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The creation of a high-pressure rhombohedral phase leads to a colossal barocaloric effect in KPF6.

The period (

Recently, thermoelectric (TE) devices have attracted much attention because they have no moving parts, simple structures, high reliability, and environmental friendly, when compared to other green energy techniques. In this paper, we report a novel thermoelectric composite constructed one with a self-assembled highly oriented Sb doped Bi2Te3 and one without doping nanoflake layer deposited on regular vertically aligned checkerboard-patterned multi-walled carbon nanotube (MWCNT) arrays (500 nm squares and 1 µm pitch) on insulated SiO2/Si substrates. The height of Bi2Te3/Bi0.4Sb1.6Te3, MWCNTs and volumetric ratio of MWCNT to Bi2Te3/ Bi0.4Sb1.6Te3 are about 3 μm, 1.5 μm, and 25%, respectively. The blending of regular vertically aligned MWCNT patterns into Bi0.4Sb1.6Te3 results in a dramatically enhancement of Seebeck coefficient and electrical conductivity. The Seebeck coefficient and power factor of Bi0.4Sb1.6Te3-MWCNTs show a maximum value of 600 μV/K and 60 μW/cm-K2 at 160 K and gradually decrease to 409 μV/K, and about 14.1 μW/cm-K2 at 300 K, respectively. The significant records of the low temperature Seebeck coefficients and relative electrical properties are extremely important for the fundamental understanding of vertically aligned MWCNT embedded thermoelectric composites.

Background/Purpose The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Methods Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. Results The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the “CTA” (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, “TCG” (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). Conclusion Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

BackgroundAdult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity.MethodsEnvironmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case–control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables.FindingsIn the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28–3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108–0.311, p2.5exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (pInterpretationThese results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.

Pupil size changes constantly and is mainly determined by global luminance signals. In addition, the pupil responds to various cognitive and arousal processes, with larger pupil dilation observed in higher levels of cognitive or arousal processing. Although these task-evoked pupillary responses are extensively used in the pupil research, pupil analysis focusing on the frequency domain, particularly in the context of arousal and cognitive modulations, is less established. Fourier Transform method (FFT) has been used to understand the modulation of task difficulty on pupil oscillations. However, physiological signals are often characterized as non-linear and non-stationary waves, and the conventional spectral analytical method with linearity presumption is less appropriate to reveal modulation dynamics between time and frequency. Here, we used Hilbert-Huang Transform (HHT) to examine the time-frequency modulations on pupil size regulated by arousal, cognitive, and global luminance signals. Consistent with previous research, using FFT, higher spectral densities were obtained with lower luminance background. Moreover, higher spectral densities were found in the high emotional arousal condition. With HHT, we further demonstrated temporal changes on amplitude spectrum and inter-trial phase coherence (ITPC) in each intrinsic mode function (IMF), with stronger amplitudes in higher IMFs (i.e., low frequencies). Moreover, although global luminance, arousal and saccade preparation modulated pupil oscillatory responses, the modulation pattern in different IMFs was different. Together, our results demonstrated dynamics between the time and frequency domain on pupil oscillatory responses, highlighting the importance of examining the time-frequency interactions in the context of various pupil modulations.

Chronic subdural hematomas (CSDHs) are common in the elderly population and patients taking antiplatelet/anticoagulation medications. Middle meningeal artery (MMA) embolization has become an adjunctive treatment to observation and surgery. Despite many embolization techniques, best practices for optimal CSDH resolution remain unknown.To report a retrospective case series of MMA embolization for CSDHs regarding rate of hematoma improvement and the significance of distal embolic penetration into the falx.Retrospective chart review was performed on all patients who underwent MMA embolization for CSDHs between January 2017 and June 2021. Patient demographics, clinical presentation, anticoagulant use, and radiographic features were collected. Pre-embolization and postembolization computed tomography scans were analyzed for volumetric changes and assessed for midline penetration of embolic material in the falx.MMA embolization was performed in 37 patients and 53 hemispheres. Older patients took longer to obtain complete resolution of CSDHs (r = 0.47, P = .03). Patients with larger pre-embolization (r = 0.57, P = .007) and postembolization (r = 0.56, P = .008) CSDH volumes took longer to completely resolve. Patients who had n-butyl cyanoacrylate embolization with midline penetration, as evidenced by the "bright falx" sign, had faster improvement rates than those who did not (5.64 cm 3 /d vs 1.2 cm 3 /d, P = .02).Distal penetration of embolic material, particularly n-butyl cyanoacrylate, into the falx may lead to more rapid improvement of CSDH.

