Search Results (10,424)

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

Background/Objectives: In soccer, scanning before receiving the ball helps players better perceive and interpret their surroundings, enabling faster and more effective passes. Despite its importance, no standardized tests currently incorporate scanning actions into assessments of passing abilities. In this study, we test the reliability and validity of a battery of passing tests that assess a player’s ability to control and pass the ball while also scanning for the appropriate target. Methods: We designed three passing tests that reflect different scanning demands that are routinely placed upon players during matches. Using players from the first and reserve teams of two professional clubs in Ghana (Club A, first-team n = 11, reserve-team n = 10; Club B, first-team n = 16, reserve-team n = 17), we: (i) tested the repeatability of each passing test (intraclass correlations), (ii) assessed whether the tests could distinguish between first and reserve team players (linear mixed-effects model), and (iii) examined whether players who were better in the passing tests had higher performances in 3v1 Rondo possession games (linear models). Results: All passing tests were significantly repeatable (ICCs = 0.77–0.85). Performance was highest in the 120-degree test (30.11 ± 7.22 passes/min), where scanning was not required, and was lowest in the 360-degree test (25.55 ± 5.94 passes/min), where players needed to constantly scan behind them. When players were scanning through an arc of 180 degrees, their average performance was 27.41 ± 6.14 passes/min. Overall passing performance significantly distinguished first from reserve team players (β = −1.47, t (51) = −4.32, p < 0.001)) and was positively associated with 3v1 Rondo possession performance (R² = 0.51, p < 0.001). Conclusions: Our results show that these passing tests are reliable, distinguish players across competitive levels, and correlate with performance in possession games. These tests offer a simple, ecologically valid way to assess scanning and passing abilities for elite players. 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

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article

This study investigates the use of a Random Forest (RF), an artificial intelligence (AI) model, to estimate the planetary boundary layer height (PBLH) over Central Amazonia from climatic elements data collected during the GoAmazon experiment, held in 2014 and 2015, as it is a key metric for air quality, weather forecasting, and climate modeling. The novelty of this study lies in estimating PBLH using only surface-based meteorological observations. This approach is validated against remote sensing measurements (e.g., LIDAR, ceilometer, and wind profilers), which are seldom available in the Amazon region. The dataset includes various meteorological features, though substantial missing data for the latent heat flux (LE) and net radiation (Rn) measurements posed challenges. We addressed these gaps through different data-cleaning strategies, such as feature exclusion, row removal, and imputation techniques, assessing their impact on model performance using the Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and $r^2$ metrics. The best-performing strategy achieved an RMSE of 375.9 m. In addition to the RF model, we benchmarked its performance against Linear Regression, Support Vector Regression, LightGBM, XGBoost, and a Deep Neural Network. While all models showed moderate correlation with observed PBLH, the RF model outperformed all others with statistically significant differences confirmed by paired t-tests. SHAP (SHapley Additive exPlanations) values were used to enhance model interpretability, revealing hour of the day, air temperature, and relative humidity as the most influential predictors for PBLH, underscoring their critical role in atmospheric dynamics in Central Amazonia. Despite these optimizations, the model underestimates the PBLH values—by an average of 197 m, particularly in the spring and early summer austral seasons when atmospheric conditions are more variable. These findings emphasize the importance of robust data preprocessing and higtextight the potential of ML models for improving PBLH estimation in data-scarce tropical environments. Full article

Background/Objectives: Non-coding microRNA-34a (miR-34a) regulates the expression of key factors involved in several cellular processes, such as differentiation, apoptosis, proliferation, cell cycle, and senescence. Deregulation of the expression of these factors is implicated in the onset and progression of several human diseases, including cancer, neurodegenerative disorders, and pathologies associated with viral infections and inflammation. Despite numerous studies, the molecular mechanisms regulated by miR-34a remain to be fully understood. The present study aimed to generate miR-34a knockout cell lines to identify novel genes potentially regulated by its expression. Methods: We employed the CRISPR-Cas9 gene editing system to knock out the hsa-miR-34a gene in HeLa and 293T cell lines, two widely used models for studying molecular and cellular mechanisms. We compared proliferation rates and gene expression profiles via RNA-seq and qPCR analyses between the wild-type and miR-34a KO cell lines. Results: Knockout of miR-34a resulted in a decreased proliferation rate in both cell lines. Noteworthy, the ablation of miR-34a resulted in increased expression of the long non-coding RNA MALAT1. Additionally, miR-34a-5p silencing in the A375 melanoma cell line led to MALAT1 overexpression. Conclusions: Our findings support the role of the miR-34a/MALAT1 axis in regulating proliferation processes. Full article

