Uncovering Biological Factors That Regulate Hepatocellular Carcinoma Growth Using Patient-Derived Xenograft Assays.

BACKGROUND AND AIMS: Several major factors limit our understanding of hepatocellular carcinoma (HCC). First, human HCCs are infrequently biopsied for diagnosis and thus are not often biologically interrogated. Second, HCC initiation and progression are strongly influenced by the cirrhotic microenvironment, and the exact contributions of intrinsic and extrinsic tumor factors are unclear. A powerful approach to examine the personalized biology of liver cancers and the influence of host tissues is with patient-derived xenograft (PDX) models. In Asia, HCCs from patients with hepatitis B virus have been efficiently converted into PDXs, but few parallel efforts from the west have been reported. APPROACH AND RESULTS: In a large-scale analysis, we implanted 93 HCCs and 8 cholangiocarcinomas (CCAs) to systematically analyze host factors and to define an optimized platform for PDX development from both surgical and biopsy samples. NOD Scid IL-2Rγ-/- (NSG) mice that had undergone partial hepatectomy (PHx) represented the best combination of engraftability, growth, and passageability, but overall rates were low and indicative of a unique intrinsic biology for HCCs in the United States. PDX models preserved the histology and genetic features of parental tumors, and ultimately, eight models were usable for preclinical studies. Intriguingly, HCC PDXs were differentially sensitive to regorafenib and sorafenib, and CCA PDXs were also highly sensitive to regorafenib. CONCLUSIONS: PDX models functionalize early and advanced stage HCCs and revealed unique biological features of liver cancers from the United States.

Helical pitch-dependent electro-optics of optically high transparent nano-phase separated liquid crystals.

Feeble light leakage in a dark state of conventional optically isotropic liquid crystal (OILC) device has a strong impact on the contrast ratio of a liquid crystal (LC) device. In order to overcome such intrinsic problem, we proposed an OILC in which the LC directors inside droplets are twisted by introducing chirality. The light leakage is effectively suppressed by matching the refractive indices between LC and polymer matrix; consequently, we achieved a high contrast ratio, 1:1401. Interestingly, the on-state transmittance is enhanced by ~49% compared to conventional OILC. The response time was also improved and the hysteresis was suppressed to be negligible. The improved electro-optic performances of the proposed OILC device would give diverse applications in upcoming flexible display and various photonic devices.

The microrandomized trial for developing digital interventions: Experimental design and data analysis considerations.

Just-in-time adaptive interventions (JITAIs) are time-varying adaptive interventions that use frequent opportunities for the intervention to be adapted-weekly, daily, or even many times a day. The microrandomized trial (MRT) has emerged for use in informing the construction of JITAIs. MRTs can be used to address research questions about whether and under what circumstances JITAI components are effective, with the ultimate objective of developing effective and efficient JITAI. The purpose of this article is to clarify why, when, and how to use MRTs; to highlight elements that must be considered when designing and implementing an MRT; and to review primary and secondary analyses methods for MRTs. We briefly review key elements of JITAIs and discuss a variety of considerations that go into planning and designing an MRT. We provide a definition of causal excursion effects suitable for use in primary and secondary analyses of MRT data to inform JITAI development. We review the weighted and centered least-squares (WCLS) estimator which provides consistent causal excursion effect estimators from MRT data. We describe how the WCLS estimator along with associated test statistics can be obtained using standard statistical software such as R (R Core Team, 2019). Throughout we illustrate the MRT design and analyses using the HeartSteps MRT, for developing a JITAI to increase physical activity among sedentary individuals. We supplement the HeartSteps MRT with two other MRTs, SARA and BariFit, each of which highlights different research questions that can be addressed using the MRT and experimental design considerations that might arise. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effect of Metal-Precursor Stacking Order on Volume-Defect Formation in CZTSSe Thin Film: Formation Mechanism of Blisters and Nanopores.

