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Critical analysis of features and quality of applications for clinical management of acne
Background: Mobile medical applications (apps) for clinical management of medical conditions are increasing in prevalence. Our aim was to identify features and overall quality of acne apps that could facilitate clinical management. Methods: We established 10 pertinent features (6 essential and 4 desirable) for an acne app through literature search and nominal group discussion. Searches were then conducted in the Apple App Store and Google Play Store. Apps which assisted with clinical management of acne were assessed for functionality and quality. Overall quality was evaluated by grading against pre-established criteria for medical apps. Results: A total of 358 Apple apps and 256 Google apps were found. After removing apps which did not assist with the clinical management of acne, 12 Apple and 13 Google apps remained. Apps were classified as interactive, informational, or teledermatology apps. Mean Masud scores were 12.8±3.7 for the Apple apps and 12.2±3.7 for the Google apps. Conclusions: Mobile acne apps can be effective in the self-management and collaborative management of acne. The current acne apps are of variable quality and none contained all 10 features crucial for effective clinical management. The shortcomings identified in this paper can guide future acne app development
Effects of Germination Season on Life History Traits and on Transgenerational Plasticity in Seed Dormancy in a Cold Desert Annual
The maternal environment can influence the intensity of seed dormancy and thus seasonal germination timing and post-germination life history traits. We tested the hypotheses that germination season influences phenotypic expression of post-germination life history traits in the cold desert annual Isatis violascens and that plants from autumn- and spring-germinating seeds produce different proportions of seeds with nondeep and intermediate physiological dormancy (PD). Seeds were sown in summer and flexibility in various life history traits determined for plants that germinated in autumn and in spring. A higher percentage of spring- than of autumn-germinating plants survived the seedling stage, and all surviving plants reproduced. Number of silicles increased with plant size (autumn- \u3e spring-germinating plants), whereas percent dry mass allocated to reproduction was higher in spring- than in autumn-germinating plants. Autumn-germinating plants produced proportionally more seeds with intermediate PD than spring-germinating plants, while spring-germinating plants produced proportionally more seeds with nondeep PD than autumn-germinating plants. Flexibility throughout the life history and transgenerational plasticity in seed dormancy are adaptations of I. violascens to its desert habitat. Our study is the first to demonstrate that autumn- and spring-germinating plants in a species population differ in proportion of seeds produced with different levels of PD
Effect of Seed Position on Parental Plant on Proportion of Seeds Produced with Nondeep and Intermediate Physiological Dormancy
The position in which seeds develop on the parental plant can have an effect on dormancy-break and germination. We tested the hypothesis that the proportion of seeds with intermediate physiological dormancy (PD) produced in the proximal position on a raceme of Isatis violascens plants is higher than that produced in the distal position, and further that this difference is related to temperature during seed development. Plants were watered at 3-day intervals, and silicles and seeds from the proximal (early) and distal (late) positions of racemes on the same plants were collected separately and tested for germination. After 0 and 6 months dry storage at room temperature (afterripening), silicles and seeds were cold stratified for 0â16 weeks and tested for germination. Mean daily maximum and minimum temperatures during development/maturation of the two groups of seeds did not differ. A higher proportion of seeds with the intermediate level than with the nondeep level of PD was produced by silicles in the proximal position than by those in the distal position, while the proportion of seeds with nondeep PD was higher in the distal than in the proximal position of the raceme. The differences were not due only to seed mass. Since temperature and soil moisture conditions were the same during development of the seeds in the raceme, differences in proportion of seeds with intermediate and nondeep PD are attributed to position on parental plant. The ecological consequence of this phenomenon is that it ensures diversity in dormancy-breaking and germination characteristics within a seed cohort, a probable bet-hedging strategy. This is the first demonstration of position effects on level of PD in the offspring
Seed Germination Ecology of the Cold Desert Annual \u3cem\u3eIsatis violascens\u3c/em\u3e (Brassicaceae): Two Levels of Physiological Dormancy and Role of the Pericarp
