The agglomeration of apolar metallic nanoparticles (NPs) brings them within nanometer distances, enabling nonradiative coupling through electron conduction tunneling and plasmonic interactions. Even stronger coupling can be achieved with metallic connections between the particles. Thermally induced coarsening is often used to join particles in this way, but typically requires high temperatures. For example, the thermal coarsening of thiol-coated NPs in apolar dispersions requires heating above 120 °C to induce ligand desorption. This leads to side reactions, notably Ostwald Ripening and the formation of small particles. Here, we introduce a new method for controlled NP coarsening in apolar dispersions at near-ambient conditions. Small amounts of reactive chemical additives are added to the dispersion and thermally activated. Transmission electron microscopy and small-angle X-ray scattering reveal that adding the cyclic sulfide additive molecule tetrahydrothiophene (R5S) to a dispersion of hexadecanethiol (HDT)-coated gold nanoparticles (AuNPs) induces aggregation at temperatures as low as 40 to 60 °C. The cores form metallic joints, forming larger continuous gold bodies. An Arrhenius analysis of the temperature-dependent aggregation kinetics identifies the exchange of HDT to R5S on the gold surfaces as the rate-limiting step. Small-angle neutron scattering and thermogravimetry confirm the mechanism and indicate that ∼80% of HDT is replaced by R5S after 5 h at 50 °C. Progressive ligand exchange reduces the steric repulsion by the shells until aggregation sets in. A comparison with the larger cyclic sulfide thionane and the cyclic amine pyrrolidine, which do not induce coarsening, shows that the prerequisite for ligand desorption at moderate temperatures to enable AuNP coarsening is a small size and strong affinity of the additives to the gold surfaces.
A dual-ratiometric assay combining fluorescence and colorimetry is constructed based on a gold(I)-triggered in situ reaction between o-phenylenediamine (OPD) and ascorbic acid (AA). OPD is oxidized by gold(I) to form fluorescent 2,3-diaminophenazine (OPDox), which has an absorption peak centered at 445 nm and a fluorescence emission at 555 nm. When AA is introduced, AA can be oxidized to dehydroascorbic acid (DHAA) by gold(I), inhibiting the production of OPDox. Simultaneously, DHAA reacts with OPD to form a fluorescent quinoxaline derivative (DFQ), which exhibits an absorption peak around 340 nm and a fluorescence emission at 425 nm. Based on this redox-modulated strategy, a highly selective dual-mode sensing assay is established with ratiometric colorimetric (A₃₄₀/A₄₄₅) and ratiometric fluorescence (F₄₂₅/F₅₅₅) signals. This method enables the quantitative analysis of AA, with limits of detection (LOD) of 0.09 μmol/L and 0.04 μmol/L, respectively. Owing to its facile analytical procedure, this assay exhibits many merits including simplicity, excellent selectivity and good biocompatibility, and has been successfully applied to detect AA in human serum samples. Such an approach based on the in situ formation of fluorophores provides a valuable tool for AA detection in clinical diagnosis and drug screening.
Considering the irreversible nature of Alzheimer's disease (AD), early diagnosis is of great importance for AD treatment. Both β-amyloid (Aβ) and monoamine oxidase B (MAO-B) are potential biomarkers for AD. This study developed a surface-enhanced Raman scattering (SERS) sensor using gold-nanocube (OX-AuNCs) to detect Aβ42 and MAO-B. OX-AuNCs, a type of gold-nanocube with open gaps, achieved a Raman enhancement factor of 8.99 × 108 due to numerous hot spots. The specific affinity between Thioflavin T (ThT) and Aβ42 inhibits ThT's intramolecular rotation, reducing its SERS signal. This reduced signal showed a linear correlation with Aβ42 concentrations from 66.70 pM to 0.20 μM, achieving a limit of detection (LOD) at 44.30 pM, while also distinguishing different aggregation levels of Aβ42. Interestingly, SERS intensity of phenethylamine (PEA) also decreased significantly when interacting with MAO-B. A linear relationship was found between the change in PEA intensity and MAO-B concentration (0.01-20.00 μg mL-1), yielding an LOD of 5.00 ng mL-1. The proposed SERS sensor effectively detected two potential AD biomarkers, Aβ42 and MAO-B, in artificial cerebrospinal fluid (ACSF) and human serum with satisfactory recovery rates, respectively. These results show promise for clinical diagnosis and drug screening for AD.
