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Abstract The IL6-GP130-STAT3 pathway facilitates lung cancer progression and resistance to tyrosine kinase inhibitors. Although glycosylation alters the stability of GP130, its effect on the ligand IL6 remains unclear. We herein find that N-glycosylated IL6, especially at Asn73, primarily stimulates JAK-STAT3 signaling and prolongs STAT3 phosphorylation, whereas N-glycosylation-defective IL6 (deNG-IL6) induces shortened STAT3 activation and alters the downstream signaling preference for the SRC-YAP-SOX2 axis. This signaling shift induces epithelial-mesenchymal transition (EMT) and migration in vitro and metastasis in vivo, which are suppressed by targeted inhibitors and shRNAs against SRC, YAP, and SOX2. Osimertinib-resistant lung cancer cells secrete a large amount of deNG-IL6 through reduced N-glycosyltransferase gene expression, leading to clear SRC-YAP activation. deNG-IL6 contributes to drug resistance, as confirmed by in silico analysis of cellular and clinical transcriptomes and signal expression in patient specimens. Therefore, the N-glycosylation status of IL6 not only affects cell behaviors but also shows promise in monitoring the dynamics of lung cancer evolution.

This study utilized blue-light epitaxial wafers and employed semiconductor processes such as maskless laser writing, dry etching, wet etching, passivation layer deposition, electron beam evaporation, and ion implantation to fabricate micro-light emitting diode (μLED) arrays with different pixel sizes but the same emitting area (900 μm²). The μLED arrays with single pixel sizes of 5 μm, 10 μm, and 15 μm were fabricated, with array numbers of 6×6, 3×3, and 2×2, respectively. This study proposes etching the material in the channel region while retaining a certain width for implantation, known as the sidewall ion implantation process, aiming to achieve better insulation characteristics by using ion implantation technology to insulate the sidewall regions. It involves ion bombardment of the defect areas generated after plasma etching and the use of a passivation layer for protection. The isolation characteristics of μLED arrays processed by sidewall implantation exhibited better electrical isolation than those of μLED arrays processed only by plasma. The light output power, external quantum efficiency, and wall-plug efficiency were all superior for the sidewall implantation process when the device was miniaturized to 5 μm. Overall, the sidewall implantation process combined with plasma dry etching effectively improved the light output characteristics, with the enhancement ratio increasing as the device was miniaturized.

Abstract In this study, a 3 × 3 blue micro-LED array with a pixel size of 10 × 10 μm2 and a pitch of 15 μm was fabricated on an epilayer grown on a sapphire substrate using metalorganic chemical vapor deposition technology. The fabrication process involved photolithography, wet and dry etching, E-beam evaporation, and ion implantation technology. Arsenic multi-energy implantation was utilized to replace the mesa etching for electrical isolation, where the implantation depth increased with the average energy. Different ion depth profiles had varying effects on electrical properties, such as forward current and leakage currents, potentially causing damage to the n-GaN layer and increasing the series resistance of the LEDs. As the implantation depth increased, the light output power and peak external quantum efficiency of the LEDs also increased, improving from 5.33 to 9.82%. However, the efficiency droop also increased from 46.3 to 48.6%.

In this study, micro-light emitting diodes array (μLEDs) with dimensions of 5 μm and 15 μm chip size were fabricated using Neutral Beam Etching (NBE) processes. Size-dependent issues of μLEDs processed by traditional inductively coupled plasma-reactive ion etching (ICPRIE) were alleviated by NBE technology, which exhibited lower equivalent resistance, turn-on voltage, and Ideality factor as compared with those of μLEDs by ICPRIE. Additionally, higher light output power of μLEDs processed by NBE with both 5 μm and 15 μm resulted in higher EQE 7.6 % and 7.7 % than those of μLEDs processed by ICPRIE. Furthermore, the size effect led to a decrease in EQEmax values of the ICPRIE sample by 0.4 %, but only a 0.1 % decay in NBE. Overall, samples fabricated by the NBE process exhibited superior optoelectronic characteristics. Finally, non-radiative recombination behaviors on the mesa sidewall were verified by cathodoluminescence analysis, showing significant decay in ICPRIE samples but not in NBE samples. These results demonstrated the potential of the NBE process for fabricating small chip sizes blue-light μLEDs required for high-brightness, high-efficiency, and high-resolution μLED displays.

BackgroundSurgical scheduling is pivotal in managing daily surgical sequences, impacting patient experience and hospital resources significantly. With operating rooms costing approximately US $36 per minute, efficient scheduling is vital. However, global practices in surgical scheduling vary, largely due to challenges in predicting individual surgeon times for diverse patient conditions. Inspired by the Toyota Production System’s efficiency in addressing similar logistical challenges, we applied its principles as detailed in the book “Lean Thinking” by Womack and Jones, which identifies processes that do not meet customer needs as wasteful. This insight is critical in health care, where waste can compromise patient safety and medical quality. ObjectiveThis study aims to use lean thinking and Toyota methods to develop a more efficient surgical scheduling system that better aligns with user needs without additional financial burdens. MethodsWe implemented the 5 principles of the Toyota system: specifying value, identifying the value stream, enabling flow, establishing pull, and pursuing perfection. Value was defined in terms of meeting the customer’s needs, which in this context involved developing a responsive and efficient scheduling system. Our approach included 2 subsystems: one handling presurgery patient data and another for intraoperative and postoperative data. We identified inefficiencies in the presurgery data subsystem and responded by creating a comprehensive value stream map of the surgical process. We developed 2 Excel (Microsoft Corporation) macros using Visual Basic for Applications. The first calculated average surgery times from intra- or postoperative historic data, while the second estimated surgery durations and generated concise, visually engaging scheduling reports from presurgery data. We assessed the effectiveness of the new system by comparing task completion times and user satisfaction between the old and new systems. ResultsThe implementation of the revised scheduling system significantly reduced the overall scheduling time from 301 seconds to 261 seconds (P=.02), with significant time reductions in the revised process from 99 seconds to 62 seconds (P

Abstract Background Some prospective studies have shown that second‐generation tyrosine kinase inhibitors (TKIs) provide better control in patients with non‐small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. However, studies comparing second‐line chemotherapy efficacy between NSCLC patients with common and uncommon EGFR mutations remain rare. This retrospective study compared treatment outcomes in these patients. Methods Patients with EGFR‐mutated advanced‐stage NSCLC who received first‐line EGFR‐TKIs in a tertiary referral center were retrospectively reviewed between January 2010 and August 2022. Patients with a negative T790M test at disease progression who received second‐line chemotherapy were enrolled. We compared progression‐free (PFS) and overall (OS) survival between advanced NSCLC patients with common and uncommon EGFR mutations using Kaplan–Meier and log‐rank tests. Results In total, 209 (54.8%) patients had a negative T790M mutation test and received second‐line chemotherapy, of which 192 (91.8%) had a common EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and 17 (8.2%) had an uncommon EGFR mutation. Patients with common EGFR mutations had significantly longer PFS than those with uncommon EGFR mutations (4.57 vs. 2.57 months, p = 0.031). A Cox proportional hazard regression analysis controlling for potential confounding factors indicated that an uncommon EGFR mutation was an independent prognostic factor for PFS. Conclusion This study suggests that patients with uncommon EGFR mutations have poorer chemotherapy responses and shorter survival than those with common EGFR mutations. The development of new treatment strategies for these patients remains an unmet need.