Background: In recent years, there has been increasing interest in the application of repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct-Current Stimulation (tDCS) to enhance and rehabilitate the language abilities in individuals with neurodegenerative diseases. Objective: The aim of this narrative literature review is to investigate the usefulness of rTMS and tDCS to improve language abilities in people with Primary Progressive Aphasia (PPA). Methods: This narrative literature review was conducted through a search of the PubMed online database to identify studies investigating the effects of multiple sessions of rTMS or tDCS on language abilities in PPA patients, applied either as stand-alone interventions or in combination with language treatment. Results: Thirty-three studies fulfilled the inclusion criteria; five studies employed rTMS without language treatment; two studies applied tDCS as stand-alone intervention; twenty-two studies combined tDCS with language treatment; and four studies assessed the effects of tDCS during verbal task without language treatment. Conclusions: rTMS and tDCS applied with or without concomitant language treatment appear to be promising interventions for enhancing language abilities in PPA, with sustained effects reported over time. Further research is necessary to optimise stimulation protocols and to improve our understanding of their long-term effects. Moreover, randomised controlled trials (RCTs) with larger sample sizes are critically needed to clarify the true impact of brain stimulation in PPA, with a focus on changes in cognitive and functional performance, neural activity, and potential molecular correlates. Full article

Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article

While the gut microbiota of obese children in Mexico has been studied, its relationship with depressive and anxiety symptoms in obese adults remains unexplored. The aim of this study was to describe the gut microbiota profile of Mexican adults with obesity and its association with depression and anxiety. We sequenced the V3-V4 region of the 16S rRNA gene from stool samples of obese adults categorized into four groups: control (OCG), with depressive symptoms (OD), with anxiety symptoms (OAx), or with both (ODAx). Alpha diversity was assessed using t-tests, beta diversity was assessed with PERMANOVA, and taxonomic differences was assessed with LEfSe. Associations between bacterial genera and clinical variables were analyzed using the Maaslin2 library. Bacteroidota was the most prevalent phylum, and Prevotella was the dominant enterotype across all groups. Although overall diversity did not differ significantly, 30 distinct taxonomic biomarkers were identified among groups as follows: 4 in OCG (Firmicutes), 5 in OD (Firmicutes, Bacteroidota), 13 in OAx (Firmicutes, Bacteroidetes, Fusobacteroidota, Proteobacteria), and 8 in ODAx (Firmicutes). This is the first study to identify distinct gut microbiota profiles in obese Mexican adults with depressive and anxiety symptoms. These findings suggest important microbial biomarkers for improving the diagnosis and treatment of mental health conditions in obesity. Full article

Background/Objectives: Extracellular vesicles (EVs) are involved in cell-to-cell communication and delivery of signaling molecules and represent an interesting approach in targeted therapy. This project focused on EV-mediated facilitation and cell-specific delivery of effector antimiR molecules carried by biologically produced gold nanoparticles (AuNPs). Methods: First, we loaded EVs derived from cancer cells 4T1 with AuNPs-antimiR. The AuNPs were also decorated with or without transferrin (Tf) molecules. We examined parental cell-specific delivery of the AuNPs-Tf-antimiR within monocultures as well as co-cultures in vitro. Subsequently, we used autologous EVs containing AuNPs-Tf-antimiR to target tumor cells in a xenograft tumor model in vivo. Efficacy of the antimir transfer was assessed by qPCR and apoptosis assessment. Results: In vitro, EVs loaded with AuNPs-antimiR were internalized only by the parental cells and the AuNPs-antimiR transfer was successful and effective only in EVs that were decorated with Tf. We achieved effective delivery of the antimiR molecule into cancer cells in vivo, which was proved by specific silencing of the target oncogenic miRNA as well as induction of cancer cells apoptosis. Conclusions: EVs represent an interesting and potent way for targeted cargo delivery and personalized medicine. On the other hand, there are various safety and efficacy challenges that remain to be addressed. Full article