Lipid-coated gold nanoparticles (LC-AuNPs) are widely explored as plasmonic nano-bio interfaces that combine membrane-mimetic surface organization with optical functionality. However, modest LSPR red-shifts and apparent salt stability are often treated as indicators of conformal bilayer formation, although population-averaged optical and colloidal measurements do not uniquely resolve nanoscale interfacial organization. Here, we compared sonication- and extrusion-based coating routes to determine how processing history governs LC-AuNP organization, plasmonic response, and colloidal stability. Hydrodynamic sizing, zeta potential analysis, spectral line-shape descriptors, PBS stability assays, electron microscopy, and semi-empirical LSPR response modeling were integrated into a unified characterization framework. Sonication-driven coating supported lipid association but produced heterogeneous populations with condition-dependent hydrodynamic sizes, reaching > 400 nm under prolonged conditions, and modest LSPR red-shifts (Δλ ≈ 2 nm) that did not uniquely resolve interparticle organization. In contrast, mechanically constrained extrusion (11 ×-13 × passes) reduced coupling-associated spectral heterogeneity, yielding optically coherent populations converging toward ∼200 nm and typically accompanied by small but reproducible blue-shifts (Δλ ≈ 0.4-1.6 nm). Incorporation of DSPE-PEG further reduced population dispersion and improved optical stability under physiological ionic strength, consistent with steric regulation of interparticle organization.Electron microscopy of DSPE-PEG-containing multicomponent formulations revealed lipid-associated layers with an apparent thickness of ∼4.6 nm, compatible with bilayer-scale organization but not diagnostic of conformal coverage across the entire population. LSPR response modeling supported a shift-direction-resolved interpretation of ensemble spectra, in which positive-shift responses were evaluated for effective dielectric/coupling contributions, whereas blue-shifted states were assessed using a physically constrained required-decoupling framework. Together, these results show that LC-AuNP plasmonic peak shifts are governed by fabrication-defined interparticle organization in addition to lipid association. The absence of a red-shift therefore does not imply the absence of lipid coating. Rather, LSPR peak position should be interpreted as an ensemble-level descriptor of processing-defined organization rather than as a direct reporter of conformal bilayer formation.
MicroRNAs (miRNAs) are emerging biomarkers for early hepatocellular carcinoma (HCC) detection, but most CRISPR-Cas12a assays rely on reverse transcription and preamplification and often lack simple visual readouts. Here, we develop a reverse transcription-free, cleavage-guided strategy that converts miRNA recognition into visual outputs. In the presence of the target miRNA, a scaffold RNA forms an active crRNA that triggers Cas12a trans-cleavage using a preformed dsDNA activator, enabling two readout formats. In a homogeneous non-crosslinking colorimetric assay (mC-NCA), Cas12a cleavage regulates π-π-stacking-mediated gold nanoparticle (AuNP) aggregation to produce a rapid visual colorimetric response. In a heterogeneous versatile lateral flow assay (mC-vLFA), the cleavage of partially hybridized DNA-magnetic bead probes generates a target-dependent test line while maintaining a built-in control line. Using miRNA-21 and miRNA-122 as targets, mC-NCA shows calculated limits of detection (LODs) of 1.62 and 1.64 fM with a linear range of 50 fM-500 pM, whereas mC-vLFA shows calculated LODs of 1.59 and 1.40 fM with a linear range of 10 fM-10 nM. In a preliminary clinical evaluation, both formats show good agreement with reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and clinical assessment while enabling faster detection with minimal instrumentation. Overall, this dual-readout platform couples RT-free CRISPR-Cas12a miRNA recognition with cleavage-directed visual signal transduction, enabling rapid and low-instrument-dependence CRISPR diagnostics for miRNAs.
Cyclic fatigue fracture remains a major concern during root canal instrumentation, particularly in curved canals. EdgeTaper Platinum and ProTaper Gold (PTG) are heat-treated nickel-titanium rotary systems designed to improve mechanical performance, but the available evidence comparing their cyclic fatigue resistance is inconsistent. This systematic review and meta-analysis was conducted to compare the cyclic fatigue resistance of these two systems. A systematic search was performed in PubMed, Scopus, Embase, EBSCOhost, and Google Scholar, along with manual searching and reference screening. No restrictions were applied for language or year of publication. In vitro studies comparing EdgeTaper Platinum and PTG for cyclic fatigue resistance were included. Data extraction and study selection were performed independently. Risk of bias was assessed using the QUIN (QUality assessment tool for IN vitro studies) tool. Quantitative synthesis was performed using a random-effects model. Seven in vitro studies were included in the qualitative synthesis, and four studies were included in the primary meta-analysis. Most individual studies reported higher cyclic fatigue resistance for EdgeTaper Platinum, although one study favored PTG and one did not show a clear direct pairwise difference. The pooled analysis demonstrated a statistically significant overall effect in favor of EdgeTaper Platinum for cyclic fatigue resistance. However, substantial heterogeneity was observed across studies, likely due to differences in canal geometry, file size, testing temperature, and environmental conditions. Within the limitations of the available in vitro evidence, EdgeTaper Platinum showed a more consistent advantage in cyclic fatigue resistance than PTG. Nevertheless, the high heterogeneity among studies suggests that this advantage is not uniform across all testing models, and more standardized comparative studies are needed.