In 2017, the Taiwanese Constitutional Court handed down Judicial Yuan Interpretation No. 748, which was a ruling in favour of same-sex marriage. The Court also ordered the national legislature to amend the law within two years. Despite a significant backslide in the Taiwanese 2018 referendum, the legislature eventually followed the Court’s order and legalized gay marriage in 2019. This victory made Taiwan the first state to legalize same-sex marriage in Asia. Many legal scholars consider the same-sex marriage ruling a progressive decision in which the Court undertook a counter-majoritarian task of protecting a minority group. While we agree with the Court’s role in promoting marriage equality, we contend that most legal scholars overlook an important question in this dynamic: the legislature had had several chances to settle this issue over the past decades, so why did it refuse to draft gay-marriage legislation but later, in 2019, defer to the Court’s decision? In this paper, we explain the political foundations of an activist judiciary by using the case of the first gay-marriage legislation in Asia. We argue that the risk of position-taking on tough issues leads incentive-facing political elites to engage in position avoidance and to see the political value in deferring to a high court’s ruling. Using original data, we present evidence of how Taiwan’s diverse constituency relative to the same-sex marriage issue influenced legislators’ position-avoidance behaviour and led them to dodge political backfire by delegating policy-making authority to the Constitutional Court.

The treatment of the peri-implantitis remains complex and challenging with no consensus on which is the best treatment approach.To examine the key local and systemic factors associated with implant loss, disease progression, or favorable outcomes after surgical peri-implantitis therapy.Records of patients treated for peri-implantitis were screened. Patient-, implant- and surgery-related variables on and prior to the day of the surgery were collected (T0: time of peri-implantitis treatment). If the treated implant was still in function when the data was collected, the patient invited to participate for a recall study visit (T1, longest follow-up after treatment). Impacts of the variables on the implant survival, success, and peri-implant bone change after treatment were investigated.Eighty patients with 121 implants with a mean follow-up of 42.6 ± 26.3 months were included. A total of 22 implants (18.2%) were removed during the follow-up period. When relative bone loss (%) was in range 25%-50%, risk for implant removal increased 15 times compared to lower bone loss25% (OR = 15.2; CI: 2.06-112.7; p = 0.008). Similarly, relative bone loss of50% increased 20 times the risk of implant failure compared to the25% (OR = 20.2; CI: 2.42-169.6; p = 0.006). For post-treatment success rate, history of periodontitis significantly increased the risk of unsuccess treatment (OR = 3.07; p = 0.04) after resective surgery).Severe bone loss (50%) poses significantly higher risk of treatment failure.

Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) with revealed activity against EGFR-sensitizing mutations and EGFR T790M mutation.Patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy were enrolled in this registrational phase 2 trial of aumolertinib at 110 mg orally once daily (NCT02981108). The primary end point was objective response rate (ORR) by independent central review.A total of 244 patients with EGFR T790M-positive NSCLC were enrolled. The ORR by independent central review was 68.9% (95% confidence interval [CI]: 62.6-74.6). The disease control rate was 93.4% (95% CI: 89.6-96.2). The median duration of response was 15.1 months (95% CI: 12.5-16.6). The median progression-free survival was 12.4 months (95% CI: 9.7-15.0). Among 23 patients with assessable central nervous system (CNS) metastases, the CNS-ORR and CNS-disease control rate were 60.9% (95% CI: 38.5-80.3) and 91.3% (95% CI: 72.0-98.9), respectively. The median CNS-duration of response was 12.5 months (95% CI: 5.6-not reached). Treatment-related adverse events of more than or equal to grade 3 occurred in 16.4% of the patients, with the most common being increased blood creatine phosphokinase level (7%) and increased alanine aminotransferase level (1.2%). The relative dose density of aumolertinib was 99.2% in this study.Aumolertinib is an effective and well-tolerated third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression on first- and second-generation EGFR TKI therapy. On the basis of these findings, aumolertinib was approved in the People's Republic of China for patients positive for EGFR T790M NSCLC.

