Content-Dependent Fine-Grained Speaker Embedding for Zero-Shot Speaker Adaptation in Text-to-Speech Synthesis

Zero-shot speaker adaptation aims to clone an unseen speaker's voice without any adaptation time and parameters. Previous researches usually use a speaker encoder to extract a global fixed speaker embedding from reference speech, and several attempts have tried variable-length speaker embedding. However, they neglect to transfer the personal pronunciation characteristics related to phoneme content, leading to poor speaker similarity in terms of detailed speaking styles and pronunciation habits. To improve the ability of the speaker encoder to model personal pronunciation characteristics, we propose content-dependent fine-grained speaker embedding for zero-shot speaker adaptation. The corresponding local content embeddings and speaker embeddings are extracted from a reference speech, respectively. Instead of modeling the temporal relations, a reference attention module is introduced to model the content relevance between the reference speech and the input text, and to generate the fine-grained speaker embedding for each phoneme encoder output. The experimental results show that our proposed method can improve speaker similarity of synthesized speeches, especially for unseen speakers.Comment: Submitted to Interspeech 202

Toll-Like Receptor 7 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus. Toll-like receptor 7 (TLR7) is involved in host innate immunity against pathogens, and its aberrant activation is linked to the development of systemic lupus erythematosus (SLE, also called ‘‘lupus’’). Type I interferons (IFN) are apparently driving forces for lupus pathogenesis. Previously, we found that EBV latent membrane protein 1 (LMP1) primes cells for IFN production. In this report, the relationship among EBV LMP1, TLRs, and IFN production are examined. We find that TLR7 activation increases the expression of EBV LMP1, and IFN regulatory factor 7 (IRF7) is involved in the stimulation process. TLR7 activation did not induce IFNs from EBV-infected cells, but potentiates those cells for IFN production by TLR3 or TLR9 activation. In addition, we find that LMP1 and IFNs are coexpressed in the same cells in some lupus patients. Therefore, the aberrant activation of TLR7 might induce LMP1 expression and LMP1-expression cells may be producing IFNs in lupus patients. These results suggest EBV might be an exacerbating factor in some lupus patients via promoting IFN production

Effect of ingested human antibodies induced by RTS, S/AS01 malaria vaccination in children on Plasmodium falciparum oocyst formation and sporogony in mosquitoes.

BACKGROUND: The circumsporozoite protein (CS protein) on the malaria parasites in mosquitoes plays an important role in sporogony in mosquitoes. The RTS,S/AS01 malaria vaccine candidate, which has shown significant efficacy against clinical malaria in a large Phase 3 trial, targets the Plasmodium falciparum CS protein, but the ability of serum from vaccinated individuals to inhibit sporogony in mosquitoes has not been evaluated. METHODS: Previously a double-blind, randomized trial of RTS,S/AS01 vaccine, as compared with rabies vaccine, in five- to 17-month old children in Tanzania was conducted. In this study, polyclonal human antibodies were purified from the pools of sera taken one month after the third vaccination. IgGs were purified from four pools of sera from 25 RTS,S/AS01 vaccinated children each, and two pools of sera from 25 children vaccinated with rabies vaccine each. The ability of antibodies to inhibit P. falciparum oocyst formation and/or sporogony in the mosquito host was evaluated by a standard membrane-feeding assay. The test antibodies were fed on day 0 (at the same time as the gametocyte feed), or on days 3 or 6 (serial-feed experiments). The oocyst and sporozoite counts were performed on days 8 and 16, respectively. In addition, two human anti-CS monoclonal antibodies (mAb) and a control mAb were also evaluated. RESULTS: Polyclonal anti-CS IgG preparations from RTS,S-vaccinated children tested at concentrations of 149-210 ELISA units (EU)/ml did not show significant inhibition in oocyst and sporozoite formation when the antibodies were fed with gametocytes at the same time, or later (serial-feed experiments). Similarly, anti-CS mAbs tested at 6,421 or 7,122 EU/ml did not show reduction in oocyst and sporozoite formation. CONCLUSIONS: This study does not support the concept that anti-CS antibodies induced by the RTS,S/AS01 vaccines in humans noticeably reduce malaria transmission by blocking P. falciparum sporozoite development or salivary gland invasion in mosquitoes when taken up during feeding