The occurrence of various species of Brassicaceae with indehiscent fruits in the cold deserts of NW China suggests that there are adaptive advantages of this trait. We hypothesized that the pericarp of the single-seeded silicles of Isatis violascens restricts embryo expansion and thus prevents germination for 1 or more years. Thus, our aim was to investigate the role of the pericarp in seed dormancy and germination of this species. The effects of afterripening, treatment with gibberellic acid (GA3) and cold stratification on seed dormancy-break were tested using intact silicles and isolated seeds, and germination phenology was monitored in an experimental garden. The pericarp has a role in mechanically inhibiting germination of fresh seeds and promotes germination of nondormant seeds, but it does not facilitate formation of a persistent seed bank. Seeds in silicles in watered soil began to germinate earlier in autumn and germinated to higher percentages than isolated seeds. Sixty-two percent of seeds in the buried silicles germinated by the end of the first spring, and only 3% remained nongerminated and viable. Twenty to twenty-five percent of the seeds have nondeep physiological dormancy (PD) and 75-80% intermediate PD. Seeds with nondeep PD afterripen in summer and germinate inside the silicles in autumn if the soil is moist. Afterripening during summer significantly decreased the amount of cold stratification required to break intermediate PD. The presence of both nondeep and intermediate PD in the seed cohort may be a bet-hedging strategy
Decreased Innate Migration of Pro-Inflammatory M1 Macrophages through the Mesothelial Membrane Is Affected by Ceramide Kinase and Ceramide 1-P
The retrograde flow of endometrial tissues deposited into the peritoneal cavity occurs in women during menstruation. Classically (M1) or alternatively (M2) activated macrophages partake in the removal of regurgitated menstrual tissue. The failure of macrophage egress from the peritoneal cavity through the mesothelium leads to chronic inflammation in endometriosis. To study the migration differences of macrophage phenotypes across mesothelial cells, an in vitro model of macrophage egress across a peritoneal mesothelial cell monolayer membrane was developed. M1 macrophages were more sessile, emigrating 2.9-fold less than M2 macrophages. The M1 macrophages displayed a pro-inflammatory cytokine signature, including IL-1α, IL-1β, TNF-α, TNF-β, and IL-12p70. Mass spectrometry sphingolipidomics revealed decreased levels of ceramide-1-phosphate (C1P), an inducer of migration in M1 macrophages, which correlated with its poor migration behavior. C1P is generated by ceramide kinase (CERK) from ceramide, and blocking C1P synthesis via the action of NVP231, a specific CERK chemical inhibitor, prohibited the emigration of M1 and M2 macrophages up to 6.7-fold. Incubation with exogenously added C1P rescued this effect. These results suggest that M1 macrophages are less mobile and have higher retention in the peritoneum due to lower C1P levels, which contributes to an altered peritoneal environment in endometriosis by generating a predominant pro-inflammatory cytokine environment
Effects of Predispersal Insect Seed Predation on the Early Life History Stages of a Rare Cold Sand-Desert Legume
Seed predation by insects is common in seeds of Fabaceae (legume) species with physical dormancy (PY). However, the consequences of insect seed predation on the life history of legumes with PY have been little studied. In the largest genus of seed plants, Astragalus (Fabaceae), only one study has tested the effects of insect predation on germination, and none has tested it directly on seedling survival. Thus, we tested the effects of insect predation on seed germination and seedling growth and survival of Astragalus lehmannianus, a central Asian sand-desert endemic. Under laboratory conditions, seeds lightly predated in the natural habitat of this perennial legume germinated to a much higher percentage than intact seeds, and seedlings from predated and nonpredated seeds survived and grew about equally well. Further, in contrast to our prediction seedlings from predated seeds that germinated âout-of-seasonâ under near-natural conditions in NW China survived over winter. The implication of our results is that individual plants from predated seeds that germinate early (in our case autumn) potentially have a fitness advantage over those from nonpredated seeds, which delay germination until spring of a subsequent year
Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study
Immunotherapy; Pembrolizumab; Thyroid neoplasmsInmunoterapia; Pembrolizumab; Neoplasias de tiroidesImmunoterĂ pia; Pembrolizumab; NeoplĂ sies de tiroidesBackground
The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers.
Methods
Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review.
Results
A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9â54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%â13.5%), and median duration of response was 18.4 (range, 4.2â47.2+) months. ORR was 8.7% (95% CI, 2.4%â20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) â„1 (n = 46) and 5.7% (95% CI, 1.2%â15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9â6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3â5, 14.6%).
Conclusions
Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD-L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study
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