Search Results (111)

To address the challenges of low land use efficiency, soil degradation, and high management costs in Ilex asprella cultivation, this study established an I. asprella–Grona styracifolia intercropping system and systematically evaluated its effects on soil nutrient cycling, microbial communities, and crop growth. Field experiments were conducted in Yunfu City, Guangdong Province, with monoculture (LCK for I. asprella, DCK for G. styracifolia) and three intercropping densities (HDT, LDT, MDT). Combining 16S rRNA sequencing and metagenomics, we analyzed the functional profile of the rhizosphere microbiome. The results showed that intercropping significantly increased the biomass of G. styracifolia, with the medium-density (MDT) treatment increasing plant length and fresh weight by 41.2% and 2.4 times, respectively, compared to monoculture. However, high-density intercropping suppressed the accumulation of medicinal compounds. In terms of soil properties, intercropping significantly enhanced soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), and available nitrogen (AN) in the rhizosphere of both plants. Specifically, AN in the I. asprella rhizosphere increased by 18.9%. Soil urease and acid phosphatase activities were also elevated, while pH decreased. Microbial analysis revealed that intercropping reshaped the rhizosphere microbial community structure, significantly increased the Shannon diversity index of bacteria in the G. styracifolia rhizosphere, and enhanced the complexity of the microbial co-occurrence network. Metagenomic analysis further confirmed that intercropping enriched functional genes related to carbon fixation, nitrogen cycling (nitrogen fixation, assimilatory nitrate reduction), and organic phosphorus mineralization (the phoD gene), thereby driving the transformation and availability of soil nutrients. These findings demonstrate that the I. asprella–G. styracifolia intercropping system, particularly at medium density, effectively improves soil fertility and land use efficiency by regulating rhizosphere microbial functions, providing a theoretical basis for the sustainable ecological cultivation of I. asprella. Full article

The overlapping circulation of influenza (Flu), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; SC2), and respiratory syncytial virus (RSV) continues to challenge clinical laboratories, particularly in settings with limited automation and fragmented healthcare coverage. This study expanded the CDC Flu-SC2 assay by incorporating a laboratory-developed test (LDT) for RSV A/B detection into a fully automated quadruplex RT-qPCR (LDRA) on the Panther Fusion^® Open Access™ system. The design, based on more than 8000 RSV genomic sequences targeting the conserved M gene, achieved optimal amplification efficiencies (97–105%) and full multiplex compatibility. Analytical assessment established limits of detection between 9.6 and 37.8 copies per reaction, absence of cross-reactivity with 30 respiratory pathogens, and inclusivity for 32 viral variants. Commutability and diagnostic performance among the LDRA, CE IVD-marked Allplex™ SARS-CoV-2/FluA/FluB/RSV, and US IVD-marked Panther Fusion^® SARS-CoV-2/Flu A/B/RSV Assays were evaluated using 405 nasopharyngeal UTM-preserved swabs. The LDRA demonstrated excellent concordance (overall agreement ≥ 98%, κ > 0.95), strong diagnostic accuracy, and reliable detection of mixed infections. This quadruplex provides a fully automated, rapid, and accurate solution for the simultaneous detection of influenza A, influenza B, SARS-CoV-2, and RSV viruses, enhancing molecular diagnostic capacity and supporting equitable, timely clinical decision-making in middle-income healthcare systems such as that of the Dominican Republic. Full article

The dissociation between emotion-label and emotion-laden words has been investigated in both behavioral and electrophysiological studies. However, how individual differences modulates the processing of emotional words has not been fully explored. Trait anxiety, as an important individual difference variable, plays a vital role in emotion processing, and may influence the processing of emotional words. To reveal the effects of trait anxiety and emotional word type on the processing of Chinese words, the present study adopted a lexical decision task (LDT) and event-related potential (ERP) technique to collect the behavioral and electrophysiological data from high-trait-anxious (HTA), medium-trait-anxious (MTA) and low-trait-anxious (LTA) individuals. Behaviorally, participants demonstrated longer reaction times (RTs) and lower accuracy (ACC) when processing emotion-laden words, as opposed to emotion-label words and neutral words. Electrophysiologically, both emotion-label and emotion-laden words induced enhanced N170 amplitudes relative to neutral ones. Compared with neutral words, emotion-laden words elicited larger early posterior negativity (EPN) amplitudes in the right hemisphere and increased late positive component (LPC) amplitudes, whereas emotion-label words elicited a stronger N400. EPN amplitudes were modulated by the interaction between trait anxiety and emotional word type. In HTA individuals, emotion-laden words evoked a larger EPN than emotion-label and neutral words, supporting the mediated emotion concept account, density hypothesis, and embodiment emotion account. During the late elaborative processing stage, LTA participants exhibited larger LPC amplitudes than HTA individuals, which aligns with the “vigilance-avoidance” pattern. Full article

