Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody–drug conjugate consisting ...of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd.
Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC.
In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% 95% confidence interval (CI) 30.0% to 52.7%, median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified.
In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.
•The phase I U31402-A-U102 study evaluated HER3-DXd in heavily pretreated patients with EGFR-mutated NSCLC.•Ninety-seven patients previously treated with EGFR TKI and PBC received HER3-DXd 5.6 mg/kg intravenously every 3 weeks.•Responses were seen across the range of HER3 expression and across diverse mechanisms of resistance to EGFR TKI therapy.•Acquired mutations in ERBB3 were characterized.•OS was 15.8 months (95% CI 10.8-21.5 months).
This study compared a single intravenous infusion of zoledronic acid with daily oral risedronate in patients with Paget's disease. At six months, 96 percent of patients receiving zoledronic acid had ...a therapeutic response, as compared with 74 percent of patients given risedronate. Single-infusion zoledronate produces more rapid, complete, and sustained responses than does daily risedronate and may increase adherence to bisphosphonate therapy.
Single-infusion zoledronate produces more rapid, complete, and sustained responses than does daily risedronate and may increase adherence to bisphosphonate therapy.
Paget's disease of bone is characterized by a dramatic increase in bone turnover (both formation and resorption) at one or more sites. Measurement of biochemical markers of bone turnover is used to assess disease activity and monitor the response to therapy. About 2 percent of the U.S population older than 60 years of age have Paget's disease,
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as do up to 6 or 7 percent of the elderly population in western Europe.
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The bone pain, skeletal deformity, pathologic fractures, secondary arthritis, neurologic complications, and deafness that may accompany this disease contribute to substantial morbidity in the older population.
Bisphosphonate therapy . . .
A Li-ion capacitor (LIC), typically composed of a pre-lithiated negative electrode and an activated-carbon positive electrode, can provide high energy and power density. In this work, we compare the ...electrochemical performances of pre-lithiated graphene nanosheets and conventional graphite as negative electrode materials for LICs. The LICs employing pre-lithiated graphene nanosheets show a specific capacitance of 168.5 F g−1 with 74% capacitance retention at 400 mA g−1 after 300 cycles. Moreover, the capacitors deliver a maximum power density of 222.2 W kg−1 at an energy density of 61.7 Wh kg−1, operated in the voltage range of 2.0–4.0 V. Therefore, pre-lithiated graphene nanosheets are promising negative electrode materials for high power LICs.
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•Pre-lithiated graphene nanosheets are explored for Li-ion capacitors.•The Li-ion capacitors exhibit high energy and power density at high voltages.•Pre-lithiated graphene nanosheets are promising for high power Li-ion capacitors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Based on electron-positron collision data collected with the BESIII detector operating at the Beijing Electron-Positron Collider II storage rings, the value of ...R≡σ(e^{+}e^{-}→hadrons)/σ(e^{+}e^{-}→μ^{+}μ^{-}) is measured at 14 center-of-mass energies from 2.2324 to 3.6710 GeV. The resulting uncertainties are less than 3.0% and are dominated by systematic uncertainties.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved.
To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled ...analysis of 10 case–control studies (5585 cases and 11 827 controls) participating in the International Pancreatic Cancer Case–Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models.
Compared with abstainers and occasional drinkers (<1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2–2.2 for subjects drinking ≥9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area.
This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.
Summary
The coronavirus disease 2019 (COVID‐19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient ...factors—including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings—that may be of utility to clinicians to predict COVID‐19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID‐19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre‐existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end‐organ dysfunction. Hypothesis‐driven research is critical to identify the key evidence‐based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID‐19 and to appropriately allocate scarce resources.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Space weather phenomena can threaten space technologies. A hazard among these is the population of relativistic electrons in the Van Allen radiation belts. To reduce the threat, artificial ...processes can be introduced by transmitting very-low-frequency (VLF) waves into the belts. The resulting wave-particle interactions may deplete these harmful electrons. However, when transmitting VLF waves in space plasma, the antenna, plasma, and waves interact in a manner that is not well-understood. We conducted a series of VLF transmission experiments in the radiation belts and measured the power and radiation impedance under various frequencies and conditions. The results demonstrate the critical role played by the plasma-antenna-wave interaction around high-voltage space antennae and open the possibility to transmit high power in space. The physical insight obtained in this study can provide guidance to future high-power space-borne VLF transmitter developments, laboratory whistler-mode wave injection experiments, and the interpretation of various astrophysical and optical phenomena.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Phases of matter are usually identified through spontaneous symmetry breaking, especially regarding unconventional superconductivity and the interactions from which it originates. In that context, ...the superconducting state of the quasi-two-dimensional and strongly correlated perovskite Sr2RuO4 is considered to be the only solid-state analogue to the superfluid 3He-A phase, with an odd-parity order parameter that is unidirectional in spin space for all electron momenta and breaks time-reversal symmetry. This characterization was recently called into question by a search for an expected 'split' transition in a Sr2RuO4 crystal under in-plane uniaxial pressure, which failed to find any such evidence; instead, a dramatic rise and a peak in a single-transition temperature were observed. Here we use nuclear magnetic resonance (NMR) spectroscopy of oxygen-17, which is directly sensitive to the order parameter via hyperfine coupling to the electronic spin degrees of freedom, to probe the nature of superconductivity in Sr2RuO4 and its evolution under strain. A reduction of the Knight shift is observed for all strain values and at temperatures below the critical temperature, consistent with a drop in spin polarization in the superconducting state. In unstrained samples, our results contradict a body of previous NMR work reporting no change in the Knight shift and the most prevalent theoretical interpretation of the order parameter as a chiral p-wave state. Sr2RuO4 is an extremely clean layered perovskite and its superconductivity emerges from a strongly correlated Fermi liquid, and our work imposes tight constraints on the order parameter symmetry of this archetypal system.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A Weyl semimetal is a new state of matter that hosts Weyl fermions as emergent quasiparticles and admits a topological classification that protects Fermi arc surface states on the boundary of a bulk ...sample. This unusual electronic structure has deep analogies with particle physics and leads to unique topological properties. We report the experimental discovery of a Weyl semimetal, tantalum arsenide (TaAs). Using photoemission spectroscopy, we directly observe Fermi arcs on the surface, as well as the Weyl fermion cones and Weyl nodes in the bulk of TaAs single crystals. We find that Fermi arcs terminate on the Weyl fermion nodes, consistent with their topological character. Our work opens the field for the experimental study of Weyl fermions in physics and materials science.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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