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

Sustained Robust Exciton Emission in Suspended Monolayer WSe_2 within the Low Carrier Density Regime for Quantum Emitter Applications

The development of semiconductor optoelectronic devices is moving toward low power consumption and miniaturization, especially for high-efficiency quantum emitters. However, most of these quantum sources work at low carrier density region, where the Shockley-Read-Hall recombination may dominant and seriously reduce the emission efficiency. In order to diminish the affection of carrier trapping and sustain a strong photoluminescence emission under low power pumping condition, we investigated on the influence of Suspending to monolayered tungsten diselenide, novel two-dimensional quantum material. Not only the PL intensity, but also the fundamental photoluminescence quantum yield has exhibited a huge, order-scale enhancement through suspending, even surprisingly, we found the PLQY improvement revealed far significantly under small pumping power and came out an exponential increase tendency toward even lower carrier density region. With its strong excitonic effect, suspended WSe_2 offers a solution to reduce carrier trapping and participate in non-radiative processes. Moreover, in the low-power range where SRH recombination dominates, suspended WSe_2 exhibited remarkably higher percentage of excitonic radiation compared to contacted WSe_2. Herein, we quantitatively demonstrate the significance of suspended WSe_2 monolayer at low carrier density region, highlighting its potential for developing compact, low-power quantum emitters in the future

Can probability of genetic mutation be an indicator of clinical relevance?

AbstractNPM1 gene mutation evaluated on a population basis is a valuable and realistic tool to reflect the pathophysiological relevance of cancer. In a comparison of the NPM1 cDNA of human bladder cancer with its consensus sequence, we have found that a higher NPM1 sequence identity in a population is consistent with poor tumor differentiation, advanced tumor stage, and likelihood of recurrence. These data imply that “probability” of NPM1 mutation is an indicator of status of malignancy

All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A.

Patients with type 1 diabetes mellitus are associated with impairment in vitamin A metabolism. This study evaluated whether treatment with retinoic acid, the biologically active metabolite of vitamin A, can ameliorate diabetes. All-trans retinoic acid (atRA) was used to treat streptozotocin (STZ)-induced diabetic mice which revealed atRA administration ameliorated blood glucose levels of diabetic mice. This hyperglycemic amelioration was accompanied by an increase in the amount of β cells co-expressed Pdx1 and insulin and by restoration of the vascular laminin expression. The atRA-induced production of vascular endothelial growth factor-A from the pancreatic islets was possibly the key factor that mediated the restoration of islet vascularity and recovery of β-cell mass. Furthermore, the combination of islet transplantation and atRA administration significantly rescued hyperglycemia in diabetic mice. These findings suggest that vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control

Eradication of Helicobacter pylori

Objective. To evaluate the effect of eradication of Helicobacter pylori (H. pylori) on the progression of dementia in Alzheimer’s disease (AD) patients with peptic ulcer. Methods. Participants with the diagnosis of AD and peptic ulcer were recruited between 2001 and 2008. We examined the association between eradication of H. pylori and the progression of AD using the multiple regression models. Medication shift from Donepezil, Rivastgmine, and Galantamine to Mematine is defined as progression of dementia according to the insurance of National Health Insurance (NHI) under expert review. Results. Among the 30142 AD patients with peptic ulcers, the ratio of medication shift in AD patients with peptic ulcers is 79.95%. There were significant lower incidence comorbidities (diabetes mellitus, hypertension, cerebrovascular disease, coronary artery disease, congestive heart failure and hyperlipidemia) in patients with H. pylori eradication as compared with no H. pylori eradication. Eradication of H. pylori was associated with a decreased risk of AD progression (odds ratio [OR] 0.35 [0.23–0.52]) as compared with no H. pylori eradication, which was not modified by comorbidities. Conclusions. Eradication of H. pylori was associated with a decreased progression of dementia as compared to no eradication of H. pylori in AD patients with peptic ulcers

Differential expression of GABAA receptor subunits δ and α6 mediates tonic inhibition in parvalbumin and somatostatin interneurons in the mouse hippocampus

Inhibitory γ-aminobutyric acid (GABA)-ergic interneurons mediate inhibition in neuronal circuitry and support normal brain function. Consequently, dysregulation of inhibition is implicated in various brain disorders. Parvalbumin (PV) and somatostatin (SST) interneurons, the two major types of GABAergic inhibitory interneurons in the hippocampus, exhibit distinct morpho-physiological properties and coordinate information processing and memory formation. However, the molecular mechanisms underlying the specialized properties of PV and SST interneurons remain unclear. This study aimed to compare the transcriptomic differences between these two classes of interneurons in the hippocampus using the ribosome tagging approach. The results revealed distinct expressions of genes such as voltage-gated ion channels and GABAA receptor subunits between PV and SST interneurons. Gabrd and Gabra6 were identified as contributors to the contrasting tonic GABAergic inhibition observed in PV and SST interneurons. Moreover, some of the differentially expressed genes were associated with schizophrenia and epilepsy. In conclusion, our results provide molecular insights into the distinct roles of PV and SST interneurons in health and disease

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Modeling customer-perceived value: an empirical investigation of on-line tourism purchase in Taiwan

The purpose of this study is to investigate online customer-perceived value in relation to the online purchase of tourism products in Taiwan. The concept of value has been discussed in different fields for a long time. This study synthesises findings from these areas in order to identify the key antecedents and consequences which influence customer-perceived value in a B2C e-commerce setting. The customer-perceived value model which is developed broadens the value literature by integrating a range of key variables (i.e. price, quality, sacrifice and satisfaction) into a single theoretical framework. A systematic process of model development is followed to ensure a robust foundation for assembling the measure. A mixed-method research approach has been employed in order to gather in-depth data from a wide area, thereby enhancing the reliability and validity of the analysis. 40 company respondents from 18 companies and 45 consumers were interviewed in the exploratory phase, which enabled the components of the customer-perceived values to be considered. By co-operating with Taiwanese travel agents 914 usable consumer questionnaires were collected in the main survey. The model was tested in a retail setting using a sample of real consumers who were in the process of searching for a tourism product. The findings suggest that Taiwanese consumers, place greater importance on the sacrifice associated with purchasing tourism products than they do on the price, quality and satisfaction elements. The proposed customer-perceived value model explains greater variance in the value construct than other models from the literature, indicating strong analytical support for the framework