Background/Objectives: Chagas disease, caused by Trypanosoma cruzi, remains a major neglected tropical disease with limited therapeutic options restricted to benznidazole and nifurtimox, both associated with significant toxicity and reduced efficacy during chronic infection. Seeking novel, safe, and sustainable chemotherapeutic candidates, two new saturated cardanol-derived phospholipid analogs—LDT10 and LDT119—were rationally designed based on the molecular scaffold of miltefosine and biosourced from cashew nut shell liquid (CNSL). This study aimed to evaluate the pharmacokinetic properties of these compounds in silico and assess their antiparasitic activity, cytotoxicity, and morphological and ultrastructural effects on all developmental forms of T. cruzi in vitro. Materials and Methods: In silico ADMET predictions (SwissADME, pkCSM) were performed to determine bioavailability, pharmacokinetic behavior, CYP inhibition, mutagenicity, and hepatotoxicity. Antiproliferative activity was evaluated in epimastigotes, trypomastigotes, and intracellular amastigotes using dose–response assays and flow cytometry. Cytotoxicity was assessed in HEPG2 and HFF-1 cells using resazurin-based viability assays. Morphological and ultrastructural alterations were investigated through scanning (SEM) and transmission (TEM) electron microscopy. Reactive oxygen species (ROS) generation was quantified with H₂DCFDA after 4 h and 24 h of exposure. Results: In silico analyses indicated favorable drug-like profiles, high intestinal absorption (>89%), absence of mutagenicity or hepatotoxicity, and non-penetration of the blood–brain barrier. LDT10 was not a P-gp substrate, and LDT119 acted as a P-gp inhibitor, suggesting reduced efflux and higher intracellular retention. Both compounds inhibited epimastigote proliferation with low IC₅₀ values (LDT10: 0.81 µM; LDT119: 1.2 µM at 48 h) and reduced trypomastigote viability (LD₅₀ LDT10: 2.1 ± 2 µM; LDT119: 1.8 ± 0.8 µM). Intracellular amastigotes were highly susceptible (IC₅₀ LDT10: 0.48 µM; LDT119: 0.3 µM at 72 h), with >90% inhibition at higher concentrations. No cytotoxicity was observed in mammalian cells up to 20 µM. SEM revealed membrane wrinkling, pore-like depressions, rounded cell bodies, and multiple flagella, indicating cell division defects. TEM showed Golgi disorganization, autophagic vacuoles, mitochondrial vesiculation, and abnormal kinetoplast replication, while host cells remained structurally preserved. Both compounds induced significant ROS production in trypomastigotes after 24 h in a dose-dependent manner. Conclusions: LDT10 and LDT119 exhibited potent and selective in vitro activity against all developmental stages of T. cruzi, with low micromolar to submicromolar IC₅₀/LD₅₀ values, minimal mammalian cytotoxicity, and extensive morphological and ultrastructural damage consistent with disruption of phospholipid biosynthesis pathways. Combined with favorable in silico pharmacokinetic predictions, these CNSL-derived phospholipid analogs represent promising candidates for future Chagas disease chemotherapy and warrant further in vivo evaluation. Full article

