Vaccination Status of Children With Epilepsy or Cerebral Palsy in Hunan Rural Area and a Relative KAP Survey of Vaccinators

Background: In China, the vaccination of children with epilepsy (EP) and cerebral palsy (CP) has no specific protocol. Parents are often concerned that vaccination of their children may cause complications due to negative recommendations from vaccinators, resulting in a decline in vaccination. It is therefore is essential to investigate the vaccination status of these specific populations, and the knowledge, attitudes, and practices (KAP) of vaccinators.Methods: This study contains two parts. For the vaccination status survey, residency- and age-matched children whose medical expenditure were covered by the New Rural Cooperative Medical System in Hunan Province were enrolled. Children who were diagnosed with EP or CP were included as the case group, while children without any chronic disease were enrolled as the control group. The vaccination rates of the two groups were compared. For the KAP survey, vaccinators who registered in Hunan CDC were recruited as respondents, and questions were asked related to their experience and attitudes toward vaccinating children with EP or CP.Results: The vaccination rates of the case group were significantly lower than the control group (P < 0.001), with the exception of BCG and Hep B1. Nine measles and two mumps cases were diagnosed in the case group, while there were no Vaccine Preventable Disease (VPD) cases in the control group. The vaccinators' knowledge of the issues related to the vaccination of children with EP or CP was weaker than their knowledge of general vaccination issues. Furthermore, when making a vaccination decision, seizure-free periods and EEG status were their main concerns.Conclusion: The vaccination status of rural children with EP and CP is in jeopardy in Hunan, China, and there are several misunderstandings regarding the contraindications of vaccines among vaccinators. We suggest that measures are taken to improve this situation

Positive response to trastuzumab deruxtecan in a patient with HER2-mutant NSCLC after multiple lines therapy, including T-DM1: a case report

Human epidermal growth factor 2 (HER2) mutations are uncommon in non-small cell lung cancer (NSCLC), and the lack of established, effective, targeted drugs has resulted in a persistently poor prognosis. Herein, we report the case of a non-smoking, 58-year-old man diagnosed with lung adenocarcinoma (cT3N0M1c, stage IVB) harboring a HER2 mutation (Y772_A775dupYVMA) and PD-L1 (-). The patient’s Eastern Cooperative Oncology Group performance status (PS) score was assessed as 1. He commenced first-line treatment with chemotherapy, followed by immuno-chemotherapy, and with disease progression, he received HER2-targeted therapy and chemotherapy with an anti-angiogenic agent. However, HER2-targeted therapy, including pan-HER tyrosine kinase inhibitors (afatinib, pyrotinib, and pozitinib) and antibody–drug conjugate (T-DM1), produced only stable disease (SD) as the best response. After the previously described treatment, primary tumor recurrence and multiple brain metastases were observed. Despite the patient’s compromised overall physical condition with a PS score of 3-4, he was administered T-DXd in addition to whole-brain radiotherapy (WBRT). Remarkably, both intracranial metastases and primary lesions were significantly reduced, he achieved a partial response (PR), and his PS score increased from 3-4 to 1. He was then treated with T-DXd for almost 9 months until the disease again progressed, and he did not discontinue the drug despite the occurrence of myelosuppression during this period. This is a critical case as it exerted an effective response to T-DXd despite multiple lines therapy, including T-DM1. Simultaneously, despite the occurrence of myelosuppression in the patient during T-DXd, it was controlled after aggressive treatment

Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment

TNFα inhibitors have shaped the landscape of rheumatoid arthritis (RA) therapy with high clinical efficiency. However, their impact on T cell recall responses is not well-elucidated. We aimed to analyze the immune profiles of memory T cells in RA patients undergoing TNFα inhibitor Golimumab (GM) treatment. Frequencies of peripheral T cell subsets and cytokine expression profiles in memory T cells (TM) upon PMA/Ionomycine stimulation were determined by flow cytometry. Antigen-specific CD8 T cell immunity was analyzed through stimulating PBMCs with CMV-EBV-Flu (CEF) viral peptide pool and subsequent intracellular IFNγ staining. Both peripheral CD8 and CD4 T cells from GM treated patients had a shift pattern characterized by an enlarged effector TM and a reduced central TM cell population when compared to GM untreated group. An increase in the frequencies of TNFα+, IL-2+, and IL-17+ CD8 TM cells was observed whereas only TNFα+CD4 TM cells increased in GM treated patients. Moreover, GM treated patients contained more peripheral IFNγ-producing CD8 T cells specific to CEF viral peptides. Together, these results show a distinct T cell subset pattern and enhanced memory T cell immunity upon GM treatment, suggesting an immunoregulatory effect of TNF inhibitor Golimumab on peripheral memory T cell responses

REFUGE Challenge: A unified framework for evaluating automated methods for glaucoma assessment from fundus photographs

[EN] Glaucoma is one of the leading causes of irreversible but preventable blindness in working age populations. Color fundus photography (CFP) is the most cost-effective imaging modality to screen for retinal disorders. However, its application to glaucoma has been limited to the computation of a few related biomarkers such as the vertical cup-to-disc ratio. Deep learning approaches, although widely applied for medical image analysis, have not been extensively used for glaucoma assessment due to the limited size of the available data sets. Furthermore, the lack of a standardize benchmark strategy makes difficult to compare existing methods in a uniform way. In order to overcome these issues we set up the Retinal Fundus Glaucoma Challenge, REFUGE (https://refuge.grand-challenge.org), held in conjunction with MIC-CAI 2018. The challenge consisted of two primary tasks, namely optic disc/cup segmentation and glaucoma classification. As part of REFUGE, we have publicly released a data set of 1200 fundus images with ground truth segmentations and clinical glaucoma labels, currently the largest existing one. We have also built an evaluation framework to ease and ensure fairness in the comparison of different models, encouraging the development of novel techniques in the field. 12 teams qualified and participated in the online challenge. This paper summarizes their methods and analyzes their corresponding results. In particular, we observed that two of the top-ranked teams outperformed two human experts in the glaucoma classification task. Furthermore, the segmentation results were in general consistent with the ground truth annotations, with complementary outcomes that can be further exploited by ensembling the results.This work was supported by the Christian Doppler Research Association, the Austrian Federal Ministry for Digital and Economic Affairs and the National Foundation for Research, Technology and Development, J.I.O is supported by WWTF (Medical University of Vienna: AugUniWien/FA7464A0249, University of Vienna: VRG12- 009). Team Masker is supported by Natural Science Foundation of Guangdong Province of China (Grant 2017A030310647). Team BUCT is partially supported by the National Natural Science Foundation of China (Grant 11571031). The authors would also like to thank REFUGE study group for collaborating with this challenge.Orlando, JI.; Fu, H.; Breda, JB.; Van Keer, K.; Bathula, DR.; Diaz-Pinto, A.; Fang, R.... (2020). 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Genomic heterogeneity of multiple synchronous lung cancer

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events

Direct and indirect effects of climate on richness drive the latitudinal diversity gradient in forest trees

Data accessibility statement: Full census data are available upon reasonable request from the ForestGEO data portal, http://ctfs.si.edu/datarequest/ We thank Margie Mayfield, three anonymous reviewers and Jacob Weiner for constructive comments on the manuscript. This study was financially supported by the National Key R&D Program of China (2017YFC0506100), the National Natural Science Foundation of China (31622014 and 31570426), and the Fundamental Research Funds for the Central Universities (17lgzd24) to CC. XW was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB3103). DS was supported by the Czech Science Foundation (grant no. 16-26369S). Yves Rosseel provided us valuable suggestions on using the lavaan package conducting SEM analyses. Funding and citation information for each forest plot is available in the Supplementary Information Text 1.Peer reviewedPostprin

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure