Search Results (5,077)

Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT₃), free thyroxine (fT₄), total triiodothyronine (tT₃), total thyroxine (tT₄) and reverse triiodothyronine (rT₃). We additionally calculated the total activity of peripheral deiodinases (G_D) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral G_D activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article

This study was designed to systematically identify novel umami peptides in lager beer, clarify their molecular interactions with the T1R1/T1R3 receptor, and determine their specific effects on multidimensional sensory attributes. The peptides were characterized by LC-MS/MS combined with de novo sequencing, and 906 valid sequences were obtained. Machine-learning models (UMPred-FRL, Tastepeptides-Meta, and Umami-MRNN) predicted 76 potential umami peptides. These candidates were docked to T1R1/T1R3 with the CDOCKER protocol, producing 57 successful complexes. Six representative peptides—KSTEL, DELIK, DIGISSK, IEKYSGA, DEVR, and PVPL—were selected for 100 ns molecular-dynamics simulations and MM/GBSA binding-energy calculations. All six peptides stably occupied the narrow cleft at the T1R1/T1R3 interface. Their binding free energies ranked as DEVR (−44.09 ± 5.47 kcal mol⁻¹) < KSTEL (−43.21 ± 3.45) < IEKYSGA (−39.60 ± 4.37) ≈ PVPL (−39.53 ± 2.52) < DELIK (−36.14 ± 3.11) < DIGISSK (−26.45 ± 4.52). Corresponding taste thresholds were 0.121, 0.217, 0.326, 0.406, 0.589, and 0.696 mmol L⁻¹ (DEVR < KSTEL < IEKYSGA < DELIK < PVPL < DIGISSK). TDA-based sensory validation with single-factor additions showed that KSTEL, DELIK, DEVR, and PVPL increased umami scores by ≈21%, ≈22%, ≈17%, and ≈11%, respectively, while DIGISSK and IEKYSGA produced marginal changes (≤2%). The short-chain peptides thus bound with high affinity to T1R1/T1R3 and improved core taste and mouthfeel but tended to amplify certain off-flavors, and the long-chain peptides caused detrimental impacts. Future formulation optimization should balance flavor enhancement and off-flavor suppression, providing a theoretical basis for targeted brewing of umami-oriented lager beer. Full article

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

Background and Significances: In patients with Epstein–Barr virus-driven hemophagocytic lymphohistiocytosis (EBV-HLH), identifying the underlying cause poses a significant diagnostic challenge. HLH may precede overt disease, and early directed treatment for HLH can obscure histopathological findings. A liquid biopsy enables the detection of tumor-derived DNA from various sources, including cell-free DNA, circulating tumor cells, extracellular vesicles, and tumor-educated platelets, and might aid in this setting. Case Presentation: This case presents a young patient with EBV-HLH, in which genomic analysis of tumor-derived DNA from circulating tumor cells led to the diagnosis of an EBV-positive NK/T-cell lymphoma—where conventional tissue biopsies had failed. Conclusions: This report underscores the potential of the liquid biopsy as a valuable diagnostic tool in complex cases of EBV-HLH. Full article

Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic accuracy of standard bone age (BA) methods remains uncertain in this context. Objective: To compare the diagnostic accuracy of the Greulich–Pyle atlas (GPA) and Tanner–Whitehouse 3 (TW3) methods in estimating skeletal age in girls with CPP and to assess the predictive value of serum hormone levels for estimating chronological age (CA). Methods: An observational, cross-sectional diagnostic study was conducted, involving n = 109 girls aged 6–12 years with confirmed CPP (Ethics Committee approval: CHUC_2023_86; 13 July 2023). Left posteroanterior hand–wrist (PA–HW) radiographs were assessed using the GPA and TW3 methods. Anthropometric measurements were recorded, and serum concentrations of estradiol, LH, FSH, DHEA-S, cortisol, TSH, and free T4 were obtained. Comparisons between CA and BA estimates were conducted using repeated-measures ANOVA, and ANCOVA was applied to examine the hormonal predictors of CA. Results: Both GPA and TW3 overestimated CA between 7 and 12 years, with the GPA showing larger deviations (up to 4.8 months). The TW3 method provided more accurate estimations, particularly at advanced pubertal stages. Estradiol (η²_p = 0.188–0.197), LH (η²_p = 0.061–0.068), and FSH (η²_p = 0.008–0.023) emerged as the strongest endocrine predictors of CA, significantly enhancing the explanatory power of both radiological methods. Conclusions: The TW3 method demonstrated superior diagnostic accuracy over GPA in girls with CPP, especially between 7 and 12 years. Integrating estradiol, LH, and FSH into BA assessment significantly improved the accuracy, supporting a more individualized and physiologically grounded diagnostic approach. Full article

