Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene, located on chromosome 16 (16p13.3) and encoding the pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of the pathological processes leading to the spontaneous and recurrent autoinflammatory attacks observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool to study the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs from an Armenian patient with FMF carrying the M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. We found that the morphology of macrophages derived from iPSCs of a patient with the MEFV mutation significantly differed from that of macrophages derived from iPSCs of a healthy donor carrying the wild-type MEFV gene. Full article

Current United States Preventive Services Task Force (USPSTF) recommendations include routine screening for breast, cervical, colorectal, and lung cancer; however, two out of every three cancer cases occur in other indications, leading to diagnoses in advanced stages of the disease and a higher likelihood of mortality. Blood-based multi-cancer early detection (MCED) tests can impact cancer screening and early detection by monitoring for multiple different cancer types at once, including indications where screening is not performed routinely today. We conducted a survey amongst healthcare providers (HCPs), payers, and patients within the U.S. health system to understand the current utilization of cancer screening tests and the anticipated barriers to widespread adoption of blood-based MCED tests. The results indicated that the community favors the adoption of blood-based MCED tests and that there is broad agreement on the value proposition. Despite this recognition, the survey highlighted that there is limited use today due to the perceived lack of clinical accuracy and utility data, high out-of-pocket patient costs, and lack of payer coverage. To overcome the hurdles for future widespread adoption of blood-based MCED tests, increased investment in data generation, education, and implementation of logistical support for HCPs will be critical. Full article

Cu²⁺ has increasingly become a great threat to the natural environment and human health due to its abundant content and wide application in various industries. DL-Mercaptosuccinic acid and ZnS-modified Fe₃O₄ nanocomposites were designed, synthesized, and applied in the determination of Cu²⁺. The prepared nanocomposites were characterized by scanning electron microscopy (SEM), transmission electron microscopes (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), and thermogravimetric analyzer (TG). The magnetic fluorescent nanoprobe exhibited highly selective and sensitive fluorescence-quenching characteristics with Cu²⁺ ions. The fluorescence detection linear range was 0–400 μM, with the detection limit being 0.489 μM. In addition, the magnetic fluorescent nanoprobe exhibited a high adsorption and removal rate for Cu²⁺. It had been successfully applied to detect Cu²⁺ in real water samples with a satisfactory recovery rate. The magnetic fluorescent nanoprobe could simultaneously realize the functions of enrichment, quantitative detection, and separation, reduce the pollution of copper ions and probes, and establish an environment-friendly detection method. Consequently, the magnetic fluorescent nanoprobe offered a new pathway for the removal and detection of not only Cu²⁺ but also other heavy metal ions in water. Full article

Pathogens that adapt to environmental stress can develop an increased tolerance to some physical or chemical antimicrobial treatments. The main objective of this study was to determine if acid adaptation increased the tolerance of Escherichia coli O157:H7 to high voltage atmospheric cold plasma (HVACP) in raw pineapple juice. Samples (10 mL) of juice were inoculated with non-acid-adapted (NAA) or acid-adapted (AA) E. coli to obtain a viable count of ~7.00 log₁₀ CFU/mL. The samples were exposed to HVACP (70 kV) for 1–7 min, with inoculated non-HVACP-treated juice serving as a control. Juice samples were analyzed for survivors at 0.1 h and after 24 h of refrigeration (4 °C). Samples analyzed after 24 h exhibited significant decreases in viable NAA cells with sub-lethal injury detected in both NAA and AA survivors (p < 0.05). No NAA survivor in juice exposed to HVACP for 5 or 7 min was detected after 24 h. However, the number of AA survivors was 3.33 and 3.09 log₁₀ CFU/mL in juice treated for 5 and 7 min, respectively (p < 0.05). These results indicate that acid adaptation increases the tolerance of E. coli to HVACP in pineapple juice. The potentially higher tolerance of AA E. coli O157:H7 to HVACP should be considered in developing safe juice processing parameters for this novel non-thermal technology. Full article