Despite cognitive workload (CW) being a critical metric in several applications, no technology exists to seamlessly and reliably quantify CW. Previously, we demonstrated the feasibility of a wearable MagnetoCardioGraphy (MCG) sensor to classify high vs. low CW based on MCG-derived heart rate variability (mHRV). However, our sensor was unable to address certain critical operational requirements, resulting in noisy signals, often to the point of being unusable. In addition, test conditions for the participants were not decoupled from motion (i.e., physical activity (PA)), raising questions as to whether the noted changes in mHRV were attributed to CW, PA, or both. This study reports software and hardware advancements to optimize the MCG data quality, and investigates whether changes in CW (in the absence of PA) can be reliably detected. Performance is validated for healthy adults (n = 10) performing three types of CW tasks (one for low CW and two for high CW to eliminate the memory effect). Results demonstrate the ability to retrieve MCG R-peaks throughout the recordings, as well as the ability to differentiate high vs. low CW in all cases, confirming that CW does modulate the mHRV. A paired Bonferroni t-test with significance $\alpha =0.01$ confirms the hypothesis that an increase in CW decreases mHRV. Our findings lay the groundwork toward a seamless, practical, and low-cost sensor for monitoring CW. Full article

Background: Claustrophobia is defined as the fear of enclosed spaces, and it is a rather common specific phobia. Although the Claustrophobia Questionnaire (CLQ) is a valid questionnaire to measure claustrophobia, there have been no studies validating this tool in Greek. Thus, our aim was to translate and validate the CLQ in Greek. Methods: We applied the forward–backward translation method to translate the English CLQ into Greek. We conducted confirmatory factor analysis (CFA) to examine the two-factor model of the CLQ. We examined the convergent and divergent validity of the Greek CLQ by using the Fear Survey Schedule-III (FSS-III-CL), the NEO Five-Factor Inventory (NEO-FFI-NL-N), and the Spielberger’s State-Trait Anxiety Inventory (STAI). We examined the convergent validity of the Greek CLQ by calculating Pearson’s correlation coefficient between the CLQ scores and scores on FSS-III-CL, NEO-FFI-NL-N, STAI-S (state anxiety), and STAI-T (trait anxiety). We examined the divergent validity of the Greek CLQ using the Fisher r-to-z transformation. To further evaluate the discriminant validity of the CLQ, we calculated the average variance extracted (AVE) score and the Composite Reliability (CR) score. We calculated the intraclass correlation coefficient (ICC) and Cronbach’s alpha to assess the reliability of the Greek CLQ. Results: Our CFA confirmed the two-factor model of the CLQ since all the model fit indices were very good. Standardized regression weights between the 26 items of the CLQ and the two factors ranged from 0.559 to 0.854. The convergent validity of the Greek CLQ was very good since it correlated strongly with the FSS-III-CL and moderately with the NEO-FFI-NL-N and the STAI. Additionally, the Greek CLQ correlated more highly with the FSS-III-CL than with the NEO-FFI-NL-N and the STAI, indicating very good divergent validity. The AVE for the suffocation factor was 0.573, while for the restriction factor, it was 0.543, which are both higher than the acceptable value of 0.50. Moreover, the CR score for the suffocation factor was 0.949, while for the restriction factor, it was 0.954. The reliability of the Greek CLQ was excellent since the ICC in test–retest study was 0.986 and the Cronbach’s alpha was 0.956. Conclusions: The Greek version of the CLQ is a reliable and valid tool to measure levels of claustrophobia among individuals. Full article