A coherent mechanistic framework for DNA adsorption on gold nanoparticles (AuNPs) remains elusive, hindering the rational construction of spherical nucleic acids (SNAs). Here, we show that ligand-defined interfacial charge regulation, achieved using weakly ionized ascorbic acid (AA) ligands, markedly lowers the kinetic barrier for DNA chemisorption on AuNPs. Under near-neutral conditions, this interface enables rapid, sequence-general functionalization of AuNPs with both thiolated and non-thiolated oligonucleotides through simple vortex mixing, even for DNA containing only a single terminal adenine. The AA-regulated interface also overcomes the long-standing incompatibility between -butanol dehydration and non-thiolated DNA, enabling sequence-general SNA formation under dehydration conditions across multiple nanoparticle systems. Mechanistic studies indicate that AA reduces interfacial electrostatic repulsion while promoting hydrogen-bond-assisted surface interactions, and base-substitution experiments identify the adenine N6-amino group as a critical site for chemisorption. The resulting ordered DNA corona generates uniform plasmonic nanogaps, enabling reproducible, label-free SERS with single-base resolution for nucleotide discrimination and cytosine methylation analysis. This work establishes a general interfacial design strategy for constructing uniform plasmonically active nucleic acid nanostructures under mild conditions.
Achieving a harmonious symbiosis between economic prosperity and environmental sustainability remains a defining challenge for global sustainable development. This study investigates China's pioneering "Two Mountains" practice pilot zones (TMPZ) as an institutional model for resolving the "dualistic paradox" between growth and conservation. Using panel data from 1688 counties (2010-2023), we construct a multidimensional framework to evaluate residents' well-being (RWB) and evaluate its coupling coordination degree (RECCD) with ecological environment quality index (EEQI). A Double Machine Learning (DML) approach is further employed to identify the causal impacts of TMPZ on RECCD. The results reveal significant improvements in both RWB and EEQI, driving the RECCD from 0.4567 to 0.6345. All three indices maintain a consistent "Southeast-High, Northwest-Low" spatial pattern. Empirical evidence confirms that TMPZ designation not only improves ecological baselines and living standards but also effectively facilitates their synergistic evolution. These findings remain robust across various sensitivity checks. Heterogeneity analysis shows that the policy effects are most pronounced in eastern regions, non-poverty counties, and counties with high government financial investment. Mechanism tests indicate that TMPZ operates through three primary channels: intensifying environmental governance, stimulating green technological innovation, and facilitating the ecological transformation of industrial structures. By providing systemic evidence on how institutional innovation converts "ecological advantages" into "developmental momentum," this research offers a vital "Chinese Template" for developing nations striving to achieve the United Nations Sustainable Development Goals (SDGs) while balancing human prosperity and planetary health.
To identify barriers that audiologists face in adopting telemedicine in adult cochlear implant care, and to determine what is needed to overcome these barriers. Prospective mixed-methods anonymous online survey of cochlear implant audiologists working with adults in the United Kingdom. Thirty-one complete responses were received in August - September 2024. Eighty-seven percent (27) had used remote care tools in their care of adults with cochlear implants. Twenty-nine percent (9) had never used remote care tools or used them rarely; no respondents used them daily. Sixty-eight percent of respondents reported frequent technical issues with remote care tools. Respondents were split equally when asked if remote care is less effective than in-person care, but 81% felt that the gold standard of clinical care is in-person care. Barriers to remote care could be overcome by improvements and enhancements to the cochlear implant manufacturers' tools, and easier and fuller integration into patient pathways and systems. The main barriers to audiologists using remote care were frequent technical problems and the perception that the gold standard of clinical care was in-person care. When telemedicine offers a seamless, accessible, person-centred care experience, perceptions about the gold standard of care may change.
