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A phase II, randomized, open-labeled study to evaluate low-dose pembrolizumab in addition to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC)
No full textBackground
Breast cancer is the most common malignancy diagnosed in women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive subtype, accounting for nearly one third of all breast cancers in India. The addition of pembrolizumab to neoadjuvant chemotherapy improved the pathological response and event free survival in patients with TNBC. However, for most patients in low- and middle-income countries, immunotherapy remains inaccessible due to its high cost. Pharmacological and early clinical data suggest that a lower dose of pembrolizumab may be effective. However, there are no prospective clinical trials in patients with TNBC.
Methods
This is a single-site phase II, randomized, open-labeled, parallel-group trial. Eligible patients will be randomized (1:1) to either of the two treatment groups. Patients in the control arm will be administered standard of care chemotherapy [4 cycles of dose-dense doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), followed by 4 cycles of dose-dense paclitaxel (175 mg/m2)]. Patients in the experimental arm will receive 3 doses of pembrolizumab 50 mg every 6 weeks along with neoadjuvant dose-dense chemotherapy. The primary objective of the study is to compare the pathological complete response with the addition of low-dose pembrolizumab to neoadjuvant chemotherapy in patients with TNBC. Secondary objectives include invasive disease-free survival and quality of life assessment.
Discussion
The PLANeT trial aims to establish the efficacy of low-dose pembrolizumab in addition to neoadjuvant chemotherapy in patients with triple-negative breast cancer patients. This strategy, if found effective, will help improve the outcomes of women with TNBC who currently have limited access to pembrolizumab
Long-term endocrine outcomes and quality of life in paediatric and young chronic myeloid leukaemia patients on tyrosine kinase inhibitor therapy: a prospective study from India
No full textBackground: Chronic myeloid leukaemia (CML) is rare in paediatric population, approximately 2–3% of leukaemia cases in children and 9% in adolescents. The introduction of tyrosine kinase inhibitors (TKIs) has significantly improved outcomes, but long-term use may lead to adverse endocrine effects and impact quality of life (QoL).
Methods: This prospective cross-sectional study evaluated 82 paediatric and young adult CML patients who were started on TKI therapy at <18 years of age. 71 patients were on TKI for >2 years and 11 patients were initiated on TKI during the study. Anthropometric measurements, Tanner staging, and laboratory parameters assessing endocrine function, bone health, glucose and lipid metabolism were evaluated. QoL was assessed with validated instruments.
Results: Median duration of TKI exposure was 7.5 years. Short stature was observed in 15% (11/71) of patients. Among those who were prepubertal at TKI initiation, 26.5% (9/34) were found to have short stature. Low Bone mineral density was found in 35·2% (24/68). Vitamin D deficiency was found in 84% and subclinical hypothyroidism in 9·8% (7/71). Two patients had poor sperm quality. One male patient had infertility. There was less impact on glucose, lipid profile, and adrenal function. In the QoL analysis, social functioning was affected among the functional scales, while financial difficulties, appetite loss, and fatigue were impacted in the symptom scales. Overall, QoL scores for physical, psychosocial, and school functioning remained well-preserved, but longer TKI treatment duration was associated to lower scores in these domains.
Discussion: This comprehensive evaluation highlights the need for close monitoring of BMD in patients who are on long-term TKI therapy. Evaluation of all other endocrine functions can be done as clinically indicated
Exploration of halogen-free sustainable superhydrophobic materials for surface protection from multi-contaminants in all weather conditions
No full textThe complex synthetic approach and utilization of toxic chemicals restrain the commercialization of numerous existing superhydrophobic materials. This article focuses on the development of a halogen-free superhydrophobic material for self-cleaning applications. HMDS-modified MCM-41 is employed as the base material. Silanization within the silica-framework is strategically improved by introducing the concept of surface-acidity enhancement by suitable heteroatom (Al, Ti and Zr) incorporation. The role of heteroatoms in defining the surface acidity of MCM-41 is analyzed in terms of solubility limit, ionic radii and electronegativity of the heteroatoms. Additionally, this work exclusively discusses the solvent selection criteria for the synthesis of hydrophobic materials and their role in enhancing hydrophobicity, evaluated via UV-visible turbidity measurements. Based on extensive studies, silane modified 25% Al-MCM-41 dispersed in acetonitrile exhibits exceptional water repellence with a water contact angle of 172.4 ± 0.7°. Higher electropositivity and the trivalent bonding nature of Al facilitate efficient silane modification and reduced surface OH concentration, leading to improved material hydrophobicity. Remarkable self-cleaning capability combined with durability and resilience towards diverse harsh conditions strengthen the practical viability of the designed material. Life cycle assessment (LCA) suggested that the material exhibits a smaller environmental footprint in terms of 18 selected midpoint indicators compared to the state-of-the-art materials
