Search Results (255)

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

The fibrillary aggregation of α-synuclein is a hallmark of Parkinson’s disease (PD) and a potential target for diagnostics and therapeutics. Although substantial effort has been devoted to the development of positron emission tomography (PET) probes for detecting α-synuclein aggregates, no clinically suitable tracer has been reported. The design and synthesis of 43 new N-(6-methoxypyridin-3-yl)quinolin-2-amine derivatives and an evaluation of their α-synuclein binding affinity is reported here. Compounds 7f, 7j, and 8i exhibited high affinity for α-synuclein and were selected for ¹¹C, ¹⁸F, ¹²⁵I, or ³H radiolabeling. A photoaffinity variant, TZ-CLX, structurally related to 7j and 8i, demonstrated preferential binding to the C-terminal region of α-synuclein fibrils. PET brain imaging studies using [¹¹C]7f, [¹⁸F]7j, and [¹¹C]8i in non-human primates indicated that these three α-synuclein PET tracers penetrated the blood–brain barrier. Both [¹¹C]7f and [¹⁸F]7j showed more favorable brain washout pharmacokinetics than [¹¹C]8i. In vitro binding assays showed that [¹²⁵I]8i is a very potent α-synuclein radioligand, with K_d values of 5 nM for both PD brain tissues and LBD-amplified fibrils; it is also selective for PD tissues versus AD or control tissues. These results strongly suggest that the PET probes based on the N-(6-methoxypyridin-3-yl)quinoline-2-amine scaffold have potential utility in detecting α-synuclein aggregates in vivo. Full article

The enzyme ABH2, one of nine human DNA dioxygenases of the AlkB family, belongs to the superfamily of Fe(II)/α-ketoglutarate-dependent dioxygenases and plays a crucial role in the direct reversal repair of nonbulky alkyl lesions in DNA nucleobases. ABH2 has broad substrate specificity, directly oxidizing DNA damages such as N¹-methyladenine, N³-methylcytosine, 1,N⁶-ethenoadenine, 3,N⁴-ethenocytosine, and a number of others. In our investigation, we sought to uncover the subtleties of the mechanisms governing substrate specificity in ABH2 by focusing on several critical amino acid residues situated in its active site. To gain insight into the function of this enzyme, we performed a functional mapping of its active site region, concentrating on pivotal residues, participating in forming a damaged binding pocket of the enzyme (Val99 and Ser125), as well as the residues directly involved in interactions with damaged bases, namely Arg110, Phe124, Arg172, and Glu175. To support our experimental data, we conducted a series of molecular dynamics simulations, exploring the interactions between the ABH2 mutant forms, bearing corresponding substitutions and DNA substrates, and harboring various types of methylated bases, specifically N¹-methyladenine or N³-methylcytosine. The comparative studies revealed compelling data indicating that alterations in most of the studied amino acid residues significantly influence both the binding affinity of the enzyme for DNA and its catalytic efficiency. Intriguingly, the findings suggest that the mutations impact the catalytic activity of ABH2 to a greater extent than its ability to associate with DNA strands. Collectively, these results show how changes to the active site affect molecular dynamics and reaction kinetics, improving our understanding of the substrate recognition process in this pivotal enzyme. Full article

Background/objectives: Racial and ethnic minority patients are underrepresented in cancer clinical trials (CCTs) and multilevel strategies are required to increase participation. This study describes barriers and facilitators to minority CCT participation alongside feedback on a multilevel intervention (MLI) designed to reduce participation barriers, as posited by the socioecological model (SEM). Methods: Interviews with Moffitt Cancer Center (MCC) physicians, community physicians, patients with cancer, community residents, and clinical research coordinators (CRCs) were conducted from June 2023–February 2024. Verbal responses were analyzed using thematic analysis and categorized into SEM levels. Mean helpfulness scores rating interventions (from 1 (not helpful) to 5 (very helpful)) were summarized. Results: Approximately 50 interviews were completed. Thematic findings confirmed CCT referral and enrollment barriers across all SEM levels. At the community level, MCC patients and community residents felt that community health educators can improve patient experiences and suggested they connect patients to social/financial resources, assist with patient registration, and provide CCT education. While physicians and CRCs reacted positively to all institutional-level tools, the highest scored tool simultaneously addressed CCT referral and enrollment at the institution (e.g., trial identification/referrals) and interpersonal level (communication platform for community and MCC physicians) (mean = 4.27). At the intrapersonal level, patients were enthusiastic about a digital CCT decision aid (mean = 4.53) and suggested its integration into MCC’s patient portal. Conclusions: Results underscore the value of conducting formative research to tailor interventions to target population needs. Our approach can be leveraged by future researchers seeking to evaluate MLIs addressing additional CCT challenges or broader health topics. Full article

