Background
Although DNA damage response and repair (DDR) gene alteration has been demonstrated as a biomarker for anti-PD-1 therapy in several cancer types, its role in esophageal squamous cell ...carcinoma (ESCC) is unknown.
Methods
Patients with advanced ESCC treated with anti-PD-1-based immunotherapy were enrolled. Tumor response was evaluated according to RECIST 1.1. Archival ESCC tissues were analyzed using FoundationOne CDx. Deleterious alterations, defined by loss of function, of DDR genes were correlated with patient survival by Cox proportional hazards model. The prognostic significance of deleterious alterations of DDR genes in The Cancer Genome Atlas (TCGA)–ESCC cohort was explored.
Results
Forty-three patients were enrolled. The objective response rate (ORR) was 19%. The median tumor mutational burden was 4 mutations/Mb (0–20); none of the tumors were microsatellite instable. Compared with patients with wild-type or other alterations of DDR genes (
N
= 35, 81%), those with deleterious alterations of DDR genes (
N
= 8, 19%) had a higher ORR (38 vs. 14%), longer median progression-free survival (4.1 vs. 2.0 months), and significantly longer median overall survival (OS; 27.7 vs. 6.1 months,
P
= 0.011). In multivariate analysis, harboring deleterious alterations of DDR genes was a favorable prognostic factor for OS (HR = 0.31 95% CI: 0.11–0.91,
P
= 0.033). In the TCGA–ESCC cohort, the presence of deleterious alterations of DDR genes was not a favorable prognostic factor.
Conclusions
Deleterious alterations of DDR genes may be associated with improved prognosis and efficacy of anti-PD-1 therapy in patients with advanced ESCC.
In this paper, we reported a ferroelectric HfAlO x negative capacitor transistor with gate-stress (GS) engineering. Compared to control device, the HfAlO x transistor with GS engineering percentage ...of <inline-formula> <tex-math notation="LaTeX">\text{I}_{ \mathrm{\scriptscriptstyle ON}} </tex-math></inline-formula> enhancement and 27% <inline-formula> <tex-math notation="LaTeX">\text{V}_{T} </tex-math></inline-formula> reduction under the assistance of the negative capacitance (NC) effect. The orthorhombic phase transition played a crucial role in realizing the NC effect. From the results of the material analysis, the theoretical Landau simulation and electrical measurement, we demonstrated that the GS is favorable for inducing orthorhombic phase crystallization of HfAlO x and stabilizing the NC effect, which shows the potential for the application of advanced technology node.
Liver-type fatty acid-binding protein (L-FABP) is widely expressed in hepatocytes and plays a role in lipid metabolism. It has been demonstrated to be overexpressed in different types of cancer; ...however, few studies have investigated the association between L-FABP and breast cancer. The aim of this study was to assess the association between plasma concentrations of L-FABP in breast cancer patients and the expression of L-FABP in breast cancer tissue.
A total of 196 patients with breast cancer and 57 age-matched control subjects were studied. Plasma L-FABP concentrations were measured using ELISA in both groups. The expression of L-FABP in breast cancer tissue was examined using immunohistochemistry.
The patients had higher plasma L-FABP levels than the controls (7.6 ng/mL (interquartile range 5.2-12.1) vs. 6.3 ng/mL (interquartile range 5.3-8.5), p = 0.008). Multiple logistic regression analysis showed an independent association between L-FABP and breast cancer, even after adjusting for known biomarkers. Moreover, the rates of pathologic stage T2+T3+T4, clinical stage III, positive HER-2 receptor status, and negative estrogen receptor status were significantly higher in the patients with an L-FABP level greater than the median. Furthermore, the L-FABP level gradually increased with the increasing stage. In addition, L-FABP was detected in the cytoplasm, nuclear, or both cytoplasm and nuclear of all breast cancer tissue examined, not in the normal tissue.
Plasma L-FABP levels were significantly higher in the patients with breast cancer than in the controls. In addition, L-FABP was expressed in breast cancer tissue, which suggests that L-FABP may be involved in the pathogenesis of breast cancer.
Adrenocorticotropic hormone (ACTH)‐producing neuroendocrine neoplasm (NEN) of the thymus is rare. Lymph nodes and bones are the most common metastatic sites. Most cases present with florid Cushing's ...syndrome (CS). Here, we reported a 58‐year‐old woman, who presented with intermittent flush and weight loss. Imaging studies revealed tumors in the mediastinum, pancreas, and bones. Contrast‐enhanced harmonic endoscopic ultrasound (EUS) of the pancreatic tumors showed heterogeneous and hyperenhancing characteristics. EUS elastography revealed a heterogeneous stiff pattern. EUS‐fine needle biopsy to the pancreatic lesion confirmed the NEN nature. Serum ACTH and cortisol levels were abnormally high. Immunohistochemical staining of the thymic and pancreatic specimens was positive for ACTH. However, the patient did not have obvious CS appearance. The patient underwent surgery, radiation, EUS‐guided ethanol injection, and anti‐cancer medications, but the disease still progressed. The patient died from infection 16 months after NEN was diagnosed. In conclusion, the pancreas can be a metastatic site for ACTH‐producing thymic NEN. EUS‐associated procedures can help in the diagnosis and treatment of pancreatic metastatic NEN.
Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common clinical treatments provide ...limited relief and have some side effects. Therefore, there is a need to develop new effective therapies to treat AD. Epi-oxyzoanthamine is a small molecule alkaloid isolated from Formosan zoanthid. Relevant studies have shown that zoanthamine alkaloids have many pharmacological and biological activities, including anti-lymphangiogenic functions. However, there are no studies on the use of epi-oxyzoanthamine on the skin. In this paper, epi-oxyzoanthamine has been shown to have potential in the treatment of atopic dermatitis. Through in vitro studies, it was found that epi-oxyzoanthamine inhibited the expression of cytokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Atopic dermatitis-like skin inflammation was induced in a mouse model using 2,4-dinitrochlorobenzene (DNCB) in vivo. The results showed that epi-oxyzoanthamine significantly decreased skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly reduced transepidermal water loss (TEWL), erythema, ear thickness, and spleen weight, while also increasing surface skin hydration. These results indicate that epi-oxyzoanthamine from zoanthid has good potential as an alternative medicine for treating atopic dermatitis or other skin-related inflammatory diseases.
Phalaenopsis represents an important cash crop worldwide. Abundant flower colors observed in Phalaenopsis orchids range from red-purple, purple, purple-violet, violet, and violet-blue. However, ...violet-blue orchids are less bred than are those of other colors. Anthocyanin, vacuolar pH and metal ions are three major factors influencing flower color. This study aimed to identify the factors causing the violet-blue color in Phalaenopsis flowers and to analyze whether delphinidin accumulation and blue pigmentation formation can be achieved by transient overexpression of heterologous F3'5'H in Phalaenopsis.
Cyanidin-based anthocyanin was highly accumulated in Phalaenopsis flowers with red-purple, purple, purple-violet, and violet to violet-blue color, but no true-blue color and no delphinidin was detected. Concomitantly, the expression of PeF3'H (Phalaenopsis equestrsis) was high, but that of PhF3'5'H (Phalaenopsis hybrid) was low or absent in various-colored Phalaenopsis flowers. Transient overexpression of DgF3'5'H (Delphinium grandiflorum) and PeMYB2 in a white Phalaenopsis cultivar resulted a 53.6% delphinidin accumulation and a novel blue color formation. In contrast, transient overexpression of both PhF3'5'H and PeMYB2 did not lead to delphinidin accumulation. Sequence analysis showed that the substrate recognition site 6 (SRS6) of PhF3'5'H was consistently different from DgF3'5'Hs at positions 5, 8 and 10. Prediction of molecular docking of the substrates showed a contrary binding direction of aromatic rings (B-ring) with the SRS6 domain of DgF3'5'H and PhF3'5'H. In addition, the pH values of violet-blue and purple Phalaenopsis flowers ranged from 5.33 to 5.54 and 4.77 to 5.04, respectively. Furthermore, the molar ratio of metal ions (including Al
, Ca
and Fe
) to anthocyanin in violet-blue color Phalaenopsis was 190-, 49-, and 51-fold higher, respectively, than those in purple-color Phalaenopsis.
Cyanidin-based anthocyanin was detected in violet-blue color Phalaenopsis and was concomitant with a high pH value and high molar ratio of Al
, Ca
and Fe
to anthocyanin content. Enhanced expression of delphinidin is needed to produce true-blue Phalaenopsis.
For the first time, we successfully demonstrated the dopant-free HfO 2 negative capacitance (NC) transistor featuring a low gate-overdrive voltage and a nearly hysteresis-free sub-40 mV/dec swing. ...These excellent performances can be ascribed to the reduction of the monoclinic phase suppressed with the thickness scaling and gate stress engineering favorably rearranging oxygen vacancies to boost orthorhombic phase transition. The highly scalable and dopant-free NC transistor shows the potential for the application of advanced CMOS technology.
The pervasiveness of the contemporary experience economy has resulted in numerous studies exploring the influence of post-experience memory on customer behavior. However, related studies have failed ...to explore the interrelations among experiential quality, nostalgia, place attachment, and behavioral intentions in the hotel industry. Therefore, this study examines the relations among the aforementioned features. Accordingly, individuals with experience in hotel accommodation were included as participants in a questionnaire survey, from which a total of 383 valid questionnaires were recovered. The results indicated that experiential quality significantly positively influenced place attachment and behavioral intention, nostalgia significantly positively influenced place attachment, and both experiential quality and place attachment significantly positively influenced behavioral intention. Finally, further suggestions are proposed for practical and academic reference.
Achieving high latch-up immunity is critical for power-rail electrostatic discharge (ESD) clamp circuits in high-voltage (HV) integrated circuit products. To investigate how shunt resistance affects ...the transmission line pulsing current-voltage characteristics of resistance-triggered stacked silicon controlled rectifiers (SCRs), a lateral SCR (LSCR) and a modified LSCR were combined in several SCR stacked structures with various shunt resistances. Compared with in tradition stacked ESD cells, the snapback margin of the SCRs does not expand and can even be reduced. A high holding voltage of 33.4 V is achieved using the resistance-triggered stacked SCR technique in a 0.11 μm 32-V HV process. A trigger voltage of approximately 51 V and a failure current of 3.3 A is achieved in this experiment. According to theorem analysis based on a voltage decoupling equation, the minimum trigger voltage can probably be further reduced to 46 V by using the resistance-triggered stacked SCR technique. This paper can offer a simple guideline for designing ESD protection circuit using the resistor-triggered SCRs stacking structure.
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