Search Results (45,623)

Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone EVT to elucidate patient characteristics and factors associated with a favorable functional outcome after EVT. Methods: We reviewed all cases of EVT at our institution between February 2018 and February 2022 in the extended time window from 6–24 h. Demographic, clinical, imaging, and procedure co-variates were included. A favorable clinical outcome was defined as a modified Rankin scale of 0–2. We included patients with M1 or internal carotid artery occlusion treated with EVT within 6–24 h after symptom onset. We used a univariate and multivariate logistic regression analysis to identify patient factors associated with a favorable clinical outcome at 90 days. Results: Our study included evaluation of 121 patients who underwent EVT at our comprehensive stroke center. Our analysis demonstrates that a higher recanalization score based on the modified Thrombolysis In Cerebral Infarction (mTICI) scale (2B-3) was a strong indicator of a favorable outcome (OR 7.33; CI 2.06–26.07; p = 0.0021). Our data also showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.0095) and the presence of pre-existing hypertension (p = 0.0035) may also be predictors of an unfavorable outcome (mRS > 2) per our multivariate analysis. Conclusion: Patients without pre-existing hypertension had more favorable outcomes following EVT in the expanded time window. This is consistent with other multicenter data in the expanded time window that demonstrates greater odds of a poor outcome with elevated pre-, peri-, and post-endovascular-treatment blood pressure. Our data also demonstrate that the mTICI score is a strong predictor of favorable outcome, even after controlling for other variables. A lower baseline NIHSS at the time of thrombectomy may also indicate a favorable outcome. Furthermore, the presence of clinical or radiographic mismatch based on the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and NIHSS per DAWN and DEFUSE-3 criteria did not emerge as a predictor of favorable outcome, which is congruent with recent randomized controlled trials and meta-analyses. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

In this study, the impact of moderate and high CO₂ and O₂ levels was compared to low and moderate gas combinations during prolonged storage on the quality of Regina sweet cherries harvested in different maturity stages, particularly in terms of decreasing internal browning. Fruits were harvested in two different maturity stages (Light and Dark Mahogany skin color) and stored in CA of 15% CO₂ + 10% O₂; 10% CO₂ + 10% O₂; 10% CO₂ + 5% O₂; 5% CO₂ + 5% O₂ and MA of 4 to 5% CO₂ + 16 to 17% O₂ for 30 and 40 days at 0 °C and 90% RH, followed by a marketing period. After the storage, both maturity stages significantly reduced internal browning, decay, and visual quality losses in CA with 10–15% CO₂ and 10% O₂. In addition, it preserved luminosity, total soluble solids (TSSs), titratable acidity (TA), and bioactive compounds such as anthocyanins and phenols. This treatment also maintained the visual appearance of the sweet cherries, favoring their market acceptance. At the same time, the light red fruits showed a better general quality compared to darker color after the storage. In conclusion, a controlled atmosphere with optimized CO₂ and O₂ concentrations, together with harvesting with a Light Mahogany external color, represents an effective strategy to extend the shelf life of Regina sweet cherries up to 40 days plus the marketing period, maintaining their physical and sensory quality for export markets. Full article

Antibiotic resistance is considered to be one of the most complex health obstacles of our time. Methicillin-resistant Staphylococcus aureus (MRSA) represents a global health challenge due to its broad treatment resistance capacity, resulting in high mortality rates. The shikimate pathway (SP) is responsible for the biosynthesis of chorismate from glycolysis and pentose phosphate pathway intermediates. This pathway plays a crucial role in producing aromatic amino acids, folates, ubiquinone, and other secondary metabolites in bacteria. Notably, SP is absent in humans, which makes it a specific and potential therapeutic target to explore for discovering new antibiotics against MRSA. The present study characterized in vitro and in silico natural products as inhibitors of the shikimate dehydrogenase from methicillin-resistant S. aureus (SaSDH). The results showed that, from the set of compounds studied, phloridzin, rutin, and caffeic acid were the most potent inhibitors of SaSDH, with IC₅₀ values of 140, 160, and 240 µM, respectively. Furthermore, phloridzin showed a mixed-type inhibition mechanism, whilst rutin and caffeic acid showed non-competitive mechanisms. The structural characterization of the SaSDH–inhibitor complex indicated that these compounds interacted with amino acids from the catalytic site and formed stable complexes. In biological activity studies against MRSA, caffeic acid showed an MIC of 2.2 mg/mL. Taken together, these data encourage using these compounds as a starting point for developing new antibiotics based on natural products against MRSA. Full article