Cancer drug indication approvals in China and the United States: a comparison of approval times and clinical benefit, 2001–2020

BACKGROUND: Perceived delays in cancer drug approvals have been a major concern for policymakers in China. Policies have been implemented to accelerate the launch of new cancer drugs and indications. This study aimed to assess similarities and differences between China and the United States in the approvals, timing, and clinical benefit evidence of cancer drug indications between 2001 and 2020. METHODS: This study retrospectively identified all cancer drugs and indications approved in both China and the United States from January 1st, 2001 to December 31, 2020, and described differences in approval times as well as in submission and review times. Information on the availability of overall survival benefit evidence by December 31, 2020, was collected. Univariate and multiple logistic regression analyses were used to assess whether evidence of benefit and other factors affected the propensity and timing of approvals of cancer drug indications in China. FINDINGS: Between 2001 and 2020, 229 indications corresponding to 145 cancer drugs approved in the United States were identified. Of those, 80 indications (34.9%) were also approved in China by the end of 2020. Cancer drug indications were approved in China at a median of 1273.5 days after approval in the United States. The median submission and review time differences for cancer drug indications in China were 1198.0 days and 180.0 days respectively. Submission time differences accounted for most of the approval time differences (p < 0.001). Indications supported by overall survival benefit evidence had shorter median review time differences (145.0 days) than those without such evidence (235.0 days, p = 0.008). Indications with overall survival benefit evidence were 3.94 times more likely to be approved in China compared to those without such evidence (p = 0.001), controlling for approval year, cancer type, and the prevalence of cancer by site. INTERPRETATION: FDA-approved cancer drug indications demonstrating a survival benefit were more likely to receive approvals in China with shorter regulatory review times compared to indications without such evidence. Given that manufacturer submission times were the main driver of cancer drug approval times in China, factors influencing submission timing should be explored. FUNDING: No funding

An inter-laboratory comparison of standard membrane-feeding assays for evaluation of malaria transmission-blocking vaccines.

BACKGROUND: An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. The standard membrane-feeding assay (SMFA) for Plasmodium falciparum infection of mosquitoes is considered a "gold standard" assay to measure transmission-blocking activity of test antibodies, and has been utilized widely in both non-clinical and clinical studies. While several studies have discussed the inherent variability of SMFA within a study group, there has been no assessment of inter-laboratory variation. Therefore, there is currently no assurance that SMFA results are comparable between different studies. METHODS: Mouse anti-Pfs25 monoclonal antibody (mAb, 4B7 mAb), rat anti-Pfs48/45 mAb (85RF45.1 mAb) and a human polyclonal antibody (pAb) collected from a malaria-exposed adult were tested at the same concentrations (6-94 μg/mL for 4B7, 1.2-31.3 μg/mL for 85RF45.1 and 23-630 μg/mL for human pAb) in two laboratories following their own standardized SMFA protocols. The mAbs and pAb, previously shown to have strong inhibition activities in the SMFA, were tested at three or four concentrations in two or three independent assays in each laboratory, and percent inhibition in mean oocyst intensity relative to a control in the same feed was determined in each feeding experiment. RESULTS: Both monoclonal and polyclonal antibodies dose-dependently reduced oocyst intensity in all experiments performed at the two test sites. In both laboratories, the inter-assay variability in percent inhibition in oocyst intensity decreased at higher levels of inhibition, regardless of which antibody was tested. At antibody concentrations that led to a >80 % reduction in oocyst numbers, the inter-laboratory variations were in the same range compared with the inter-assay variation observed within a single laboratory, and the differences in best estimates from multiple feeds between the two laboratories were <5 percentage points. CONCLUSIONS: This study confirms previous reports that the precision of the SMFA increases with increasing percent inhibition. Moreover, the variation between the two laboratories is not greater than the variation observed within a laboratory. The findings of this study provide guidance for comparison of SMFA data from different laboratories

Epidemiology of Classical Hodgkin Lymphoma and Its Association with Epstein Barr Virus in Northern China