This paper presents a traffic-driven scaling framework for a digital twin proxy pool (DTPP) in vehicular edge computing (VEC), designed to eliminate the latency and synchronization issues inherent in conventional digital twin (DT) migration approaches. The core innovation lies in replacing the migration of vehicle DTs between edge servers (ESs) with instantaneous switching within a pre-allocated pool of DT proxies, thereby achieving zero migration latency and continuous synchronization. The proposed architecture differentiates between short-term DTs (SDTs) hosted in edge-side in-memory databases for real-time, low-latency services, and long-term DTs (LDTs) in the cloud for historical data aggregation. A queuing-theoretic model formulates the DTPP as an M/M/c system, deriving a closed-form lower bound for the minimum number of proxies required to satisfy a predefined queuing-delay constraint, thus transforming quality-of-service targets into analytically computable resource allocations. The scaling mechanism operates on a cloud–edge collaborative principle: a cloud-based predictor, employing a TCN-Transformer fusion model, forecasts hourly traffic arrival rates to set a baseline proxy count, while edge-side managers perform monotonic, 5 min scale-ups based on real-time monitoring to absorb sudden traffic bursts without causing service jitter. Extensive evaluations were conducted using the PeMS dataset. The TCN-Transformer predictor significantly outperforms single-model baselines, achieving a mean absolute percentage error (MAPE) of 17.83%. More importantly, dynamic scaling at the ES reduces delay violation rates substantially—for instance, from 13.57% under static provisioning to just 1.35% when the minimum proxy count is 2—confirming the system’s ability to maintain service quality under highly dynamic conditions. These findings shows that the DTPP framework provides a robust solution for resource-efficient and latency-guaranteed DT services in VEC. Full article

Understanding how insects adapt to temperature is crucial to elucidating the ecological factors shaping their life history traits. Phenological models are influenced by temperature, allowing researchers to examine how temperature affects population dynamics, geographical distribution, and the management of various insect species. This study was conducted at seven constant temperatures (15.3, 20.8, 25.0, 27.0, 30.1, 35.0, and 40.0 °C) under temperature-controlled conditions in an incubator to assess temperature-dependent development of D. baccarum. Clusters of eggs were put into Petri dishes and kept in a humidity chamber. The humidity chamber was then placed inside the incubator. Temperature affected the developmental parameters and mortality of D. baccarum reared on sesame seed pods. Stage-specific parameters, including the lower developmental threshold (LDT) and thermal constant (K, in degree days [DD]), were estimated using linear (GLM) and nonlinear (Lactin2) models, respectively. Total development time from egg to adult decreased with increasing temperature. Successful development occurred between 20.8 and 35.0 °C, and failed under 15.3 and 40.0 °C (100% nymph mortality). Egg stage duration ranged from 30.56 days at 15.3 °C to 2.07 days at 40 °C, while nymphal development ranged from 64.75 days at 20.8 °C to 21.17 days at 35.0 °C. The estimated LDT and K-values were 14.22 °C and 492.22 degree days (DD), respectively. Based on these thermal requirements, we developed a predictive model to better understand population dynamics and inform pest management strategies, which can help predict the spring occurrence, number of generations, and population dynamics of D. baccarum. Full article

Despite prostate cancer being one of the most common malignancies in men, its pathological diagnosis remains plagued by inter-observer variability and diagnostic ambiguity. Traditional morphological assessment and currently available biomarkers such as PSA (Prostate-Specific Antigen), AMACR (Alpha methylacyl CoA racemase), and p63 suffer from poor specificity and clinical reliability. In this review, we present a pathogenesis-guided biomarker discovery strategy that led to the development of a clinically validated biomarker panel—Appl-1, Sortilin, and Syndecan-1. These biomarkers, which reflect fundamental biological processes within the endosome–lysosome system, offer improved diagnostic precision and prognostic utility for patients with prostate cancer. This review discusses the rationale behind their discovery, the multidisciplinary approach that enabled it, the evidence supporting their use, and their implementation in U.S. clinical practice as a lab-developed test (LDT). We propose this approach as a new diagnostic standard that bridges mechanistic insight with real-world application. Full article

