Sea surface temperature (SST) patterns both local to and remote from tropical cyclone (TC) development regions are important drivers of the variability of TC activity. Therefore, reliable simulations and predictions of TC activity depend on a realistic representation of tropical SST. Nevertheless, severe SST biases are common to the current generation of global climate models, especially in the tropical Pacific and Atlantic. These biases are strongly positive in the southeastern tropical basins, and negative, but weaker, in the northwestern tropical basins. To investigate the impact of the tropical SST biases on simulated TC activity, an atmospheric-only tropical channel model was used to conduct several sets of ensemble simulations. The simulations suggest an underrepresentation in Atlantic TC activity caused by the Atlantic cold bias alone, and an overrepresentation in Eastern North Pacific (ENP) TC activity due to the Atlantic cold bias and Pacific warm bias jointly. While the local impact of SST biases on TC activity is generally induced by the local anomalous SST and the associated changes in atmospheric conditions, the remote impact of the Atlantic bias on the ENP TCs is strongly driven by the change in topographically forced regional circulation. Moreover, an eastward shift in Western North Pacific TCs was generated by the Pacific SST biases, even though basin-wide TC activity indicators change insignificantly. The results indicate the importance of considering SST bias effects on simulated TC activity in climate model studies and highlight key regions where reducing SST biases could potentially improve TC representation in climate models.

A p-n junction maintained at above ambient temperature can work as a heat engine, converting some of the supplied heat into electricity and rejecting entropy by interband emission. Such thermoradiative cells have potential to harvest low-grade heat into electricity. By analyzing the entropy content of different spectral components of thermal radiation, we identify an approach to increase the efficiency of thermoradiative cells via spectrally selecting long-wavelength photons for radiative exchange. Furthermore, we predict that the near-field photon extraction by coupling photons generated from interband electronic transition to phonon polariton modes on the surface of a heat sink can increase the conversion efficiency as well as the power generation density, providing more opportunities to efficiently utilize terrestrial emission for clean energy. An ideal InSb thermoradiative cell can achieve a maximum efficiency and power density up to 20.4% and 327 Wm-2, respectively, between a hot source at 500 K and a cold sink at 300 K. However, sub-bandgap and non-radiative losses will significantly degrade the cell performance.

BACKGROUND:Skin marker-based three-dimensional kinematic gait analysis were commonly used to assess the functional performance and movement biomechanics of the pelvic limb in dogs. Unfortunately, soft tissue artefact would compromise the accuracy of the reproduced pelvic limb kinematics. Multibody kinematics optimization framework was often employed to compensate the soft tissue artefact for a more accurate description of human joint kinematics, but its performance on the determination of canine pelvic limb skeletal kinematics has never been evaluated. This study aimed to evaluate a multibody kinematics optimization framework used for the determination of canine pelvic limb kinematics during gait by comparing its results to those obtained using computed tomography model-based fluoroscopy analysis. RESULTS:Eight clinically normal dogs were enrolled in the study. Fluoroscopy videos of the stifle joint and skin marker trajectories were acquired when the dogs walked on a treadmill. The pelvic limb kinematics were reconstructed through marker-based multibody kinematics optimization and single-body optimization. The reference kinematics data were derived via a model-based fluoroscopy analysis. The use of multibody kinematics optimization yielded a significantly more accurate estimation of flexion/extension of the hip and stifle joints than the use of single-body optimization. The accuracy of the joint model parameters and the weightings to individual markers both influenced the soft tissue artefact compensation capability. CONCLUSIONS:Multibody kinematics optimization designated for soft tissue artefact compensation was established and evaluated for its performance on canine gait analysis, which provided a further step in more accurately describing sagittal plane kinematics of the hip and stifle joints.

Skeletal stem cells from the suture mesenchyme, which are referred to as suture stem cells (SuSCs), exhibit long-term self-renewal, clonal expansion, and multipotency. These SuSCs reside in the suture midline and serve as the skeletal stem cell population responsible for calvarial development, homeostasis, injury repair, and regeneration. The ability of SuSCs to engraft in injury site to replace the damaged skeleton supports their potential use for stem cell-based therapy. Here, we identified BMPR1A as essential for SuSC self-renewal and SuSC-mediated bone formation. SuSC-specific disruption of Bmpr1a in mice caused precocious differentiation, leading to craniosynostosis initiated at the suture midline, which is the stem cell niche. We found that BMPR1A is a cell surface marker of human SuSCs. Using an ex vivo system, we showed that SuSCs maintained stemness properties for an extended period without losing the osteogenic ability. This study advances our knowledge base of congenital deformity and regenerative medicine mediated by skeletal stem cells.

