Human vocal development occurs through two parallel interactive processes that transform infant cries into more mature vocalizations, such as cooing sounds and babbling. First, natural categories of ...sounds change as the vocal apparatus matures. Second, parental vocal feedback sensitizes infants to certain features of those sounds, and the sounds are modified accordingly. Paradoxically, our closest living ancestors, nonhuman primates, are thought to undergo few or no production-related acoustic changes during development, and any such changes are thought to be impervious to social feedback. Using early and dense sampling, quantitative tracking of acoustic changes, and biomechanical modeling, we showed that vocalizations in infant marmoset monkeys undergo dramatic changes that cannot be solely attributed to simple consequences of growth. Using parental interaction experiments, we found that contingent parental feedback influences the rate of vocal development. These findings overturn decades-old ideas about primate vocalizations and show that marmoset monkeys are a compelling model system for early vocal development in humans.
Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of ...anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM.
We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan–Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies.
In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group 6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03).
Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.
•Acral melanoma is a distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma.•We retrospectively examined advanced-stage acral melanoma patients treated with an anti-PD-1 antibody.•Anti-PD-1 antibodies have limited efficacy in Japanese acral melanoma patients.•Patients with nail apparatus melanoma had poorer response and survival than patients with palm and sole melanoma.
We investigated conditions to prepare cellulosic cholesteric liquid crystalline (ChLC) films in order to accomplish dual mechanochromism,
, colour control and circular dichroic inversion upon ...mechanical stimulus, at room temperature. Flexible propionylated hydroxypropyl cellulose (PHPC) was prepared by a simple reaction and found to be capable of forming lyotropic ChLC in various monomeric solvents. The ChLC solutions were subjected to
polymerization to obtain PHPC/synthetic polymer composite films incorporating the ChLC structure. However, the immobilization behaviour depended on the type of original monomers. Differential scanning calorimetry and solid-state NMR measurement revealed that the ChLC structure was more highly fixed when the compatibility between PHPC and the coexisting polymers was lower. Eventually, thus obtained ChLC composite films exhibited dual mechanochromism under ambient temperature.
Summary
Background
Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors ...associated with ALM have only been verified in small‐sized cohorts because of the low incidence of ALM worldwide.
Objectives
To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society.
Methods
The Kaplan–Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease‐specific survival (DSS) curves, which were compared using the log‐rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS.
Results
In total, 2050 patients with ALM were identified from 58 949 patients with CM recorded by the CMMR with follow‐up data. In multivariate analyses, age (P = 0·006), ulceration (P = 0·013), tumour thickness (P < 0·001) and tumour spread (P < 0·001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors.
Conclusions
ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.
What's already known about this topic?
Acral lentiginous melanoma (ALM) has a poorer prognosis than other cutaneous melanoma subtypes.
Several published articles have reported various factors that influence the prognosis in ALM but the results of these studies were based on small‐sized cohorts because of the rarity of ALM.
What does this study add?
This study investigated prognostic factors in the largest‐ever cohort of patients with ALM documented by the Central Malignant Melanoma Registry of the German Dermatologic Society.
Four parameters including age, ulceration, tumour thickness and tumour spread were identified as independent significant prognostic factors for disease‐specific survival in ALM.
The present American Joint Committee on Cancer classification is valid for ALM.
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Background
Surgery is the gold standard for basal cell carcinomas (BCC). Current recommended surgical margins for BCCs are determined from studies in Caucasian populations. However, the appropriate ...surgical margins for BCCs in non‐white races are unclear.
Objectives
To investigate the accuracy of preoperative determination of clinical tumour borders and appropriate surgical margins in Japanese patients with BCC.
Methods
The maximum calculated differences in distance between the preoperatively determined surgical margins and the actual histologic tumour side margins were considered as ‘accuracy gaps’ of clinical tumour borders. Estimated side margin positivity rates (ESMPRs) with narrower (2 and 3 mm) surgical margins were calculated on the basis of the accuracy gaps.
Results
Overall, 1000 surgically excised BCCs from 980 Japanese patients were included. The most frequent histologic subtype was nodular BCC (67%). The median accuracy gap was 0.3 mm interquartile range (IQR): −0.5 to +1 mm. The ESMPRs with 2‐ and 3‐mm surgical margins were 3.8% and 1.4%, respectively. Only the ESMPRs between the well‐defined (n = 921) and poorly defined clinical tumour border groups (n = 79) showed statistical difference 2‐mm margin: 3.1% vs. 11.7%, OR: 3.89, 95% confidential interval (CI): 1.41–10.71, P <0.01; 3‐mm margin: 0.97% vs. 6.3%, OR: 6.58, 95% CI: 1.67–25.99, P <0.01. No significant differences in ESMPRs were noted in other subgroups including risk classifications.
Conclusions
The determined clinical tumour border accuracy gaps in this Japanese cohort were negligible. Dermatologic surgeons may use narrower surgical margins with acceptable margin positivity rates. The clarity of clinical tumour borders could be an appropriate guide for selection of different surgical margins in the Japanese cohort.
Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies ...suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients.
We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4.
Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001).
First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.
•Anti-PD-1 plus anti-CTLA-4 antibody therapy (PD1 + CTLA4) is an option for patients with advanced mucosal melanoma (MCM).•Data on the efficacy of PD1 + CTLA4 compared with PD-1 monotherapy (PD1) for MCM, however, are limited.•We retrospectively analyzed data from 329 Japanese patients with advanced MCM treated with PD1 or PD1 + CTLA4.•No significant differences in objective response rate, progression-free survival, or overall survival were observed.•Immune-related adverse events resulting in treatment cessation were higher in the PD1 + CTLA4 group.
This paper presents the effects of polarity on the electrohydrodynamic (EHD) spray of water (deionized and tap water) in air and pure CO2 environments. Its influence in the interaction of the EHD ...spray and corona discharges was experimentally measured and analyzed. In contrast to the various spray patterns observed under positive polarity, negative polarity induced only two modes (dripping and spindle) under the typical conditions used in this study. Mapping of electrospray modes is presented in conjunction with current–voltage characteristics, discharge and spray images obtained with ICCD and high-speed camera. We also first report the intermittent multi-jet mode in water in pure CO2. The essential differences in the spindle mode were the shape and elongation direction of the water filaments according to the negative or positive polarity. The different spray patterns in the spindle mode seemed to be associated with the movement of ion species in water. From the combined analysis of the corona discharges, one may conclude that the different properties of the coronas were associated with the spray patterns in both air and pure CO2. Typical onset streamers in air under positive polarity had minimal influence on the spray mode because they were found to be separated in time and space from the water meniscus. In contrast to the stable glow under positive polarity, many current pulses (Trichel pulse) were observed in the negative EHD spray.
•Multidisciplinary analysis of the polarity effects on EHD spray.•The influence of surrounding gases.•The correlation between corona discharges and the EHD spray of water.
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