Early detection of Acute Kidney Injury (AKI) remains a clinical challenge, requiring rapid and sensitive monitoring of biomarkers like Neutrophil Gelatinase-Associated Lipocalin (NGAL). This study presents a flow-enhanced electrochemical aptamer-based (E-AB) biosensor designed for the nanomolar detection of NGAL in complex matrices. By integrating optimised hydrodynamic flow (35 μL/min) with miniaturised gold microelectrodes, we leveraged enhanced mass transport and radial diffusion to significantly improve analyte flux and binding kinetics. A critical finding was the role of the protein matrix in surface passivation; the inclusion of 4% BSA resulted in a >20-fold sensitivity improvement compared to standard PBS buffer, attributed to additional passivation during measurement. This synergistic approach enabled a limit of detection (LOD) of 0.2 nM with a dynamic range spanning 0.2-24 nM. As a preliminary proof-of-concept, the clinical utility was validated using unprocessed human plasma samples from AKI patients, demonstrating a moderate correlation (R2 = 0.7731) with gold-standard ELISA measurements and accuracy in clinical risk stratification. These results highlight the potential of flow-enhanced E-AB sensors for continuous, near-real-time monitoring of critical biomarkers in clinical settings.
The significant cross-reactivity between bovine, ovine, and caprine pregnancy-associated glycoproteins (PAGs) enables the adaptation of bovine-specific diagnostics for use in other ruminants; consequently, the Alertys OnFarm Pregnancy Test (AOFPT)-a blood-based lateral flow assay-provides a rapid and practical solution for pregnancy detection directly at the animal's head under field conditions. This study evaluated to assess and validate the performance of AOFPT in goats at days 21 and 28 post-mating, by comparing the results with serum progesterone (P4) analysis and using transabdominal ultrasonography (TAUS) as the gold standard. The study involved 85 Kilis goats, five months post-partum. Estrus was synchronized using an 11-day progestagen device, d-cloprostenol, and PMSG. Whole blood and serum samples were collected on Days 21 and 28 post-mating. AOFPT was performed on-farm immediately after collection. For validation, serum progesterone concentrations were measured via electrochemiluminescence immunoassay, and TAUS was performed on Days 35 and 42, with Day 42 findings serving as the gold standard. Results indicated that on Day 21, AOFPT sensitivity, specificity, positive predictive value, and negative predictive value were 79.4%, 93.8%, 98.2%, and 51.7%, respectively. By Day 28, these metrics reached 100%, 81.3%, 95.8%, and 100%. Statistical agreement between AOFPT and the reference method was K = 0.55 (82.14%) on Day 21 and K = 0.87 (96.43%) on Day 28 (p <0.001). Median ± interquartile range (IQR) of P4 concentrations were 5.95±2.60 ng/mL on day 21 and 6.92 ± 2.93 ng/mL on Day 28. AOFPT-identified pregnant goats exhibited significantly higher P4 levels (p < 0.001) than non-pregnant goats on Day 21 (5.98 ± 3.21 vs. 4.05 ± 5.46) and Day 28 (6.84 ± 3.06 vs. 0.75 ± 5.96). AOFPT demonstrated accuracy and reliability closely matching P4 measurements and the reference method. This test provides a practical tool for early on-farm pregnancy diagnosis in goats, potentially enhancing reproductive management and productivity in dairy goat farms and large herds.
The limit of detection (LOD) is a key parameter for determining the lowest measurable analyte concentration. Despite the widespread use of theoretical equations to estimate LOD, significant discrepancies are often observed between calculated and empirically achievable values. This study critically examines these discrepancies by applying multiple calculation approaches - including blank signal statistics, error propagation, and graphical methods - to square-wave voltammetry (SWV) and differential pulse voltammetry (DPV) measurements of [Fe(CN)6]3-/4- at a gold electrode. The results reveal that commonly used equations can yield LOD values that differ from experimental observations by up to an order of magnitude, depending on the technique and calculation method. Critically, we demonstrate that numerous literature reports incorrectly equate the limit of detection with the limit of quantification (LOQ), leading to overoptimistic sensitivity claims. Furthermore, we revisit the mechanistic understanding of the [Fe(CN)6]3-/4-/Au system, showing that the gold electrode is not inert but participates via Au(CN)2- formation, which contributes to signal instability at low concentrations. Based on these findings, we propose a statistically rigorous experimental framework for empirical LOD determination that accounts for matrix effects and electrode stability, thereby improving the reliability of electroanalytical methods for real-world applications.
