A multiple imputation approach in enhancing causal inference for overall survival in randomized controlled trials with crossover.

Crossover or treatment-switching in randomized controlled trials presents notable challenges not only in the development and approval of new drugs but also poses a complex issue in their reimbursement, especially in oncology. When the investigational treatment is superior to control, crossover from control to investigational treatment upon disease progression or for other reasons will likely cause the underestimation of treatment benefit. Rank Preserving Structural Failure Time (RPSFT) and Two-Stage Estimation (TSE) methods are commonly employed to adjust for treatment switching by estimating counterfactual survival times.

Copper-catalyzed asymmetric 1,2-arylboration of enamines: access to chiral borate-containing 3,3'-disubstituted isoindolinones.

An enantioselective copper-catalyzed 1,2-arylboration reaction of enamines has been developed by employing ()-xyl-BINAP as a chiral ligand. A number of chiral borate-containing 3,3'-disubstituted isoindolinones were obtained in moderate to good yields and good to excellent enantioselectivities from the reactions of -(-iodobenzoyl)enamines and bis(pinacolato)diboron (Bpin) under mild reaction conditions. Synthetic transformations of the products were conducted to demonstrate the practicality of this reaction.

Ponatinib vs Imatinib in Frontline Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

Importance: In newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), disease progression due to acquired resistance to first- or second-generation BCR::ABL1 tyrosine kinase inhibitors is common. Ponatinib inhibits BCR::ABL1 and all single-mutation variants, including T315I.

Objective: To compare frontline ponatinib vs imatinib in adults with newly diagnosed Ph+ ALL.

A WO/MoO hybrid oxide based SERS FET and investigation on its tunable SERS performance.

Active control of the surface-enhanced Raman scattering (SERS) enhancement shows great potential for realizing smart detection of different molecules. However, conventional methods usually involve time-consuming structural design or a sophisticated fabrication process. Herein, we reported an electrically tunable field effect transistor (FET) comprising a WO/MoO hybrid as the SERS active layer.

Nonlinear photonic crystals for completely independent asymmetric holographic imaging.

Nonlinear photonic crystals (NPCs) are microstructures characterized by a spatially modulated second-order nonlinear coefficient that have been extensively used for the generation and beam-shaping of coherent light at new frequencies. NPCs for asymmetric optical transmission have a significant impact on novel and multifunction photonic devices. However, nonreciprocal NPCs capable of completely independent asymmetric holographic imaging for the opposite propagation directions have not been reported.

Asymmetric wavefront shaping with nonreciprocal 3D nonlinear detour phase hologram.

Asymmetric control of light with nonlinear material is of great significance in the design of novel micro-photonic components, such as asymmetric imaging devices and nonreciprocal directional optical filters. However, the use of nonlinear photonic crystals for asymmetric optical transmission, to the best of our knowledge, is still an untouched area of research. Herein we propose the 3D nonlinear detour phase holography for realizing asymmetric SH wavefront shaping by taking advantage of the dependence of the SH phase on the propagation direction of the excitation beam.

Ixazomib Versus Placebo as Postinduction Maintenance Therapy in Newly Diagnosed Multiple Myeloma Patients: An Analysis by Age and Frailty Status of the TOURMALINE-MM4 Study.

Background: The TOURMALINE-MM4 trial demonstrated a significant and clinically meaningful progression-free survival (PFS) benefit with ixazomib versus placebo as postinduction maintenance in nontransplant, newly-diagnosed multiple myeloma patients, with a manageable and well-tolerated toxicity profile.

Materials And Methods: In this subgroup analysis, efficacy and safety were assessed by age (< 65, 65-74, and ≥ 75 years) and frailty status (fit, intermediate-fit, and frail).

Results: In this analysis, PFS benefit with ixazomib versus placebo was seen across age subgroups, including patients aged < 65 years (hazard ratio [HR], 0.

Moderate white light exposure enhanced spatial memory retrieval by activating a central amygdala-involved circuit in mice.

Light exposure can profoundly affect neurological functions and behaviors. Here, we show that short-term exposure to moderate (400 lux) white light during Y-maze test promoted spatial memory retrieval and induced only mild anxiety in mice. This beneficial effect involves the activation of a circuit including neurons in the central amygdala (CeA), locus coeruleus (LC), and dentate gyrus (DG).

Single cell molecular alterations reveal target cells and pathways of conditioned fear memory.

Objectives: Recent evidence indicates that hippocampus is important for conditioned fear memory (CFM). Though few studies consider the roles of various cell types' contribution to such a process, as well as the accompanying transcriptome changes during this process. The purpose of this study was to explore the transcriptional regulatory genes and the targeted cells that are altered by CFM reconsolidation.

MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials.

