Using T-cell repertoire profiles as predictor in a primary mucosal melanoma

Dear Editor, Primary mucosal melanoma is a rare subtype of melanoma that carries poor prognosis. Traditional treatment options of mucosal melanoma are surgery, radiation, and chemotherapy; but the overall survival remains low.1 Cytotoxic T‐lymphocyte associated protein 4 (CLTA‐4) and programmed cell death protein 1 (PD‐1), both inhibitory immune checkpoints commonly seen on activated T cells, have been found to be promising targets for treatment of advanced cancers.2 However, the efficacy and response to immunotherapy in mucosal melanoma remains unknown. Herein, we report a case involving a patient, who was a 70‐year‐old male and referred to Taipei Medical University Hospital with confirmed diagnosis of mucosa melanoma over hard plate of mouth. The patient was admitted and subjected to anti‐PD‐1 immunotherapy (pembrolizumab 200 mg every 3 weeks) (Figure 1A). Serial imaging of primary malignant melanoma of the hard palate showed that the tumor size gradually decreased after treatment with pembrolizumab, suggesting partial response/stable disease secondary to continuous immunotherapy (Figure 1B). However, after seventh cycle of treatment, magnetic resonance imaging (MRI) revealed enlarged previous known metastatic lesions and new tumor nodules in brain (Figure 1B). The patient received stereotactic radiation therapy before treatment cycle 14 (Figure 1A). Although the primary metastatic brain lesions were smaller and stationary after radiotherapy, the following brain MRI displayed several hyperdensity masses in the right frontal lobe with perifocal edema and mild mass effect (Figure 1B). Subsequently, patient suffered from infection and respiratory distress and died 2 months after 17th cycle of pembrolizumab therapy

Using T-cell repertoire profiles as predictor in a primary mucosal melanoma

Dear Editor, Primary mucosal melanoma is a rare subtype of melanoma that carries poor prognosis. Traditional treatment options of mucosal melanoma are surgery, radiation, and chemotherapy; but the overall survival remains low.1 Cytotoxic T‐lymphocyte associated protein 4 (CLTA‐4) and programmed cell death protein 1 (PD‐1), both inhibitory immune checkpoints commonly seen on activated T cells, have been found to be promising targets for treatment of advanced cancers.2 However, the efficacy and response to immunotherapy in mucosal melanoma remains unknown. Herein, we report a case involving a patient, who was a 70‐year‐old male and referred to Taipei Medical University Hospital with confirmed diagnosis of mucosa melanoma over hard plate of mouth. The patient was admitted and subjected to anti‐PD‐1 immunotherapy (pembrolizumab 200 mg every 3 weeks) (Figure 1A). Serial imaging of primary malignant melanoma of the hard palate showed that the tumor size gradually decreased after treatment with pembrolizumab, suggesting partial response/stable disease secondary to continuous immunotherapy (Figure 1B). However, after seventh cycle of treatment, magnetic resonance imaging (MRI) revealed enlarged previous known metastatic lesions and new tumor nodules in brain (Figure 1B). The patient received stereotactic radiation therapy before treatment cycle 14 (Figure 1A). Although the primary metastatic brain lesions were smaller and stationary after radiotherapy, the following brain MRI displayed several hyperdensity masses in the right frontal lobe with perifocal edema and mild mass effect (Figure 1B). Subsequently, patient suffered from infection and respiratory distress and died 2 months after 17th cycle of pembrolizumab therapy

Ample Pairs

We show that the ample degree of a stable theory with trivial forking is preserved when we consider the corresponding theory of belles paires, if it exists. This result also applies to the theory of $H$-structures of a trivial theory of rank $1$.Comment: Research partially supported by the program MTM2014-59178-P. The second author conducted research with support of the programme ANR-13-BS01-0006 Valcomo. The third author would like to thank the European Research Council grant 33882

VoiceBank-2023: A Multi-Speaker Mandarin Speech Corpus for Constructing Personalized TTS Systems for the Speech Impaired

Services of personalized TTS systems for the Mandarin-speaking speech impaired are rarely mentioned. Taiwan started the VoiceBanking project in 2020, aiming to build a complete set of services to deliver personalized Mandarin TTS systems to amyotrophic lateral sclerosis patients. This paper reports the corpus design, corpus recording, data purging and correction for the corpus, and evaluations of the developed personalized TTS systems, for the VoiceBanking project. The developed corpus is named after the VoiceBank-2023 speech corpus because of its release year. The corpus contains 29.78 hours of utterances with prompts of short paragraphs and common phrases spoken by 111 native Mandarin speakers. The corpus is labeled with information about gender, degree of speech impairment, types of users, transcription, SNRs, and speaking rates. The VoiceBank-2023 is available by request for non-commercial use and welcomes all parties to join the VoiceBanking project to improve the services for the speech impaired.Comment: submitted to 26th International Conference of the ORIENTAL-COCOSD