To address the central cracking problem in continuous casting slabs of 38CrMoAl steel, high-temperature tensile tests were performed using a Gleeble-3800 thermal simulator to characterize the hot ductility of the steel within the temperature range of 600–1200 °C. The phase transformation behavior was computationally analyzed via the Thermo-Calc software, while the microstructure, fracture morphology, and precipitate characteristics were systematically investigated using a metallographic microscope (MM), a field-emission scanning electron microscope (FE-SEM), and transmission electron microscopy (TEM). Additionally, the effects of different holding times and cooling rates on the microstructure and precipitates of 38CrMoAl steel were also studied. The results show that the third brittle temperature region of 38CrMoAl steel is 645–1009 °C, and the fracture mechanisms can be classified into three types: (I) in the α single-phase region, the thickness of intergranular proeutectoid ferrite increases with rising temperature, leading to reduced hot ductility; (II) in the γ single-phase region, the average size of precipitates increases while the number density decreases with increasing temperature, thereby improving hot ductility; and (III) in the α + γ two-phase region, the precipitation of proeutectoid ferrite promotes crack propagation and the dense distribution of precipitates at grain boundaries causes stress concentration, further deteriorating hot ductility. Heat treatment experiments indicate that the microstructures of the specimen transformed under water cooling, air cooling, and furnace cooling conditions as follows: martensite + proeutectoid ferrite → bainite + ferrite → ferrite. The average size of precipitates first decreased, then increased, and finally decreased again with increasing holding time, while the number density exhibited the opposite trend. Therefore, when the holding time was the same, reducing the cooling rate could increase the average size of the precipitates and decrease their number density, thereby improving the hot ductility of 38CrMoAl steel. Full article

Acute kidney injury (AKI) is a serious clinical condition that is linked to markedly higher rates of morbidity and mortality in cirrhosis patients. Its diagnosis is challenging due to overlapping clinical and laboratory features among causes such as hepatorenal syndrome (HRS), acute tubular injury (ATI), and prerenal hypovolemia. In order to address the distinct pathophysiology and clinical context of cirrhosis, the definitions and classification of AKI have changed over time, moving from RIFLE and AKIN to KDIGO and ICA-AKI. Because cirrhosis patients have altered muscle mass and fluid retention, traditional markers like serum creatinine (sCr) and urine output have significant limitations. Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and cystatin C (CysC) are some of the new biomarkers that have shown promise in early AKI detection and in differentiating structural from functional kidney injury. NGAL and KIM-1 are sensitive indicators of tubular damage with potential prognostic implications. IL-18 reflects inflammatory injury, and CysC offers a more reliable measure of glomerular filtration. Incorporating these markers may improve early diagnosis, risk stratification, and treatment decisions, representing a key direction for future research in managing AKI in cirrhosis. Full article

Tumor heterogeneity encompasses genetic, epigenetic, and phenotypic diversity, impacting treatment response and resistance. Spatial heterogeneity occurs both inter- and intra-lesionally, while temporal heterogeneity results from clonal evolution. High-throughput technologies like next-generation sequencing (NGS) enhance tumor characterization, but conventional biopsies still do not adequately capture genetic heterogeneity. Liquid biopsy (LBx), analyzing circulating tumor DNA (ctDNA), provides a minimally invasive alternative, offering real-time tumor evolution insights and identifying resistance mutations overlooked by tissue biopsies. This study evaluates the capability of LBx to capture tumor heterogeneity by comparing genetic profiles from multiple metastatic lesions and LBx samples. Eight patients from the Augsburger Longitudinal Plasma Study with various types of cancer provided 56 postmortem tissue samples, which were compared against pre-mortem LBx-derived circulating-free DNA sequenced by NGS. Tissue analyses revealed significant mutational diversity (4–12 mutations per patient, VAFs: 1.5–71.4%), with distinct intra- and inter-lesional heterogeneity. LBx identified 51 variants (4–17 per patient, VAFs: 0.2–31.1%), which overlapped with mutations from the tissue samples by 33–92%. Notably, 22 tissue variants were absent in LBx, whereas 18 LBx-exclusive variants were detected (VAFs: 0.2–2.8%). LBx effectively captures tumor heterogeneity, but should be used in conjunction with tissue biopsies for comprehensive genetic profiling. Full article

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

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

This study focused on the poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer, which was recently reported as a novel material for polymeric nanoparticles to replace poly(DL-lactide-co-glycolide) (PLGA) as a drug carrier for prednisolone (PSL), and aimed to evaluate the efficacy of PSL-loaded PLGA-PEG-PLGA nanoparticles (NPs) against allergic contact dermatitis (ACD). PSL-loaded PLGA-PEG-PLGA NPs were prepared using the nanoprecipitation method, and their particle size distribution and mean particle size were measured using dynamic light scattering. 1-Fluoro-2,4-dinitrobenzene (DNFB) was used to create a mouse model of contact hypersensitivity (CHS). PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization with DNFB, and the therapeutic effect was evaluated by quantifying intracutaneous TNF-α and IL-4 levels suing ELISA. When PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization, TNF-α expression and IL-4 statements were significantly lower in the PSL-loaded PLGA-PEG-PLGA NP group than in the non-treated group. No significant difference was observed between the PSL-loaded PLGA-PEG-PLGA NP and PSL-loaded ointment groups, even though the steroid dose was 40 times lower than in the PSL-containing ointment. These results suggest that PSL-loaded PLGA-PEG-PLGA NPs may have a better effect in the treatment of ACD than PSL-loaded PLGA NPs. Full article

