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Heterozygous missense mutations in TUBB3 have been implicated in various neurological disorders encompassing either isolated congenital fibrosis of the extraocular muscles type 3 (CFEOM3) or complex cortical dysplasia with other brain malformations 1 (CDCBM1). The description of seizures in patients with TUBB3 mutations is rare. Here, we reported a patient who had febrile seizures before and focal seizure this time, which was diagnosed as epilepsy in combination with an abnormal EEG. MRI showed hypoplastic corpus callosum. Mutation analysis showed a novel de novo heterozygous variant of TUBB3 gene (NM_006086), c.763G>A (p.V255I). He had global developmental delay, photophobia and elliptic pupil, but lacking extraocular muscles involvement and malformations of cortical development, which might be a less severe phenotype of TUBB3 mutations. This was the first report of elliptic pupil in patients with TUBB3 mutations and expanded the spectrum of TUBB3 phenotypes. It indicated that the phenotypic range of TUBB3 mutations might be more continuous than discrete, with a severity ranging from mild to severe. Further studies are needed to elucidate the complete spectrum of TUBB3-related phenotypes.

This paper presents the instructional design and development process for a fashion design education programme promoting creativity in a VR (Virtual Reality) environment. We designed the instruction...

Spectral decomposition has been widely used to detect frequency-dependent anomalies associated with hydrocarbons. By ignoring the time-variant feature of the frequency content of individual reflected wavelets, we have adopted a sparse time-frequency spectrum and developed a matching pursuit-based sparse spectral analysis (MP-SSA) method to estimate the sparse time-frequency representation of the seismic data. Further, we evaluate a generalized nonstationary convolution model concerning propagation attenuation and frequency-dependent reflectivity, and we mathematically evaluate the sparse time-frequency spectrum of the nonstationary seismic data as being equal to the product of the Fourier spectrum of the source wavelet, frequency-dependent reflection coefficient, and the cumulative attenuation during seismic wave propagation. Therefore, the reflectivity spectrum, which is a combination of the frequency-dependent reflectivity and the propagation attenuation, can be determined by dividing the sparse time-frequency spectrum of the seismic data by the Fourier spectrum of the source wavelet. Application of the matching pursuit-based decomposition methods to synthetic nonstationary convolutional data illustrates that the adopted MP-SSA spectrum shows a higher time resolution than the matching pursuit-based Wigner-Ville distribution and the matching pursuit-based instantaneous spectral analysis spectra. Notably, the MP-SSA method can avoid spectral smearing, which may introduce distortions to the frequency-dependent anomaly estimation. Application of the amplitude versus frequency analysis based on MP-SSA to field data illustrates the potential of using the sparse reflectivity spectral intercept and gradient to detect the hydrocarbon reservoirs.

Background MED13L-related intellectual disability is a new syndrome that is characterized by intellectual disability (ID), motor developmental delay, speech impairment, hypotonia and facial dysmorphism. Both the MED13L haploinsufficiency mutation and missense mutation were reported to be causative. It has also been reported that patients carrying missense mutations have more frequent epilepsy and show a more severe phenotype. Case presentation We report a child with ID, speech impairment, severe motor developmental delay, facial deformity, hypotonia, muscular atrophy, scoliosis, odontoprisis, abnormal electroencephalogram (EEG), and congenital ureteropelvic junction obstruction (UPJO) combined with high ureter attachment. We used whole-exome sequencing (WES) to detect the genetic aberration of the child and found a de novo mutation, c.2605C > T (p.Pro869Ser), in the MED13L gene. Neither of her parents carried the mutation. Additionally, we review the literature and summarize the phenotypes and features of reported missense mutations. After reviewing the literature, approximately 17 missense mutations in 20 patients have been reported thus far. For 18 patients (including our case) whose clinical manifestations were provided, 100% of the patients had ID or developmental delay (DD). A total of 88.9, 83.3 and 66.7% of the patients had speech impairment, delayed milestones and hypotonia, respectively. A total of 83.3% of the patients exhibited craniofacial deformity or other dysmorphic features. Behavioral difficulties and autistic features were observed in 55.6% of the patients. Cardiac anomalies were seen in only 27.8% of the patients. Of these patients, 44.4% had epileptic seizures. Of the 17 mutations, 2 were located in the N-terminal domain, 8 were located in the C-terminal domain, and 1 was located in an α-helical sequence stretch. One of them was located in the MID domain of the MedPIWI module. Conclusions We report a new patient with a reported missense mutation, c.2605C > T (p.Pro869Ser), who exhibited some infrequent manifestations except common phenotypes, which may broaden the known clinical spectrum. Additionally, by reviewing the literature, we also found that patients with missense mutations have a higher incidence of seizures, MRI abnormalities, autistic features and cardiac anomalies. They also have more severe ID and hypotonia. Our case further demonstrates that Pro869Ser is a hotspot mutation of the MED13L gene.

