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Deep learning-based ordinal classification overcomes subjective assessment limitations in intraoral free flap monitoring

Engineered vesicles enhance oral antibiotic absorption in proximal small intestine and mitigate gut dysbiosis

Enhancing rapeseed germination by nano zinc oxide and zinc sulfate particles under interrupted irrigation

Abstract The manuscript investigates the effect of zinc oxide nanoparticles and zinc sulfate (applied singly or in combination) on seed germination traits of four spring rapeseed cultivars, including three open-pollinated varieties (Delgan, Zafar, and RGS003) and the hybrid variety Hayola 50, under varying drought stress conditions imposed on the mother plants. The study employs a split–plot design over two years, assessing several germination and vigor indices. The results showed that application of zinc fertilizer in the form of a combination of foliar application of zinc sulfate and zinc oxide nanoparticles (at a concentration of 5 ppm) to the mother plant at three growth stages, namely germination, flowering, and pod formation, generally improves germination performance, especially under drought stress.

Ultrasensitive multi-degree-of-freedom piezoionic sensor via synergistic hydrogel-ion interactions

Transcriptional responses in feeder time-trained foragers suggest diverse interactions between the circadian clock and mushroom bodies in honey bees

Machine learning-assisted kinetic matching model for rational electrode design in aqueous zinc-ion batteries

Enhancing healthcare classification with hybrid multimedia data processing and deep learning TNBO FCNN approach in IoT-enabled environments

The consequences of using statistical tests on proxy measurements in place of gold standard measurements: an application to magnetic resonance spectroscopy

Abstract The use of proxy measurements in biomedical science is ubiquitous, due to the infeasibility or unavailability of gold-standard (i.e., most precise, accurate, and/or validated) measurements. For example, in magnetic resonance spectroscopy (MRS), short-echo time (TE) sequences are frequently employed to estimate difficult-to-measure metabolites such as GABA, despite J-difference editing being the recommended gold-standard due to improved metabolic specificity. This work investigates the critical relationship between the correlation of proxy and gold-standard measurements and the associated false positive (FPR) and false negative (FNR) rates of statistical tests performed on proxy measurements. Through statistical simulations, we demonstrate that even moderately high correlations (0.6–0.7), reported in the literature for short-TE vs. J-edited estimated GABA, can lead to drastically inflated FPRs and FNRs. We show that these rates are highly sensitive to the magnitude of differential bias in the proxy measurement (δ) and the underlying true effect size (Δ). For instance, a small, unmeasured bias in short-TE estimated GABA, potentially arising from macromolecule contamination, can substantially inflate FPRs. Conversely, imperfect correlation can substantially reduce statistical power, leading to high FNRs, which may explain some discrepancies within the literature. Although this work focuses specifically on the relationship between short-TE and MEGA-edited GABA, the arguments presented here apply more broadly to other difficult-to-measure metabolites in MRS (e.g., glutathione, 2-hydroxyglutarate), or generally to any circumstance where statistical tests are performed on the readily available proxy measurements in place of gold-standard measurements.

Failure mechanisms of energy redistribution in excavation roadways: experimental and numerical investigation

An application of FBGs sensors to measuring the strains of industrial boiler hanger rods

Babesiosis precipitating immune thrombotic thrombocytopenic purpura

Molecular propensity and stress tolerance of dehydrins from desert plants

Domain and residue mapping of autoantibodies to β2GPI reveals differences among antiphospholipid syndrome phenotypes

Abstract Antiphospholipid antibodies targeting β2-glycoprotein I (β2GPI) are a hallmark of antiphospholipid syndrome (APS), associated with an increased risk of thrombosis and pregnancy morbidity. Among these, antibodies targeting domain I (DI) are common in individuals at higher risk; however, their epitopes and prevalence among APS phenotypes remain unclear. Here, we use a large collection of 29 structurally and functionally validated β2GPI variants to provide new insights into the molecular mechanisms of autoantibody recognition in APS. Using the prototypic human-derived monoclonal anti-DI antibody MBB2, we identified positively charged residue R39 as the key driver of MBB2 binding, followed by residues R43, N56, and T57. Structural analyses revealed that although R39 is solvent exposed, R43 is not, because it is caged by residues N56 and T57. The narrow epitope footprint explains why MBB2 exhibits a modest affinity for soluble β2GPI. The cage structure accounts for the epitope being conformational rather than linear. Mutational analyses of immunoglobulin G anti-β2GPI antibodies from 52 patients with triple-positive APS, 37 with a history of thrombosis and 15 nonvascular obstetric patients, confirmed significant reactivity against DI and showed signatures of 2 conformational epitopes: one similar to MBB2 (epitope I), in which the presence of R39 is essential, and another that does not require R39 (epitope II). Although less frequent than epitope II in our cohort, epitope I reactivity was notably enriched in patients with vascular-obstetric APS. Varying epitope specificities for DI may therefore aid in identifying different APS phenotypes and predicting clinical outcomes.