The quantromon: a qubit-resonator system with orthogonal qubit and readout modes
No full textThe measurement of a superconducting qubit is implemented by coupling it to a resonator. The common choice is transverse coupling, which, in the dispersive approximation, introduces an interaction term that enables the measurement. This cross-Kerr term provides a qubit-state dependent dispersive shift in the resonator frequency with the device parameters chosen carefully to get sufficient signal while minimizing Purcell decay of the qubit. We introduce a two-mode circuit, nicknamed quantromon, with two orthogonal modes implementing a qubit and a resonator. Unlike before, where the coupling term emerges as a perturbative expansion, the quantromon has intrinsic cross-Kerr coupling by design. Our experiments implemented in a hybrid 2D–3D circuit QED architecture demonstrate some unique features of the quantromon like weak dependence of the dispersive shift on the qubit-resonator detuning and intrinsic Purcell protection. In a tunable qubit-frequency device, we show that the dispersive shift (2χ/2π ) changes by only 0.8 MHz, while the qubit-resonator detuning (Δ/2π) is varied between 0.398 and 3.288 GHz. We also demonstrate Purcell protection in a second device where we tune the orthogonality between the two modes. Finally, we demonstrate a single-shot readout fidelity of 98.3%, which is comparable to the state-of-the-art measurements without the use of a parametric amplifier and suggests a potential simplification of the measurement circuitry for scaling up quantum processors
CLINICAL utility of assessing CDKN2A status in recurrent astrocytomas
No full textIDH-mutant astrocytomas exhibit a more indolent natural history and better prognosis compared to their IDH-wild type counterparts. WHO 2021 classification integrated CDKN2A/B homozygous deletion as a crucial criterion for grading these tumors, emphasizing its prognostic implications. FISH assay is commonly used to assess CDKN2A status, but guidelines for interpreting FISH results for glioma prognostication are not well-defined in the literature. We conducted an ambispective study involving 22 cases of recurrent IDH-mutant astrocytomas, including primary tumor samples. Histopathological assessments, including WHO grading and molecular profiling, were performed. Immunohistochemistry confirmed IDH mutation status, and FISH analysis evaluated CDKN2A homozygous deletion. Homozygous CDKN2A deletion was detected in only 1/22 (4.8%) of primary tumors, which was grade 3 astrocytoma, and significantly more frequent in recurrent cases, particularly in histological grade 2/3 tumors (35.3%). Patients harboring CDKN2A deletions exhibited significantly poorer overall survival, highlighting its prognostic significance. Our findings highlight the clinical relevance of CDKN2A assessment in recurrent IDH-mutant astrocytomas and its utility as a prognostic marker. We propose a selective approach to FISH testing, focusing on primary grade 3 and all recurrent cases, regardless of histology grade, to optimize diagnostic accuracy and stratification for personalized treatment strategies
Enhanced Phonon-Assisted Tunneling in Metal-Twisted Bilayer Graphene Junctions
No full textWe report planar tunneling spectroscopy measurements on metal-WSe2-twisted bilayer graphene heterostructures across a broad range of gate and bias voltages. The observed experimental features are attributed to phonon-assisted tunneling and the significantly high density of states within the moiré bands. A notable finding is the enhanced phonon-assisted tunneling in twisted bilayer graphene compared to Bernal bilayer graphene, which arises from a more relaxed in-plane momentum matching criterion. Theoretical calculations of phonon dispersions enable us to identify low-energy phonon modes in both Bernal and twisted bilayers of graphene, thereby elucidating the underlying mechanism of tunneling. Our results establish planar tunneling as a versatile tool to further understand electron–phonon coupling in twisted van der Waals materials
Development time integrates temperature and host plant cues for eyespot size in three tropical satyrine butterflies
No full textMany tropical butterflies have distinct wet and dry season adult morphs differing in the size of wing eyespots. Eyespot size is influenced by the environment experienced by developing larvae, and this plasticity is adaptive because the morphs have higher survival in their respective seasons. Higher temperature during the larval phase produces adults with larger eyespots in many species. This reaction norm is adaptive when high temperatures precede the wet season, which is not the case in all regions. Therefore, butterflies may rely on another environmental cue such as host plant species, and may also integrate information from multiple environmental variables through their combined effect on larval developmental time. To test this, we manipulated developmental time of sympatric populations of three butterflies − Ypthima huebneri, Mycalesis mineus and Melanitis leda − using combinations of temperatures and host plant species. Higher rearing temperature correlated with larger eyespot size in all species. Host plant species independently affected eyespot size. The effects of temperature and host plant differed between species, sexes, and between the forewing and hindwing, suggesting differential selection pressures on eyespots. Nevertheless, information about temperature and host plant species may be integrated through developmental time, because shorter larval development time was correlated with larger eyespots in adults. However, there were exceptions within specific treatments, species, and eyespots. Our results highlight the complex control of eyespot size, which is likely influenced by a network of interacting factors. Our study also demonstrates how sympatric populations of different species interpret similar environmental cues differently