The heterogeneity of etiology may serve as a crucial factor in the challenges of treatment, including the low response rate and the delay in establishing therapeutic effect. In the present study, we examined whether social experience since early life is one of the etiologies, with the involvement of the 5-HT1A receptors, and explored the potentially therapeutic action of the subchronic administration of buspirone, a partial 5-HT1A agonist. Rats were isolation reared (IR) since their weaning, and the depressive profile indexed by the forced-swim test (FST) was examined in adulthood. Nonspecific locomotor activity was used for the IR validation. Buspirone administration (1 mg/kg/day) was introduced for 14 days (week 9–11). The immobility score of the FST was examined before and after the buspirone administration. Tissue levels of serotonin (5-HT) and its metabolite 5-HIAA were measured in the hippocampus, the amygdala, and the prefrontal cortex. Efflux levels of 5-HT, dopamine (DA), and norepinephrine (NE) were detected in the hippocampus by brain dialysis. Finally, the full 5-HT1A agonist 8-OH-DPAT (0.5 mg/kg) was acutely administered in both behavioral testing and the dialysis experiment. Our results showed (i) increased immobility time in the FST for the IR rats as compared to the social controls, which could not be reversed by the buspirone administration; (ii) IR-induced FST immobility in rats receiving buspirone was corrected by the 8-OH-DPAT; and (iii) IR-induced reduction in hippocampal 5-HT levels can be reversed by the buspirone administration. Our data indicated the 5-HT1A receptor-linked early life social experience as one of the mechanisms of later life depressive mood. Full article

In this review, we aim to provide a summary of the diverse immunophenotypic presentations of distinct entities associated with plasmacytoid dendritic cell (pDC) proliferation. These entities include the following: (1) blastic plasmacytoid dendritic cell neoplasm (BPDCN); (2) mature pDC proliferation (MPDCP), most commonly seen in chronic myelomonocytic leukemia (CMML); and (3) myeloid neoplasms with pDC differentiation, in which pDCs show a spectrum of maturation from early immature pDCs to mature forms, most commonly seen in acute myeloid leukemia (pDC-AML). Our aim is to provide a flow cytometry diagnostic approach to these distinct and sometimes challenging entities and to clarify the immunophenotypic spectrum of neoplastic pDCs in different disease presentations. In this review, we also cover the strategies in the evaluation of residual disease, as well as the challenges and pitfalls we face in the setting of immune and targeted therapy when evaluating residual disease by flow cytometry. The differential diagnosis will also be discussed, as blasts in some AML cases can have a pDC-like immunophenotype, mimicking pDCs. Full article

Bloodstream infections (BSI) caused by multidrug-resistant (MDR) bacteria, pose a major threat for patients, especially for those who are immunosuppressed. Rapid pathogen detection and characterization from positive blood cultures are crucial in the management of patients with BSI to enable an adequate and timely antimicrobial therapy. This study aimed to investigate the potential role of the Molecular Mouse system, a new CE IVD molecular test designed to rapidly detect the causative agents of bacteremia and their resistance determinants, in the management of the therapy in critically ill patients. Agreement between the results of the Molecular Mouse and the conventional routine method was also considered. Overall, 100 positive blood cultures were collected from septic critically ill patients from May 2023 to January 2024 and analyzed with Molecular Mouse and routine protocols. The new instrument consistently agreed with the routine protocols in the case of monomicrobial blood cultures, while some discrepancies were obtained in the polymicrobial samples. Antimicrobial resistance genes were detected in 35 samples, with vanA and CTX-M-1/9 groups being the most frequently detected targets. Therapy was adjusted in 42 critically ill patients confirming the importance of new rapid molecular tests in the management of positive blood cultures, to adjust empirical therapy and use new antibiotics accurately. Full article