Minimal time robust control for two superconducting qubits

Abstract High-fidelity quantum gates are crucial for achieving fault-tolerant quantum computing; however, decoherence significantly reduces gate fidelities during long operation times. Although optimal control techniques can theoretically minimize these operation times, they often neglect realistic uncertainties in system parameters. In this work, we demonstrate that by using robust optimal control strategies, the cross-resonance gate in superconducting systems can be operated within 64 ns, achieving fidelities of $$\mathcal {F} > 0.99$$ while maintaining robustness against up to 10% uncertainty in a single parameter. Alternatively, by extending the control time to 71 ns, we achieve fidelities of $$\mathcal {F} > 0.999$$ with robustness against up to 3% uncertainty. Our results identify the minimal control times attainable with experimentally feasible pulses and system parameters, as well as the maximum allowable static parameter error for high-fidelity operations. Furthermore, we demonstrate simultaneous robustness against both static and time-dependent errors by generating 100 ns control pulses ( $$\mathcal {F} > 0.99$$ ) that maintain robustness against 10% static parameter error and time-dependent parameter fluctuations two orders of magnitude stronger than typical experimental noise. These findings demonstrate a viable open-loop strategy for implementing fast, high-fidelity quantum gates in the presence of realistic system uncertainties that would otherwise degrade conventional control pulses.

CD371-targeted CAR T cells secreting interleukin-18 exhibit robust expansion and clear refractory acute myeloid leukemia

Abstract Success of chimeric antigen receptor (CAR) T-cell therapy in lymphoid malignancies has not yet been recapitulated in acute myeloid leukemia (AML). We developed CAR T cells targeting CD371 with a mutated CD28 costimulatory domain to limit T-cell exhaustion, and constitutive interleukin-18 (IL-18) secretion to enhance immune function (CD371/SAVVY/IL-18 CAR). We initiated a phase 1 trial (NCT06017258), successfully manufactured and administered CD371/SAVVY/IL-18 CAR T cells in 5 patients with relapsed/refractory AML and observed expansion following a single infusion of 3 × 104 or 3 × 105 CAR T cells per kg; 3 patients refractory to ≥5 lines of therapy and postallogeneic transplant exhibited AML clearance and no evidence of graft-versus-host disease. Dose-limiting toxicity in the 2 patients treated with 3 × 105 CAR T cells per kg dose (prolonged cytopenias with marrow hypoplasia; severe cytokine release syndrome) led to dose reduction to 3 × 104 CAR T cells per kg in the following 3 patients. Single-cell analyses revealed that circulating CAR T cells in responders included predominantly cytotoxic CD8+ effector T cells 2 weeks after infusion while coexisting natural killer (NK) cells expressed markers of activation. This pilot study highlights the activity of low-dose IL-18 “armored” CAR T cells against refractory AML and their potential to promote CAR T-cell cytotoxicity and innate endogenous antitumor immunity. This trial was registered at www.ClinicalTrials.gov as #NCT06017258.

SkinAttn-Net: a multi-level attention-based network for skin lesion segmentation

Asquith NL, Carminita E, Camacho V, et al. The bone marrow is the primary site of thrombopoiesis. <i>Blood</i> . 2024;143(3):272-278.

Explainable machine learning identifies immune-inflammatory biomarkers and therapeutic candidates in drug-resistant epilepsy

Alternative AAV gene therapy for hemophilia A using expression of Bi8, a novel single-chain FVIII-mimetic antibody

Abstract The recent approval of adeno-associated virus (AAV)–based gene therapies for hemophilia A (HA) represents a major advancement in the management of this X-linked bleeding disorder, offering multiyear bleed protection and improved quality of life over factor VIII (FVIII) replacement. However, challenges remain, including concerns over long-term durability of expression and the difficulty of packaging the oversized FVIII transgene into AAV vectors. To address these limitations, we developed AAV8-Bi8, a liver-directed gene therapy encoding Bi8, a novel 54.5-kilodalton FVIII-mimetic antibody. Bi8 is expressed as a compact, single-chain tandem, single-chain fragment variable, and is delivered via a 4.4-kilobase expression cassette packaged within AAV8 capsids, well within the vector packaging capacity. In vitro, Bi8 demonstrated FVIII-mimetic activity, and effectively corrected FVIII-deficient human plasma to levels comparable with emicizumab, the current market standard. In vivo, a single administration of AAV8-Bi8 in FVIII-deficient mice resulted in dose-dependent, durable expression of Bi8, complete phenotypic correction of bleeding, and therapeutic equivalence to both emicizumab-treated and wild-type animals. Importantly, no toxicity or antidrug antibody responses were observed. This approach, based on delivering FVIII-mimetic antibodies through AAV rather than truncated FVIII transgenes, could provide a more flexible and efficient platform for gene therapy in HA. AAV8-Bi8 has the potential to offer sustained, lifelong hemostatic control, including in patients who have developed inhibitors to FVIII.

Species richness and Spatial distribution of three Pieridae subfamilies across mainland China under past and future climates