Abstract In this study, we have demonstrated the potential of InGaN-based red micro-LEDs with single quantum well (SQW) structure for visible light communication applications. Our findings indicate the SQW sample has a better crystal quality, with high-purity emission, a narrower full width at half maximum, and higher internal quantum efficiency, compared to InGaN red micro-LED with a double quantum wells (DQWs) structure. The InGaN red micro-LED with SQW structure exhibits a higher maximum external quantum efficiency of 5.95% and experiences less blueshift as the current density increases when compared to the DQWs device. Furthermore, the SQW device has a superior modulation bandwidth of 424 MHz with a data transmission rate of 800 Mbit/s at an injection current density of 2000 A/cm2. These results demonstrate that InGaN-based SQW red micro-LEDs hold great promise for realizing full-color micro-display and visible light communication applications.

Osimertinib has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) in clinical trials. However, real-world data on its effectiveness remain scarce. Taiwanese patients with T790M-positive locally advanced or metastatic NSCLC and progressive disease following treatment with at least one EGFR tyrosine kinase inhibitor (TKI) were enrolled from the osimertinib early access program. Of the 419 patients (mean age, 63 years; female, 67%), 53% were heavily pretreated (≥ third-line [3L]), making osimertinib a fourth-line (4L) intervention. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI]: 8.95-11.41); the 18-month PFS rate was 26.5%. The median overall survival (OS) was 19.0 months (95% CI: 16.30-20.95); the 24-month OS rate was 40.9%. The objective response rate was 32.46%, and the disease control rate was 86.38%. The median time to treatment discontinuation of osimertinib monotherapy was 11.9 months (95% CI: 10.49-13.11). Subgroup analyses of median PFS and OS in the chemotherapy combination group vs. the osimertinib monotherapy group yielded no difference. Central nervous system (CNS) metastasis, number of prior lines of therapy, and types of initial EGFR-TKIs did not significantly impact outcomes. The median PFS values were 9.0 (95% CI: 5.18-11.34) and 10.9 (95% CI: 9.18-11.90) months with and without CNS metastasis, respectively, and 10.8 (95% CI: 8.59-12.69), 13.6 (95% CI: 10.89-16.3), and 9.2 (95% CI: 7.8-10.62) months for second-line (2L), 3L, and ≥4L therapy, respectively. In patients who received osimertinib as 2L therapy, the median PFS values in response to prior afatinib, erlotinib and gefitinib treatment were 11.2 (95% CI: 4.85-4.79), 10.5 (95% CI: 8.59-20.26) and 8.7 (95% CI: 7.21-16.79) months, respectively. Overall, real-world data from Taiwan support the clinical benefits of osimertinib in EGFR T790M -positive NSCLC.

Abstract Alveolar macrophages (AMs) are the drivers of pulmonary cytokine storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to investigate clinical–regulatory factors for the entrance protein of SARS-CoV-2, angiotensin–converting enzyme 2 (ACE2) in AMs. Human AMs were collected from 56 patients using bronchoalveolar lavage. ACE2 expression in AMs was positively correlated with smoking pack-year (Spearman’s r = 0.347, P = 0.038). In multivariate analysis, current smoking was associated with increased ACE2 in AMs (β-coefficient: 0.791, 95% CI 0.019–1.562, P = 0.045). In vitro study, ex-vivo human AMs with higher ACE2 were more susceptible to SARS-CoV-2 pseudovirus (CoV-2 PsV). Treating human AMs using cigarette smoking extract (CSE) increases the ACE2 and susceptibility to CoV-2 PsV. CSE did not significantly increase the ACE2 in AMs of reactive oxygen species (ROS) deficient Cybb–/– mice; however, exogenous ROS increased the ACE2 in Cybb–/– AMs. N-acetylcysteine (NAC) decreases ACE2 by suppressing intracellular ROS in human AMs. In conclusion, cigarette smoking increases the susceptibility to SARS-CoV-2 by increasing ROS–induced ACE2 expression of AMs. Further investigation into the preventive effect of NAC on the pulmonary complications of COVID-19 is required.

Abstract The role of Programmed Cell Death Ligand 1 (PD-L1) expression in predicting epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) efficacy remains controversial. Recent studies have highlighted that tumor-intrinsic PD-L1 signaling can be modulated by STAT3, AKT, MET oncogenic pathway, epithelial–mesenchymal transition, or BIM expression. This study aimed to investigate whether these underlying mechanisms affect the prognostic role of PD-L1. We retrospectively enrolled patients with EGFR mutant advanced stage NSCLC who received first-line EGFR-TKI between January 2017 and June 2019, the treatment efficacy of EGFR-TKI was assessed. Kaplan–Meier analysis of progression-free survival (PFS) revealed that patients with high BIM expression had shorter PFS, regardless of PD-L1 expression. This result was also supported by the COX proportional hazard regression analysis. In vitro, we further proved that the knockdown of BIM, instead of PDL1, induced more cell apoptosis following gefitinib treatment. Our data suggest that among the pathways affecting tumor-intrinsic PD-L1 signaling, BIM is potentially the underlying mechanism that affects the role of PD-L1 expression in predicting response to EGFR TKI and mediates cell apoptosis under treatment with gefitinib in EGFR-mutant NSCLC. Further prospective studies are required to validate these results.

We propose a new method for fabricating arrays of colloidal quantum dots for color conversion layers (CCLs) with atomic layer deposited (ALD) encapsulation. Semiconductor processes were used to transfer the CCL onto a transparent glass substrate. This method enables pixels as small as 5 μm, and the pixel's size and pitch can be controlled through the semiconductor process and mask layout. A dual-color array with a red-and-green CCL was also demonstrated to be suitable for microdisplay applications in experiments. The best color conversion efficiency of a single color CCL reached as high as 20.7%. A set of distributed Bragg reflector mirrors was used to increase photon recycling, and these mirrors yielded an increase in peak intensity of 35.7%. We formulated a model of incoherent reflection and transmission to calculate the changes in CCL properties when mirrors are added; this model had close fit with results from experiments in which mirrors of different reflection coefficients were used. Through the use of ALD, the CCL can be stored at a normal room-temperature environment for more than 9000 hours, and the projected lifetime is linearly extrapolated to be 44,041 hours.