This study aimed to determine the absolute and relative reliability of concentric and eccentric flexion, extension, horizontal abduction, and adduction movements of the shoulder using a functional electromechanical dynamometer (FEMD). Forty-three active male university students (23.51 ± 4.72 years) were examined for concentric and eccentric strength of shoulder flexion, extension, horizontal abduction, and horizontal adduction with an isokinetic test at 0.80 m·s⁻¹. Relative reliability was determined by intraclass correlation coefficients (ICCs) with 95% confidence intervals. Absolute reliability was quantified by the standard error of measurement (SEM) and coefficient of variation (CV). Reliability was very high to extremely high for all movements on concentric and eccentric strength measurements (ICC: 0.76–0.94, SEM: 0.63–6.57%, CV: 9.40–19.63%). The results of this study provide compelling evidence for the absolute and relative reliability of concentric and eccentric flexion, extension, horizontal abduction, and horizontal adduction shoulder isokinetic strength tests in asymptomatic adults. The mean concentric force was the most reliable strength value for all tests. Full article

Michael acceptors represent a class of compounds with potential anti-cancer properties. They act by binding to nucleophilic sites in biological molecules, thereby disrupting cancer cell function and inducing cell death. This mode of action, as well as their ability to be modified and targeted, makes them a promising avenue for advancing cancer therapy. We are investigating the molecular mechanisms underlying Michael acceptors and their interactions with cancer cells, in particular their ability to interfere with cellular processes and induce apoptosis. The anti-cancer properties of Michael acceptors are not accidental but are due to their chemical structure and reactivity. The electrophilic nature of these compounds allows them to selectively target nucleophilic residues on disease-associated proteins, resulting in significant therapeutic benefits and minimal toxicity in various diseases. This opens up new perspectives for the development of more effective and precise cancer drugs. Nevertheless, further studies are essential to fully understand the impact of our discoveries and translate them into clinical practice. Full article

While technical optimization focuses on maximizing the annual energy yield of utility-scale PV parks, the ultimate goal for power plant owners is to maximize investment profit. This paper aims to bridge the gap between technical and economic approaches by using simulation data from a real-case utility-scale PV park. It analyzes how changes in configuration parameters such as the DC–AC ratio and string length and PV technologies like solar tracking systems and bifacial modules impact the economic metrics of the project, i.e., net present value (NPV) and internal rate of return (IRR). PVSyst software was utilized as a simulation tool, while in-house developed software implementing appropriate technical and economic models served as a comparison platform and was used to validate the outputs generated through PVSyst. Results indicate that the commonly used horizontal single-axis tracking configuration may economically underperform compared with fixed-tilt setups. The optimal DC–AC ratio fell within the range of 1.30 to 1.35. Extending the string length from 25 to 28 modules improved economic indexes. Additionally, fixed-tilt bifacial modules can enhance project economics if a 10% cost premium compared with standard monofacial PV modules is considered. Full article

With the impact of size on low-pressure turbines (LPTs) increasing, the gap between the blades has shrunk, inevitably influencing the unsteady effects inside the turbine. In this study, the aerodynamic effect of the blade gap size is investigated using a compressible unsteady Reynolds-averaged Navier–Stokes (URANS) model on the basis of a four-stage LPT. Simulations are conducted in which the gap between the third-stage stator (S3) and rotor (R3) varies from 0.2 to 0.8 times the axial chord length of the R3 blade. The multi-stage environment reflects the complexity of real low-Reynolds flow fields. Computational fluid dynamics is used to analyze the flow field in detail. The results demonstrate that in the small-gap (AG-0.2) case, the turbulence kinetic energy (TKE) level of the S3 wake close to the R3 leading edge is four-thirds of that in the large-gap (AG-0.8) case. The higher intensity of the wake impacting on the blade results in a higher inverse pressure gradient in the rear part of the R3 suction surface, which increases the profile loss. However, the AG-0.2 case leads to fewer losses caused by the passage vortex in the hub area under the influence of the higher intensity of the wake. Full article

