Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

Synthesis of Transition-Metal-Doped Nanocatalysts with Antibacterial Capabilities Using a Complementary Green Method.

A facile single-step wet chemical synthesis of a transition-metal-doped molybdate derivative was achieved via an Ocimum tenuiflorum extract-mediated green approach. The Synthesized nanomaterials of doped molybdate were characterized by optical and other spectroscopic techniques, which confirmed the size of nanocrystalline (~27.3 nm). The thermal stability of the nanomaterials confirmed through thermogravimetric analysis showed similarity with nanomaterials of Mn-ZnMoO4. Moreover, the nanoparticles displayed a non-toxic nature and showed antibactericidal activity. The impact of doping was reflected in band gap measurements; undoped ZnMoO4 showed relatively lower band gap in comparison to Mn-doped ZnMoO4. In the presence of light, ZnMoO4 nanomaterials a exhibited photocatalytic response to solochrome dark blue dye with a concentration of 50 ppm. OH- and O2*- radicals also destroyed the blue color of the dye within 2 min and showed potential antibactericidal activity towards both Gram-positive and Gram-negative bacteria, representing a unique application of the green-synthesized nanocatalyst.

Determination of size dependent carrier capture in InGaN/GaN quantum nanowires by femto-second transient absorption spectroscopy: effect of optical phonon, electron-electron scattering and diffusion.

Understanding the ultrafast processes corresponding to carrier capture, thermalization and relaxation is essential to design high speed optoelectronic devices. Here, we have investigated a size dependent carrier capture process in InGaN/GaN 20, 50 nm nanowires and quantum well systems. Femto-second transient absorption spectroscopy reveals that the carrier capture is a two-step process. The carriers are captured in the barrier by polar optical phonon (POP) scattering. They further scatter into the active region by electron-electron and POP scatterings. The capture is found to slow down for quantum confined structures. A significant number of carriers are found to disappear from the barrier during the diffusion process. All the experimental observations are explained in a simulation framework depicting various scattering mechanisms.

Strong Size Dependency on the Carrier and Photon Dynamics in InGaN/GaN Single Nanowalls Determined Using Photoluminescence and Ultrafast Transient Absorption Spectroscopy.

Here, we have demonstrated strong size dependency of quasi-equilibrium and nonequilibrium carrier and photon dynamics in InGaN/GaN single nanowalls using photoluminescence and transient absorption spectroscopy. We demonstrate that two-dimensional carrier confinement, strain relaxation, and modified density of states lead to a reduced Stokes shift, smaller full width at half-maxima, increased exciton binding energy, and reduced nonradiative recombination. The ultrafast transient spectroscopy shows that carrier capture is a two-step process dominated by optical phonons and carrier-carrier scattering in succession. The carrier capture is a strongly size-dependent process and becomes slower due to modulation of the density of available states for progressively decreasing nanowall sizes. The slowest process is the electron-hole recombination, which is also extremely size-dependent and the rate increases by almost an order of magnitude in comparison to that of quantum-well structures. Electron-hole wave function overlap and modified density of states are among the key aspects in determining all the properties of these structures.

Observation of B

We report the first observation of the decays B^{0}→pΛ[over ¯]D^{(*)-}. The data sample of 711 fb^{-1} used in this analysis corresponds to 772×10^{6} BB[over ¯] pairs, collected at the ϒ(4S) resonance by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We observe 19.8σ and 10.8σ excesses of events for the two decay modes and measure the branching fractions of B^{0}→pΛ[over ¯]D^{-} and B^{0}→pΛ[over ¯]D^{*-} to be (25.1±2.6±3.5)×10^{-6} and (33.6±6.3±4.4)×10^{-6}, respectively, where the first uncertainties are statistical and the second are systematic. These results are not compatible with the predictions based on the generalized factorization approach. In addition, a threshold enhancement in the dibaryon (pΛ[over ¯]) system is observed, consistent with that observed in similar B decays.

Measurement of the Direct CP Asymmetry in B¯â†’X(s+dγ) Decays with a Lepton Tag.

