BACKGROUND:Stereotactic body radiation therapy (SBRT) is the standard of care for early-stage, medically inoperable non-small-cell lung cancer (NSCLC). We aimed to test the addition of neoadjuvant, concurrent, and adjuvant atezolizumab with SBRT for early-stage NSCLC. METHODS:In this multicentre, open-label, phase 3, randomised controlled trial, eligible patients from 146 institutions across the USA who had T1-T3N0M0 NSCLC ≤7 cm, and were medically inoperable or declined surgery, and had at least one risk factor suggestive of increased risk of recurrence, were included in the study. Patients underwent open-label equal and stratified randomisation to SBRT over three to eight fractions with or without up to eight cycles of neoadjuvant, concurrent, and adjuvant atezolizumab 1200 mg intravenously every 21 days for up to eight cycles, with SBRT initiated with cycle three. The primary objective was to compare overall survival between the two groups. The group sequential design included four interim analyses. Target accrual was 480 patients (432 eligible). The trial is registered with ClinicalTrials.gov (NCT04214262) and is closed to new participants. FINDINGS:Between March 25, 2020, and Sept 9, 2024, 417 patients were enrolled and randomly assigned to atezolizumab plus SBRT (n=210) or SBRT alone (n=207). 402 were eligible and made up the modified intention-to-treat population (201 per group). The median age was 72·8 years (IQR 67·4-78·4), 218 (54%) of 402 participants were female, and 184 (46%) were male. Accrual closed at the first interim analysis of all randomly assigned participants for futility with 76 progression-free survival (PFS) events and 41 deaths among 400 eligible participants (200 per group). An updated analysis was performed with 140 PFS events, 92 deaths, and a median of 24·8 months (range 0·1-64·9; IQR 18·6-36·0) of follow-up among living patients. The overall survival hazard ratio was 1·04 (95% CI 0·69-1·58; one-sided p=0·58). Estimated 2-year overall survival was 82% in both groups (95% CI 75-87). Grade 3 or higher adverse event rates were 12% with atezolizumab plus SBRT and 3% with SBRT. Two grade 5 respiratory events occurred in the atezolizumab plus SBRT group. INTERPRETATION:In the first fully reported phase 3 cooperative group trial to assess immunotherapy in inoperable early-stage NSCLC, we observed no improvement in overall survival with atezolizumab plus SBRT, and more grade 3 or higher adverse events were reported with atezolizumab combined with SBRT. FUNDING:US National Institutes of Health, US National Cancer Institute, and Genentech.
Small-cell lung cancer (SCLC) is an exceptionally aggressive malignancy: highly proliferative, heterogeneous, and frequently metastatic at diagnosis. Although initially responsive to chemotherapy, such responses are typically transient, and recurrent disease has been largely refractory to standard cytotoxics. The past decade has been notable for major advances in our understanding of SCLC biology, and this preclinical progress is now informing multiple novel therapeutic approaches for this disease. Of particular note, defining cell-surface proteins that are uniquely or differentially expressed in SCLC has led to various targeted therapies showing substantial preliminary evidence of efficacy in patients with SCLC. Approaches in active development include T-cell engagers, antibody-drug conjugates, radioconjugates, and cell therapies, among others. In this Series paper, we summarise current standards of care, recent advances, and highlight emerging approaches showing early promise for better management of SCLC. Together, these advances are providing new hope for patients with what has been a particularly lethal disease.
Magnetite (Fe3O4) nanoparticles (NPs) were obtained through polyol synthesis followed by a particle-growth treatment at 260 °C, without external surfactants, to evaluate the method's efficiency for producing magnetic nanoparticles with a well-defined crystalline structure, colloidal stability, and surface functionalization. The NPs were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, thermal analyses, dynamic light scattering, transmission electron microscopy, Mössbauer spectroscopy, and magnetometry. X-ray diffraction confirmed predominant magnetite formation, with a cubic spinel-type structure and an average crystallite size of approximately 16.75 nm. The FTIR and TG/DSC analyses indicated the presence of organic groups derived from Terathane on the nanoparticles' surface, highlighting the polyol's role as a stabilizing agent. No visible sedimentation or macroscopic aggregation was observed in ethanol, THF, or chloroform after 45 days. DLS analysis indicated an average hydrodynamic diameter of 31 nm, while TEM images revealed nearly spherical particles with an average diameter of approximately 10.41 nm. Mössbauer spectroscopy confirmed the predominance of magnetite and indicated magnetic relaxation effects, while magnetometry revealed a magnetically soft response, with a saturation magnetization of 54.91 emu·g−1, a coercive field of 0.188 kOe, and a remanent magnetization of 12.63 emu·g−1. Thus, the proposed route proved to be simple and efficient for synthesizing Fe3O4 nanoparticles with promising properties for applications in magnetic colloids, nanocomposites, environmental remediation, and biomedical technologies.