Radiodermatitis is commonly experienced by patients with breast cancer undergoing radiotherapy, affecting their quality of life and potentially leading to cancer treatment postponement. Recently, people who use natural substances to treat radiodermatitis have attracted more and more attention. However, there is no unanimous conclusion to follow.We conducted a meta-analysis of randomized controlled trials (RCTs) that compared hyaluronic acid with other topical agents in patients with breast cancer.PubMed, Cochrane Library, and Embase databases were searched for eligible articles. The primary outcome indicating symptom relief was a decreased radiodermatitis grade. The secondary outcome indicating symptom relief was preference and desquamation. The study is registered with PROSPERO (number: CRD42021237793).Eight RCTs that together enrolled 500 patients were analyzed. Six studies assessed the radiodermatitis grade and found significant differences in three of eight subgroups. The subgroups comparing hyaluronic acid with phytosterol, omega-3, 6, 9, and vitamin E showed significantly lower risk ratios. In two subgroups, the effect of hyaluronic acid was not significantly different from that of grapevine extract and Avene thermal water. The remaining three studies reported that other topical agents exerted a nonsignificantly better effect than hyaluronic acid did. Physicians' preference was better for the control group, while the patients' preference for hyaluronic acid was better, and there was no statistical difference. In addition, our study showed that desquamation events were few in the hyaluronic group.Hyaluronic acid can show a better effect than other topical drugs and the lower incidence in desquamation events. Since hyaluronic acid has no obvious side effects, we recommend it as one of the alternative options. Further research is required to evaluate this effect comprehensively.

Hydrodynamic herringbone-grooved journal bearings (HGJBs) are analyzed by solving Navier–Stokes and energy equations. It is well known that the load capacity of hydrodynamic bearings may be affected by high temperatures and low oil viscosity. Therefore, the main objective of this study is to understand the pressure distribution of hydrodynamic HGJBs under different oil viscosity and eccentricity ratios. In this paper, 3 different configurations are studied, namely, a HGJB, a combined HGJB and thrust bearing, and a combined HGJB and grooved thrust bearing. The bearing characteristics, such as load capacity and attitude angle that vary with different eccentricity ratios, are also discussed. The results show that the load capacity of the bearing decreases with increasing temperature. The pressure difference also increases as the eccentricity ratio increases. The high-pressure region is concentrated at the tip of the groove for the HGJB. In addition, the combined HGJB and grooved thrust bearing can be used to stabilize the journal because of the low attitude angle. These findings may help and facilitate the design of hydrodynamic bearings suitable for working in warm and hot environments in the future.

Although RD43 rice is characterized by high amounts of undigestible starch, its potential health benefits for prediabetic individuals remain unknown. Thus, the effect of regular consumption of RD43 rice on the glycemic response, body composition, and metabolic markers was investigated in a sample of 34 participants with prediabetes (aged from 32 to 68 years) who were randomly allocated to either the treatment or the control group. The first were required to consume RD43 rice (Glycemic Index [GI] = 78) containing 14.1 g of undigestible starch daily as a substitute for two meals per day while the second were given the Taiken9 rice (GI = 98) for 12 continuous weeks. The evaluations were performed at baseline, at the end of week 6 and 12, and at follow-up conducted two weeks after the intervention had ended. The results obtained at the week 12 assessment clearly showed a significant decrease in fasting plasma glucose, insulin, HbA1c, and HOMA-IR in the group that consumed RD43 rice. In addition, daily ingestion of RD43 rice markedly reduced body weight, Body Mass Index (BMI), total fat mass, and waist circumference at both week 6 and 12 compared with the baseline. When compared with the controls, the treatment group also exhibited a significant decrease in fasting plasma insulin and HOMA-IR at week 12. However, no significant inter- or intra-group differences in lipid profiles were detected. These findings suggest that RD43 rice could be a potential staple food with the capacity to improve glycemic control and body composition in prediabetic individuals.

