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

Functional Effects of let-7g Expression in Colon Cancer Metastasis.

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Additional file 3: of V-J combinations of T-cell receptor predict responses to erythropoietin in end-stage renal disease patients

Summary of repertoire sequencing output and overlapping proportions in end-stage renal disease samples. (DOCX 14 kb