We report the measurement of the direct CP asymmetry in the radiative B¯â†’X(s+dγ) decay using a data sample of (772 ± 11)×10(6) BB[over ¯] pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The CP asymmetry is measured as a function of the photon energy threshold. For Eγ*≥2.1 GeV, where Eγ* is the photon energy in the center-of-mass frame, we obtain A(CP)(B¯â†’X(s+dγ))=(2.2±3.9±0.9)%, consistent with the standard model prediction.

Search for the dark photon and the dark Higgs boson at belle.

The dark photon A^{'} and the dark Higgs boson h^{'} are hypothetical constituents featured in a number of recently proposed dark sector models. Assuming prompt decays of both dark particles, we search for their production in the so-called Higgstrahlung channel e^{+}e^{-}→A^{'}h^{'}, with h^{'}→A^{'}A^{'}. We investigate ten exclusive final states with A^{'}→e^{+}e^{-}, µ^{+}µ^{-}, or π^{+}π^{-} in the mass ranges 0.1 GeV/c^{2}

Serum lipoprotein ratios as markers of insulin resistance: a study among non-diabetic acute coronary syndrome patients with impaired fasting glucose.

BACKGROUND & OBJECTIVES: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS) patients. METHODS: Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR) was used for insulin resistance. The fasting serum total cholesterol (TC), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC) of the receiver operating characteristic (ROC) curves were used to compare the power of these serum lipoprotein ratios as markers. RESULTS: Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05). Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05). The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93), 0.78 (95% CI, 0.65 to 0.91), respectively. INTERPRETATION & CONCLUSIONS: The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

Observation of e+e- → π+π-π(0)(χbJ) and Search for X(b) → ωϒ(1S) at sqrt[s] = 10.867 GeV.

The e(+)e(-) → π(+)π(-)π(0)χ(bJ) (J = 0,1,2) processes are studied using a 118 fb(-1) data sample acquired with the Belle detector at a center-of-mass energy of 10.867 GeV. Unambiguous π(+)π(-)π(0)χ(bJ) (J = 1,2), ωχ(b1) signals are observed, and indication for ωχ(b2) is seen, both for the first time, and the corresponding cross section measurements are presented. No significant π(+)π(-)π(0)χ(b0) or ωχ(b0) signals are observed, and 90% confidence level upper limits on the cross sections for these two processes are obtained. In the π(+)π(-)π(0) invariant mass spectrum, significant non-ω signals are also observed. We search for the X(3872)-like state (named X(b)) decaying into ωϒ(1S); no significant signal is observed with a mass between 10.55 and 10.65 GeV/c(2).

Measurement of the branching fraction B(Λc+ → pK-π+).

We present the first model-independent measurement of the absolute branching fraction of the Λ(c)(+) → pK(-)π(+) decay using a data sample of 978 fb(-1) collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The number of Λ(c)(+) baryons is determined by reconstructing the recoiling D((*)-) pπ(+) system in events of the type e(+)e(-) → D((*)-) pπ(+)Λ(c)(+). The branching fraction is measured to be B(Λ(c)(+) → pK(-)π(+)) = (6.84 ± 0.24(-0.27)(+0.21))%, where the first and second uncertainties are statistical and systematic, respectively.

Observation of D0-D0 mixing in e+e- collisions.

We observe D(0)-D(0) mixing in the decay D(0) → K+π- using a data sample of integrated luminosity 976 fb(-1) collected with the Belle detector at the KEKB e+e- asymmetric-energy collider. We measure the mixing parameters x'(2) = (0.09 ± 0.22) × 10(-3) and y'=(4.6 ± 3.4) × 10(-3) and the ratio of doubly Cabibbo-suppressed to Cabibbo-favored decay rates R(D) = (3.53 ± 0.13) × 10(-3), where the uncertainties are statistical and systematic combined. Our measurement excludes the no-mixing hypothesis at the 5.1 standard deviation level.

Measurement of the τ-lepton lifetime at Belle.

