Browse Articles

Deferential nephrotoxicity effect of lanthanum oxide nanoparticle responses to concentration and time in vivo

Optimizing structured surfaces for diffractive waveguides

Abstract We introduce universal diffractive waveguide designs that can match the performance of conventional dielectric waveguides and achieve various functionalities. Optimized using deep learning, diffractive waveguides can be cascaded to form any desired length and are comprised of transmissive diffractive surfaces that permit the propagation of desired modes with low loss and high mode purity. In addition to guiding the targeted modes through cascaded diffractive units, we also developed various waveguide components and introduced bent diffractive waveguides, rotating the direction of mode propagation, as well as spatial and spectral mode filtering and mode splitting diffractive waveguide designs, and mode-specific polarization control. This framework was experimentally validated in the terahertz spectrum to selectively pass certain spatial modes while rejecting others. Without the need for material dispersion engineering diffractive waveguides can be scaled to operate at different wavelengths, including visible and infrared spectrum, covering potential applications in, e.g., telecommunications, imaging, sensing and spectroscopy.

Fluorescence-guided ureteral identification in robotic surgery for advanced endometriosis: a comparison of junior versus senior surgeons

A self-directed Trojanbot-enzymatic nanobot in neutrobot for active target therapy of glioblastoma

Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy

Directly printed standing ceramic circuit boards for rapid prototyping of miniaturization and high-power of electronics

The effect of pericapsular nerve group block and lateral femoral cutaneous nerve block on postoperative recovery after hip arthroplasty

Functional recruitment and connectivity of the cerebellum is associated with the emergence of Theory of Mind in early childhood

Abstract There is accumulating evidence that the human cerebellum is heavily implicated in adult social cognition. Yet, its involvement in the development of Theory of Mind (ToM), a hallmark of social cognition, remains elusive. Using openly available functional MRI data of children with emerging ToM abilities (N = 41, age range: 3-12 years) and adults (N = 78), we show that children who pass a false-belief assessment of ToM abilities activate cerebellar Crus I-II in response to ToM events during a movie-watching task, similar to adults. This activation is not statistically significant in children who do not pass the ToM assessment. Functional connectivity profiles between cerebellar and cerebral ToM regions differ as a function of children’s ToM abilities. Notably, task-driven connectivity shifts from upstream to downstream connections between cerebellar and cerebral ToM regions from childhood to adulthood. Greater dependence on connections emerging from the cerebellum early in life suggests an important role of the cerebellum in establishing the cognitive processes underlying ToM in childhood and thus for the undisrupted development of social cognition.

An explorative study on movement detection using wearable sensors in acute care hospital patients

Single-cell microRNA-mRNA co-sequencing techniques convey large potential for understanding microRNA regulations but require careful and systemic approaches

Boosting oxygen reduction performances in Pd-based metallenes by co-confining interstitial H and p-block single atoms

Ca2+-dependent cytoplasmic and nuclear phosphorylation of STOP1 by CPK21 and CPK23 confers ALMT1-dependent aluminum resistance

Reshaping the landscape of locoregional treatments for breast cancer liver metastases: A novel, intratumoral, p21-targeted percutaneous therapy increases survival in BALB/c mice inoculated with 4T1 triple negative breast cancer cells in the liver

Patients with disseminated metastatic disease from breast cancer are likely to have liver involvement in >50% of cases at some point during disease progression. These patients have a poor prognosis; and, when treated with the standard of care systemic therapy they have a median survival of <9-months. Increasing survival in breast cancer patients will likely require the administration of better therapies that are specifically targeted to treat distant metastases. One approach to increasing treatment efficacy for breast cancer liver metastases is through the application locoregional therapies. Locoregional therapies are an appealing interventional approach for breast cancer patients with liver metastases since these tumor lesions are accessible via minimally invasive procedures that can be administered using either ultrasound or CT imaging. Current locoregional therapies to treat breast cancer liver metastases are non-specific and have not produced significant increases in survival. The goal of this study was to design and test a targeted locoregional therapeutic intervention for breast cancer liver metastases. The lead candidate, a fixed-dose small-molecule drug called MBC-005, was tested in vitro and then the efficacy was evaluated in a BALB/c mouse liver metastases model. A novel formulation of N-allyl noroxymorphone hydrochloride incorporated into an alginate-based gel overcomes many of the limitations associated with the administration of small-molecule drugs, which include solubility, off-target toxicity, and enzymatic degradation. In vitro results demonstrated that MBC-005 mediated its anti-tumorigenic effect through a p21-dependent mechanism via a novel molecular pathway, in which N-allyl noroxymorphone component of MBC-005 stimulated the opioid growth factor receptor to increase p21 expression. Intratumoral administration of MBC-005 increased survival 3.9-fold in mice and significantly decreased tumor volume 4-fold. While many cytotoxic therapies increase p21 expression as a response to DNA damage, MBC-005 increased p21 expression independent cytotoxic DNA damage. MBC-005 did not induce off-target toxicity; and, as such, would be amenable to multiple rounds of administration. Nevertheless, it is notable that the positive effects of MBC-005 treatment on increasing survival and decreasing tumor volume in mice was achieved using a single dose.