Background

The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC), after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real-world setting.

Materials and methods

Patients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real-world patient cohort who received standard-of-care from a deidentified clinico-genomics database (CGDB). Primary and secondary endpoints were to compare progression-free survival (PFS), estimated by the Kaplan-Meier method, and the proportion of patients remaining progression-free at 6 months, respectively, between the two cohorts.

Results

A total of 855 patients with PIK3CA-mutant disease who had prior CDK4/6i plus hormone therapy were selected from the CGDB; further matching to 120 patients from BYLieve selected 95 patients without exposure to HER2-targeting agents, clinical study drug, or alpelisib. In unadjusted and postmatching results, primary and secondary endpoints favored treatment with alpelisib with fulvestrant in BYLieve more than standard treatments in the real-world cohort. Postadjustment, median PFS for patients treated with alpelisib in BYLieve was 7.3 versus 3.7 months in the real-world cohort, and 6-month PFS was 54.6% versus 40.1%, respectively.

Conclusion

Matched/weighted analysis comparing BYLieve with the real-world setting further supports the clinical benefit of alpelisib with fulvestrant for treatment of HR+, HER2-, PIK3CA-mutant ABC after CDK4/6i treatment.

Implications for practice

Approximately 40% of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) have PIK3CA-mutated tumors, which have been associated with endocrine therapy resistance. Alpelisib, an α-selective phosphatidylinositol-3-kinase inhibitor, demonstrated significantly improved progression-free survival in SOLAR-1 and demonstrated clinical efficacy in BYLieve when combined with fulvestrant. Data are limited in comparing the efficacy of alpelisib combined with fulvestrant with effectiveness of standard therapy after CDK4/6i treatment. Using real-world data, this is the first analysis comparing alpelisib combined with fulvestrant with standard treatments for HR+, HER2-, PIK3CA-mutant ABC in the post-CDK4/6i setting.

The electrochemical carbon dioxide reduction reaction (CO₂RR) is a promising route to close the carbon cycle by reducing CO₂ into valuable fuels and chemicals. Electrocatalysts with high selectivity toward a single product are economically desirable yet challenging to achieve. Herein, we demonstrated a highly (111)-oriented Cu foil electrocatalyst with dense twin boundaries (TB) (tw-Cu) that showed a high Faradaic efficiency of 86.1 ± 5.3% toward CH₄ at -1.2 ± 0.02 V vs the reversible hydrogen electrode. Theoretical studies suggested that tw-Cu can significantly lower the reduction barrier for the rate-determining hydrogenation of CO compared to planar Cu(111) under working conditions, which suppressed the competing C-C coupling, leading to the experimentally observed high CH₄ selectivity.

Epidermal growth factor receptor exon 20 insertion mutations (EGFRexon20ins) are detected in approximately 2% of patients with non-small cell lung cancer (NSCLC). Due to a lack of effective therapy, the prognosis of these patients is typically poor. Sunvozertinib (DZD9008) was designed as an oral, potent, irreversible, and selective EGFR tyrosine kinase inhibitor, showing activity against EGFRexon20ins and other mutations. In both cell lines and xenograft models, sunvozertinib shows potent antitumor activity. In the two ongoing phase I clinical studies, sunvozertinib was tolerated up to 400 mg once daily. The most common drug-related adverse events included diarrhea and skin rash. Antitumor efficacy was observed at the doses of 100 mg and above in patients with EGFRexon20ins NSCLC across different subtypes, with prior amivantamab treatment as well as with baseline brain metastasis. The median duration of response has not been reached.

Significance

We report the discovery and early clinical development of sunvozertinib, a potential treatment option for the unmet medical need of EGFRexon20ins NSCLC. This article is highlighted in the In This Issue feature, p. 1599.