The lifetime of the τ lepton is measured using the process e+ e- → τ+ τ- , where both τ leptons decay to 3πν(τ). The result for the mean lifetime, based on 711 fb(-1) of data collected with the Belle detector at the ϒ(4S) resonance and 60 MeV below, is τ=(290.17±0.53(stat)±0.33(syst))×10(-15) s. The first measurement of the lifetime difference between τ+ and τ- is performed. The upper limit on the relative lifetime difference between positive and negative τ leptons is |Δτ|/τ<7.0×10(-3) at 90% C.L.

Factors associated with diarrhoea in young children and incidence of symptomatic rotavirus infection in rural West Bengal, India.

Socio-behavioural factors and pathogens associated with childhood diarrhoea are of global public health concern. Our survey in 696 children aged ⩽2 years in rural West Bengal detected rotavirus as sole pathogen in 8% (17/199) of diarrhoeic stool specimens. Other organisms were detected along with rotavirus in 11% of faecal specimens. A third of the children with rotavirus diarrhoea, according to Vesikari score, had severe illness. The top four rotavirus genotypes were G9P[4] (28%), G1P[8] (19%), G2P[4] (14%) and G8P[4] (8%). In the multivariate model, the practice of 'drawing drinking water by dipping a pot in the storage vessel' [adjusted odds ratio (aOR) 2·21, 95% confidence interval (CI) 1·03-4·74, P = 0·041], and 'children aged ⩽6 months with non-exclusive breastfeeding' (aOR 2·07, 95% CI 1·1-3·82, P = 0·024) had twice the odds of having diarrhoea. Incidence of rotavirus diarrhoea was 24/100 child-years in children aged >6-18 months, 19/100 child-years in children aged >18-24 months and 5/100 child-years in those aged ⩽6 months. Results have translational implications for future interventions including vaccine development.

Evidence for B- → τ- ν(τ) with a hadronic tagging method using the full data sample of Belle.

We measure the branching fraction of B- → τ- ν(τ) using the full Υ(4S) data sample containing 772×10(6) BB pairs collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider. Events with BB pairs are tagged by reconstructing one of the B mesons decaying into hadronic final states, and B- → τ- ν(τ) candidates are detected in the recoil. We find evidence for B- → τ- ν(τ) with a significance of 3.0 standard deviations including systematic errors and measure a branching fraction B(B- → τ- ν(τ))=[0.72(-0.25)(+0.27)(stat)±0.11(syst)]×10(-4).

Search for bottomonium states in exclusive radiative Υ(2S) decays.

We search for bottomonium states in Υ(2S) → (bb)γ decays with an integrated luminosity of 24.7 fb(-1) recorded at the Υ(2S) resonance with the Belle detector at KEK, containing (157.8±3.6)×10(6) Υ(2S) events. The (bb) system is reconstructed in 26 exclusive hadronic final states composed of charged pions, kaons, protons, and K(S)(0) mesons. We find no evidence for the state recently observed around 9975 MeV (X(bb)) in an analysis based on a data sample of 9.3×10(6) Υ(2S) events collected with the CLEO III detector. We set a 90% confidence level upper limit on the branching fraction B[Υ(2S) → X(bb)γ] × ∑(i)B[X(bb) → h(i)] < 4.9×10(-6), summed over the exclusive hadronic final states employed in our analysis. This result is an order of magnitude smaller than the measurement reported with CLEO data. We also set an upper limit for the ηb(1S) state of B[Υ(2S) → ηb(1S)γ] × ∑(i)B[ηb(1S) → h(i)] < 3.7×10(-6).

Study of e+ e- → π+ π- J/ψ and observation of a charged charmoniumlike state at Belle.