The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell quality in aged hens. Two hundred eighty-eight Hubbard Efficiency Plus broiler breeder hens (50-week-old) were randomly allocated to three dietary treatments containing 0, 40, or 200 mg/kg puerarin (PU), with 8 replicates of 12 birds each, for an 8-week trial. The results demonstrated that dietary PU ameliorated the eggshell thickness and strength, which in turn reduced the broken egg rate (p < 0.05). Histological analysis showed that PU improved uterus morphology and increased epithelium height in the uterus (p < 0.05). Antioxidative capacity was significantly improved via upregulation of Nrf2, HO-1, and GPX1 mRNA expression in the uterus (p < 0.05), along with enhanced total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity, and decreased levels of the oxidative stress marker malondialdehyde (MDA) (p < 0.05). Meanwhile, PU treatment reduced the apoptotic index of the uterus, followed by a significant decrease in expression of pro-apoptotic genes Caspase3 and BAX and the rate of BAX/BCL-2. Additionally, calcium content in serum and uterus, as well as the activity of Ca²⁺-ATPase in the duodenum and uterus, were increased by dietary PU (p < 0.05). The genes involved in calcium transport including ERα, KCNA1, CABP-28K, and OPN in the uterus were upregulated by PU supplementation (p < 0.05). The 16S rRNA gene sequencing revealed that dietary PU supplementation could reverse the age-related decline in the relative abundance of Bacteroidota within the uterus (p < 0.05). Overall, dietary PU can improve eggshell quality and calcium transport through enhanced antioxidative defenses and mitigation of age-related uterine degeneration. Full article

Background/Objectives: Gallbladder cancer (GBC) is a lethal malignancy curable only by surgical resection in early stages (Tis, T1, T2). Significant controversy exists regarding the optimal extent of surgery. This review summarizes recent trends and evidence on surgical strategies for Tis, T1, and T2 GBC to guide practice and research. Methods: This narrative review synthesizes recent literature on surgical management of Tis, T1a, T1b, and T2 GBC based on American Joint Committee on Cancer (AJCC) 8th edition staging. It examines simple vs. extended cholecystectomy (simple cholecystectomy (SC) vs. extended/radical cholecystectomy (EC/RC)), the role of lymphadenectomy (LND) and hepatectomy, and minimally invasive surgery (MIS). Results: Simple cholecystectomy is curative for Tis/T1a GBC. For T1b, regional LND is essential for staging/potential benefit, especially examining ≥5–6 nodes. Tumor size is critical; SC alone may suffice for T1b < 1 cm (low lymph node metastasis (LNM) risk), while EC/RC with LND is indicated for ≥1 cm (higher LNM risk). Routine hepatectomy for T1b lacks survival support. For T2 GBC, mandatory regional LND (≥6 nodes) is required for both T2a and T2b substages due to high LNM rates; T2b has higher LNM than T2a. Routine hepatectomy for T2 is debated; evidence suggests no routine benefit for T2a beyond LND, with conflicting findings for T2b. R0 resection is paramount. MIS is feasible for early stages in experienced hands. Conclusions: Management of early GBC is moving towards risk stratification. SC is standard for Tis/T1a. Adequate regional LND is crucial for T1b (especially ≥1 cm) and mandatory for T2 GBC. Routine hepatectomy, particularly for T2b, remains controversial. Tailored surgery prioritizes R0 resection and comprehensive LND, necessitating further standardized research. Full article

In order to achieve 0.1 m resolution and fully polarimetric observation capabilities for airborne SAR systems, the adoption of stepped-frequency modulation waveform combined with the polarization time-division transmit/receive (T/R) technique proves to be an effective technical approach. Considering the issue of range resolution degradation and paired echoes caused by multichannel amplitude–phase mismatch in fully polarimetric airborne SAR with 0.1 m resolution, an amplitude–phase error estimation algorithm based on echo data is proposed in this paper. Firstly, the subband amplitude spectrum correction curve is obtained by the statistical average of the subband amplitude spectrum. Secondly, the paired-echo broadening function is obtained by selecting high-quality sample points after single-band imaging and the nonlinear phase error within the subbands is estimated via Sinusoidal Frequency Modulation Fourier Transform (SMFT). Thirdly, based on the minimum entropy criterion of the synthesized compressed pulse image, residual linear phase errors between subbands are quickly acquired. Finally, two-dimensional cross-correlation of the image slice is utilized to estimate the positional deviation between polarization channels. This method only requires high-quality data samples from the echo data, then rapidly estimates both intra-band and inter-band amplitude/phase errors by using SMFT and the minimum entropy criterion, respectively, with the characteristics of low computational complexity and fast convergence speed. The effectiveness of this method is verified by the imaging results of the experimental data. Full article