In this study, we investigated the effect of the stacking order of metal precursors on the formation of volume defects, such as blisters and nanopores, in CZTSSe thin-film solar cells. We fabricated CZTSSe thin films using three types of metal-precursor combinations, namely, Zn/Cu/Sn/Mo, Cu/Zn/Sn/Mo, and Sn/Cu/Zn/Mo, and studied the blister formation. The blister-formation mechanism was based on the delamination model, taking into consideration the compressive stress and adhesion properties. A compressive stress could be induced during the preferential formation of a ZnSSe shell. Under this stress, the adhesion between the ZnSSe film and the Mo substrate could be maintained by the surface tension of a metallic liquid phase with good wettability, or by the functioning of ZnSSe pillars as anchors, depending on the type of metal precursor used. Additionally, the nanopore formation near the back-contact side was found to be induced by the columnar microstructure of the metal precursor with the Cu/Zn/Mo stacking order and its dezincification. Based on the two volume-defect-formation mechanisms proposed herein, further development of volume-defect-formation suppression technology is expected to be made.

Estimating time-varying causal excursion effect in mobile health with binary outcomes.

Advances in wearables and digital technology now make it possible to deliver behavioral mobile health interventions to individuals in their everyday life. The micro-randomized trial is increasingly used to provide data to inform the construction of these interventions. In a micro-randomized trial, each individual is repeatedly randomized among multiple intervention options, often hundreds or even thousands of times, over the course of the trial. This work is motivated by multiple micro-randomized trials that have been conducted or are currently in the field, in which the primary outcome is a longitudinal binary outcome. The primary aim of such micro-randomized trials is to examine whether a particular time-varying intervention has an effect on the longitudinal binary outcome, often marginally over all but a small subset of the individual's data. We propose the definition of causal excursion effect that can be used in such primary aim analysis for micro-randomized trials with binary outcomes. Under rather restrictive assumptions one can, based on existing literature, derive a semiparametric, locally efficient estimator of the causal effect. Starting from this estimator, we develop an estimator that can be used as the basis of a primary aim analysis under more plausible assumptions. Simulation studies are conducted to compare the estimators. We illustrate the developed methods using data from the micro-randomized trial, BariFit. In BariFit, the goal is to support weight maintenance for individuals who received bariatric surgery.

Achieving Low VOC-deficit Characteristics in Cu2ZnSn(S,Se)4 Solar Cells through Improved Carrier Separation.

Kesterite-based thin-film solar cells (TFSCs) have recently gained significant attention in the photovoltaic (PV) sector for their elemental earth abundance and low toxicity. An inclusive study from the past reveals basic knowledge about the grain boundary (GB) and grain interior (GI) interface. However, the compositional dependency of the surface potential within GBs and GIs remains unclear. The present work provides insights into the surface potential of the bulk and GB interfaces. The tin (Sn) composition is sensitive to the absorber morphology, and therefore, it significantly impacts absorber and device properties. The absorber morphology improves with the formation of larger grains as the Sn content increases. Additionally, the presence of Sn(S,Se)2 and increased [ZnCu + VCu] A-type defect cluster density are observed, validated through Raman analysis. The secondary ion mass spectroscopy analysis reveals the altered distribution of sulfur (S) and sodium (Na) with higher near-surface accumulation. The synergistic outcome of the increased density of defects and the accumulation of S near the interface provides a larger GB and GI difference and expedites carrier separation improvement. Consequently, at an optimum compositional ratio of Cu/(Zn+Sn) = ∼0.6, the power conversion efficiency (PCE) is significantly improved from 6.42 to 11.04% with a record open-circuit voltage (VOC) deficit of 537 mV.

Provider Care Team Segregation and Operative Mortality Following Coronary Artery Bypass Grafting.