Void Structures in Regularly Patterned ZnO Nanorods Grown with the Hydrothermal Method

The void structures and related optical properties after thermal annealing with ambient oxygen in regularly patterned ZnO nanrorod (NR) arrays grown with the hydrothermal method are studied. In increasing the thermal annealing temperature, void distribution starts from the bottom and extends to the top of an NR in the vertical (c-axis) growth region. When the annealing temperature is higher than 400°C, void distribution spreads into the lateral (m-axis) growth region. Photoluminescence measurement shows that the ZnO band-edge emission, in contrast to defect emission in the yellow-red range, is the strongest under the n-ZnO NR process conditions of 0.003 M in Ga-doping concentration and 300°C in thermal annealing temperature with ambient oxygen. Energy dispersive X-ray spectroscopy data indicate that the concentration of hydroxyl groups in the vertical growth region is significantly higher than that in the lateral growth region. During thermal annealing, hydroxyl groups are desorbed from the NR leaving anion vacancies for reacting with cation vacancies to form voids

SIRT1 mediated gastric cancer progression under glucose deprivation through the FoxO1-Rab7-autophagy axis

PurposeSilent mating type information regulator 2 homolog 1 (SIRT1) and autophagy have a two-way action (promoting cell death or survival) on the progression and treatment of gastric cancer (GC) under different conditions or environments. This study aimed to investigate the effects and underlying mechanism of SIRT1 on autophagy and the malignant biological behavior of GC cells under conditions of glucose deprivation (GD).Materials and methodsHuman immortalized gastric mucosal cell GES-1 and GC cell lines SGC-7901, BGC-823, MKN-45 and MKN-28 were utilized. A sugar-free or low-sugar (glucose concentration, 2.5 mmol/L) DMEM medium was used to simulate GD. Additionally, CCK8, colony formation, scratches, transwell, siRNA interference, mRFP-GFP-LC3 adenovirus infection, flow cytometry and western blot assays were performed to investigate the role of SIRT1 in autophagy and malignant biological behaviors (proliferation, migration, invasion, apoptosis and cell cycle) of GC under GD and the underlying mechanism.ResultsSGC-7901 cells had the longest tolerance time to GD culture conditions, which had the highest expression of SIRT1 protein and the level of basal autophagy. With the extension of GD time, the autophagy activity in SGC-7901 cells also increased. Under GD conditions, we found a close relationship between SIRT1, FoxO1 and Rab7 in SGC-7901 cells. SIRT1 regulated the activity of FoxO1 and upregulated the expression of Rab7 through deacetylation, which ultimately affected autophagy in GC cells. In addition, changing the expression of FoxO1 provided feedback on the expression of SIRT1 in the cell. Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD.ConclusionThe SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC

Single-cell profiling reveals distinct immune response landscapes in tuberculous pleural effusion and non-TPE

BackgroundTuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and remains a major health threat worldwide. However, a detailed understanding of the immune cells and inflammatory mediators in Mtb-infected tissues is still lacking. Tuberculous pleural effusion (TPE), which is characterized by an influx of immune cells to the pleural space, is thus a suitable platform for dissecting complex tissue responses to Mtb infection.MethodsWe employed singe-cell RNA sequencing to 10 pleural fluid (PF) samples from 6 patients with TPE and 4 non-TPEs including 2 samples from patients with TSPE (transudative pleural effusion) and 2 samples with MPE (malignant pleural effusion).ResultCompared to TSPE and MPE, TPE displayed obvious difference in the abundance of major cell types (e.g., NK, CD4+T, Macrophages), which showed notable associations with disease type. Further analyses revealed that the CD4 lymphocyte population in TPE favored a Th1 and Th17 response. Tumor necrosis factors (TNF)-, and XIAP related factor 1 (XAF1)-pathways induced T cell apoptosis in patients with TPE. Immune exhaustion in NK cells was an important feature in TPE. Myeloid cells in TPE displayed stronger functional capacity for phagocytosis, antigen presentation and IFN-γ response, than TSPE and MPE. Systemic elevation of inflammatory response genes and pro-inflammatory cytokines were mainly driven by macrophages in patients with TPE.ConclusionWe provide a tissue immune landscape of PF immune cells, and revealed a distinct local immune response in TPE and non-TPE (TSPE and MPE). These findings will improve our understanding of local TB immunopathogenesis and provide potential targets for TB therapy