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. In recent years, both clinical guidelines and therapeutic options have evolved significantly. The aim of the DELFIN COPD 2 study (Deutsche Expert*innenbefragung: Leitlinien, Fakten, Informationen, Nutzereinschätzungen zur COPD 2), was to provide an up-to-date overview of outpatient care for COPD patients led by pulmonologists in Germany. As part of a nationwide cross-sectional survey, 377 office-based pulmonologists were interviewed using a standardised questionnaire between March and October 2024. Data were analysed descriptively.The results show that fixed combinations of long-acting muscarinic antagonists (LAMA) and long-acting beta-agonists (LABA) are commonly used as the preferred initial therapy in clinical practice. Many pulmonologists consider twice-daily inhalation beneficial, particularly in cases of evening and night-time symptoms. The majority of respondents observe the circadian pattern of COPD symptoms. They attribute this to a combination of physiological changes, waning medication effects and insufficient nocturnal ventilation. International recommendations, especially those from the Global Initiative for Chronic Obstructive Lung Disease (GOLD), play a key role in therapeutic decision-making, whereas economic factors, such as rebate contracts with health insurance providers, are less influential. Correct inhaler use is typically demonstrated by practice staff. Two-thirds of respondents offer smoking cessation support and half use digital tools to assist with patient care.DELFIN COPD 2 highlights the typical challenges of managing COPD in an outpatient setting, such as underutilisation of digital support options. Key elements of future COPD care include consistent smoking cessation efforts, personalised treatment strategies and greater integration of digital health tools. Die chronisch obstruktive Lungenerkrankung (COPD) zählt weltweit zu den häufigsten Todesursachen. In den letzten Jahren haben sich sowohl Leitlinien als auch Therapieoptionen deutlich weiterentwickelt. Ziel der Versorgungsstudie DELFIN COPD 2 (Deutsche Expert*innenbefragung: Leitlinien, Fakten, Informationen, Nutzereinschätzungen zur COPD 2) war es, ein aktuelles Bild der lungenfachärztlichen Versorgung von COPD-Patientinnen und -Patienten in Deutschland zu erheben. Im Rahmen einer bundesweiten Querschnittsbefragung wurden zwischen März und Oktober 2024 insgesamt 377 niedergelassene Pneumologinnen und Pneumologen mittels eines standardisierten Fragebogens interviewt. Die Auswertung erfolgte deskriptiv.Die Ergebnisse zeigen, dass Fixkombinationen aus langwirksamen muskarinergen Antagonisten (LAMA) und langwirksamen Beta-2-Agonisten (LABA) in der Praxis als bevorzugte Initialtherapie eingesetzt werden. Insbesondere bei Symptomen in den Abend- und Nachtstunden bewerten viele Pneumologinnen und Pneumologen die zweimal tägliche Inhalation als vorteilhaft. Die zirkadiane Rhythmik der COPD-Symptomatik wird von der Mehrheit der Befragten beobachtet. Ursachen hierfür sehen sie in einer Kombination aus physiologischen Veränderungen, nachlassender Medikamentenwirkung und unzureichender nächtlicher Ventilation. Internationale Empfehlungen wie der Bericht der Global Initiative for Chronic Obstructive Lung Disease (GOLD) sind für die Therapieentscheidung maßgeblich, während wirtschaftliche Aspekte wie Rabattverträge mit Krankenkassen eine geringere Rolle spielen. Die korrekte Inhalationstechnik wird mehrheitlich durch das Praxisteam geschult. Zwei Drittel der Befragten bieten Tabakentwöhnung an, etwa die Hälfte nutzt digitale Begleittools.DELFIN COPD 2 zeigt typische Herausforderungen in der ambulanten Versorgung, wie z. B. ungenutzte digitale Potenziale. Für eine zukunftsorientierte COPD-Versorgung sind konsequente Rauchentwöhnung, individualisierte Therapien und eine stärkere digitale Unterstützung zentrale Punkte.Schlüsselwörter: COPD, Praxisbefragung, Deutschland, Inhalationstherapie, zirkadianer RhythmusEingereicht am 4. Dezember 2025 – Revision akzeptiert am 30. März 2026.