LD-Transpeptidases (LDTs) are a widely conserved class of peptidoglycan (PG) crosslinking enzymes in bacteria. They are sometimes overlooked as they often act secondary to penicillin binding proteins (PBPs) under standard conditions. However, LDTs are essential in key pathogens such as Clostridioides difficile and are responsible for β-lactam resistance in Mycobacterium tuberculosis and Enterococcus faecium due their low affinity for penicillins and cephalosporins, allowing them to form LD-crosslinks when DD-crosslinking PBPs are inactivated. This role makes LDTs a promising target when developing new treatments for these pathogens. LDTs can perform different enzymatic reactions. Most commonly they reinforce the PG with 3,3-LD-crosslinks or, in a few cases, 1,3-LD-crosslinks, during stationary phase or stress responses. Some LDTs also incorporate endogenous and exogenous non-canonical D-amino acids into the PG. In many Gram-negative bacteria, specialised LDTs tether lipoproteins or outer membrane proteins (OMPs) to the PG to maintain cell envelope integrity; in some cases this regulates virulence factors. Specialised LDTs have also been implied to have roles in polar growth, toxin secretion, and symbiotic colonisation. Recent discoveries include novel subgroups of the major YkuD family and the identification of the VanW family; this has opened new research directions surrounding LDTs. We aim to understand LDTs and their roles to expand our knowledge of PG synthesis and modification and how these enzymes can be targeted for antibiotic treatment. Full article

The San Niccolò’ Tower-Gate in Florence, designed by Andrea dell’Orcagna, was built in 1328 as part of the third ring of the city walls of Florence. In the frame of a conservation project promoted by the Municipality of Florence, Belle Arti Office, the Department of Earth Sciences of the University of Florence conducted a series of studies, using NDT and LDT (No Destructive Test, Low Destructive Test) techniques, to characterize the tower’s masonry. The knowledge path followed the Italian Guide Line emitted by the Ministry of Culture for the conservation of historical buildings and the principles established by the International Restoration Charts. This knowledge path had already been tested and followed for the study of several other historical Florentine cultural heritage buildings. The first step regards the geometric survey and the 3D H-BIM restitution. Particular attention had been paid to the geological and foundation setting as an integral part of the building and to the local seismicity, too. The definition of the masonry structure and assemblages had been performed by using seismic, georadar, sonic, and sclerometric investigations. The Tower-Gate’s masonry results showed it to be very well constructed, being in the standard of the historical Florentine buildings of that time. After eight centuries since its construction, the San Niccolò’ Tower-Gate displays a good conservation condition according to the principles of Integrity and Authenticity. Full article

Day-ahead wind power forecasting is often limited to on-site Supervisory Control and Data Acquisition (SCADA) datasets without Numerical Weather Prediction (NWP) information. In this regime, practitioners extend autoregressive windows over many variables, so the input size grows with both features and lags. Many lag–feature pairs are redundant, increasing the training time and overfitting risk. A lightweight, differentiable joint gate over the lag–feature plane trained with a temperature-annealed sigmoid is proposed. Sparsity is induced by capped penalties that (i) bound the total open mass to the top-M features and (ii), within each selected feature, bound the mass to the top-k lags. An additional budget-aware off-state term pushes unused logits negative in proportion to the excess density over the $(M\times k)$ budget. A lightweight, per-feature softmax pooling head supplies the forecasting loss during selection. After training, the learned probabilities are converted into compact, non-contiguous lag–feature subsets (top-M features; per-feature top-k lags) and reused by downstream predictors. Tests on the Offshore Renewable Energy (ORE) Catapult Platform for Operational Data (POD) from the Levenmouth Demonstration Turbine (LDT) dataset show that the joint gate reduces the input dimensionality and training time while improving accuracy and stability relative to Pearson’s correlation, mutual information, and cross-correlation function selectors. Full article

