generalized linear models with Lasso or Elastic Net regularization, and support vector machines, was used to study the spatial variation of Mn, Cd, Pb, and nitrate in Qom-Kahak Aquifers, Iran. The stacking strategy proved to be an effective substitute predictor for existing machine learning approaches due to its high accuracy and stability when compared to individual learners...

Mutations of the SCN1A gene, which encodes the voltage-dependent Na+ channel's α subunit, are associated with diverse epileptic syndromes ranging in severity, even intra-family, from febrile seizures to epileptic encephalopathy. The underlying cause of this variability is unknown, suggesting the involvement of additional factors. The aim of our study was to describe the properties of mutated channels and investigate genetic causes for clinical syndromes' variability in the family of five SCN1A gene p...

Several ortho-carboranes bearing a phenoxy or a phenylamino group in the B9 position were prepared employing various protection and deprotection strategies. Following established protocols, dendritic compounds were synthesized from a hexachlorocyclotriphosphazene or thiophosphoryl chloride core, and possible anchoring options for the B9-substituted ortho-carboranes were investigated experimentally and theoretically (DFT). Furthermore, 1- or 1,2-phosphanyl-substituted carborane derivatives were obtained. The resulting diethyl-, diisopropyl-, di-tert-butyl-, diphenyl- or diethoxyphosphines bearing a tunable ortho-carborane moiety are intriguing ligands for future applications in homogeneous catalysis or the medicinal sector...

BACKGROUND: There is an increasing rate of procedures being performed for concomitant injuries during anterior cruciate ligament (ACL) surgery. Few studies have examined risk factors for these associated injuries in young patients. HYPOTHESIS: There are patient-related factors predictive of concomitant knee pathology that differ between age-based cohorts. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Natural language processing was used to extract clinical variables from available notes of patients undergoing ACL surgery between 2000 and 2020 at a single institution (5174 ACL surgeries; mean age, 17 ± 4 years; 53...

Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer...

(1) Background: Lyme borreliosis (LB) is a tick-borne disease known for its diagnostic challenges. Conventional two-tiered testing (CTTT) for antibodies is time-consuming, has low sensitivity in the early stages of disease, and sometimes generates false-positive IgM immunoblots. To tackle this issue, modified two-tiered testing (MTTT) was introduced, incorporating recombinant VlsE and C6 antigens to enhance diagnostic accuracy. (2) Methods: In this prospective study, we enrolled children exhibiting symptoms indicative of LB...

BACKGROUND: Hepatic encephalopathy (HE) symptoms associated with liver insufficiency are linked to the neurotoxic effects of ammonia and other toxic metabolites reaching the brain via the blood-brain barrier (BBB), further aggravated by the inflammatory response. Cumulative evidence documents that the non-coding single-stranded RNAs, micro RNAs (miRs) control the BBB functioning. However, miRs' involvement in BBB breakdown in HE is still underexplored. Here, we hypothesized that in rats with acute liver failure (ALF) or rats subjected to hyperammonemia, altered circulating miRs affect BBB composing proteins...

Recent reports have demonstrated that endothelial injury is critical in the pathogenesis of systemic sclerosis (SSc) and is associated with increased levels of circulating inflammatory biomarkers. This study aims to analyze the serum concentrations of selected cytokines and evaluate their relationship with SSc clinics and the long-term course of the disease. This study included 43 SSc patients and 24 matched healthy controls. In both groups, we measured serum levels of inflammatory cytokines related to the inflammatory response, such as tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)-4, IL-6, IL-10, and IL-17, and fibroblast activation protein (FAP)...

This paper focuses on the role of n-3 fatty acids as a nutrient crucial to the proper functioning of reproductive and immune systems in cattle. Emphasis was placed on the connection between maternal and offspring immunity. The summarized results confirm the importance and beneficial effect of n-3 family fatty acids on ruminant organisms. Meanwhile, dietary n-3 fatty acids supplementation, especially during the critical first week for dairy cows experiencing their peripartum period, in general, is expected to enhance reproductive performance, and the impact of its supplementation appears to be dependent on body condition scores of cows during the drying period, the severity of the negative energy balance, and the amount of fat in the basic feed ration...