Osteoarthritis (OA) is a degenerative joint disease that frequently affects the knee, particularly in older adults. Asymptomatic atherosclerosis (AS) in femoral and popliteal arteries may complicate surgical outcomes in patients undergoing total knee arthroplasty (TKA). (A narrative review. Arthroplasty, 4(1), 11). This study aimed to assess the prevalence of AS in advanced knee OA and evaluate the role of Doppler ultrasonography in preoperative vascular risk assessment. This cross-sectional study included 121 patients over 40 years of age with Kellgren-Lawrence grade III and IV knee OA. Bilateral Doppler ultrasonography was performed to measure peak systolic velocity (PSV) in the common femoral and popliteal arteries. Thresholds of 120 cm/sec (femoral) and 80 cm/sec (popliteal) were considered significant for stenosis. Correlation analyses were performed between Doppler parameters and clinical factors including BMI, symptom duration, and comorbidities. The prevalence of asymptomatic AS was 34.7% in the femoral artery and 36.6% in the popliteal artery. Abnormal waveforms were observed in 22.7% of femoral and 13.6% of popliteal arteries. PSV values correlated significantly with KL grade (femoral r = 0.513, popliteal r = 0.468, p 0.001) and with clinical risk factors such as higher BMI, longer symptom duration, hypertension, and smoking. ROC analysis showed high discriminatory power of PSV values for predicting OA severity. A high prevalence of asymptomatic AS was observed in patients with advanced knee OA. Doppler ultrasonography proved effective in identifying vascular risk factors, suggesting its value in preoperative planning for TKA. Incorporating vascular screening, particularly in patients with high BMI, smoking, or hypertension, may reduce postoperative complications. Further studies with gold goldstandard imaging validation are recommended.
Adequate bowel perfusion is essential for anastomotic healing in colorectal surgery. Indocyanine green (ICG) fluorescence angiography (FA) is currently considered the gold standard for intraoperative perfusion assessment. Laser speckle contrast imaging (LSCI) is an emerging, dye-free technology that enables real-time evaluation of microvascular blood flow. The aim of this study is to assess the feasibility of LSCI in elective colorectal surgery and to compare its performance with ICG-FA for intraoperative evaluation of bowel perfusion. A prospective study was conducted including consecutive patients undergoing elective laparoscopic colorectal surgery between September 2025 and March 2026. Bowel perfusion was assessed intraoperatively using both LSCI and ICG-FA. The primary endpoint was feasibility of LSCI, while the secondary endpoint was concordance between these two technologies in determining the bowel section line. Twenty-two patients were included: 7 right hemicolectomies, 11 left hemicolectomies, and 4 anterior rectal resections. LSCI and ICG-FA were successfully performed in all cases (100%). Overall concordance between LSCI and ICG-FA was 86.2%. Concordance was 100% for ileum and 57.1% for transverse colon in right hemicolectomy, 100% in left hemicolectomy and 75% in anterior resection of the rectum. Two postoperative complications were observed, both following anterior resection of the rectum: one patient developed postoperative ileus (Clavien-Dindo I), and one patient developed abdominal pain, fever of unknown origin, and intra-abdominal fluid collection requiring revision surgery, which did not reveal an anastomotic leak (Clavien-Dindo III-b). Mean hospital stay was 6 ± 4 days. LSCI appears to be a feasible tool for intraoperative assessment of bowel perfusion, demonstrating high concordance with ICG-FA. Its dye-free and real-time capabilities make it a promising adjunct to ICG-FA. Larger prospective, multicentre, randomized studies are warranted to further define the clinical impact of LSCI in evaluating bowel vascularization and its potential role in improving surgical outcomes.
En-bloc excision with limb salvage is the gold standard for aggressive bone tumors around the knee, but up to 15% of cases occur in skeletally immature patients, creating a risk of limb-length discrepancy. Growing distal femoral prostheses with passive sliding tibial components address this issue but introduce unique mechanical challenges and potential complications. This study aimed to evaluate the incidence of tibial pain and complications beneath extendable distal femoral endoprostheses, and to correlate clinical symptoms and revision surgery. The study comprised a retrospective review of 31 extendible distal femur endoprostheses from a single tertiary institution between 2008 and 2018. Measurements of radiographic parameters included coronal alignment, cortical thickness, cortical stem distances, stress shielding, and pedestal and periosteal reaction. The radiographic features were correlated with clinical evidence of tibial pain and the need for subsequent revision of the tibial component. 17 patients reported tibial pain during the follow-up period, with a mean time of onset of 62.2 months (range, 27-132). There were 14 revisions in 12 patients, 4 revisions for tibial pain. Stress shielding and pedestal formation were seen in all patients after 28 months following insertion. Lateral cortical hypertrophy was more prominent in the group with pain with a mean thickness of 5.8 mm (range, 4-9.8). Varus shift of the tibial stem was radiographically evident during follow-up (n = 18). 95% of the patients with tibial pain had radiographic evidence of stem migration, 88% showed a periosteal reaction, and 76% had varus malalignment. In 13 patients (76%) with pain, all three of these parameters were present. There is a strong correlation between radiographic evidence of tibial stem migration and periosteal reaction and the development of symptoms. Patients should be warned of the need for revision of the tibial component for pain during the lifetime of the implant. IV.