Stem cell-derived liver cells, organoids, and lab-grown liver tissue are promising regenerative therapies for liver disease. However, current culture conditions are sub-optimal, producing end-target cells and tissue phenotypes that are immature or unstable when compared to primary liver cells and tissue. Biopolymers used in culture substrates and scaffolds for tissue engineering significantly impact the quality of the end-target cells and tissue, influencing the efficacy of regenerative treatments. In addition, the biochemical properties of some biopolymers may preclude the translation of downstream bioengineered products into clinical practice. Therefore, this systematic review aims to evaluate the recent advances in biopolymers within liver tissue engineering, providing an overview of the current usage in the field and highlighting novel substrates that have strong potential to be translated into clinical therapy. Full article

Zoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans, with varying degrees of morbidity and mortality. However, no Food and Drug Administration (FDA) vaccines or therapeutics have been approved for the treatment of these diseases. In an effort to identify antiviral bioactive molecules, we isolated four oligomeric phloroglucinols from Callistemon rigidus leaves, including two new phloroglucinol trimers, callistemontrimer A and B, along with two previously characterized phloroglucinol dimers, rhodomyrtosone B and rhodomyrtone. We evaluated the anti-Hantaan virus (HTNV) activity of these compounds. Notably, callistemontrimer A demonstrated higher anti-HTNV activity compared to ribavirin. Mechanistic studies revealed that callistemontrimer A exerted its antiviral effects by inhibiting viral replication, likely through interaction with RNA-dependent RNA polymerase (RdRp) of HTNV, as supported by molecular docking analysis. These results highlight oligomeric phloroglucinols as promising lead candidates for the development of anti-HV therapeutics. Full article

Background/Objectives: While anterior lumbar interbody fusion (ALIF) is a well-established treatment for degenerative lumbar spine pathology, the timing and pace of postoperative recovery remain poorly defined. Understanding these temporal trends is clinically important for setting patient expectations and optimizing postoperative care. Methods: This retrospective single-institution study evaluated functional recovery in patients undergoing primary, single-level stand-alone (SA) ALIF, or with percutaneous posterior instrumentation (PI). Patient-reported outcome measures (PROMs), including the Oswestry Disability Index (ODI), the Visual Analog Scale (VAS) for back and leg pain, and the SF-12 Physical Component Score (PCS), were assessed preoperatively and at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Achievement of minimum clinically important difference (MCID), global rating change (GRC), and return-to-activity milestones were also analyzed. Results: A total of 143 patients were included (90 SA; 53 PI). PROMs showed significant improvement through 1 year. VAS-back improved by 2 weeks, while ODI and SF12 PCS initially worsened but improved after 6 weeks. By 6 months, over half of the cohort achieved MCID, with continued gains through 1 year. Most patients returned to driving and work, and over 90% discontinued narcotics. Recovery trajectories were comparable between groups, despite early delays in the instrumented cohort. Conclusions: These findings provide time-specific recovery benchmarks that can guide surgical decision-making, patient education, and expectations around functional milestones. Full article

In this study, we sequenced and characterized the complete mitochondrial genome of Acorssocheilus spinifer, an endemic stream-dwelling cyprinid species from South China first described in 2006. The mitogenome is 16,591 bp in length and contains the standard set of 37 genes (13 protein-coding genes, 22 tRNA genes, 2 rRNA genes) plus a control region. The genome exhibits typical cyprinid characteristics, with most genes encoded on the H-strand and a nucleotide composition biased toward A + T (55.9%). All tRNA genes display the typical cloverleaf secondary structure, except for tRNA^Ser (GCU), which lacks the dihydrouridine (DHU) arm. Phylogenetic analysis using complete mitogenomes from 14 Acrossocheilus species revealed that 12 species form a monophyletic assemblage with three distinct clades. Within this framework, A. spinifer clusters closely with A. beijiangensis, supporting previous morphological observations. Our findings provide valuable genetic data for further taxonomic refinement and conservation efforts for Chinese barred species of Cyprinidae. Full article