Abstract Tumor resection could increase treatment efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). This study aimed to retrospectively analyze patients with advanced EGFR-mutant NSCLC from a Taiwanese tertiary center and receiving EGFR-TKI treatment with or without tumor resection. A total of 349 patients were enrolled. After propensity score matching, 53 EGFR-TKI treated patients and 53 EGFR-TKI treated patients with tumor resection were analyzed. The tumor resection group showed improved progression-free survival (PFS) (52.0 vs. 9.8 months; hazard ratio [HR] = 0.19; p

Background: Invasive pulmonary aspergillosis (IPA) can negatively impact cancer patients’ survival. It remains uncertain whether IPA’s impact on patient outcomes varies by treatment approach in advanced lung cancer. Objectives: To explore the association between IPA and outcomes in patients with advanced lung cancer receiving different treatments. Design: A retrospective cohort study. Methods: We enrolled patients with advanced-stage lung cancer between 2013 and 2021 at a college hospital in Taiwan and used the 2021 European Organization for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium consensus for IPA diagnosis. Multivariable logistic regression was used to identify the IPA risk factors. We compared overall survival (OS) and postgalactomannan (GM) test survival between the IPA and control groups using multivariable Cox proportional hazards regression and the Kaplan–Meier method with propensity score matching (PSM). Results: Among 2543 patients with advanced-stage lung cancer, 290 underwent a GM test, of which 34 (11.7%) were diagnosed with IPA. Patients undergoing chemotherapy (HR = 4.02, p = 0.027) and immunotherapy [hazard ratio (HR) = 3.41, p = 0.076] tended to have IPA. Compared to the control group, the IPA group had shorter median OS (14.4 versus 9.9 months, p = 0.030) and post-GM test survival (4.5 versus 1.9 months, p = 0.003). IPA was associated with shorter OS (log-rank p = 0.014 and 0.018 before and after PSM, respectively) and shorter 1-year and 2-year survival post-GM test (HR = 1.65 and 1.66, respectively). Patients receiving chemotherapy or immunotherapy had a shorter post-GM test survival if they had IPA. Conclusions: IPA tended to be diagnosed more frequently in patients receiving chemotherapy or immune checkpoint inhibitors. Patients diagnosed with IPA are associated with shorter survival. Larger cohort studies are needed to verify the observations.

A special micro LED whose light emitting area is laid out in a U-like shape is fabricated and integrated with colloidal quantum dots (CQDs). An inkjet-type machine directly dispenses the CQD layer to the central courtyard-like area of this U-shape micro LED. The blue photons emitted by the U-shape mesa with InGaN/GaN quantum wells can excite the CQDs at the central courtyard area and be converted into green or red ones. The U-shape micro LEDs are coated with Al2O3 by an atomic layer deposition system and exhibit moderate external quantum efficiency (6.51% max.) and high surface recombination because of their long peripheries. Low-temperature measurement also confirms the recovery of the external quantum efficiency due to lower non-radiative recombination from the exposed surfaces. The color conversion efficiency brought by the CQD layer can be as high as 33.90%. A further continuous CQD aging test, which was evaluated by the strength of the CQD emission, under current densities of 100 A/cm2 and 200 A/cm2 injected into the micro LED, showed a lifetime extension of the unprotected CQD emission up to 1321 min in the U-shape device compared to a 39 min lifetime in the traditional case, where the same CQD layer was placed on the top surface of a squared LED.

Although combination therapy including chemotherapy and immune checkpoint inhibitors (ICIs) improves overall survival (OS) of patients with non-small-cell lung cancer (NSCLC), there is a higher incidence of adverse events and treatment discontinuation. Since programmed death-ligand 1 (PD-L1) could not serve as a predictive biomarker, we investigated the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker. In our previous research, we demonstrated that a low NLR could predict survival benefits when patients with high PD-L1 expression (> 50%) received chemoimmunotherapy as opposed to immunotherapy alone. In this current study, our objective is to evaluate this predictive capacity in patients with low PD-L1 expression (< 50%). A total of 142 patients were enrolled, 28 receiving combination therapy and 114 receiving chemotherapy alone. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Patients who received combination therapy had significantly better PFS and OS than those who received monotherapy. In the subgroup of patients with low NLR, those who received combination therapy exhibited extended PFS and OS with clinical significance, which was also confirmed by multivariate Cox regression analysis. Our study demonstrates the potential use of NLR as a biomarker for predicting survival benefits when receiving combination therapy with chemotherapy and ICIs in patients with advanced NSCLC and low PD-L1 expression.

Abstract Neoadjuvant immunotherapy and chemotherapy have improved the major pathological response (MPR) in patients with early-stage operable non-small cell lung cancer (NSCLC). This study aimed to assess whether the presence of targetable driver mutations affects the efficacy of the combination of immunotherapy and chemotherapy. We enrolled patients with early-stage operable NSCLC who received preoperative neoadjuvant therapy between January 1, 2017, and December 30, 2020. Neoadjuvant therapy was delivered with platinum-doublet chemotherapy; moreover, pembrolizumab was added at the attending physician’s discretion based on patient’s request. Pathological responses were assessed; moreover, disease-free survival was estimated. Next-generation sequencing was performed in case sufficient preoperative biopsy specimens were obtained. We included 23 patients; among them, 11 received a combination of neoadjuvant immunotherapy and chemotherapy while 12 received neoadjuvant chemotherapy alone. The MPR and pathological complete response rates were 54.5% and 27.3%, respectively, in patients who received a combination of neoadjuvant immunotherapy and chemotherapy. These rates were significantly higher than those in patients who only received neoadjuvant chemotherapy. Three patients in the combination group experienced disease recurrence during the follow-up period even though two of them showed an MPR. These three patients had targetable driver mutations, including an EGFR exon 20 insertion, EGFR exon 21 L858R substitution, and MET exon 14 skipping. Only one patient who remained disease-free had a targetable driver mutation. Among patients with early-stage operable NSCLC requiring neoadjuvant therapy, comprehensive genomic profiling is crucial before the administration of the combination of neoadjuvant immunotherapy and chemotherapy.