Via a One Health approach, this study concomitantly assessed the susceptibility of humans and dogs to Trypanosoma cruzi infections on three islands and in two mainland seashore areas of southern Brazil. Human serum samples were tested using an enzyme-linked immunosorbent assay (ELISA) to detect anti-T. cruzi antibodies, while dog serum samples were tested using indirect fluorescent antibodies in an immunofluorescence assay (IFA). Seropositive human and dog individuals were also tested using quantitative polymerase chain reaction (qPCR) in corresponding blood samples. Overall, 2/304 (0.6%) human and 1/292 dog samples tested seropositive for T. cruzi by ELISA and IFA, respectively, and these cases were also molecularly positive for T. cruzi by qPCR. Although a relatively low positivity rate was observed herein, these cases were likely autochthonous, and the individuals may have been infected as a consequence of isolated events of disturbance in the natural peridomicile areas nearby. Such a disturbance could come in the form of a fire or deforestation event, which can cause stress and parasitemia in wild reservoirs and, consequently, lead to positive triatomines. In conclusion, T. cruzi monitoring should always be conducted in suspicious areas to ensure a Chagas disease-free status over time. Further studies should also consider entomological and wildlife surveillance to fully capture the transmission and spread of T. cruzi on islands and in seashore mainland areas of Brazil and other endemic countries. Full article

Objective: The objective of this study was to assess changes in body composition, with a specific focus on fat mass (FM) and fat-free mass (FFM), in obese adults with type 2 diabetes (T2D) treated with once-weekly (OW) subcutaneous (s.c.) semaglutide. Methods: This was a single-center, 12-month, real-world, ambispective study (6-month prospective and 6-month retrospective). Body composition parameters were assessed via segmental multifrequency bioelectrical impedance analysis (SMF-BIA). Results: A total of 117 patients with DM2, with a median age of 56 years, a median HbA1c level of 9.4%, and a median body weight of 102.5 kg, were included in the study. The median body weight, body fat mass, and visceral fat significantly decreased at 6 months, with values of −9.3, −7.5, and −1.8 kg, respectively. There were further reductions from 6 to 12 months, albeit at a slower rate. The median skeletal muscle mass significantly decreased at 6 months (−1.2 kg), although no further significant reductions were observed at 12 months. Conclusions: OW s.c. semaglutide for 12 months significantly improved body composition parameters, mainly at the expense of fat mass loss, with the preservation of skeletal muscle mass. These changes are clinically meaningful, since they impact general metabolic health and are associated with improvements in metabolic control and clinical parameters associated with renal and CV risks, as well as presumable improvements in quality of life. Full article

The article presents a new AM (Additive Manufacturing) process development, necessary to repair parts made from Aluminum 6061 material, with T6 treatment. The laser Directed Energy Deposition (DED) and Extreme High-Speed Directed Energy Deposition (EHLA) capabilities are evaluated for repairing Al large components. To optimize the process parameters, single-track depositions were analyzed for both laser-powder DED (feed rate of 2 m/min) and EHLA (feed rate 20 m/min) for AlSi10Mg and Al6061 powders. The cross-sections of single tracks revealed the bonding characteristics and provided laser-powder DED, a suitable parameter selection for the repair. Three damage types were identified on the Al component to define the specification of the repair process and to highlight the capabilities of laser-powder DED and EHLA in repairing intricate surface scratches and dents. Our research is based on variation of the powder mass flow and beam power, studying the influence of these parameters on the weld bead geometry and bonding quality. The evaluation criteria include bonding defects, crack formation, porosity, and dilution zone depth. The bidirectional path planning strategy was applied with a fly-in and fly-out path for the hatching adjustment and acceleration distance. Samples were etched for a qualitative microstructure analysis, and the HV hardness was tested. The novelty of the paper is the new process parameters for laser-powder DED and EHLA deposition strategies to repair large Al components (6061 T6), using AlSi10Mg and Al6061 powder. Our experimental research tested the defect-free deposition and the compatibility of AlSi10Mg on the Al6061 substrate. The readers could replicate the method presented in this article to repair by laser-powder DED/EHLA large Al parts and avoid the replacement of Al components with new ones. Full article