BACKGROUND:Kidney xenotransplantation offers a potential solution to the organ shortage, but questions remain regarding durability, zoonotic infection risk, and whether the immunological response to the xenograft elicits sensitisation that could complicate subsequent allotransplantation. We report outcomes from a porcine kidney xenograft in a living recipient followed by human allotransplantation. METHODS:A patient with end-stage kidney disease, a prolonged anticipated waiting time for deceased donor transplantation, and with no suitable living donor underwent transplantation at Massachusetts General Hospital (Boston, MA, USA) with a gene-edited porcine kidney (EGEN-2784; eGenesis [Cambridge, MA, USA]) incorporating the deletion of major glycan xenoantigens, inactivation of porcine endogenous retroviruses, and insertion of seven human transgenes. The recipient received costimulation blockade-based immunosuppression with complement inhibition. Monitoring included renal function, flow cytometric crossmatch, anti-HLA antibodies, and porcine microbial surveillance, including metagenomic sequencing. This report describes the first recipient in a planned three-patient study conducted under a US Food and Drug Administration Expanded Access Investigational New Drug application. FINDINGS:The xenograft functioned immediately after transplantation on Jan 25, 2025, and sustained dialysis independence for 271 days. A biopsy on day 14 showed T-cell-mediated rejection, which resolved with treatment. Graft function remained stable for approximately 6 months until immunosuppression was reduced in the setting of non-zoonotic bacterial infection. Microvascular inflammation with endothelial injury subsequently emerged, progressing to thrombotic microangiopathy despite persistently negative donor-specific crossmatch, leading to graft failure and nephrectomy. Tissue analysis showed a macrophage and natural-killer-cell-predominant infiltrate with minimal T-cell involvement. No porcine pathogen transmission was detected. Anti-HLA antibodies remained unchanged. 82 days after explantation, the patient underwent human kidney allotransplantation with immediate graft function and no evidence of sensitisation during 231 days of follow-up. INTERPRETATION:This case shows that porcine kidney xenotransplantation can provide prolonged renal support and be discontinued without clinically significant allosensitisation or zoonotic infection. Early cellular rejection resolved with treatment, whereas later graft failure was associated with microvascular injury progressing to thrombotic microangiopathy despite a negative donor-specific crossmatch, supporting the possibility that mechanisms beyond conventional antibody-mediated rejection contributed to late graft injury. Kidney xenotransplantation has the potential to provide prolonged dialysis-free support while also serving as a bridge to subsequent human allotransplantation. FUNDING:Massachusetts General Hospital and eGenesis.
The Lieb lattice, featuring the coexistence of Dirac-like dispersions and a perfectly flat band, constitutes a paradigmatic platform for investigating the interplay between band topology, many-body interactions, and external perturbations. In this work, we present a comprehensive theoretical study of the combined effects of Holstein electron–phonon coupling and a perpendicular magnetic field on the dynamical and static charge structure factors of a doped Lieb lattice. Employing a full-band Green’s function formalism combined with the random-phase approximation, we derive the phonon-mediated effective electron–electron interaction and compute the charge susceptibilities. Our results reveal that the frequency, intensity, and spectral weight of plasmon peaks in the dynamical charge structure factor can be systematically tuned. The controlling parameters are the electron–phonon coupling strength, Zeeman field, next-nearest-neighbor hopping, staggered on-site potential, and carrier doping. In particular, increasing the Holstein coupling induces a pronounced blueshift of the high-frequency plasmon mode. This blueshift is accompanied by a non-monotonic variation of the mode intensity. In contrast, the perpendicular magnetic field produces a redshift and a suppression of the plasmon resonance. The static charge structure factor exhibits rich non-monotonic dependencies on magnetic field and hopping amplitude. These dependencies reflect the competition between thermal fluctuations, spin polarization, and polaronic effects. These findings establish a unified framework for the control of collective charge excitations and charge correlations via Holstein electron–phonon coupling and perpendicular magnetic fields. The resulting tunability of plasmon frequencies, spectral weights, and static charge correlations offers concrete design principles for reconfigurable plasmonic responses and engineered charge correlations in artificial quantum lattices and photonic platforms.