The internal growth patterns and surface micromorphology of diamonds provide a record of their multi-stage evolution, from initial formation within the mantle to their eventual ascent to the Earth’s surface via deeply derived kimberlite magmas. In this study, gemological microscopic examination, Diamond View^TM, Raman spectroscopy, and electron probe analysis were employed to analyze the surface features, internal patterns, and inclusions of the Tancheng alluvial diamonds in Shandong Province, China. The results show that surface features of octahedra with triangular and sharp edges, thick steps with irregular contours or rounded edges, and thin triangular or serrated layers are developed on diamonds during deep-mantle storage, as well as during the growth process of diamonds, when they are not subjected to intense dissolution. The rounding of octahedral and cubic diamond edges and their transformation into tetrahedral (THH) shapes are attributed to resorption in kimberlitic magma. These characteristics indicate that the Tancheng diamonds were commonly resorbed by carbonate–silicate melts during mantle storage. Abnormal birefringence phenomena, including irregular extinction patterns, petaloid and radial extinction patterns, and banded birefringence, were formed during the diamond growth stage. In contrast, fine grid extinction patterns and composite superimposed extinction patterns are related to later plastic deformation. The studied diamonds mainly contain P-type inclusions of olivine and graphite, with a minority of E-type inclusions, including coesite and omphacite. The pressure of entrapment of olivine inclusions within the Tancheng diamonds ranges from 4.3 to 5.9 GPa, which is consistent with that of coesite inclusions, which yield pressure ranging from 5.2 to 5.5 GPa, and a temperature range of 1083–1264 °C. Overall, the evidence suggests that Tancheng diamonds probably originated from hybrid mantle sources metasomatized by the subduction of ancient oceanic lithosphere. Full article

Background/Objectives: Adolescents and young adults (AYAs) with opioid use disorder (OUD) frequently have co-occurring psychiatric conditions and substance use disorders (SUDs). This study evaluated the association of psychiatric comorbidities and other SUDs with treatment retention and urine drug test (UDT) results in AYAs with OUD. Methods: This retrospective cohort study included AYAs enrolled in the Substance Use Treatment and Recovery clinic from 2009 to 2022. Participants were categorized into four groups: no comorbidities, only mental health disorders, only other SUDs, and both disorders. Treatment outcomes included retention time and UDT results for medication for OUD (MOUD) and illicit substances, including tetrahydrocannabinol (THC). Kruskal–Wallis tests were used to evaluate differences across groups, and regression models identified variables associated with outcomes. Statistical significance was set at p < 0.05. Results: Among 157 patients, the median retention time was 300 days. Depression (p = 0.04), post-traumatic stress disorder (p = 0.002), and alcohol use disorder (p = 0.04) were associated with prolonged retention, whereas cannabis use disorder predicted shorter retention (p = 0.02). The median proportion of positive UDTs was 0.9 for MOUD, 0.1 for illicit substances, and 0.0 for THC. Older age (p = 0.02) and the use of antidepressants and anxiolytics were associated with greater adherence to MOUD. Cannabis use disorder (p = 0.02) and male sex (p = 0.04) predicted positive UDTs for THC, while MOUD use was linked to lower THC positivity (p = 0.02). The main limitations of this study were related to its retrospective study design and single-center setting. Conclusions: Psychiatric and substance use comorbidities significantly influence retention and treatment adherence in AYAs with OUD. Integrated treatment may improve engagement and outcomes. Further research is needed to tailor interventions for AYAs with co-occurring disorders. Full article

The development of BPD in preterm neonates is increased by poor growth and nutritional deficits. The involvement of the fatty acid DHA in the development of BPD has been a focus for over a decade. However, recent clinical trials show that isolated DHA supplementation may increase BPD in subgroups of preterm neonates. One explanation for poor lung outcomes in DHA-supplemented neonates is a disruption of global fatty acid profiles and increased expression of a dominant-negative splice variant of a key driver of lung development, PPARγ. We previously developed a rat model of postnatal growth restriction (PGR) in which pups have impaired lung function and altered PPARγ activity. Here, we use our PGR rat model to assess the effects of DHA supplementation on lung outcomes. We hypothesize that the PPARγ splice variant, PPARγΔ5, will be expressed in the rat lung, and that DHA supplementation of PGR rat pups will alter circulating lipid profiles, lung mechanics, and PPARγ variant expression. Our findings demonstrate that PPARγΔ5 is expressed in the developing rat lung and that DHA supplementation of PGR rat pups alters global circulating fatty-acid profiles and does not normalize PGR-induced impaired lung mechanics or PPARγ activity. Full article

This study explores the combined effects of nanosilica (NS) and basalt fibers (BF) on the mechanical and microstructural properties of superabsorbent polymer (SAP)-modified concrete. NS (0–1.5% replaced by cement weight) and BF (0–1.2% by volume fraction) were incorporated to optimize compressive, flexural, and split-tensile strengths using response surface methodology. Digital Image Correlation (DIC) was employed to analyze failure mechanisms. Results show that while SAP alone reduced strength, the addition of NS and BF mitigated this loss through synergistic microstructure enhancement and crack-bridging reinforcement. The optimal mix (0.9% NS and 1.2% BF) increased compressive, flexural, and split-tensile strengths by 15.3%, 10.0%, and 14.0%, respectively. SEM analysis revealed that NS filled SAP-induced pores, while BF limited crack propagation, contributing to improved mechanical strength of SAP-modified concrete. This hybrid approach offers a promising solution for durable and sustainable concrete pavements. Full article