Coyaima is a town in the department of Tolima, Colombia, that was prioritized in a pilot program under Colombia’s National Plan for the Control of the Taeniasis/Cysticercosis Complex, focusing on this neglected health issue. The project engaged local indigenous communities, promoting education and outreach within the One Health framework. The study included 444 randomly selected volunteers, who filled a Knowledge, Attitudes, and Practices (KAP) survey on the taeniasis/cysticercosis complex. The baseline study found no Taenia spp. eggs via microscopy on 383 stool samples examined, and no T. solium DNA was detected on human stool and soil samples by Copro-qPCR. However, seroprevalence was 8.5% for human cysticercosis and 14% for porcine cysticercosis, as detected by in-house ELISA testing for T. solium. Moreover, 57.9% of participants who provided a stool sample were positive for at least one parasite. Following the sampling and characterization activities, local health workers implemented mass treatment with Niclosamide, based on evidence of ongoing transmission, high porcine seroprevalence, poor basic sanitation, and the presence of free-roaming pigs reported in the KAP survey. These findings provide scientific evidence to apply national public health policies for controlling taeniasis/cysticercosis complex in Coyaima. Full article

Accounting for 15–30% of colorectal cancer cases, the serrated pathway remains poorly characterized compared to the adenoma–carcinoma sequence. It involves sessile serrated lesions as precursors and is characterized by BRAF mutations (BRAF^V600E), CpG island hypermethylation, and microsatellite instability (MSI). Using label-free proteomics, we compared normal tissue margins from patients with diverticular disease, sessile serrated lesions, low-grade adenomas, and high-grade adenomas. We identified S100A14 as significantly overexpressed in sessile serrated lesions compared to low-grade adenomas, high-grade adenomas, and normal tissues. This overexpression was confirmed by immunohistochemical scoring in an independent cohort. Gene expression analyses of public datasets showed higher S100A14 expression in BRAF^V600E-mutated and MSI-H colorectal cancers compared to microsatellite stable BRAF^wt tumors. This finding was confirmed by immunohistochemical scoring in an independent colorectal cancer cohort. Furthermore, single-cell RNA sequencing analysis from the Human Colon Cancer Atlas revealed that S100A14 expression in tumor cells positively correlated with the abundance of tumoral CD8⁺ cytotoxic T cells, particularly the CD8⁺ CXCL13⁺ subset, known for its association with a favorable response to immunotherapy. Collectively, our results demonstrate for the first time that S100A14 is a potential biomarker of serrated neoplasia and further suggests its potential role in predicting immunotherapy responses in colorectal cancer. Full article

The widespread adoption of the Internet of Things (IoT) has driven major advancements in wireless communication, especially in rural and suburban areas where low population density and limited infrastructure pose significant challenges. Accurate Path Loss (PL) prediction is critical for the effective deployment and operation of Wireless Sensor Networks (WSNs) in such environments. This study explores the use of Convolutional Neural Networks (CNNs) for PL modeling, utilizing a comprehensive dataset collected in a smart campus setting that captures the influence of terrain and environmental variations. Several CNN architectures were evaluated based on different combinations of input features—such as distance, elevation, clutter height, and altitude—to assess their predictive accuracy. The findings reveal that CNN-based models outperform traditional propagation models (Free Space Path Loss (FSPL), Okumura–Hata, COST 231, Log-Distance), achieving lower error rates and more precise PL estimations. The best performing CNN configuration, using only distance and elevation, highlights the value of terrain-aware modeling. These results underscore the potential of deep learning techniques to enhance IoT connectivity in sparsely connected regions and support the development of more resilient communication infrastructures. Full article

Aloe vera gel is a valuable raw material used in the cosmetic industry for its skin care properties. The present study analyzed the effects of the fermentation of aloe vera gel with a tea fungus kombucha, which is a symbiotic consortium of bacteria and yeast, carried out for 10 and 20 days (samples F10 and F20, respectively). The resulting ferments and unfermented gel were subjected to chromatographic analysis to determine the content of biologically active compounds. The permeability and accumulation of these compounds in pig skin were evaluated. In addition, the methods of DPPH, ABTS and the determination of intracellular free radical levels in keratinocytes (HaCaT) and fibroblasts (HDF) cell lines were used to determine antioxidant potential. The results showed a higher content of phenolic acids and flavonoids and better antioxidant properties of the ferments, especially after 20 days of fermentation. Cytotoxicity tests against HaCaT and HDF cells confirmed the absence of toxic effects; moreover, samples at the concentrations tested (mainly 10 and 25 mg/mL) showed cytoprotective effects. The analysis of enzymatic activity (collagenase, elastase and hyaluronidase) by the ELISA technique showed higher levels of inhibition for F10 and F20. The kombucha ferments also exhibited better moisturizing properties and lower levels of transepidermal water loss (TEWL), confirming their cosmetic potential. Full article