This article presents the research results of depositing anti-friction coatings (Babbitt) using three different casting methods: static casting, flame soldering, and clad welding. Babbitt alloy coatings deposited with different casting methods are discussed and explained in terms of changes in the coating properties, such as the microstructure, hardness, strength, and chemical composition. The results showed significant differences in the aforementioned properties, depending on the chosen coating deposition method. The results of the tests confirmed the importance of using shielding gas during deposition to ensure the chemical composition of the coating. The analysis revealed that decreases in the amounts of antimony and copper in the Babbitt coating compared with the initial concentrations were influenced by selective evaporation, oxidation, and the coating process parameters associated with different coating methods. To maintain the desired balance of mechanical properties in Babbitt coatings, it is important to control the antimony and copper contents. Clad welding deposition using a non-consumable tungsten electrode and argon shielding gas achieved a chemically stable coating quite close to the initial chemical composition of the Babbitt alloy. Full article

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients’ survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI. The accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed to develop a prognostic model to evaluate the tumor progression potential of GBM patients following standard therapies. We applied a dictionary learning scheme to obtain imaging features of GBM patients with PsP or true tumor progression (TTP) from the Wake dataset. Based on these radiographic features, we conducted a radiogenomics analysis to identify the significantly associated genes. These significantly associated genes were used as features to construct a 2YS (2-year survival rate) logistic regression model. GBM patients were classified into low- and high-survival risk groups based on the individual 2YS scores derived from this model. We tested our model using an independent The Cancer Genome Atlas Program (TCGA) dataset and found that 2YS scores were significantly associated with the patient’s overall survival. We used two cohorts of the TCGA data to train and test our model. Our results show that the 2YS scores-based classification results from the training and testing TCGA datasets were significantly associated with the overall survival of patients. We also analyzed the survival prediction ability of other clinical factors (gender, age, KPS (Karnofsky performance status), normal cell ratio) and found that these factors were unrelated or weakly correlated with patients’ survival. Overall, our studies have demonstrated the effectiveness and robustness of the 2YS model in predicting the clinical outcomes of GBM patients after standard therapies. Full article

Fire is one of the biggest threats to the safety of utility tunnels, and establishing camera-based monitoring systems is conducive to early fire finding and better understanding of the evolution of tunnel fires. However, conventional monitoring systems are being faced with the challenge of high energy consumption. In this paper, the camera operation in a utility tunnel was optimized considering both fire risk and energy consumption. Three design variables were investigated, namely the camera sight, the number of cameras in simultaneous operation, and the duration of camera operation. Cellular automata were used as a simple but effective method to simulate the spread of fire in a utility tunnel. Results show that as the number of cameras in simultaneous operation increases, the probability of fire capture also increases, but the energy consumption decreases. A shorter duration of camera operation can lead to a higher probability of fire capture, and meanwhile, lower energy consumption. For the duration of camera operation shorter than or equal to the allowable time, the probability of fire capture is significantly higher than that for the duration longer than the allowable time. Increasing the camera sight will significantly increase the probability of fire capture and lower the total energy consumption when a blind monitoring area exists. The total energy consumption of a camera-based monitoring system roughly satisfies hyperbolic correlation with the duration of camera operation, while the probability of fire capture can be predicted based on the number of cameras in simultaneous operation through a power model. The optimal design for the modeled tunnel section is two cameras in simultaneous operation with a tangent monitoring area. The duration of camera operation should be as short as possible, at least shorter than the allowable time. The study is expected to provide a reference for the sustainable design of energy-saving utility tunnels with lower fire risk. Full article

Environmental pollution caused by organic effluents emitted by industry has become a worldwide issue and poses a serious threat to the public and the ecosystem. Metal–organic frameworks (MOFs), comprising metal-containing clusters and organic bridging ligands, are porous and crystalline materials, possessing fascinating shape and size-dependent properties such as high surface area, abundant active sites, well-defined crystal morphologies, and huge potential for surface functionalization. To date, numerous well designated MOFs have emerged as critical functional materials to solve the growing challenges associated with water environmental issues. Here we present the recent progress of MOF-based materials and their applications in the treatment of organic effluents. Firstly, several traditional and emerging synthesis strategies for MOF composites are introduced. Then, the structural and functional regulations of MOF composites are presented and analyzed. Finally, typical applications of MOF-based materials in treating organic effluents, including chemical, pharmaceutical, textile, and agricultural wastewaters are summarized. Overall, this review is anticipated to tailor design and regulation of MOF-based functional materials for boosting the performance of organic effluent remediation. Full article