Klebsiella pneumoniae is a WHO critical-priority pathogen associated with a substantial antimicrobial resistance (AMR) burden. Conventional microbiology workflows, including antimicrobial susceptibility testing, often require 36-72 hours, prolonging empirical therapy and contributing to antibiotic overuse. Artificial intelligence (AI) has emerged as a promising approach for enhancing the detection and prediction of antimicrobial resistance. We searched four databases (PubMed, EMBASE, MEDLINE, and CENTRAL) from 1 January 2010 to 3 January 2026 for peer-reviewed, original research studies evaluating AI methods for the detection and/or prediction of AMR in K. pneumoniae. Studies without K. pneumoniae-specific extractable outcomes were excluded. Data on study characteristics, input modalities, AI methods, performance, workflow gains, and validation methods were extracted and narratively synthesised. Risk of bias was assessed using PROBAST and QUADAS-2 according to study design. Fifty-seven studies were included, with publication output accelerating sharply in 2024-2025 (27/57, 47.4%). Most studies originated from East Asia and predominantly aimed to classify resistance phenotypes from pre-AST data (37/57, 64.9%) using machine learning approaches. MALDI-TOF mass spectrometry was the most common input modality (27/57, 47.4%), followed by genomic sequencing and vibrational spectroscopy (12/57 each, 21.1%). Random forests were the most frequently studied model family (28/57, 49.1%), with high reported discrimination. Among AUROC/AUC-primary studies, 26/35 (74.3%) reported best-model performance ≥0.90; however, overall risk of bias was high, present in 45/57 studies (78.9%). Internally validated study designs predominated, with external validation reported in only 17/57 studies (29.8%), and prospective, real-world evaluation in 1/57. AI-based AMR prediction and detection in K. pneumoniae is advancing rapidly, with MALDI-TOF-enabled approaches appearing most readily translatable to clinical microbiology workflows. However, the field remains dominated by retrospective, internally validated studies, often using imperfect automated susceptibility systems as reference standards. Progress now depends on rigorous external and prospective multicentre validation using geographically diverse datasets. Klebsiella pneumoniae is a bacterium that can cause serious infections, especially in people admitted to hospital. Many strains are now resistant to antibiotics, which means some medicines no longer work well. Standard laboratory tests to find the right antibiotic usually take 36 to 72 hours. During this time, doctors often need to start treatment with broad-spectrum antibiotics before the full results are ready, which can contribute to antibiotic resistance. We reviewed published studies to understand whether artificial intelligence (AI) could help identify antibiotic resistance in Klebsiella pneumoniae more quickly. AI is a type of computer system that can look for patterns in complex data. We found 57 studies published between 2018 and 2025. Most looked at whether AI could use information already produced in the microbiology laboratory, especially from a common test called “MALDI-TOF mass spectrometry” (a test that identifies bacteria from their protein “fingerprint”), to predict resistance earlier than standard testing. Studies predominantly originated from East Asia. Most reported good accuracy, and almost half said AI could provide faster results than usual laboratory methods. This means AI could help doctors choose better antibiotics sooner and reduce unnecessary use of broad-spectrum treatment. However, we identified some important limitations. Most studies tested the AI on past data rather than in real-time patient care. In some studies, the AI learned from automated systems rather than the best available (“gold standard”) methods, meaning it may reproduce their weaknesses. More real-world studies across different hospitals are needed before AI can be used safely.