Conformer‐Mediated Helical Chirality in 2D Layered Hybrid Perovskites
No full textTwo-dimensional (2D) chiral hybrid perovskites A2PbI4 (A: chiral organic ion) enable chirality controlled optoelectronic and spin-based properties. A+ organic sublattice induces chirality into the semiconducting [PbI4]2- inorganic sublattice through non-covalent interactions at organic–inorganic interface. Often, the A+ cations in the lattice have different orientations, leading to asymmetry in the non-covalent interactions. In a novel approach, we use different conformers of A+ cations to create asymmetry in the non-covalent interactions, thereby, achieving chiral perovskites with rare helical enantiomorphic structures. We prepared (R-IdPA)2PbI4 and (S-IdPA) 2PbI4 (IdPA: 1-iodopropan-2-ammonium) which crystallize in the helical enantiomorphic space groups P43212 and P41212, respectively. The gauche- and anti-conformers of IdPA+ are arranged alternatively in the hybrid structure. Importantly, the anti-conformer of IdPA+ ion have significantly stronger electrostatic, N−H⋅⋅⋅I hydrogen bonding, and I⋅⋅⋅I halogen bonding interactions with the [PbI4]2- sublattice, compared to the gauche-conformer. This periodic asymmetry in non-covalent interactions caused by the alternative arrangement of gauche- and anti-conformers induces chirality in the inorganic sublattice with four-fold screw axes (43 and 41). The enantiomers (R-/S-IdPA)2PbI4 show mirror-image like circular dichroism from excitonic absorption of the inorganic sublattice. This conformer-based design of chiral hybrid perovskites in helical space groups broadens material choices for advanced optoelectronic application
Defect-mediated electron–phonon coupling in halide double perovskite
No full textOptically active defects often play a crucial role in governing the light emission as well as the electronic properties of materials. Moreover, defect-mediated states in the midgap region can trap electrons, thus opening a path for the recombination of electrons and holes in lower energy states that may require phonons in the process. Considering this, we have probed electron–phonon interaction in halide perovskite systems with the introduction of defects and investigated the thermal effect on this interaction. Here, we report Raman spectroscopic study of the thermal evolution of electron–phonon coupling, which is tunable with the crystal growth conditions, in the halide perovskite systems Cs2AgInCl6 andCs2NaInCl6. The signature of electron–phonon coupling is observed as a Fano anomaly in the lowest frequency phonon mode (51 cm-1), which evolves with temperature. In addition, we observe a broad band in the photoluminescence (PL) measurements for the defect-mediated systems, which is otherwise absent in defect-free halide perovskite. The simultaneous observation of the Fano anomaly in the Raman spectrum and the emergence of the PL band suggests the defect-mediated midgap states and the consequent existence of electron–phonon coupling in the double perovskite
Covalent organic–inorganic layered 2D CdCl<sub>2</sub>(<i>n</i>-hexylamine)<sub>2</sub> and not Cd<sub>2</sub>S<sub>2</sub>(<i>n</i>-hexylamine)
No full textOrganic ammonium cations (A+) and inorganic [PbX4]2- (X: Cl, Br, I) anions bind to each other through electrostatic interactions, forming layered two-dimensional (2D) A2PbX4 hybrid perovskites. Thus, they dissociate in water. In contrast, charge-neutral organic amines (L) can covalently bind to metal M (M: Zn, Cd), forming M2Q4(L) (Q: S, Se, Te) hybrid II–VI semiconductors. We attempted to explore the optoelectronic properties of such a reported hybrid II–VI compound, Cd2S2(n-hexylamine), but surprisingly it did not form. Instead, the obtained product, referred to here as product-1, is a mixture of a new layered halide compound CdCl2(n-hexylamine)2 and CdS nanocrystals (NCs). The quantum confinement in ∼3 nm CdS NCs shows interesting optoelectronic properties, which were initially misinterpreted as signatures of a Cd2S2 (n-hexylamine) quantum well structure. The obtained layered compound CdCl2 (n-hexylamine)2 crystallizes in the P21/c space group. Each Cd2+ is coordinated with 4 equatorial Cl− and two axial n-hexylamines, forming distorted octahedra that propagate in 2D, forming the layered structure. Note that the organic and inorganic components in CdCl2 (n-hexylamine)2 are covalently bound (coordinate bonds), making the compound water-stable, unlike the electrostatically bound A2PbX4 perovskites. The covalent organic–inorganic bonding nature of the layered 2D hybrid halide compounds might be explored further for designing water-stable hybrid halide perovskite-like materials