BACKGROUND: Studies have shown that Black patients die more frequently following coronary artery bypass grafting than their White counterparts for reasons not fully explained by disease severity or comorbidity. To examine whether provider care team segregation within hospitals contributes to this inequity, we analyzed national Medicare data. METHODS: Using national Medicare data, we identified beneficiaries who underwent coronary artery bypass grafting at hospitals where this procedure was performed on at least 10 Black and 10 White patients between 2008 and 2014 (n=12 646). After determining the providers who participated in their perioperative care, we examined the extent to which Black and White patients were cared for by unique networks of provider care teams within the same hospital. We then evaluated whether a lack of overlap in composition of the provider care teams treating Black versus White patients (ie, high segregation) was associated with higher 90-day operative mortality among Black patients. RESULTS: The median level of provider care team segregation was high (0.89) but varied across hospitals (interquartile range, 0.85-0.90). On multivariable analysis, after controlling for patient-, hospital-, and community-level differences, mortality rates for White patients were comparable at hospitals with high and low levels of provider care segregation (5.4% [95% CI, 4.7%-6.1%] versus 5.8% [95% CI, 4.7%-7.0%], respectively; P=0.601), while Black patients treated at high-segregation hospitals had significantly higher mortality than those treated at low-segregation hospitals (8.3% [95% CI, 5.4%-12.4%] versus 3.3% [95% CI, 2.0%-5.4%], respectively; P=0.017). The difference in mortality rates for Black and White patients treated at low-segregation hospitals was nonsignificant (-2.5%; P=0.098). CONCLUSIONS: Black patients who undergo coronary artery bypass grafting at a hospital with a higher level of provider care team segregation die more frequently after surgery than Black patients treated at a hospital with a lower level.

Influence of the Reaction Pathway on the Defect Formation in a Cu2ZnSnSe4 Thin Film.

Point defect engineering in Cu2ZnSnSe4 (CZTSe) thin films is the main issue to improve its device performance. This study reveals the correlation between the reaction pathway and the point defects in the CZTSe film. The reaction pathway from a metallic precursor (Mo/Zn/Sn/Cu) to a kesterite CZTSe film is varied by changing the annealing process. The synthesized CZTSe films under different reaction pathways induce different device performances with different defect energy levels, although all CZTSe films have similar structural and optical properties (Eg ∼ 1.0 eV). The admittance spectroscopy demonstrates the correlations between point defect types (VZn, ZnSn, ZnCu, CuZn, and VCu) and the reaction pathways for the formation of CZTSe films. The different growth rates of binary selenides, such as ZnSe and/or Sn-Se phases, during the annealing process are especially strongly related to the formation of point defects, leading to the different open-circuit voltages (396-451 mV) and fill factors (51-65%). The results of this study suggest that controlling the reaction pathway is an effective approach to adjust the formation of defects in the kesterite CZTSe film as well as to fabricate high-performance solar cell devices.

A Facile Process for Partial Ag Substitution in Kesterite Cu2ZnSn(S,Se)4 Solar Cells Enabling a Device Efficiency of over 12.

A cation substitution in Cu2ZnSn(S,Se)4 (CZTSSe) offers a viable strategy to reduce the open-circuit voltage (Voc)-deficit by altering the characteristics of band-tail states, antisite defects, and related defect clusters. Herein, we report a facile single process, i.e., simply introducing a thin Ag layer on a metallic precursor, to effectively improve the device characteristics and performances in kesterite (Agx,Cu1-x)2ZnSn(Sy,Se1-y)4 (ACZTSSe) solar cells. Probing into the relationship between the external quantum efficiency derivative (dEQE/dλ) and device performances revealed the Voc-deficit characteristics in the ACZTSSe solar cells as a function of Cu and Ag contents. The fabricated champion ACZTSSe solar cell device showed an efficiency of 12.07% and a record low Voc-deficit of 561 mV. Thorough investigations into the mechanism underpinning the improved performance in the ACZTSSe device further revealed the improved band-tailing characteristic, effective minority carrier lifetime, and diode factors as well as reduced antisite defects and related defect clusters as compared to the CZTSSe device. This study demonstrates the feasibility of effectively suppressing antisite defects, related defect clusters, and band-tailing characteristics by simply introducing a thin Ag layer on a metallic precursor in the kesterite solar cells, which in turn effectively reduces the Voc-deficit.