Pulsed electric field (PEF) and high-pressure processing (HPP) are non-thermal treatments, developed to ensure preservation of food products whilst maintaining taste and valuable nutrients. In this study, we investigated their potential for the inactivation of 3 commercial exogenous pectinases (polygalacturonase, pectin transeliminase, pectin esterase) commonly used in juice processing for clarification of juices. The inactivation of these enzymes after processing is mandatory by European law. Clear apple juice was treated with both non-thermal processing methods, as well as with thermal pasteurization as the standard method. For HPP, 3 pressures (250, 450, and 600 MPa) and different holding times (from 2 to 12 min) were tested. For PEF, 3 electric field intensities (10, 13, and 15 kV/cm) and different specific energy values (from 121 to 417 kJ/kg). Standard thermal pasteurization resulted in a complete inactivation of all tested pectinases. HPP treatment only showed marginal effects on polygalacturonase and pectin transeliminase at the highest pressure and holding times, which are beyond levels used in industrial settings. For PEF, dependence upon high electric field strength and specific energy values was evident; however, here too, the effect was only moderate at the levels attainable within the scope of this study. Assuming a continued linear relationship, usable results could be achieved in an industrial setting, albeit under more extreme conditions. Full article

Green synthesis of copper oxide (CuO) nanoparticles offers a sustainable alternative to conventional chemical methods that often involve toxic reagents and harsh conditions. This study investigates the use of Tithonia diversifolia, an invasive species in Sri Lanka, as a bioreductant for the eco-friendly fabrication of CuO nanoparticles. Using copper sulfate (CuSO₄·5H₂O) as a precursor, eight treatments were conducted by varying precursor concentration, temperature, and reaction time to determine optimal conditions. A visible color change in the reaction mixture initially indicated nanoparticle formation. Among all the conditions, treatment T4 (5 mM CuSO₄, 80 °C, 2 h) yielded the most favorable results in terms of stability, morphology, and crystallinity. UV-Vis spectroscopic analysis confirmed the synthesis, with absorbance peaks between 265 and 285 nm. FTIR analysis revealed organic functional groups and characteristic metal–oxygen vibrations in the fingerprint region (500–650 cm⁻¹), confirming formation. SEM imaging showed that particles were mainly spherical to polygonal, averaging 125–150 nm. However, dynamic light scattering showed larger diameters (~240 nm) due to surface capping agents. Zeta potential values ranged from −16.0 to −28.0 mV, indicating stability. XRD data revealed partial crystallinity with CuO-specific peaks. These findings support the potential of T. diversifolia in green nanoparticle synthesis, suggesting a low-cost, eco-conscious strategy for future applications. 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

Scrofuloderma, a cutaneous manifestation of tuberculosis, is a rare but clinically significant form of mycobacterial infection. It typically results from the local spread of Mycobacterium tuberculosis from an infected lymph node or bone area to the overlying skin. This disease is mainly characterized by chronic granulomatous inflammation, leading to skin ulcers and abscesses. Due to its nonspecific clinical presentation, scrofuloderma can mimic various dermatological conditions, making its diagnosis particularly challenging. This case report presents the clinical course of a patient who was positive for the Human Immunodeficiency Virus (HIV) with a diagnosis of scrofuloderma, managed at a tertiary healthcare center, with follow-up before and after treatment. A literature review was also made, highlighting the importance of maintaining a high index of clinical suspicion and utilizing appropriate diagnostic methods to ensure timely diagnosis. Full article

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder that frequently affects bulbar function, including feeding and swallowing. Although disease-modifying therapies have improved motor outcomes, little is known about the persistence of oromotor difficulties, particularly with regard to solid food intake. Objective: This study aimed to evaluate mastication and swallowing performance in children with SMA undergoing treatment, and to investigate the association between tongue strength and feeding efficiency. Methods: Twenty-two children with SMA types 1–3 were assessed using the Test of Masticating and Swallowing Solids in Children (TOMASS-C) and the Iowa Oral Performance Instrument (IOPI). Key TOMASS-C outcomes included the number of bites, chewing cycles, swallows, and total eating time. Tongue strength was measured in kilopascals. Results: Most participants showed deviations from age-specific normative values in at least one TOMASS-C parameter. Tongue strength was significantly lower than reference values in 86% of participants and correlated negatively with all TOMASS-C outcomes (p < 0.001). Children with weaker tongue pressure required more swallows, more chewing cycles, and longer eating times. Conclusions: Despite pharmacological treatment, children with SMA experience persistent difficulties in eating solid foods. Tongue strength may serve as a non-invasive biomarker for bulbar dysfunction and support dietary decision-making and therapeutic planning. Full article