Background
Vemurafenib, a selective inhibitor of BRAF kinase, is approved for the treatment of adult stage IIIc/IV BRAF V600 mutation‐positive melanoma. We conducted a phase I, open‐label, ...dose‐escalation study in pediatric patients aged 12–17 years with this tumor type (NCT01519323).
Procedure
Patients received vemurafenib orally until disease progression. Dose escalation was conducted using a 3 + 3 design. Patients were monitored for dose‐limiting toxicities (DLTs) during the first 28 days of treatment to determine the maximum tolerated dose (MTD). Safety/tolerability, tumor response, and pharmacokinetics were evaluated.
Results
Six patients were enrolled (720 mg twice daily BID, n = 3; 960 mg BID n = 3). The study was terminated prematurely due to low enrollment. No DLTs were observed; thus, the MTD could not be determined. All patients experienced at least one adverse event (AE); the most common were diarrhea, headache, photosensitivity, rash, nausea, and fatigue. Three patients experienced serious AEs, one patient developed secondary cutaneous malignancies, and five patients died following disease progression. Mean steady‐state plasma concentrations of vemurafenib following 720 mg and 960 mg BID dosing were similar or higher, respectively, than in adults. There were no objective responses. Median progression‐free survival and overall survival were 4.4 months (95% confidence interval CI = 2.7–5.2) and 8.1 months (95% CI = 5.1–12.0), respectively.
Conclusions
A recommended and effective dose of vemurafenib for patients aged 12–17 years with metastatic or unresectable melanoma was not identified. Extremely low enrollment in this trial highlights the importance of considering the inclusion of adolescents with adult cancers in adult trials.
The increased pervasiveness of digital health technology is producing large amounts of person-generated health data (PGHD). These data can empower people to monitor their health to promote prevention ...and management of disease. Women make up one of the largest groups of consumers of digital self-tracking technology.
In this scoping review, we aimed to (1) identify the different areas of women's health monitored using PGHD from connected health devices, (2) explore personal metrics collected through these technologies, and (3) synthesize facilitators of and barriers to women's adoption and use of connected health devices.
Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews, we searched 5 databases for articles published between January 1, 2015, and February 29, 2020. Papers were included if they targeted women or female individuals and incorporated digital health tools that collected PGHD outside a clinical setting.
We included a total of 406 papers in this review. Articles on the use of PGHD for women steadily increased from 2015 to 2020. The health areas that the articles focused on spanned several topics, with pregnancy and the postpartum period being the most prevalent followed by cancer. Types of digital health used to collect PGHD included mobile apps, wearables, websites, the Internet of Things or smart devices, 2-way messaging, interactive voice response, and implantable devices. A thematic analysis of 41.4% (168/406) of the papers revealed 6 themes regarding facilitators of and barriers to women's use of digital health technology for collecting PGHD: (1) accessibility and connectivity, (2) design and functionality, (3) accuracy and credibility, (4) audience and adoption, (5) impact on community and health service, and (6) impact on health and behavior.
Leading up to the COVID-19 pandemic, the adoption of digital health tools to address women's health concerns was on a steady rise. The prominence of tools related to pregnancy and the postpartum period reflects the strong focus on reproductive health in women's health research and highlights opportunities for digital technology development in other women's health topics. Digital health technology was most acceptable when it was relevant to the target audience, was seen as user-friendly, and considered women's personalization preferences while also ensuring accuracy of measurements and credibility of information. The integration of digital technologies into clinical care will continue to evolve, and factors such as liability and health care provider workload need to be considered. While acknowledging the diversity of individual needs, the use of PGHD can positively impact the self-care management of numerous women's health journeys. The COVID-19 pandemic has ushered in increased adoption and acceptance of digital health technology. This study could serve as a baseline comparison for how this field has evolved as a result.
RR2-10.2196/26110.
The agriculture sector responsible for global food and nutrition security has an urgent need to examine climatic trends so that adaptations can be exercised in advance. Freely available dataset from ...satellite sources can greatly ease rainfall analysis, especially for smallholder farmers who typically operate under limited resources. Tests to determine their accuracy, however, are so far not deployed in tropical Southeast Asia. We compared in situ observations with dataset from the Global Satellite Mapping of Precipitation (GSMaP) and the Prediction of Worldwide Energy Resources (POWER) in two sites located 180 km apart in the tropical Malay Peninsula for 30 days. We found that in situ precipitation values were markedly overestimated by GSMaP (34.9–67.5%) and POWER (180.5–289.2%), and the possible reasons are discussed. Nonetheless, we conclude that GSMaP remains the best hope for smallholder farmers and its dataset can still be used under the precaution of error margins determined by the practical method described herein.