BACKGROUND: The incidence of classical Hodgkin lymphoma (cHL) and its association with Epstein-Barr virus (EBV) varies significantly with age, sex, ethnicity and geographic location. This is the first report on epidemiological features of cHL patients from Northern regions of China. These features are compared to data from a previously published Dutch cHL population. METHODOLOGY/PRINCIPAL FINDINGS: 157 cHL patients diagnosed between 1997 and 2008 in the North of China were included after histopathological re-evaluation. The Dutch population-based cohort consisted of 515 cHL patients diagnosed between 1987 and 2000. EBV status was determined by in situ hybridization of EBV- encoded small RNAs. In the Chinese population, tumor cells of 39% of the cHL patients were EBV+ and this was significantly associated with male sex, mixed cellularity subtype and young age (<20 y). The median age of the Chinese patients was 9 years younger than that of the Dutch patients (28 y vs. 37 y). In addition, the age distribution between the two populations was strikingly different in both the EBV+ subgroups (p<0.001) and the EBV- subgroups (p = 0.01). The mixed cellularity subtype was almost 3x more frequent amongst the Chinese (p<0.001). CONCLUSION/SIGNIFICANCE: CHL patients from Northern regions of China show a distinctive age distribution pattern with a striking incidence peak of EBV+ mixed cellularity cases among children and adolescents and another high incidence peak of EBV- nodular sclerosis cases in young adults. In comparison to Dutch cHL patients there are pronounced differences in age distribution, subtype and EBV status, presumably caused by complex gene-environmental interactions

Boosting Multi-Label Image Classification with Complementary Parallel Self-Distillation

Multi-Label Image Classification (MLIC) approaches usually exploit label correlations to achieve good performance. However, emphasizing correlation like co-occurrence may overlook discriminative features of the target itself and lead to model overfitting, thus undermining the performance. In this study, we propose a generic framework named Parallel Self-Distillation (PSD) for boosting MLIC models. PSD decomposes the original MLIC task into several simpler MLIC sub-tasks via two elaborated complementary task decomposition strategies named Co-occurrence Graph Partition (CGP) and Dis-occurrence Graph Partition (DGP). Then, the MLIC models of fewer categories are trained with these sub-tasks in parallel for respectively learning the joint patterns and the category-specific patterns of labels. Finally, knowledge distillation is leveraged to learn a compact global ensemble of full categories with these learned patterns for reconciling the label correlation exploitation and model overfitting. Extensive results on MS-COCO and NUS-WIDE datasets demonstrate that our framework can be easily plugged into many MLIC approaches and improve performances of recent state-of-the-art approaches. The explainable visual study also further validates that our method is able to learn both the category-specific and co-occurring features. The source code is released at https://github.com/Robbie-Xu/CPSD.Comment: accepted by IJCAI202

Cell Phone Addiction and Apps Activities among Chinese Medical Students: Prevalence and Risk Factors

Objective To investigate the prevalence of cell phone addiction and the association with apps use and preference among medical students in China to offer suggestions for phone addiction prevention and management. Methods A total of 3058 medical undergraduate students from six medical universities/colleges located in five provinces of China were randomly sampled and interviewed. An adapted “Questionnaire of Mobile APP” from “Manolis/Roberts Cell-Phone Addiction Scale” was used to conduct the interview. Chi-squared (χ2) test and binary logistic regression analysis were used for data analysis. A database was built with EpiData 3.1, and statistical analysis was conducted using SPSS 23.0. Results Cell phone addiction was reported by 16.25% of medial undergraduates. Univariate analysis found statistical difference among addictive students with different genders, hukou status, monthly cell phone bills and in-love status. The following were reported as the risk factors for mobile addiction among medical students by logistic regression analysis: medical students who were female (odds ratio [OR]=1.704, 95% confidence interval [CI]=1.386, 2.095), were from urban (OR=1.307, 95% CI=1.046, 1.634), had boyfriend or girlfriend (OR=1.333, 95% CI=1.080, 1.646), used reading apps (OR=1.254, 95% CI=1.015, 1.549), were using reading apps (OR=1.254, 95% CI=1.015, 1.549), and were using chat apps (OR=2.222 , 95% CI=1.146, 4.310). Conclusion Medical students who are female, from urban, in-love, or frequent users of reading and chat apps may face a higher risk of cell phone addiction. Therefore, gender-specific and app type-specific interven-tions should be developed to intervene college students’ cell phone addiction