Abstract Background Although epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) have been the standard treatment for advanced EGFR‐mutant adenocarcinoma, the effects of upfront EGFR‐TKI use in unresectable stage III EGFR‐mutant adenocarcinoma remain unexplored. Here, we conducted a retrospective study to compare different treatment strategies in these patients. Methods From October 2010 to June 2019, patients with unresectable stage III adenocarcinoma who received treatment at a tertiary referral center were enrolled. Patients were classified into three groups: EGFR‐mutant adenocarcinoma treated with concurrent chemoradiotherapy (group 1) or EGFR‐TKI (group 2) and EGFR wild‐type adenocarcinoma treated with concurrent chemoradiotherapy (group 3). Progression‐free survival, progression‐free survival‐2, and overall survival were estimated and compared using Kaplan–Meier and log‐rank tests. Results A total of 92 patients were enrolled; 10, 40, and 42 patients were assigned to groups 1, 2, and 3, respectively. Patients with EGFR mutations who received upfront EGFR‐TKIs had significantly longer progression‐free and overall survival than those who received upfront concurrent chemoradiotherapy (hazard ratio 0.33 vs. 0.34, p = 0.006 vs. 0.031) according to a Cox model adjusted for possible confounders. Moreover, upfront concurrent chemoradiotherapy did not lead to higher survival rates in patients with EGFR mutations than in those with EGFR wild‐type adenocarcinoma (progression‐free survival; hazard ratio 0.37, p = 0.036; overall survival; hazard ratio 0.35, p = 0.080) by Cox regression analysis. Conclusion This current study suggests that EGFR‐TKIs is a better choice for patients with unresectable stage III EGFR‐mutant adenocarcinoma. However, further randomized studies are required to validate the results.

This study fabricated and analyzed AlGaInP-based red micro–light-emitting diodes (LEDs) ranging from 2 to 15 μm in size. To collect photons from a single micro-LED at this scale, a solar cell chip near the micro-LEDs was used. Quantum efficiency decreased at a faster rate than that predicted by the standard ABC model under high currents, and a leakage current component was added to fully describe this phenomenon. The modified model can be used to extract valuable information regarding the micro-LEDs, such as the Shockley–Read–Hall coefficient. A size dependency analysis revealed that the bulk Shockley–Read–Hall coefficient and surface recombination velocity of the micro-LEDs were 6.81 × 107 1/sec and 5.99 × 104 cm/sec, respectively. Further analysis of the size-dependent recombination effect can help us solve the side wall problem and maximize the light output of AlGaInP-based micro-LEDs for ultrahigh-resolution displays.

BackgroundSending a patient to the operating room is the first step in surgery. Delayed patient transport causes the patient to go hungry for a longer time, aggravating the patient’s physical discomfort and psychological stress. The issue of delays in transporting inpatients to the operating room has rarely been discussed in the literature. The Toyota production system is a famous and excellent scientific method of reducing waste and increasing efficiency. Our goal is to use the Toyota method to decrease the time required to transport the inpatient to the operating room and to review the concepts underlying lean thinking.MethodsWe employed an A3 8-step problem-solving process. A current value stream map featuring numerical data (concerning 46 patients) measured in the workplace was developed. The total time spent on transport was 53 min, but we expected patients to be transported within 30 min. We hoped to reduce the time wasted by half, i.e., by 23*50% = 12 min. These 12 min were saved by reducing the time spent on “waiting for an attendant at the ward” by 9 min and the time spent on “elevator transport” by 3 min. According to the value stream map featuring the time measurements, the root causes of delayed transportation can be divided into process-related, attendant-related, and elevator-related factors. We formulated 5 countermeasures. The ECRS (Eliminate, Combine, Rearrange, Simplify) technique was used to rearrange, combine, and simplify the existing process. Hospital executives established norms for attendant prioritization of work and rules for elevator use.ResultsAccording to the original indicators, all goals were attained. “Total time spent” decreased by 62.3%. The time required for attendants to report to the nursing station decreased by 56.5%. The time spent on elevator transport decreased by 44.4%. We developed a process for future use based on information-assisted patient and staff identification. Finally, we standardized successful processes.ConclusionThe seemingly trivial factors that delay patient transport are associated with seven types of waste. The A3 8-step problem-solving process is useful in this context. In proposing this improvement process, we believe that we are following the spirit of the Toyota production system.

Abstract C‐ros oncogene 1 receptor tyrosine kinase (ROS1) rearrangement has been detected in patients with advanced non‐small cell lung cancer (NSCLC). Although ROS1 tyrosine kinase inhibitors (TKIs) provide a survival benefit for patients with ROS1‐rearranged advanced NSCLC, subsequent therapy remains limited. Small cell transformation is an important mechanism of drug resistance in epidermal growth factor receptor‐mutant NSCLC. However, its significance in mediating ROS1 resistance has not been determined yet. Here, we present the case of a 63‐year‐old man with ROS1‐rearranged advanced NSCLC who had disease progression with small cell transformation of the mediastinal lymph node after 8 months of treatment with crizotinib. More importantly, fluorescence in situ hybridization of post‐progression tumor biopsy demonstrated retention of ROS1 rearrangement. Tissue biopsy remains indispensable for patients who acquire resistance to ROS1 TKIs.

Background: Recent study showed that the combination of erlotinib and bevacizumab had better disease control than erlotinib monotherapy in patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). However, there is lack of real-world evidence for this therapeutic regimen. We aimed to compare outcomes between patients with EGFR mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKI) and bevacizumab and those treated with EGFR-TKI alone in a real-world setting. Methods: Patients with advanced EGFR-mutant NSCLC who received first-line EGFR-TKI in a tertiary referral center from October 1, 2013 to December 31, 2019 were retrospectively analyzed. We performed 1:2 propensity score-matching: one EGFR-TKI and bevacizumab recipient with two patients who received EGFR-TKI alone. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan–Meier method. The prognostic factors were analyzed using Cox proportional hazards regression analysis. Results: Total 313 patients were enrolled. After propensity score matching, 45 patients who received first-line EGFR-TKI and bevacizumab and 89 patients who received EGFR-TKI alone were analyzed. The combination group showed improved PFS (17.0 vs. 11.0 months; hazard ratio [HR] = 0.48; p = 0.002) compared to the monotherapy group. In subgroup analysis of patients with an L858R mutation, the combination group showed longer PFS (23.1 vs. 10.7 months; HR = 0.40; p = 0.011) and OS (not reached vs. 40.6 months; HR = 0.27; p = 0.040) than the EGFR-TKI monotherapy group. Conclusion: Our data suggest that the combination of EGFR-TKI and bevacizumab could improve PFS in patients with EGFR-mutant NSCLC. In patients harboring L858R mutation, the combination therapy provides better OS than TKI alone.

Quantum dot (QD)-based RGB micro light-emitting diode (μ-LED) technology shows immense potential for achieving full-color displays. In this study, we propose a novel structural design that combines blue and quantum well (QW)-intermixing ultraviolet (UV)-hybrid μ-LEDs to achieve high color-conversion efficiency (CCE). For the first time, the impact of various combinations of QD and TiO2 concentrations, as well as thickness variations on photoluminescence efficiency (PLQY), has been systematically examined through simulation. High-efficiency color-conversion layer (CCL) have been successfully fabricated as a result of these simulations, leading to significant savings in time and material costs. By incorporating scattering particles of TiO2 in the CCL, we successfully scatter light and disperse QDs, effectively reducing self-aggregation and greatly improving illumination uniformity. Additionally, this design significantly enhances light absorption within the QD films. To enhance device reliability, we introduce a passivation protection layer using low-temperature atomic layer deposition (ALD) technology on the CCL surface. Moreover, we achieve impressive CCE values of 96.25% and 92.91% for the red and green CCLs, respectively, by integrating a modified distributed Bragg reflector (DBR) to suppress light leakage. Our hybrid structure design, in combination with an optical simulation system, not only facilitates rapid acquisition of optimal parameters for highly uniform and efficient color conversion in μ-LED displays but also expands the color gamut to achieve 128.2% in the National Television Standards Committee (NTSC) space and 95.8% in the Rec. 2020 standard. In essence, this research outlines a promising avenue towards the development of bespoke, high-performance μ-LED displays.

Telisotuzumab vedotin is a MET-targeting antibody–drug conjugate that has demonstrated a good treatment response in patients with EGFR wild-type MET-overexpressing non-squamous non-small cell lung cancer. However, patients have been reported to acquire resistance to this drug, and the subsequent therapy has not been standardized. Here, we present a case of a 56-year-old woman diagnosed with KIF5B-MET fusion-positive non-small cell lung cancer who had a durable response to capmatinib after acquired resistance to telisotuzumab vedotin.

Abstract Background Few studies have compared the efficacy of the irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), afatinib, with that of reversible EGFR‐TKIs. Therefore, this study assessed the effectiveness of afatinib, erlotinib, and gefitinib in terms of OS (overall survival) and progression‐free survival (PFS) in EGFR mutation‐positive advanced non‐small cell lung cancer (NSCLC) patients. Methods Patients with EGFR mutation‐positive advanced NSCLC who sought treatment from December 2013 to June 2018, at a tertiary referral center were retrospectively analyzed. These patients were treated with afatinib or a reversible EGFR‐TKI (erlotinib or gefitinib) until disease progression, intolerable adverse events, or death. The Kaplan‐Meier and log‐rank tests were then used to compare the OS and PFS of the patients. We further analyzed the survival differences among the subgroup of patients without brain metastases. Results Of the 363 patients enrolled, 134 and 229 received first‐line afatinib and first‐line reversible EGFR‐TKI, respectively. Those given afatinib had better OS (39.3 vs. 26.0 months; HR 0.65, P = 0.033) and PFS (14.1 vs.11.2 months; HR 0.58, P

A Sn-ball was integrated with a colloidal quantum dot light-emitting diode package to achieve effective heat and reliability management. The electric, optical intensity, and heat distributions of the package were evaluated under various radiant fluxes; data were collected at the 90th hour of aging. Under 1 W/cm2, the areal temperature decreased from 38.5 °C (without Sn-ball) to 32.3 °C (with Sn-ball), which helped extend the lifetime of the colloidal quantum dots in the package. Specifically, the introduction of the metal ball structure engendered a two- to three-fold increase in lifetime. The study findings could contribute toward integrating quantum dots into photonic devices.

Abstract A three-section distributed feedback laser with a 2.5 InP/air pair of distributed Bragg reflectors (DBRs) was fabricated and analyzed in terms of its microwave generation capability. A widely tunable single radio frequency (RF) signal can be detected using optical heterodyning, and the tuning range is from 2 to 45 GHz. The incorporation of the third section provides an opportunity to present the dual RF operation when three emission peaks are near to each other in the wavelength domain. The proposed design provides a 21.3% enhancement in the RF tuning range compared with the range of a two-section laser (35.29 GHz versus 42.81 GHz). The compactness of the proposed device can be useful for future radio-over-fiber applications.

BackgroundTo compare the testing costs and testing turnaround times of tissue-first, plasma-first, and complementary next-generation sequencing (NGS) approaches in patients with treatment-naïve metastatic lung adenocarcinoma.Materials and MethodsWe developed a decision tree model to compare three different approaches. Patients were entered into the model upon cancer diagnosis and those with both insufficient tissue specimens and negative liquid-based NGS were subjected to tissue re-biopsy. Actionable gene alterations with the U.S. Food and Drug Administration (FDA)-approved therapies included epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangement, ROS proto-oncogene 1 (ROS1) rearrangement, B-Raf proto-oncogene (BRAF) V600E mutation, rearranged during transfection (RET) gene rearrangement, mesenchymal-epithelial transition factor (MET) mutation, neurotrophic tyrosine receptor kinase (NTRK) gene rearrangement, K-Ras proto-oncogene (KRAS) G12C mutation, and human epidermal growth factor receptor 2 (HER2) mutation. Model outcomes were testing costs, testing turnaround times, and monetary losses taking both cost and time into consideration. We presented base-case results using probabilistic analysis. Stacked one-way and three-way sensitivity analyses were also performed.ResultsIn terms of testing costs, tissue-first approach incurred US$2,354($1,963–$2,779) and was the most cost-efficient strategy. Complementary approach testing turnaround time (days) of 12.7 (10.8 to 14.9) was found as the least time-consuming strategy. Tissue-first, complementary, and plasma-first approaches resulted in monetary losses in USD of $4,745 ($4,010–$5,480), $6,778 ($5,923–$7,600), and $7,006 ($6,047–$7,964) respectively, and identified the same percentage of patients with appropriate FDA-approved therapies. Costs for liquid-based NGS, EGFR mutation rates, and quantity of tissue specimens were the major determinants in minimizing monetary loss. Plasma-first approach would be the preferable strategy if its testing price was reduced in USD to $818, $1,343, and $1,869 for populations with EGFR mutation rates of 30%, 45%, and 60% respectively.ConclusionThe tissue-first approach is currently the best strategy in minimizing monetary loss. The complementary approach is an alternative for populations with a low EGFR mutation rate. The plasma-first approach becomes increasingly preferable as EGFR mutation rates gradually increase.

BRAF fusions are rare driver oncogenes in non-small cell lung cancer (NSCLC). Similar with BRAF V600E mutation, it could also activate the MAPK signaling pathway. There are a few case reports which had indicated the potential response to BRAF inhibitors and its important role as de novo driver mutation. In addition, the co-occurring MET amplification has been defined as a poor prognostic factor in patients with epidermal growth factor receptor (EGFR) mutant NSCLC. Currently, there are ongoing clinical trials which investigate the MET amplification as a therapeutic target in patients with EGFR mutant NSCLC and acquired resistance to osimertinib, which imply that the MET amplification also had a therapeutic significance. However, the co-occurring MET amplification had not been studied in patients with BRAF fusion before. A 67-year-old man was diagnosed with metastatic poorly-differentiated adenocarcinoma. He received first-line therapy with the combination of pembrolizumab and chemotherapy because the genomic test revealed wild-type EGFR, and negativity of ALK and ROS1 by immunohistochemical stain. Upon disease progression, the next-generation sequencing revealed co-occurring KIAA1549-BRAF fusion and MET amplification. Subsequent dabrafenib, trametinib, and capmatinib combination therapy showed a remarkable treatment effect. The combination therapy targeting the co-occurring driver mutations is a potential effective treatment for NSCLC patients. Further prospective study is still warranted to investigate the role of co-occurring driver mutations and the relevant treatment strategy.