Coronary Microvascular Dysfunction (CMVD) can lead to myocardial ischemia and increase the risk of adverse cardiovascular events. In clinical practice, early and accurate diagnosis of CMVD is essential for effective intervention and management. However, because CMVD and obstructive coronary artery disease share similar clinical presentations, distinguishing CMVD remains challenging. We conducted a narrative review by searching PubMed, Web of Science, and Google Scholar. Two reviewers independently screened studies and extracted technical and clinical details from the included articles. This review elaborates on noninvasive tools for CMVD evaluation. Positron Emission Tomography (PET) quantifies Myocardial Blood Flow (MBF). Cardiovascular Magnetic Resonance (CMR) provides a quantitative myocardial perfusion reserve index. Myocardial computed tomography perfusion, in static or dynamic modes, enables concurrent anatomic and functional assessment. Echocardiography includes transthoracic Doppler-derived coronary flow reserve and myocardial contrast echocardiography for bedside perfusion evaluation. SPECT supports MBF quantification in selected settings. CMVD pathobiology is reflected in circulating biomarkers, with microRNAs showing promise. Artificial Intelligence (AI) and computational fluid dynamics can further assist in noninvasive CMVD diagnosis. Each imaging modality has distinct strengths and limitations. Blood biomarkers and computational models are promising for scalable clinical use, but require confirmation in prospective studies. Cardiovascular imaging and circulating biomarkers reveal CMVD-related changes in anatomy, hemodynamics, and metabolism, while computational models can improve diagnostic precision. Future research should include large, multicenter, prospective studies, such as trials comparing the diagnostic accuracy of AI-enhanced CMR with the invasive gold standard, the index of microvascular resistance, to validate these methods and establish integrated, cost-effective diagnostic pathways for early CMVD detection across diverse cohorts.
To evaluate the clinical performance of two novel self-contained darkroom refractive screeners (Columba 300, YD-SX-A) and a traditional tabletop autorefractor (Topcon KR8800) in refractive screening for children and adolescents, using cycloplegic retinoscopy (CR) as the gold standard, and to provide evidence for equipment selection. A total of 1354 participants aged 6-18 years were enrolled from December 2025 to February 2026. Non-cycloplegic measurements were performed sequentially with the three devices, followed by CR after cycloplegia with 0.5% tropicamide. Statistical analyses included Wilcoxon signed-rank test, Bland-Altman analysis, linear regression, and ROC curve analysis. The prevalence of myopia, hyperopia, and astigmatism measured by CR was 73.2%, 15.0%, and 35.8%, respectively. All three devices showed strong positive correlation with CR in spherical equivalent (SE, r > 0.9), with Topcon KR8800 presenting the optimal correlation and consistency. YD-SX-A had the smallest mean difference in cylinder power with CR. All devices achieved excellent myopia diagnostic efficacy (AUC > 0.95), while Topcon KR8800 was superior in hyperopia and astigmatism diagnosis. Topcon KR8800 has the highest accuracy for clinical precise screening. Columba 300 and YD-SX-A are portable, rapid, and sensitive for myopia screening, suitable for large-scale preliminary screening. A two-level "initial screening-confirmation" process is recommended for myopia prevention and control in children and adolescents.
The reciprocal evolutionary processes among phytophagous insects and host plants involve host shift in the herbivorous insects in response to defense chemicals, such as plant-derived terpenoid compounds that comprise a key element for adaptive radiation, leading to chemosensory diversification. To reveal the multimodal chemosensory targets mediating avoidance behavior of insects in response to irritant stimuli, in this study, we explored multimodal target molecules toward (-)-α-thujone, a bicyclic monoterpenoid compound, focusing on the red flour beetle, Tribolium castaneum. The area-preference test revealed significant avoidance behavior in adult T. castaneum toward (-)-α-thujone. We applied systemic RNAi methodology to knock down hypothesized targets; knocking down the resistance to a dieldrin (Rdl) subunit comprising a γ-aminobutyric acid (GABA)-activated receptor significantly suppressed the avoidance behavior toward (-)-α-thujone, rather than l-menthol. Avoidance behaviors were significantly suppressed after knocking down thermo (TcTRPM) and non-thermo (TcTRPL) TRP channels. Subsequently, quantitative reverse transcription (qRT)-PCR-based spatial expression analysis of TcRdl and TcTRPL revealed high TcRdl transcript expression in the head, followed by the antenna, and prominent TcTRPL transcript expression in the head. Furthermore, the reduced avoidance behavior in antenna-dissected and knockdown of the olfactory receptor coreceptor (TcOrco) lines confirmed the involvement of antenna in the underlying mechanism. The results reflected potential molecular targets including non-thermo TRP channel involved in (-)-α-thujone-mediated avoidance behavior in T. castaneum and indicated multimodality, as exhibited by N,N-diethyl-3-methylbenzamide (DEET), the gold standard of repellent, providing useful insight for further research on the development of new repellents and excito-repellents. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.