Widespread freshwater non-native fishes exhibit synchronized population dynamics with functionally similar natives

Enhanced α2-3–linked sialylation determines the extended half-life of CHO-rVWF

Abstract The half-life of recombinant human von Willebrand factor (rVWF) expressed in CHO cells (CHO-rVWF; Vonicog alfa; and Vonvendi/Veyvondi) is significantly longer than that of plasma-derived VWF (pdVWF). This finding is intriguing because CHO cells do not generate α2-6 sialylation, which constitutes the majority of human pdVWF sialylation. We hypothesized that glycan differences might regulate the longer half-life of CHO-rVWF. In lectin plate-binding assays and liquid chromatography–mass spectrometry analysis, we confirmed that CHO-rVWF lacked α2-6–linked sialylation. Conversely, however, α2-3–linked sialylation was significantly increased on CHO-rVWF, which also had reduced exposed β-galactose (β-Gal) compared to pdVWF. Consistent with human data, CHO-rVWF clearance was significantly (P < .001) reduced in VWF–/– mice compared to pdVWF. However, clearance of asialo-pdVWF and asialo–CHO-rVWF were identical. In keeping with the in vivo half-life prolongation, CHO-rVWF binding to murine macrophages (P = .012) and HepG2 cells (P = .001) was significantly decreased compared to pdVWF. Furthermore, CHO-rVWF binding to purified macrophage-galactose-type lectin (MGL) receptor and asialoglycoprotein receptor (ASGPR) was also significantly reduced. In contrast to pdVWF, in vivo studies in MGL1–/– mice and Asgr1–/– mice demonstrated that neither MGL nor ASGPR plays significant roles in regulating CHO-rVWF clearance. Together, our findings demonstrate that enhanced α2-3–linked sialylation on CHO-rVWF is responsible for its extended half-life.

β-propeller protein-associated neurodegeneration protein WDR45 regulates stress granule disassembly via phase separation with Caprin-1

Determination of radiocarbon in environmental objects

This article presents the results of radiocarbon distribution in natural components of ‘Degelen’ test location. It was used to conduct underground nuclear tests at the Semipalatinsk Test Site. Near-entry areas with water inflows were selected for research. Soil, plant and water samples were taken, in which the radiocarbon content was determined. The 14С activity concentration was determined using a highly sensitive alpha-beta radiometer SL-300 (ISO 13162, 2021). Sample preparation was carried out using a modern automated system Pyrolyser-6 Trio (Raddec International Ltd, UK). In the course of research undertaken, radiocarbon was revealed to be nonuniformly distributed in environmental objects. The effectiveness of Pyrolyser-6 Trio calcination and ashing system for 14C determination in environmental matrices has been demonstrated.

A method for spatial interpretation of weakly supervised deep learning models in computational pathology

Abstract Deep learning enables the modelling of high-resolution histopathology whole-slide images (WSI). Weakly supervised learning of tile-level data is typically applied for tasks where labels only exist on the patient or WSI level (e.g. patient outcomes or histological grading). In the weakly supervised learning context, there is a need for a methodology that facilitates the identification of the precise spatial regions in WSI that drive the prediction of the slide label. Such information is also needed for any further spatial interpretation of predictions from such models. We propose a novel method, Wsi rEgion sElection aPproach (WEEP), for model interpretation. It provides a principled yet straightforward way to establish the spatial area of WSI required for assigning a particular prediction label. We demonstrate WEEP on a binary classification task in the area of breast cancer computational pathology. WEEP facilitates the identification of spatial regions in WSI that are driving the decision making of a particular weakly supervised learning model, which can be further visualised and analysed to provide spatial interpretability of the model. The method is easy to implement, is directly connected to the model-based decision process, and offers information relevant to both research and diagnostic applications.

Classic Hodgkin lymphoma in the cerebellum: a rare site for a common disease

A phase I/II trial of WT1-specific TCR gene therapy for patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation: skewing towards NK-like phenotype impairs T cell function and persistence

Abstract Relapsed and/or refractory acute myeloid leukemia (AML) post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. We previously reported that post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8+ T cells engineered to express a Wilms Tumor Antigen 1-specific T-cell receptor (TTCR-C4) appeared to prevent relapse in high-risk patients. In this phase I/II clinical trial (NCT01640301), we evaluated safety (primary endpoint), persistence and efficacy (secondary endpoints) of EBV- or Cytomegalovirus (CMV)-specific TTCR-C4 in fifteen patients with active AML post-HCT. Infusions were well tolerated, with no dose-limiting toxicities or serious adverse events related to the product. However, TTCR-C4 cells did not clearly improve outcomes despite EBV-specific TTCR-C4 cells showing enhanced potential for prolonged persistence compared to CMV-specific TTCR-C4. Investigating the fate of persisting TTCR-C4, we identified a shift towards natural killer-like (NKL) terminal differentiation, distinct from solid tumor-associated canonical exhaustion programs. In one patient, treatment with azacitidine appeared to mitigate this NKL skewing, promoting TTCR-C4 persistence. These findings suggest that AML drives a distinct form of T-cell dysfunction, highlight the need for targeted approaches that preserve T-cell fitness, ultimately improving the efficacy of cellular therapies for AML.