The monolithic integration of InGaN-based micro-LEDs is being of interest toward developing full-color micro-displays. However, the color stability in InGaN red micro-LED is an issue that needs to be addressed. In this study, the modified distributed Bragg reflectors (DBRs) were designed to reduce the transmission of undesired spectra. The calculated optical properties of the InGaN red micro-LEDs with conventional and modified DBRs have been analyzed, respectively. The CIE 1931 color space and the encoded 8-bit RGB values are exhibited for the quantitative assessment of color stability. The results suggest the modified DBRs can effectively reduce the color shift, paving the way for developing full-color InGaN-based micro-LED displays.

Colloidal CdSe/ZnS quantum dots (QD) enhanced micro-LEDs with sizes varying from 10 to 100 μm were fabricated and measured. The direct photolithography of quantum-dot-contained photoresists can place this color conversion layer on the top of an InGaN-based micro-LED and have a high throughput and semiconductor-grade precision. Both the uncoated and coated devices were characterized, and we determined that much higher brightness of a QD-enhanced micro-LED under the same current level was observed when compared to its AlGaInP counterpart. The color stability across the device sizes and injection currents were also examined. QD LEDs show low redshift of emission wavelength, which was recorded within 1 nm in some devices, with increasing current density from 1 to 300 A/cm2. On the other hand, the light conversion efficiency (LCE) of QD-enhanced micro-LEDs was detected to decrease under the high current density or when the device is small. The angular intensities of QD-enhanced micro-LEDs were measured and compared with blue devices. With the help of the black matrix and omnidirectional light emission of colloidal QD, we observed that the angular intensities of the red and blue colors are close to Lambertian distribution, which can lead to a low color shift in all angles. From our study, the QD-enhanced micro-LEDs can effectively increase the brightness, the color stability, and the angular color match, and thus play a promising role in future micro-display technology.

Micro light-emitting diode (micro-LED) will play an important role in the future generation of smart displays. They are found very attractive in many applications, such as maskless lithography, biosensor, augmented reality (AR)/mixed reality etc, at the same time. A monitor that can fulfill saturated color rendering, high display resolution, and fast response time is highly desirable, and the micro-LED-based technology could be our best chance to meet these requirements. At present, semiconductor-based red, green and blue micro-LED chips and color-conversion enhanced micro-LEDs are the major contenders for full-color high-resolution displays. Both technologies need revolutionary ways to perfect the material qualities, fabricate the device, and assemble the individual parts into a system. In this roadmap, we will highlight the current status and challenges of micro-LED-related issues and discuss the possible advances in science and technology that can stand up to the challenges. The innovation in epitaxy, such as the tunnel junction, the direct epitaxy and nitride-based quantum wells for red and ultraviolet, can provide critical solutions to the micro-LED performance in various aspects. The quantum scale structure, like nanowires or nanorods, can be crucial for the scaling of the devices. Meanwhile, the color conversion method, which uses colloidal quantum dot as the active material, can provide a hassle-free way to assemble a large micro-LED array and emphasis the full-color demonstration via colloidal quantum dot. These quantum dots can be patterned by porous structure, inkjet, or photo-sensitive resin. In addition to the micro-LED devices, the peripheral components or technologies are equally important. Microchip transfer and repair, heterogeneous integration with the electronics, and the novel 2D material cannot be ignored, or the overall display module will be very power-consuming. The AR is one of the potential customers for micro-LED displays, and the user experience so far is limited due to the lack of a truly qualified display. Our analysis showed the micro-LED is on the way to addressing and solving the current problems, such as high loss optical coupling and narrow field of view. All these efforts are channeled to achieve an efficient display with all ideal qualities that meet our most stringent viewing requirements, and we expect it to become an indispensable part of our daily life.

Owing to the development of modern display technology, micro- and mini-light-emitting diodes (LEDs) have affected technological advancements in the display industry. The structure of mini-LEDs is completely different than that of traditional LED backlights because the former employs a display technology with an LED array structure, optical resonant cavity, and color conversion layer. Display backlight technology encounters difficulty in achieving a truly effective energy-loss mechanism when designing or measuring mini-LED performance. The present study proposes three major mini-LED energy loss mechanisms: cross-talk, resonant, and quantum conversion losses. Herein, the spectrum was obtained through the integrating sphere system, and the calculation mechanism was formed by the down-conversion theorem as the decoupling principle, which successfully calculated the independent energy-loss efficiency of each mechanism and effectively deduced the brightness and color saturation performance of this design combination.

We determined the optical and electrical characteristics of GaN-based, ultraviolet micro light emitting diodes (microLEDs). Such microLEDs are essential to next-generation high-resolution micro-displays. Square-shaped microLEDs of different sizes (side lengths: 5-50 μm) were designed. The peak emission wavelength of these devices shifted

Abstract Background Osimertinib yields significant tumor responses and durations of progression‐free survival (PFS) in patients with acquired T790M mutations. However, the evidence supporting liquid biopsy‐guided treatment is still limited. This study examined the real‐world benefits of osimertinib in patients with tissue or plasma T790M mutations. Methods From January 2016 to June 2018, a total of 183 non‐small‐cell lung cancer patients were enrolled. The presence of the T790M mutation was assessed by either tissue or plasma. The PFS, overall survival, and tumor response rates of the patients were calculated and compared with those of previous clinical trials. Results T790M mutations were detected in 51.5% of the patients, including 64 of 140 (45.7%) who underwent liquid biopsies and 23 of 29 (79.3%) who underwent tumor biopsies. After excluding those in clinical trials, 46 patients received osimertinib, including 33 with positive plasma and 13 with positive tissue results for T790M mutations. The median PFS was 11.3 months (interquartile range: 5.2‐NR) in all the T790M‐positive patients and 10.1 months (interquartile range: 5.9‐NR) in the plasma T790M‐positive patients. The overall survival, meanwhile, was not reached, whereas the one‐year survival rate was 66.1% in all the patients and 61.4% in those who were plasma T790M‐positive. The objective response rate and disease control rate were 37.8% and 91.9% in all the patients and 34.6% and 92.3% in the plasma T790M‐positive group, respectively. Using a Cox proportional hazards regression, we determined that male gender was a poor prognostic factor for PFS. Conclusions In this retrospective real‐world analysis, it was determined that both tissue and plasma T790M mutations can be used to guide treatment with osimertinib. Similar disease control rates and survival durations were observed in comparison to those of phase 3 clinical trials.