Background/Objectives: Global warming and rising CO₂ concentrations pose significant challenges to plant systems. Amid these pressures, this study contributes to understanding how tropical species respond by simultaneously evaluating reproductive and genetic traits. It specifically investigates the effects of maternal exposure to warming and elevated CO₂ on progeny physiology, genetic diversity, and population structure in Stylosanthes capitata, a resilient forage legume native to Brazil. Methods: Maternal plants were cultivated under controlled treatments, including ambient conditions (control), elevated CO₂ at 600 ppm (eCO₂), elevated temperature at +2 °C (eTE), and their combined exposure (eTEeCO₂), within a Trop-T-FACE field facility (Temperature Free-Air Controlled Enhancement and Free-Air Carbon Dioxide Enrichment). Seed traits (seeds per inflorescence, hundred-seed mass, abortion, non-viable seeds, coat color, germination at 32, 40, 71 weeks) and abnormal seedling rates were quantified. Genetic diversity metrics included the average (A) and effective (Ae) number of alleles, observed (Ho) and expected (He) heterozygosity, and inbreeding coefficient (Fis). Population structure was assessed using Principal Coordinates Analysis (PCoA), Analysis of Molecular Variance (AMOVA), number of migrants per generation (Nm), and genetic differentiation index (Fst). Two- and three-way Analysis of Variance (ANOVA) were used to evaluate factor effects. Results: Compared to control conditions, warming increased seeds per inflorescence (+46%), reduced abortion (−42.9%), non-viable seeds (−57%), and altered coat color. The germination speed index (GSI +23.5%) and germination rate (Gr +11%) improved with warming; combined treatments decreased germination time (GT −9.6%). Storage preserved germination traits, with warming enhancing performance over time and reducing abnormal seedlings (−54.5%). Conversely, elevated CO₂ shortened GSI in late stages, impairing germination efficiency. Warming reduced Ae (−35%), He (−20%), and raised Fis (maternal 0.50, progeny 0.58), consistent with the species’ mixed mating system; A and Ho were unaffected. Allele frequency shifts suggested selective pressure under eTE. Warming induced slight structure in PCoA, and AMOVA detected 1% (maternal) and 9% (progeny) variation. Fst = 0.06 and Nm = 3.8 imply environmental influence without isolation. Conclusions: Warming significantly shapes seed quality, reproductive success, and genetic diversity in S. capitata. Improved reproduction and germination suggest adaptive advantages, but higher inbreeding and reduced diversity may constrain long-term resilience. The findings underscore the need for genetic monitoring and broader genetic bases in cultivars confronting environmental stressors. Full article

The development of technology has driven a rising need for high-accuracy and high-efficiency manufacturing of low-volume products. Incremental forming technology, characterized by die-free flexibility and low production costs, can effectively replace stamping processes for manufacturing customized small-batch products. However, high-performance aluminum alloys generally exhibit poor room-temperature plasticity but excellent high-temperature plasticity, necessitating the integration of thermal-assisted methods for manufacturing such products. However, the temperature of the forming region will excessively rise without temperature control, which will affect the forming performance of the material in hot incremental sheet forming of AA2024-T4 aluminum alloy. This study focuses on AA2024-T4 aluminum alloy and proposes a uniform temperature control method for the electric hot tube-assisted incremental sheet forming process, incorporating an adaptive fuzzy PID algorithm. The temperature difference of the forming region is lower than 6% under the various temperatures. On this basis, the forming limit angle and the microstructure state of the material are analyzed, and the grain feature of the material exhibits significantly refined grains and the uniform fine grain distribution under 180 °C with the temperature control of the adaptive fuzzy PID algorithm. Full article

This study investigated the effects of Lactococcus lactis subsp. 1.2472 (L)-, Streptococcus thermophilus 1.2718 (S)-, and thermostable Lactobacillus rhamnosus HCUL 1.1901-1912 (T)-fermented rice flour with inoculum levels of 3–11% (w/w) on rice bread staling. Optimal staling resistance was achieved, as follows: 9% L-fermented rice bread (LRB), 7% T-fermented rice bread (TRB), and 5% S-fermented rice bread (SRB). Lactic acid bacteria-fermented rice flour significantly enhanced hydration properties. LF-NMR analysis revealed that T₂₁ (strongly bound water) and T₂₂ (weakly bound water) relaxation times decreased, while T₂₃ (free water) increased with prolonged storage. Fermented-rice-flour groups had significantly more strongly bound water than the control group on 7 d. The optimized formulations exhibited exceptional volumetric stability with specific volume change rates of 17.63% (LRB), 17.60% (TRB), and 19.58% (SRB), coupled with maximal porosities of 10.34%, 9.05%, and 9.41%, respectively. This study provides a theoretical foundation for improving rice bread’s anti-staling properties. Full article