Abstract Studies in Western populations have shown that Black and Hispanic patients have an earlier age of Multiple Sclerosis (MS) onset and a more severe disease course characterised by faster ...disability accrual compared to Whites. It is yet unclear whether MS disease characteristics and clinical course differ amongst Asian racial groups. Singapore is uniquely poised to investigate this as its multi-racial population comprises three genetically diverse Asian racial groups—Chinese, Malay and South Asian. Herein, we sought to elucidate differences in the clinical phenotypes, disease-modifying therapy (DMT) usage, and disease course amongst these three Asian racial groups by performinga retrospective observational study on MS patients seen at the National Neuroscience Institute, Singapore. Data on demographics, disease characteristics, ancillary investigations, and DMT usage were collected. One hundred and eighty-eight patients were included (90 Chinese, 32 Malay, and 66 South Asian). Our findings showed that MS prevalence was the highest in South Asians followed by Malays and Chinese, while demographics, healthcare access, and longer-term disease course were identical across the racial groups. However, several differences and trends were elucidated: (1) South Asian patients had milder sentinel attacks (p = 0.006), (2) a higher proportion of Malay patients had enhancing lesions on their initial MRI (p = 0.057) and the lesion topography differed across the races (p = 0.034), and (3) more Malay patients switched out of their initial DMT (p = 0.051). In conclusion, MS disease characteristics were largely similar across these three Asian racial groups, and while there were some clinical and radiological differences at presentation, these did not influence longer-term outcomes.
Abstract
Background
To drive translational medicine, modern day biobanks need to integrate with other sources of data (clinical, genomics) to support novel data-intensive research. Currently, vast ...amounts of research and clinical data remain in silos, held and managed by individual researchers, operating under different standards and governance structures; a framework that impedes sharing and effective use of data. In this article, we describe the journey of British Columbia’s Gynecological Cancer Research Program (OVCARE) in moving a traditional tumour biobank, outcomes unit, and a collection of data silos, into an integrated data commons to support data standardization and resource sharing under collaborative governance, as a means of providing the gynecologic cancer research community in British Columbia access to tissue samples and associated clinical and molecular data from thousands of patients.
Results
Through several engagements with stakeholders from various research institutions within our research community, we identified priorities and assessed infrastructure needs required to optimize and support data collections, storage and sharing, under three main research domains: (1) biospecimen collections, (2) molecular and genomics data, and (3) clinical data. We further built a governance model and a resource portal to implement protocols and standard operating procedures for seamless collections, management and governance of interoperable data, making genomic, and clinical data available to the broader research community.
Conclusions
Proper infrastructures for data collection, sharing and governance is a translational research imperative. We have consolidated our data holdings into a data commons, along with standardized operating procedures to meet research and ethics requirements of the gynecologic cancer community in British Columbia. The developed infrastructure brings together, diverse data, computing frameworks, as well as tools and applications for managing, analyzing, and sharing data. Our data commons bridges data access gaps and barriers to precision medicine and approaches for diagnostics, treatment and prevention of gynecological cancers, by providing access to large datasets required for data-intensive science.
The liver-expressed antimicrobial peptide 2 (LEAP2) is essential in host immunity against harmful pathogens and is only known to act as an extracellular modulator to regulate embryonic development in ...amphibians. However, there is a dearth of information on the antimicrobial function of amphibian LEAP2. Hence, a LEAP2 homologue from Leptobrachium liui was identified, characterized, and chemically synthesized, and its antibacterial activities and mechanisms were determined.
In this study, LEAP2 gene (Ll-LEAP2) cDNA was cloned and sequenced from the Chong'an Moustache Toad (Leptobrachium liui). The predicted amino acid sequence of Ll-LEAP2 comprises a signal peptide, a mature peptide, and a prodomain. From sequence analysis, it was revealed that Ll-LEAP2 belongs to the cluster of amphibian LEAP2 and displays high similarity to the Tropical Clawed Frog (Xenopus tropicalis)'s LEAP2. Our study revealed that LEAP2 protein was found in different tissues, with the highest concentration in the kidney and liver of L. liui; and Ll-LEAP2 mRNA transcripts were expressed in various tissues with the kidney having the highest mRNA expression level. As a result of Aeromonas hydrophila infection, Ll-LEAP2 underwent a noticeable up-regulation in the skin while it was down-regulated in the intestines. The chemically synthesized Ll-LEAP2 mature peptide was selective in its antimicrobial activity against several in vitro bacteria including both gram-positive and negative bacteria. Additionally, Ll-LEAP2 can kill specific bacteria by disrupting bacterial membrane and hydrolyzing bacterial gDNA.
This study is the first report on the antibacterial activity and mechanism of amphibian LEAP2. With more to uncover, the immunomodulatory functions and wound-healing activities of Ll-LEAP2 holds great potential for future research.