Background The aim of the study was to assess programmed death‐ligand‐1 (PD‐L1) expression in different histological types and gene mutation status of patients with non‐small cell lung cancer (NSCLC). Methods A total of 4062 pathology‐confirmed lung cancer patients were retrospectively screened at Kaohsiung Chang Gung Memorial Hospital from November 2010 to June 2017. There were 699 NSCLC patients with confirmed PD‐L1 expression level retrospectively enrolled for analysis. Results There was a trend of higher PD‐L1 expression in squamous cell carcinoma and adenosquamous cell carcinoma than in adenocarcinoma (p = 063). Significant higher PD‐L1 expression in EGFR wild‐type was noted (p, A trend or significant differences in PD‐L1 expression between different histologic types in NSCLC, different EGFR status, and different ALK status, and different tumor tissue storage time. A higher survival benefit (TTF or OS) was observed in no PD‐L1 expression than with PD‐L1 expression in adenocarcinoma, EGFR mutation, and ALK mutation patients. PD‐L1 assay should be performed as early as possible if tissue is available.

Quasicrystals (QCs), first discovered in 1984, generally do not exhibit long-range magnetic order. Here, we report on long-range magnetic order in the real icosahedral quasicrystals (i QCs) Au–Ga–Gd and Au–Ga–Tb. The Au65Ga20Gd15i QC exhibits a ferromagnetic transition at TC = 23 K, manifested as a sharp anomaly in both magnetic susceptibility and specific heat measurements, along with an appearance of magnetic Bragg peak below TC. This is the first observation of long-range magnetic order in a real quasicrystal, in contrast to the spin-glass-like behaviors observed for the other magnetic quasicrystals found to date. Moreover, when Gd is replaced by Tb, i.e., for the Au65Ga20Tb15i QC, a ferromagnetic behavior is still retained with TC = 16 K. Although the sharp anomaly in the specific heat observed for the Au65Ga20Gd15i QC becomes broadened upon Tb substitution, neutron diffraction experiments clearly show marked development of magnetic Bragg peaks just below TC, indicating long-range magnetic order for the Au65Ga20Tb15i QC also. Our findings can contribute to the further investigation of exotic magnetic orders formed on real quasiperiodic lattices with unprecedented highest global symmetry, i.e., icosahedral symmetry.

Saccades are rapid eye movements that are used to move the high acuity fovea in a serial manner in the exploration of the visual scene. Stimulus contrast is known to modulate saccade latency and metrics possibly via changing visual activity in the superior colliculus (SC), a midbrain structure causally involved in saccade generation. However, the quality of visual signals should also be modulated by the amount of lights projected onto the retina, which is gated by the size of the pupil. Although absolute pupil size should modulate visual signals and in turn affect saccade responses, research examining this relationship is very limited. Besides, pupil size is associated with motor preparation. However, the role of pupil dilation in saccade metrics remains unexplored. Through varying peripheral background luminance level and target visual contrast in the saccade task, we investigated the role of absolute pupil size and baseline-corrected pupil dilation in saccade latency and metrics. Higher target detection accuracy was obtained with lower background luminance level, and larger absolute pupil diameter correlated with smaller saccade amplitude and higher saccade peak velocities. More interestingly, the comparable modulation between pupil dilation and stimulus contrast was obtained, showing larger pupil dilation (or higher contrast stimuli) correlating with faster saccade latencies, larger amplitude, higher peak velocities, and smaller endpoint deviation. Together, our results demonstrated the influence of absolute pupil size induced by global luminance level and baseline-corrected pupil dilation associated with motor preparation on saccade latency and metrics, implicating the role of the SC in this behavior.

Microbial fuel cells (MFCs) are recognized as an efficient method to utilize biomass to generate power while simultaneously treats wastewater. Micro-electro-mechanical system (MEMS) technology enables miniaturization of the MFCs system. Miniaturized MFCs through MEMS strengthen the system’s reaction capacity that makes it suitable for environmental sense field applications such as sensors or biomedical actuators. In this work, MEMS technology is employed to deposit metal layers on the surface of the anode/cathode electrode to enhance the power density of the MFC. Hence, micromixers and micro-pillars in the anode tank along with the influence of the electron transport media on MFC performance were evaluated. The introduction of the micro-mixers promotes the full mixing of the anolyte. The inclusion of the micro-pillars increases the surface area of the electrode, thereby enhancing the electrical energy output of the MFC. Results revealed that the introduction of the microstructure and the electron transfer media to the anolyte in the MFC have yielded a maximum current of 66.55 μ A cm−2, a maximum power density of 3.28 μ W cm−2, and an internal resistance value of 2 . 57 k Ω . Moreover, the inclusion of several micro-mixers and micro-pillar structures to the anode tank has shown the performance enhancement of MFC. Relevant research results will provide a reference for future research on the combination of MFCs and sensors.

Purpose To investigate the survival benefit with first/second generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) and osimertinib in different treatment sequences. Methods We retrospectively screened 3807 patients diagnosed with cancer between 2013 and 2019 at Kaohsiung Chang Gung Memorial Hospital. In total, 76 patients with EGFR T790M mutation who received osimertinib after re‐biopsy or liquid biopsy were enrolled for the analysis. Results The median progression‐free survival (PFS), median overall survival (OS), and median OS2 of the 76 patients were 11.93, 66.53, and 29.57 months, respectively. A significant difference was observed in the disease control rate between those who received osimertinib treatment after chemotherapy (group A) and those who received osimertinib immediately following EGFR‐TKI therapy (group B) (34 [94.4%] vs. 31 [77.5%], p = 0.036). In addition, chronic obstructive pulmonary disease tended to be a poor prognostic factor for PFS and OS. Conclusion This real‐world analysis revealed that previous chemotherapy could affect the treatment outcomes of patients with non‐small cell lung cancer treated with osimertinib. Osimertinib treatment following first/second generation EGFR‐TKI treatment or chemotherapy resulted in improved survival benefit., Osimertinib treatment after one line of chemotherapy (group A) had a better response rate and a better PFS than osimertinib treatment immediately following treatment with first/second generation EGFR‐TKIs (group B). COPD tended to a poor prognostic factor for PFS and OS2 in patients with osimertinib use.

Recycled duck bones (DBs) and fish shells were processed into natural derivatives. Through innovative design, these natural derivatives were then combined with biopolymers to create a new type of ecofriendly filament suitable for three-dimensional (3D) printing of scaffolds for bone regeneration. The DBs and fish shells were thermally processed to produce DB-derived hydroxyapatite (HA) and fish shell-derived Ca(OH)2 (TAS), respectively. Poly(ε-caprolactone) (PCL), HA, and TAS were combined and fabricated into new composite filaments, which were then transformed into scaffolds using 3D printing technology. The structure and antibacterial behaviors of the obtained composite scaffolds were studied. Alone, PCL showed no bacterial inhibition. MHA (a mix of HA and TAS) was added to PCL to form a PCL/MHA composite material, which significantly improved the functional properties of PCL and enhanced cell attachment and proliferation. The Ca(OH)2 content of TAS was responsible for the antibacterial effect. The PCL/MHA composites were porous and displayed enhanced osteoblast proliferation in vitro. The osteoblast cell population do not affected when cultured on the PCL/HA and PCL/MHA series composites according to cell cycle distribution analysis. The surfaces of the various PCL/HA and PCL/MHA composites showed elevated levels of calcium and phosphorus compounds when exposed to simulated body fluids. Calcium and phosphate ions were rapidly deposited on PCL/HA and PCL/MHA composite scaffolds in osteoblasts according to the cell mineralization assay. Our findings suggest great potential of the PCL/HA and PCL/MHA composite scaffolds in bone tissue engineering applications.