Bimetallic nanowires (NWs) integrating magnetic, electrical, and catalytic functionalities are of interest for multifunctional nanostructured systems. Herein, Ag@Ni core-shell NWs were synthesized through a two-step route using preformed Ag NWs as the core and a Ni-containing shell. SEM, TEM, EDS elemental mapping, line-scan analysis, and XRD collectively supported the formation of an Ag-rich core surrounded by a spike-decorated polycrystalline Ni-containing shell. Magnetic hysteresis measurements revealed ferromagnetic behavior at 300 and 10 K, with coercivities of approximately 53 and 80 Oe, respectively. ZFC/FC measurements under 100 Oe showed thermomagnetic irreversibility, with the two curves becoming nearly coincident near the upper end of the measured temperature range of 340–350 K. Representative individual-NW devices exhibited approximately linear I-V characteristics under zero magnetic field, and the effective resistivity of the Ag@Ni NWs was 4.4×10−4Ω⋅cm, intermediate between those of Ag and Ni NWs. In NaBH4 hydrolysis, the Ag@Ni NWs showed the fastest overall hydrogen-evolution profile among the tested samples under identical total-catalyst-mass conditions. These results show that the prepared Ag@Ni core-shell NWs exhibit ferromagnetic behavior, electrical conduction, and catalytic hydrogen-generation activity under the respective measurement conditions.
As early as in 1988, the IEC discussed the application of tangential field coil (H-coil) for physically more correct Single Sheet Testers. The reason was the starting insight that the calculation of the magnetic field strength H(t) from the magnetization current i(t) by a nominal path length LM involves a systematic source of error that impedes correct loss determination, a priori. The main aim of the current paper is to analyze and compare in the literature existing H-coil types. For most accurate measurement, the H-coil should be arranged in zero-distance from the sample surface. The newly developed PCB-H-coils prevail the widespread wire-wound coils in indisputable ways, mainly due to their incompressibility. We present here a coil design that fulfils the corresponding demands in acceptable ways. This is attained by an incompressible H-coil of minimum thickness, extreme coil area and elastic on-press to the sample surface.
Pre-eclampsia is a multisystem disorder that arises in at least 2–4% of pregnancies and is characterised by hypertension and new-onset organ dysfunction. The pathophysiology of pre-eclampsia is diverse but mostly involves a mismatch between fetoplacental demands and uteroplacental supply, combined with a maternal predisposition to cardiometabolic disease. While our understanding of the mechanisms underlying pre-eclampsia has advanced in recent years, maternal and perinatal mortality remains high in low-income and middle-income countries (LMICs), where pre-eclampsia incidence is higher. Risk factors include maternal chronic hypertension, diabetes, obesity, and previous pre-eclampsia. Preventive strategies include structured behavioural changes focused on diet quality and moderate-intensity physical activity for women with metabolic risk factors, low-dose aspirin for women at high risk, and risk-stratified timed birth at term. To date, the only recourse for pre-eclampsia is delivery of the placenta, and many discrepancies in care remain between high-income countries and LMICs. Current efforts primarily focus on the prediction, accurate diagnosis, and prevention of pre-eclampsia.
We present a first-principles study of Cr-capped Co5/Pd(111) ultrathin films in the near-compensated regime where Co stacking, structural relaxation, and Cr–Co exchange coupling compete on comparable energy scales and jointly determine the magnetic anisotropy. Three representative Co growth stackings are considered: pure fcc, hcp-rich, and mixed fcc+hcp. The hcp-rich stacking is found to be the lowest-energy structure and the most favorable configuration for approaching perpendicular magnetic anisotropy (PMA). We find that the magnetocrystalline anisotropy (MCA) of the non-relaxed films remains in-plane, whereas structural relaxation strongly suppresses the in-plane anisotropy and brings the system close to the spin-reorientation transition (SRT). Within PBE and the magnetic-force-theorem approach, antiferromagnetic Cr–Co coupling shifts the anisotropy toward the perpendicular side and yields the largest positive MCA for the relaxed hcp-rich film. The inclusion of moderate on-site Coulomb corrections through the Ueff parameter further shows that the hcp-rich AF configuration remains the structural ground state, but reveals that the Cr–Co exchange-energy scale and the precise balance between magnetocrystalline and shape anisotropy are Ueff-dependent. Within PBE, inclusion of the dipolar shape-anisotropy term keeps all configurations effectively in-plane. More generally, the results identify Cr/Co5/Pd(111) as a correlation-sensitive system close to a spin-reorientation boundary, rather than as either a universally in-plane film or a robust PMA state. Layer- and k-resolved analyses reveal that this near compensation originates from a competition between buried and middle Co layers, which favor in-plane magnetization, and the upper Pd region, the top Co layer beneath Cr, and the Cr cap, which favor the out-of-plane direction. In reciprocal space, the MCA is governed by the cancellation of positive and negative finite-k hot spots rather than by states near the Γ-point. Fully self-consistent spin–orbit calculations show that the relaxed AF configurations are especially fragile: the frozen-potential approximation overestimates the tendency toward perpendicularity and can even reverse the direction of the easy-axis. Our results identify the relaxed hcp-rich AF Cr/Co5/Pd(111) film as the closest precursor to robust PMA and establish stacking, relaxation, and interfacial exchange as key control parameters for tuning Cr/Co/Pd-based films across the SRT.