Background/Objectives: The diagnosis of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacterial (NTM) infections is accomplished by three main diagnostics methods: smear microscopy, culture, and molecular testing. Diagnostic algorithms used by laboratories can significantly impact clinical and infection control management. Current Canadian Tuberculosis Standards recommend the use of nucleic acid amplification testing (NAAT) for smear-positive patients and smear-negative patients upon request. An alternative algorithm is to utilize NAAT in the Panel approach on all samples, pulmonary and extrapulmonary, to potentially reduce time to diagnosis and treatment. This alternative approach was implemented in November 2019 at the Newfoundland and Labrador Public Health and Microbiology Laboratory (NL PHML) using a laboratory-developed multiplex real-time PCR (LDT m-qPCR) assay targeting Mycobacterium spp. (Myco spp.) and MTBC, performed in parallel with smear and culture. Methods: To investigate the impact of this alternate testing approach, we conducted an observational retrospective analysis of laboratory diagnostic and treatment data, recognizing that temporal changes in epidemiology, clinical practice, and laboratory workflow may also have influenced outcomes. To complete this, study data from three years before and four years after implementation were gathered. Results: The sensitivity/specificity of the smear, m-LDT qPCR-MTBC, m-LDT qPCR-Myco spp., and culture assays in this study were 18.1%/100%, 96.7%/99.8%, 47.6%/99.0%, and 96.8%/100%, respectively. The gold standard utilized for these calculations was clinical diagnosis for active MTBC disease and culture for NTM infections, recognizing that the use of clinical diagnosis may introduce subjectivity. The Panel approach reduced the time to diagnosis of tuberculosis MTBC by 29 days (p < 0.0001) for NL PHML, and when modelled for a laboratory with rapid culture identification, diagnosis was reduced by 14 days (p = 0.003). Among non-empirically treated tuberculosis patients, the time to treatment was decreased by 25.5 days (p < 0.001). For NTM infections, rapid diagnostics only affected one patient’s treatment. This finding agrees with clinical management guidelines, which do not routinely utilize rapid diagnostics for the diagnosis of disease or treatment decisions. The cost implications of additional NAAT testing were calculated to be an increase of CAD 23.62 per sample. Conclusions: Our findings support the adoption of a molecular assay for MTBC as an initial diagnostic tool to decrease time to diagnosis and time to treatment, depending on local epidemiology and irrespective of smear status. Utilizing a molecular assay for genus level identification of NTM had minimal impact on clinical management suggesting its limited diagnostic utility in a broad population setting. Full article

TP53 genetic alterations represent a critical molecular feature in diffuse large B-cell lymphoma (DLBCL), with well-established associations with aggressive disease behavior and therapeutic resistance. However, significant controversy persists regarding the clinical utility of p53 immunohistochemical (IHC) expression as a surrogate marker. This study presents a thorough investigation of TP53 genetic alterations and their correlation with p53 protein expression in 664 cases of DLBCL. Using targeted next-generation sequencing (tNGS), we identified TP53 alterations (mutations and/or copy number losses (CNLs)) in 170 cases (25.6%). Among them, 161 cases had mutations. Concurrent analysis of copy number variations (CNVs) in 109 cases revealed TP53 CNLs in 17.4% (19/109), with 68.4% (13/19) of these showing coexisting mutations. Immunohistochemical evaluation of p53 expression in 371 cases demonstrated strong positivity (≥65% cells) in 21% (78/371), complete negativity (<1%) in 5.7% (21/371), and wild-type pattern (1–65%) in 73.3% (272/371) of cases. The p53 IHC laboratory-developed test (LDT) showed 79.2% sensitivity and 91.6% specificity for detecting TP53 alterations overall, though sensitivity varied significantly by mutation type: 86.2% for missense mutations but only 14.3% for nonsense mutations. Clinically, cases with TP53 alterations exhibited more aggressive disease characteristics, including higher ECOG performance scores, increased frequency of B symptoms, and poorer initial treatment responses (complete response rate 68.3% vs. 82.5% in wild-type cases). Most importantly, TP53 genetic alterations, but not p53 protein expression patterns, emerged as an independent prognostic factor for progression-free survival. Our findings demonstrate that tNGS effectively identifies most TP53 alterations and complementary CNV analysis enhances detection of copy number losses. The p53 IHC LDT serves as a useful but imperfect screening tool, with high specificity but variable sensitivity depending on mutation types. These results have important implications for molecular diagnostics in DLBCL, supporting the necessity for comprehensive genetic testing rather than reliance on protein expression analysis alone for accurate risk stratification and treatment planning. Full article