We present a pulse-preserving multilayer-based extreme-ultraviolet (XUV) monochromator providing ultra-narrow bandwidth ($\Delta E<0.6\mathrm{eV}$, $E_{\mathrm{c}}=92\mathrm{eV}$) and compact footprint ($28\times 10{\mathrm{cm}}^2$) for easy integration into high-harmonic generation (HHG) or free-electron laser (FEL) sources. The temporal resolution of the novel design supports pulse durations of typical pump–probe setups in the femtosecond and attosecond regime, depending on the mirror design and focusing geometries over the tuning range of the monochromator. The theoretical design is analyzed and experimentally characterized in a laser-driven HHG setup. Full article

Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries. Full article

This study was conducted on SAC105 (Sn-1wt.%Ag-0.5wt.%Cu) lead-free solder modified with Bi and Sb. The wetting, melting point, and mechanical properties were analysed with the addition of 1~5 wt.%Bi and 1~5 wt.%Sb for SAC105 base alloy. The wetting characteristics were assessed by wetting time (zero cross time, ZCT) obtained from wetting balance tests. The mechanical properties were analysed by tensile tests. Considering two factors (Bi, Sb), a three-level (0, 1, 2 wt.%) design of experiment (DOE) method array was applied for Taguchi optimization. The results indicated that the solder wetting increased as Bi content increased, while it decreased with Sb. The ZCT decreased with increasing Bi content up to 4 wt.%, while it increased proportionally to Sb content. The melting point, measured using a differential scanning calorimeter (DSC), showed that the melting point tended to decrease according to Bi increase, while it increases depending on the Sb content. Increase in Bi and Sb levels resulted in enhanced tensile strength in the mechanical properties tests, with Bi having a more noticeable impact. The Taguchi optimized conditions for the Bi and Sb studies were found to be 2 wt.%Bi and 2 wt.%Sb. This led to an optimal set of 0.9 s of wetting time, a 222.55 °C melting point, a 55 MPa tensile strength, and a 50% elongation. Full article

Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes. Full article

Fetal cardiology has evolved over the last 40 years and changed the timing of diagnosis and counseling of congenital heart disease, decision-making, planning for treatment at birth, and predicting future surgery from the postnatal to the prenatal period. Ethical issues in fetal cardiology transect multiple aspects of biomedical ethics including improvement in prenatal detection and diagnostic capabilities, access to equitable comprehensive care that preserves a pregnant person’s right to make decisions, access to all reproductive options, informed consent, complexity in shared decision-making, and appropriate use of fetal cardiac interventions. This paper first reviews the literature and then provides an ethical analysis of accurate and timely diagnosis, equitable delivery of care, prenatal counseling and shared decision-making, and innovation through in utero intervention. Full article

Worsening wildfire seasons in recent years are reversing decadal progress on the reduction of harmful air pollutants in the US, particularly in Western states. Measurements of the contributions of wildfire smoke to ambient air pollutants, such as fine particulate matter (PM_2.5), at fine resolution scales would be valuable to public health research on climate vulnerable populations and compound climate risks. We estimate the influence of wildfire smoke emissions on daily PM_2.5 at fine-resolution, 3 km, for California 2011–2020, using a geostatistical modeled ambient PM_2.5 estimate and wildfire smoke plume data from NOAA Hazard Mapping System. Additionally, we compare this product with the US Environmental Protection Agency (EPA) daily and annual standards for PM_2.5 exposure. Our results show wildfires significantly influence PM_2.5 in California and nearly all exceedances of the daily US EPA PM_2.5 standard were influenced by wildfire smoke, while annual exceedances were increasingly attributed to wildfire smoke influence in recent years. This wildfire-influenced PM_2.5 product can be applied to public health research to better understand source-specific air pollution impacts and assess the combination of multiple climate hazard risks. Full article