Measurable residual disease (MRD) evaluation may help to guide treatment duration in multiple myeloma (MM). Paradoxically, limited longitudinal data exist on MRD during maintenance. We investigated the prognostic value of MRD dynamics in 1280 transplant-eligible and -ineligible patients from the TOURMALINE-MM3 and -MM4 randomized placebo-controlled phase 3 studies of 2-year ixazomib maintenance.

High-flow nasal cannula oxygen therapy versus noninvasive ventilation for patients with blunt chest trauma: protocol for a randomized controlled trial.

Background: High-flow nasal cannula oxygen therapy (HFNC) is recommended by some scholars as an optimized respiratory support method for blunt chest trauma (BCT) patients. The basis of this recommendation is limited, however, and the efficacy of HFNC or noninvasive ventilation (NIV) in BCT patients has not yet been rigorously explored. This study aims to determine if HFNC is non-inferior to NIV in reducing treatment failure in moderate to severe BCT patients with acute respiratory failure.

Bias and Type I error Control in Correcting Treatment Effect for Treatment Switching Using Marginal Structural Models in Phase III Oncology Trials.

This research focuses on the bias and type I error control issues when the marginal structural models (MSMs) are applied to evaluate the causal survival benefits of active intervention versus control in randomized clinical trials (RCTs) with treatment switching after disease progression. When MSMs are applied in the RCT setting, the question of interest, model specifications, strategies for type I error control, bias reduction, etc. differ somewhat from those for observational studies.

Mid-infrared biomimetic moth-eye-shaped polarization-maintaining and angle-insensitive metalens.

Metalenses can potentially reduce the size and complexity of existing cameras, displays, and other optical devices, owing to their capability of flexible manipulation of the polarization, amplitude, and phase of light. However, metalenses capable of maintaining polarization and broadband wavefront shaping under arbitrarily polarized excitation have not been studied. In this study, we present the first demonstration of a biomimetic moth-eye-shaped metalens for polarization-maintaining, broadband and angle-insensitive focusing under an arbitrarily polarized excitation in the mid-infrared waveband (3.

Oxyberberine Prevented Lipopolysaccharide-Induced Acute Lung Injury through Inhibition of Mitophagy.

Acute lung injury (ALI) is a serious respiratory syndrome characterized with uncontrolled inflammatory response. Oxyberberine has strong potential for clinical usage since it showed strong anti-inflammatory, antifungal, and antiarrhythmic effects in various diseases. In the present study, we evaluated whether oxyberberine can inhibit lipopolysaccharide- (LPS-) induced ALI and further evaluated the possible involvement of mitophagy by using A549 cells, a human lung epithelial cell line.

Large second-harmonic vortex beam generation with quasi-nonlinear spin-orbit interaction.

A harmonic vortex beam is a typical vector beam with a helical wavefront at harmonic frequencies (e.g., second and third harmonics).

Nonlinear detour phase holography.

Nonlinear photonic crystals are capable of highly efficient nonlinear wavefront manipulation, providing a promising platform for compact and large-scale integrated nonlinear devices. However, the current nonlinear encoding methods for nonlinear photonic crystals inherently require a number of disordered and complex microstructures, which are quite challenging in a real fabrication process. Herein we propose and experimentally demonstrate a nonlinear detour phase method for nonlinear wavefront manipulation in nonlinear photonic crystals.

Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial.

Purpose: Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed.

Patients And Methods: The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months.

High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial.

Background: High-flow nasal cannula (HFNC) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation. However, evidence to support the use of HFNC in chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure after extubation is limited. This study was conducted to test if HFNC is non-inferior to non-invasive ventilation (NIV) in preventing post-extubation treatment failure in COPD patients previously intubated for hypercapnic respiratory failure.

Chirality-selected second-harmonic holography with phase and binary amplitude manipulation.

Recently, multi-functional nonlinear wavefront control has attracted extensive attention. In particular, nonlinear holography can carry information and has potential for application in information encoding and computing. However, it is quite challenging because it puts forward higher requirements with nonlinear conversion efficiency and wavefront control performance.

Nonlinear wavefront shaping with optically induced three-dimensional nonlinear photonic crystals.

Generation of coherent light with desirable amplitude and phase profiles throughout the optical spectrum is a key issue in optical technologies. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting an incident light beam into the beam (or beams) of different frequency with spatially modulated amplitude and phase. The realization of such frequency conversion and shaping processes critically depends on the matching of phase velocities of interacting waves, for which nonlinear photonic crystals (NPCs) with spatially modulated quadratic nonlinearity have shown great potential.

[Benefits and risks of stress ulcer prevention with proton pump inhibitors for critical patients: an observational cohort study with 1 972 patients].

Objective: To investigate the benefits and risks of stress ulcer prevention (SUP) using proton pump inhibitors (PPI) for critical patients.

Methods: The clinical data of adult critically ill patients admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients who were treated with PPI for SUP within the first 48 hours after ICU admission were enrolled in the SUP group.