The cross section for ee+ e- → π+ π- J/ψ between 3.8 and 5.5 GeV is measured with a 967 fb(-1) data sample collected by the Belle detector at or near the Υ(nS) (n = 1,2,…,5) resonances. The Y(4260) state is observed, and its resonance parameters are determined. In addition, an excess of π+ π- J/ψ production around 4 GeV is observed. This feature can be described by a Breit-Wigner parametrization with properties that are consistent with the Y(4008) state that was previously reported by Belle. In a study of Y(4260) → π+ π- J/ψ decays, a structure is observed in the M(π(±)J/ψ) mass spectrum with 5.2σ significance, with mass M = (3894.5 ± 6.6 ± 4.5) MeV/c2 and width Γ = (63 ± 24 ± 26) MeV/c2, where the errors are statistical and systematic, respectively. This structure can be interpreted as a new charged charmoniumlike state.

Evidence of a new narrow resonance decaying to χ(c1)γ in B→χ(c1)γK.

We report measurements of B→χ(c1)γK and χ(c2)γK decays using 772×10(6) BB[over ¯] events collected at the Υ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. Evidence of a new resonance in the χ(c1)γ final state is found with a statistical significance of 3.8σ. This state has a mass of 3823.1±1.8(stat)±0.7(syst) MeV/c(2), a value that is consistent with theoretical expectations for the previously unseen 1(3)D(2) cc[over ¯] meson. We find no other narrow resonance and set upper limits on the branching fractions of the X(3872)→χ(c1)γ and χ(c2)γ decays.

Search for an H-dibaryon with a mass near 2mΛ in Υ(1S) and Υ(2S) decays.

We report the results of a high-statistics search for H dibaryon production in inclusive Υ(1S) and Υ(2S) decays. No indication of an H dibaryon with a mass near the M(H)=2m(Λ) threshold is seen in either the H→Λpπ(-) or ΛΛ decay channels and 90% confidence level branching-fraction upper limits are set that are between one and two orders of magnitude below the measured branching fractions for inclusive Υ(1S) and Υ(2S) decays to antideuterons. Since Υ(1S,2S) decays produce flavor-SU(3)-symmetric final states, these results put stringent constraints on H dibaryon properties. The results are based on analyses of 102 million Υ(1S) and 158 million Υ(2S) events collected with the Belle detector at the KEKB e(+)e(-) collider.

Doped Carbon Quantum Dots Reinforced Hydrogels for Sustained Delivery of Molecular Cargo.

Hydrogels have emerged as important soft materials with numerous applications in fields including biomedicine, biomimetic smart materials, and electrochemistry. Because of their outstanding photo-physical properties and prolonged colloidal stability, the serendipitous findings of carbon quantum dots (CQDs) have introduced a new topic of investigation for materials scientists. CQDs confined polymeric hydrogel nanocomposites have emerged as novel materials with integrated properties of the individual constituents, resulting in vital uses in the realm of soft nanomaterials. Immobilizing CQDs within hydrogels has been shown to be a smart tactic for preventing the aggregation-caused quenching effect and also for manipulating the characteristics of hydrogels and introducing new properties. The combination of these two very different types of materials results in not only structural diversity but also significant improvements in many property aspects, leading to novel multifunctional materials. This review covers the synthesis of doped CQDs, different fabrication techniques for nanostructured materials made of CQDs and polymers, as well as their applications in sustained drug delivery. Finally, a brief overview of the present market and future perspectives are discussed.

Fluorescent-Nanoparticle-Impregnated Nanocomposite Polymeric Gels for Biosensing and Drug Delivery Applications.

Nanocomposite polymeric gels infused with fluorescent nanoparticles have surfaced as a propitious category of substances for biomedical purposes owing to their exceptional characteristics. The aforementioned materials possess a blend of desirable characteristics, including biocompatibility, biodegradability, drug encapsulation, controlled release capabilities, and optical properties that are conducive to imaging and tracking. This paper presents a comprehensive analysis of the synthesis and characterization of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels, as well as their biomedical applications, such as drug delivery, imaging, and tissue engineering. In this discourse, we deliberate upon the merits and obstacles linked to these substances, encompassing biocompatibility, drug encapsulation, optical characteristics, and scalability. The present study aims to provide an overall evaluation of the potential of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels for biomedical applications. Additionally, emerging trends and future directions for research in this area are highlighted.