Abstract We have studied the characteristics of frequency response at 850-nm GaAs high-speed vertical-cavity surface-emitting lasers (VCSELs) with different kinds of oxide aperture sizes and cavity length using the PICS3D simulation program. Using 5-μm oxide aperture sizes, the frequency response behavior can be improved from 18.4 GHz and 15.5 GHz to 21.2 GHz and 19 GHz in a maximum of 3 dB at 25 °C and 85 °C, respectively. Numerical simulation results also suggest that the frequency response performances improved from 21.2 GHz and 19 GHz to 30.5 GHz and 24.5 GHz in a maximum of 3 dB at 25 °C and 85 °C due to the reduction of cavity length from 3λ/2 to λ/2. Consequently, the high-speed VCSEL devices were fabricated on a modified structure and exhibited 50-Gb/s data rate at 85 °C.

The use of immune checkpoint inhibitors (ICIs) has provided overall survival (OS) benefits in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. However, studies comparing ICIs monotherapy with combination therapy either with chemotherapy or radiotherapy in programmed death-ligand 1 high expressors remain limited. This study aimed to retrospectively compare the treatment efficacy of the therapies by studying 47 patients with treatment-naïve advanced NSCLC who received ICI monotherapy (n = 28) or combination therapy either with chemotherapy or radiotherapy (n = 19). Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method and compared using log–rank tests. It was observed that patients who received combination therapy had a better PFS than monotherapy, but no such significant benefit was observed in OS. The difference in PFS was higher in the subgroup of patients with low neutrophil-to-lymphocyte ratio (NLR) than in the high-NLR patient subgroup. This study suggests that pembrolizumab in combination with chemotherapy or radiotherapy could provide a significant benefit in PFS, especially in patients with treatment-naïve advanced NSCLC with low NLR. Furthermore, our study also demonstrates the potential use of NLR as a biomarker for prediction of treatment outcomes in patients with advanced NSCLC receiving combination therapy.

Targeted therapy with combined dabrafenib and trametinib has been proven to provide clinical benefits in patients with NSCLC with a BRAF V600E mutation. Nevertheless, the treatment strategy for patients with NSCLC with BRAF non-V600E mutations remains limited. Here, we present a patient with NSCLC with a BRAF K601E mutation, a class II BRAF mutation, who had a durable response to targeted therapy with combined dabrafenib and trametinib.

Immune checkpoint inhibitors (ICIs) have been approved to treat patients with various cancer types, including lung cancer, in many countries. This study aims to investigate the effectiveness and safety of ICIs under different treatment conditions of non-small cell lung cancer patients. A population-based retrospective cohort study was conducted using the electronic health records of three medical centers in Taiwan. From January 01, 2016, to November 30, 2018, a total of 91 ICIs and 300 traditional chemotherapy users who had undergone stage III and IV lung cancer treatment were included in the study. We performed the randomized matched pair design by selecting a Chemotherapy subject for each ICI patient in the sample population. All subjects were monitored from the date of taking ICIs or chemotherapy drugs until the event of death, loss to follow-up, or were occurred with any defined adverse events. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the overall survival, efficacy, and safety of the ICIs group. The median overall survival (OS) in the ICI and Chemo groups after matching was 11.2 months and 10.5 months, respectively. However, the results showed no significant OS differences between ICIs and chemo groups for both before and after matching (HR,1.30; 95%CI, 0.68-2.46; p=0.428 before matching and HR,0.96; 95CI%, 0.64-1.44; p=0.838 after matching). We observed that with the higher amount of PD-L1, the length of the patients’ overall survival was (positive vs. negative PD-L1, HR,0.21; 95%CI, 0.05-0.80; p=0.022). The incidences of serious adverse drug events above grade 3 in the ICIs and traditional chemo groups were 12.7% and 21.5%, respectively. We also found that the number of AEs was less in ICIs than in the Chemo group, and the AEs that occurred after treatments were observed earlier in the ICIs compared to the Chemo group. ICIs drugs were observed to be safer than traditional chemotherapy as they had a lower risk of serious adverse drug events. It is necessary to pay attention to immune-related side effects and provide appropriate treatment. Furthermore, the patient’s physical status and PD-L1 test can be used to evaluate the clinical effectiveness of ICIs.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

Approximately 5-7% of non-small cell lung cancer (NSCLC) cases harbor an anaplastic lymphoma kinase (ALK) fusion gene and may benefit from ALK inhibitor therapy. To detect ALK fusion genes, we developed a novel test using reverse transcription polymerase chain reaction (RT-PCR) for the ALK kinase domain (KD). Since ALK expression is mostly silenced in the adult with the exception of neuronal tissue, the normal lung tissue, mesothelial lining, and inflammatory cells are devoid of ALK transcript, making ALK KD RT-PCR an ideal surrogate test for ALK fusion transcripts in lung or pleural effusion. The test was designed with a short PCR product (197 bp) to work for both malignant pleural effusion (MPE) and formalin-fixed, paraffin-embedded (FFPE) NSCLC samples. Using ALK IHC as a reference, the sensitivity of the test was 100% for both MPE and FFPE. The specificity was 97.6% for MPE and 97.4% for FFPE. Two false positive cases were found. One was a metastatic brain lesion which should be avoided in the future due to intrinsic ALK expression in the neuronal tissue. The other one resulted from ALK gene amplification. Due to potential false positivity, subsequent confirmation tests such as fluorescence in situ hybridization or multiplex PCR would be preferable. Nevertheless, the test is simple and inexpensive with no false negativity, making it a desirable screening test. It also offers an advantage over multiplex RT-PCR with the capability to detect novel ALK fusions. Indeed through the screening test, we found a novel ALK fusion partner (sperm antigen with calponin homology and coiled-coil domains 1 like gene, SPECC1L) with increased sensitivity to crizotinib in vitro. In summary, a novel RNA-based ALK KD analysis was developed for ALK rearrangement screening in MPE and FFPE specimens of NSCLC. This simple inexpensive test can be implemented as routine diagnostics.

Fine-pitch backlight technology is rapidly evolving along with display technology, and chips are increasingly designed for direct integration with modules. This study used a distributed Bragg reflector (DBR) for mini light-emitting diode (mini-LED) backlights with high dynamic contrast and developed a digital twin design by using a light-emitting diode (LED) and a distributed Bragg reflector (DBR).