Forest canopy image is a necessary technical means to obtain canopy parameters, whereas image segmentation is an essential factor that affects the accurate extraction of canopy parameters. To address the limitations of forest canopy image mis-segmentation due to its complex structure, this study proposes a forest canopy image segmentation method based on the parameter evolutionary barnacle optimization algorithm (PEBMO). The PEBMO algorithm utilizes an extensive range of nonlinear incremental penis coefficients better to balance the exploration and exploitation process of the algorithm, dynamically decreasing reproduction coefficients instead of the Hardy-Weinberg law coefficients to improve the exploitation ability; the parent generation of barnacle particles ($pl$ = 0.5) is subjected to the Chebyshev chaotic perturbation to avoid the algorithm from falling into premature maturity. Four types of canopy images were used as segmentation objects. Kapur entropy is the fitness function, and the PEBMO algorithm selects the optimal value threshold. The segmentation performance of each algorithm is comprehensively evaluated by the fitness value, standard deviation, structural similarity index value, peak signal-to-noise ratio value, and feature similarity index value. The PEBMO algorithm outperforms the comparison algorithm by $91.67\%,55.56\%,62.5\%,69.44\%$, and $63.89\%$ for each evaluation metric, respectively. The experimental results show that the PEBMO algorithm can effectively improve the segmentation accuracy and quality of forest canopy images. Full article

Asthma has long been associated with increased susceptibility to viral respiratory infections, leading to significant exacerbations and poorer clinical outcomes. Contrarily and interestingly, emerging data and research surrounding the COVID-19 pandemic have shown that patients with asthma infected with SARS-CoV-2 experienced decreased severity of disease, lower hospitalization rates, as well as decreased morbidity and mortality. Research has shown that eosinophils could enhance immune defense against viral infections, while inhaled corticosteroids can assist in controlling systematic inflammation. Moreover, reduced ACE-2 expression in individuals with asthma may restrict viral entry, and the Th2 immune response may offset the Th1 response typically observed in severe COVID-19 patients. These factors may help explain the favorable outcomes seen in asthmatic patients during the COVID-19 pandemic. This review highlights potential protective mechanisms seen in asthmatic patients, including eosinophilia, the use of inhaled corticosteroids, reduced ACE-2 expression, and a dominate Th2 immune response. Such a study will be helpful to better manage patients with asthma who have contracted COVID-19. Full article

Recycling end-of-life wind turbines poses a significant challenge due to the increasing number of turbines going out of use. After many years of operation, turbines lose their functional properties, generating a substantial amount of composite waste that requires efficient and environmentally friendly processing methods. Wind turbine blades, in particular, are a problematic component in the recycling process due to their complex material composition. They are primarily made of composites containing glass and carbon fibers embedded in polymer matrices such as epoxies and polyester resins. This study presents an innovative approach to analyzing and valorizing these composite wastes. The research methodology incorporates integrated processing and analysis techniques, including mechanical waste treatment using a novel compression milling process, instead of traditional knife mills, which reduces wear on the milling tools. Based on the differences in the structure and colors of the materials, 15 different kinds of samples named WT1-WT15 were distinguished from crushed wind turbines, enabling a detailed analysis of their physicochemical properties and the identification of the constituent components. Fourier transform infrared spectroscopy (FTIR) identified key functional groups, confirming the presence of thermoplastic polymers (PET, PE, and PP), epoxy and polyester resins, wood, and fillers such as glass fibers. Thermogravimetric analysis (TGA) provided insights into thermal stability, degradation behavior, and the heterogeneity of the samples, indicating a mix of organic and inorganic constituents. Differential scanning calorimetry (DSC) further characterized phase transitions in polymers, revealing variations in thermal properties among samples. The fractionation process was carried out using both wet and dry methods, allowing for a more effective separation of components. Based on the wet separation process, three fractions—GF1, GF2, and GF3—along with other components were obtained. For instance, in the case of the GF1 < 40 µm fraction, thermogravimetric analysis (TGA) revealed that the residual mass is as high as 89.7%, indicating a predominance of glass fibers. This result highlights the effectiveness of the proposed methods in facilitating the efficient recovery of high-value materials. Full article