Background: The management of irreparable posterosuperior rotator cuff tears with an isolated loss of external rotation presents significant challenges. Latissimus dorsi tendon transfer in conjunction with medialized reverse total shoulder arthroplasty has been employed to rectify external rotation deficits; however, lateralized RTSA designs may yield similar outcomes with a reduced incidence of complications. The objective of this study was to compare the clinical outcomes of lateralized reverse total shoulder arthroplasty without latissimus dorsi tendon transfer against medialized RTSA with LDT in patients with ILER and a positive external rotation lag sign. Methods: This retrospective cohort study involved 34 patients diagnosed with CTA and severe external rotation deficiency, characterized by a positive ER lag sign and 0° active ER. The patients were treated with either lateralized reverse total shoulder arthroplasty (n = 21) or medialized RTSA with LDT (n = 13). Outcomes evaluated preoperatively and at the 24-month follow-up comprised range of motion, ER lag sign, Constant–Murley Score, SPADI, and radiographic offset parameters. Statistical analyses were adjusted for age, sex, and baseline values. Results: At follow-up, 70% of patients undergoing lateralized RTSA exhibited resolution of ER lag, compared to 23% in the LDT group (p < 0.05). Active external rotation improvement was more significant in the LDT group (34.6° compared to 18.5°, p < 0.05). However, both groups exhibited comparable final external rotation and functional scores (CMS: 63 ± 9 vs. 63 ± 16; SPADI: 73 ± 20 vs. 74 ± 22). Lateralized RTSA demonstrated superior preservation of internal rotation, as evidenced by a higher percentage of patients achieving a negative Apley scratch test (67% compared to 23%, p < 0.05). A greater glenoidal offset correlated with improved postoperative external rotation and resolution of external rotation lag. The influence of teres minor integrity was more significant in the LDT group. Conclusions: Lateralized reverse total shoulder arthroplasty without latissimus dorsi tendon transfer provides similar functional restoration of external rotation in irreparable posterosuperior rotator cuff tear patients, accompanied by reduced complications, shorter surgical durations, and improved preservation of internal rotation. LDT has the potential to provide enhanced ER gains from a low baseline; however, it is characterized by increased invasiveness and technical complexity. Prosthetic lateralization is a biomechanically effective method for restoring external rotation in patients with rotator cuff arthropathy and external rotation deficits. Full article

This study responds to the urgent need for education that fosters sustainable, self-directed development by introducing a five-phase narrative instruction pre-module grounded within the Life Design Thinking (LDT) framework. Integrating design thinking with narrative theory, LDT promotes learner agency, identity coherence, and adaptive future planning through structured autobiographical reflection. The intervention was conducted in a group setting with 14 adult learners (n = 14) from China. Although participant demographics were not the primary focus, the study emphasized theoretical and methodological development through iterative instructional design. A mixed-methods approach was employed, including rubric-based scoring of 101 written narratives and a thematic analysis of the reflective content. The results demonstrated significant improvements in narrative competence, especially in technical application (+80.91%), reflective depth (+70.0%), with thematic clarity (+58.11%), also showing notable gains related to meaning synthesis and narrative focus. Learners also exhibited enhanced thematic continuity and future-oriented integration. These outcomes highlight the value of narrative pedagogy as a transformative learning approach aligned with SDG 4.7. By cultivating metacognitive awareness and future-readiness, the module contributes to education for sustainable development and provides initial evidence for a potentially scalable and transferable model that supports learners in navigating complexity with meaning and purpose. Full article

Background: Monkeypox virus, the etiological agent of Mpox, is a double-stranded DNA virus belonging to the Orthopoxvirus genus that has attracted increasing attention due to sporadic outbreaks in humans. In 2022, it was responsible for the largest Mpox outbreak outside the African continent, infecting over 117,000 individuals worldwide. In Brazil, since the first confirmed case in June 2022, more than 13,000 people have been diagnosed with the virus. Methods: In July 2022, we developed the first molecular test for the detection of monkeypox virus in the Midwest region of the country, allowing the diagnosis of the disease in various patients, mainly residents of the Federal District. Thus, in this work, we present the validation of a laboratory-developed qPCR test (LDT) for monkeypox virus detection, as well as a retrospective epidemiological analysis based on laboratory results. Results: The developed qPCR test demonstrated 100% accuracy, with a detection limit of 21.25 copies per reaction, and was validated for samples from swabbed pustule exudates and lesion crusts. To date, 295 tests have been conducted, with 88 (30%) returning positive. The positivity rate was 41.15% in male patients and 2.41% in female patients. A peak in positivity was observed in August 2022. From 2023 to 2024, there was a marked decline in test demand with occasional positive results. Conclusions: The rapid implementation of the test by our laboratory allowed for an immediate response to patients and provided important data for understanding the dynamics of monkeypox virus spread in Brazil, particularly in the Midwest region. Full article