Background Cathelicidins are vital antimicrobial peptides expressed in diverse vertebrates, crucial for immunity. Despite being a new field, amphibian cathelicidin research holds promise. Results We ...isolated the cDNA sequence of the cathelicidin (Ll-CATH) gene from the liver transcriptome of the Chong'an Moustache Toad (Leptobrachium liui). We confirmed the authenticity of the cDNA sequence by rapid amplification of cDNA ends and reverse transcription PCR, and obtained the Ll-CATH amino acid sequence using the Open Reading Frame Finder, an online bioinformatics tool. Its translated protein contained a cathelin domain, signal peptide, and mature peptide, confirmed by amino acid sequence. The comparative analysis showed that the mature peptides were variable between the amphibian species, while the cathelin domain was conserved. The concentration of Ll-CATH protein and the expression of its gene varied in the tissues, with the spleen showing the highest levels. The expression levels of Ll-CATH in different tissues of toads was significantly increased post infection with Aeromonas hydrophila. Chemically synthesized Ll-CATH effectively combated Proteus mirabilis, Staphylococcus epidermidis, Vibrioharveyi, V. parahaemolyticus, and V. vulnificus; disrupted the membrane of V. harveyi, hydrolyzed its DNA. Ll-CATH induced chemotaxis and modulated the expression of pro-inflammatory cytokine genes in RAW264.7 macrophages. Conclusions This study unveiled the antibacterial and immunomodulatory potential of amphibian cathelicidin, implying its efficacy against infections. Ll-CATH characterization expands our knowledge, emphasizing its in a bacterial infection therapy. Keywords: Antimicrobial peptides, Antibacterial activity, Cathelicidin, Immunomodulatory activity, Leptobrachium liui
Elevational gradients provide an excellent opportunity to assess biodiversity patterns and community structure. Previous studies mainly focus on higher elevations or are limited to small areas in ...mountainous regions. Little information can be found on amphibian biodiversity in middle- and low-elevational areas, hence our study was devoted to filling up the current gaps in these research areas. To understand the variability of biodiversity of amphibian species in the Fujian Junzifeng National Nature Reserve in eastern China, our study included taxonomic and phylogenetic components to describe the various patterns of regional and elevational distribution. The results showed that (1) most of the taxonomic and phylogenetic diversity metrics were correlated; with regard to the surveyed area, Faith's phylogenetic diversity index (
) and net relatedness index (
) were positively correlated with the Shannon-Wiener index (
), Margalef index (
), and species richness (
), while negatively with the Pielou index; whereas for elevation, only the Pielou index was positively correlated with the nearest taxon index (
), but negatively with other indices; (2) taxonomic and phylogenetic diversities did not differ among the three survey locations but differed significantly along the elevational gradient; Simpson index,
,
, and
had a hump-shaped relationship with elevations, and
decreased gradually with the increase in elevation, whereas
and
sharply increased at the elevation above 900 m; (3) the species range size and the corresponding midpoint of amphibians were affected by a strong phylogenetic signal, which supports the elevational Rapoport's rule upon removal of
and
from the study.
Bamboo charcoal, a type of manufactured biochar, is produced by pyrolyzing bamboo residue under anoxic conditions. Its beneficial properties in absorption, catalyst support, and agricultural function ...have attracted significant attention; however, relatively few studies have examined its effects on the soil microbiota. In this study, we analyzed the effects of bamboo charcoal on soil physicochemical properties, enzymes, and microbial community structure in tea plantations and investigated the optimal amount of bamboo charcoal to be added to organic fertilizer. The results show that bamboo charcoal can further increase soil available nitrogen, total and available phosphorus and potassium, organic carbon content, pH, and urease activity. However, only the combined use of bamboo charcoal and organic fertilizer significantly increased total nitrogen, sucrase, and β-glucosidase activities in the soil. Bamboo charcoal also significantly increased the Chao1 and Shannon indices of microbiota diversity in a concentration-dependent manner. The structure of the bacterial community changed significantly after the bamboo charcoal addition, with
,
, and
increasing and
decreasing. This study provides fundamental insights into the suitability of bamboo charcoal application for the ecological remediation of diseased soils.
The Chinese tiger frog (
) is extensively farmed in southern China. Due to cramped living conditions, skin diseases are prevalent among unhealthy tiger frogs which thereby affects their welfare. In ...this study, the differences in microbiota present on healthy versus ulcerated
skin were examined using 16S rRNA sequences. Proteobacteria were the dominant phylum on
skin, but their abundance was greater on the healthy skin than on the ulcerated skin. Rhodocyclaceae and Comamonadaceae were the most dominant families on the healthy skin, whereas Moraxellaceae was the most dominant family on the ulcerated skin. The abundance of these three families was different between the groups.
was the most dominant genus on the healthy skin, whereas
was the most dominant genus on the ulcerated skin, and its abundance was greater on the ulcerated skin than on the healthy skin. Moreover, the genes related to the Kyoto Encyclopedia of Genes and Genomes pathways of levels 2-3, especially those genes that are involved in cell motility, flagellar assembly, and bacterial chemotaxis in the skin microbiota, were found to be greater on the healthy skin than on the ulcerated skin, indicating that the function of skin microbiota was affected by ulceration. Overall, the composition, abundance, and function of skin microbial communities differed between the healthy and ulcerated
skin. Our results may assist in developing measures to combat diseases in
.
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