The solar cell has a poor spectral response in the UV region, which affects its power conversion efficiency (PCE). The utilization of a luminescent downshifting (LDS) layer has been suggested to improve the spectral response of the photovoltaics in the short wavelength region through photoluminescence (PL) conversion and antireflection effects, which then enhance the PCE of the solar cell. Recently, colloidal quantum dots (CQDs) or perovskite quantum dots (PQDs) have been gaining prime importance as an LDS material due to their eminent optical characteristics, such as their wide absorption band, adjustable visible emission, short PL lifetime, and near-unity quantum yields. However, the instability of QDs that occurs under certain air, heat, and moisture conditions limits its commercialization. Thus, in this review, we will focus on the physical and optical characteristics of QDs. Further, we will discuss different synthesis approaches and the stability issues of QDs. Different approaches to improve the stability of QDs will be discussed in detail alongside the recent breakthroughs in QD-based solar cells for various applications and their current challenges. We expect that this review will provide an effective gateway for researchers to fabricate LDS-layer-based solar cells.

Abstract High-brightness white-light-emitting diodes (w-LEDs) with excellent color quality is demonstrated by using nontoxic nanomaterials. Previously, we have reported the high color quality w-LEDs with heavy-metal phosphor and quantum dots (QDs), which may cause environmental hazards. In the present work, liquid-type white LEDs composed of nontoxic materials, named as graphene and porous silicon quantum dots are fabricated with a high color rendering index (CRI) value gain up to 95. The liquid-typed device structure possesses minimized surface temperature and 25% higher value of luminous efficiency as compare to dispensing-typed structure. Further, the as-prepared device is environment friendly and attributed to low toxicity. The low toxicity and high R9 (87) component values were conjectured to produce new or improve current methods toward bioimaging application.

The authors wish to make following corrections in this paper [...]

This paper describes a four-layer-stacked chip with 45-nm dynamic random access memory (DRAM) dice and 65-nm logic controller, which are interconnected by backside-via-last through-silicon via (TSV) processes. Fabrication of backside-via-last process and multiple die stacking using chip-to-chip bonding are presented with electrical connection between TSV (5-μm-diameter/50-μm-length) and Cu interconnects. Excellent fabrication of stacked dice verified that the micro bumps with 12-μm diameter are bonded using three step temperature bonding profile. Further stacked DRAM/Logic performance and system verifications are demonstrated successfully using 3-D heterogeneous integration.

The luminescent down-shifting (LDS) effect of a colloidal quantum dot layer on a dual junction solar cell is explored and analyzed. A 5.47% enhancement of power conversion efficiency is recorded when green quantum dots are dispersed on device surface. The surface reflectance spectra before and after the quantum dot dispenses are necessary to decouple the different mechanisms between antireflective and LDS effects. A further deduction of formulation on the dual-junction device with antireflection and LDS effect is presented and as high as 44.6% of short-circuit current increase in the green quantum dot case can be attributed to the LDS effect according to our calculation.

Quantum dot (QD)-based RGB micro-LED technology is seen as one of the most promising approaches towards full color micro-LED displays. In this work, we present a novel nanoporous GaN (NP-GaN) structure that can scatter light and host QDs, as well as a new type of micro-LED array based on an NP-GaN embedded with QDs. Compared to typical QD films, this structure can significantly enhance the light absorption and stability of QDs. As a result, the green and red QDs exhibited light conversion efficiencies of 90.3% and 96.1% respectively, leading to improvements to the luminous uniformity of the green and red subpixels by 90.7% and 91.2% respectively. This study provides a viable pathway to develop high-uniform and high-efficient color conversion micro-LED displays.

Abstract Background It is known that the medicinal herb Alpinia oxyphylla Miq. is widely used as a remedy for diarrhea as well as the symptoms accompanying hypertension and cerebrovascular disorders. Moreover, it has also been reported that Alpinia oxyphylla Miq. has beneficial effects on anti-senescence and neuro-protection. This study focuses on the molecular mechanisms by which the Alpinia oxyphylla Miq. fruits promote neuron regeneration. Methods A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with various doses of Alpinia oxyphylla Miq. fruits to assess their regenerative effect on damaged nerves. Further, we investigated the role of Alpinia oxyphylla Miq. fruits in RSC96 Schwann cell proliferation. Results Our current results showed that treatment with the extract of Alpinia oxyphylla Miq. fruits triggers the phosphorylated insulin-like growth factor-1 receptor- phosphatidylinositol 3-kinase/serine-threonine kinase pathway, and up-regulated the proliferating cell nuclear antigen in a dose-dependent manner. Cell cycle analysis on RSC96 Schwann cells showed that, after exposure to Alpinia oxyphylla Miq. fruit extract, the transition from the first gap phase to the synthesis phase occurs in 12–18 h. The expression of the cell cycle regulatory proteins cyclin D1, cyclin E and cyclin A increased in a dose-dependent manner. Transfection with a small interfering RNA blocked the expression of phosphatidylinositol 3-kinase and induced down-regulation both on the mRNA and protein levels, which resulted in a reduction of the expression of the survival factor B-cell lymphoma 2. Conclusion We provide positive results that demonstrate that Alpinia oxyphylla Miq. fruits facilitate the survival and proliferation of RSC96 cells via insulin-like growth factor-1 signaling.

Third-generation tyrosine kinase inhibitors (TKIs) were developed to overcome T790M-mediated resistance to earlier generations of epidermal growth factor receptor (EGFR)-targeted TKIs. We compared four well-established and one in-house method for the analysis of the EGFR T790M mutation in plasma cell-free DNA (cfDNA), in hope to find a better way to select non-small cell lung cancer (NSCLC) patients appropriate for 3rd-generation TKI therapy. For sensitivity levels of each method, plasmid DNA with EGFR T790M mutations was serially diluted with cfDNA from healthy controls with wild type EGFR. The clinical performance was analyzed in a clinical cohort of EGFR mutation-positive NSCLC patients with acquired EGFR TKI resistance (n = 40). All methods except the therascreen kit (Qiagen) had a sensitivity level of 10 copies of T790M plasmid DNA in the spiked specimen. The detection rates of the EGFR T790M mutation in plasma cfDNA from the clinical cohort were 42.5, 35, 32.5, 22.5, and 17.5% for the in-house ARMS method, Bio-Rad droplet digital PCR, PANAMutyper, Therascreen EGFR Plasma RGQ PCR Kit and Cobas EGFR Mutation kit (with suboptimal template amounts), respectively. Osimertinib was given to 17 of 20 patients with EGFR T790M mutations. The best treatment responses, based on the RECIST criteria, included 6 partial responses (PR) and 7 stable diseases (SD). The PANAMutyper and the Bio-Rad droplet digital PCR were comparable, the Cobas EGFR Mutation kit required significantly more template for testing. The best combination would be the in-house ARMS method plus the PANAMutyper or Bio-Rad droplet digital PCR, which would have a detection rate of 50% (20/40) and a disease control rate of 76% (13/17).