We report the successful growth of high-quality single crystals of Sr

Despite the treatment of lung adenocarcinoma (LUAD) having partially improved in recent years, LUAD patients still have poor prognosis rates. Therefore, it is especially important to explore effective biomarkers and exploit novel therapeutic developments. High-throughput technologies are widely used as systematic approaches to explore differences in expressions of thousands of genes for both biological and genomic systems. Recently, using big data analyses in biomedicine research by integrating several high-throughput databases and tools, including The Cancer Genome Atlas (TCGA), cBioportal, Oncomine, and Kaplan–Meier plotter, is an important strategy to identify novel biomarkers for cancer therapy. Here, we used two different comprehensive bioinformatics analysis and revealed protein tyrosine phosphatase non-receptor type (PTPN) family genes, especially PTPN1 and PTPN22, were downregulated in lung cancer tissue in comparison with normal samples. The survival curves indicated that LUAD patients with high transcription levels of PTPN5 were significantly associated with a good prognosis. Meanwhile, Gene Ontology (GO) and MetaCore analyses indicated that co-expression of the PTPN1, PTPN5, and PTPN21 genes was significantly enriched in cancer development-related pathways, including GTPase activity, regulation of small GTPase-mediated signal transduction, response to mechanical stimuli, vasculogenesis, organ morphogenesis, regulation of stress fiber assembly, mitogen-activated protein kinase (MAPK) cascade, cell migration, and angiogenesis. Collectively, this study revealed that PTPN family members are both significant prognostic biomarkers for lung cancer progression and promising clinical therapeutic targets, which provide new targets for treating LUAD patients.

IntroductionUncommon epidermal growth factor receptor (EGFR) mutations include single and complex mutations. However, the association of the smoking status of patients with uncommon and complex EGFR mutations remains unclear.MethodsThis retrospective study evaluates the spectrum of uncommon EGFR mutations and investigates the influence of smoking status on the frequency of various uncommon EGFR mutations using a multi-institutional medical database.ResultsBetween 2010 and 2019, 5,608 non-small cell lung cancer (NSCLC) patients were analyzed. EGFR mutations were detected in 3,155 (56.3%) patients. Among the 399 (12.6%) patients with uncommon mutations, 198 had single uncommon and 201 complex mutations, including 87 exon 20 insertions, 79 de novo T790M, 70 complex common, and 52 complex uncommon mutations. For comparison, we also included 402 patients with common EGFR mutations. The percentage of ever-smokers was significantly higher in patients with uncommon EGFR mutations than in patients with common EGFR mutations (25.8% vs. 17.4%, p = 0.005). Furthermore, the percentage of ever-smokers was higher in those with a complex mutation than in those with a single uncommon mutation (30.3% vs. 21.2%, p = 0.040). Among patients carrying uncommon EGFR mutations, ever-smokers had significantly more complex uncommon EGFR mutations than never-smokers (22.3% vs. 9.8%, p = 0.002). Among patients carrying G719X, L861Q, and S768I, ever-smokers tended to have complex EGFR mutations more frequently than never-smokers (64.7% vs. 28.7%, 50.0% vs. 18.7%, 88.9% vs. 81.2%, respectively).ConclusionsOur study demonstrates not only a comprehensive spectrum of uncommon EGFR mutations, but also a positive relationship between smoking status and uncommon EGFR mutation frequency, especially complex uncommon EGFR mutations. The results suggest that smoking contributes to the development of complex EGFR mutations.

OBJECTIVES Osimertinib is the main treatment choice for pretreated patients with advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) T790M mutations. However, the choice of subsequent therapy when progressive disease has developed after osimertinib treatment remains a major therapeutic challenge. This study evaluated the efficacy of osimertinib-based combination therapies in patients who developed progressive disease after treatment with osimertinib. MATERIAL AND METHODS We enrolled NSCLC patients harbouring T790M mutations pretreated with first- or second-generation EGFR tyrosine-kinase inhibitors and were receiving osimertinib at two tertiary referral centres between August 2015 and July 2019, and the subsequent treatment efficacy was assessed. RESULTS Osimertinib-based combination therapy yielded better overall survival (OS) than chemotherapy alone (not achieved vs. 7.8 months; hazard ratio, 0.39; 95 % confidence interval 0.17-0.89; P = 0.025) according to the Cox proportional hazards model adjusted for possible confounders. Synergism (combination index

Slot-die coating is a promising technology for the development of integrated circuits. In this study, we used ANSYS Fluent, to investigate slot-die coating for different die lip configurations. We...