To characterize the clinical and genetic characteristics of a large cohort of patients with pyridoxine-dependent epilepsy (PDE).We retrospectively collected clinical and genetic information of 33 (15 males, 18 females; mean [SD] age 4y 11mo [2y 5mo]; 1y 3mo-10y 4mo) patients with PDE from 31 unrelated families at a single centre.There were many types of seizures, with focal seizures in 32 cases. Dravet syndrome was suspected clinically in two patients. Electroencephalogram (EEG) was normal in seven patients at the initial stage and then in 17 patients during pyridoxine maintenance therapy. Genetic studies revealed 26 kinds of variants in ALDH7A1 and four in PLPBP with 18 variants unreported previously, and 48 ALDH7A1 variants were located in exon 11, 12, 14, and 17 or intron 9 and 11. In addition, three patients carried different exons deletion. Among these, seizures could be controlled for several years in one patient by levetiracetam monotherapy. Another patient remained seizure free for up to 7 months without therapy. All patients received oral pyridoxine treatment, with only one case (with exon 8-13 deletion) showing poor control.This study illustrates the range of clinical presentations and genetic causes in PDE, as well as responsiveness to antiepileptic drugs. A relationship between EEG and pyridoxine therapy could be seen in many cases. Seizure control was seen in all with pyridoxine monotherapy except for one patient.There is a parallel relationship between electroencephalogram and pyridoxine therapy in many patients. Patients with pyridoxine-dependent epilepsy may respond well to low-dose pyridoxine.目的: 总结33例吡哆醇依赖性癫痫（pyridoxine-dependent epilepsy, PDE）患者的临床特征及遗传学特点。 方法: 回顾性收集33例PDE患者的临床资料（15位男性，18位女性；平均年龄[SD]：4岁11个月[2岁5个月]；1岁3个月~10岁4个月), 所有患者均进行遗传学检测。 结果: 癫痫发作类型多样，32例患者出现局灶性发作。2例患者在未经遗传学确诊前临床疑诊为Dravet综合征。7例患者初次脑电图正常，随后，在吡哆醇维持治疗期间，17的患者脑电图恢复正常。基因检测结果提示有26种不同的ALDH7A1突变，4种PLPBP突变。其中，18种突变国际上未见相关报道。48个ALDH7A1突变位于外显子11、12、14和17或内含子9和11。此外，3例患者携带不同的外显子缺失。33例患者中，1例经左乙拉西坦单药治疗可控制数年无发作，另1例在接受治疗前，可7个月无癫痫发作。所有患者均口服吡哆醇治疗，仅有1例携带8-13号外显子缺失的患者经吡哆醇单药治疗后，发作未控制。 结论: 本研究总结了33例PDE患者临床及遗传学特征，以及抗癫痫药的治疗效果。本研究揭示了脑电图与长期吡哆醇维持治疗之间的一种平行关系。另外，在本研究中，32例患者可被吡哆醇单药控制。.

The first-line treatment for colorectal cancer (CRC) is 5-fluorouracil (5-FU). However, the efficacy of this treatment is sometimes limited owing to chemoresistance as well as treatment-associated intestinal mucositis and other adverse events. Growing evidence suggests that certain phytochemicals have therapeutic and cancer-preventing properties. Further, the synergistic interactions between many such plant-derived products and chemotherapeutic drugs have been linked to improved therapeutic efficacy. Polysaccharides extracted from Albuca bracteata (Thunb.) J.C.Manning and Goldblatt (ABP) have been reported to exhibit anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, murine CRC cells (CT26) and a murine model of CRC were used to examine the anti-tumor properties of ABP and explore the mechanism underlying the synergistic interactions between ABP and 5-FU. Our results revealed that ABP could inhibit tumor cell proliferation, invasion, and migratory activity in vitro and inhibited tumor progression in vivo by suppressing β-catenin signaling. Additionally, treatment with a combination of ABP and 5-FU resulted in better outcomes than treatment with either agent alone. Moreover, this combination therapy resulted in the specific enrichment of Ruminococcus, Anaerostipes, and Oscillospira in the intestinal microbiota and increased fecal short-chain fatty acid (SCFA) levels (acetic acid, propionic acid, and butyric acid). The improvement in the intestinal microbiota and the increase in beneficial SCFAs contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Together, these data suggest that ABP exhibits anti-neoplastic activity and can effectively enhance the efficacy of 5-FU in CRC treatment. Therefore, further research on the application of ABP in the development of novel anti-tumor drugs and adjuvant compounds is warranted and could improve the outcomes of CRC patients.

Background: Although radiotherapy (RT) has been widely used in cancer treatment, it provides limited benefits in patients with metastatic cancers due to rare abscopal antitumor effects. The recent progression in cancer immunotherapy provides a potential new strategy to boost abscopal antitumor effects of RT.Methods: we fused Interleukin 10 (IL10) dimer onto an anti-epidermal growth factor receptor antibody Cetuximab (Erbitux) to form a new bispecific protein Erb-(IL10)2. The antitumor effect and biological activity of Erb-(IL10)2 was measured in B16-EGFR-OVA tumor model. In vivo cell depletion and flow cytometry analysis were used to access the mechanism of antitumor effects.Results: Erb-(IL10)2 treatment alone showed modest tumor growth inhibition, while local single dose RT (10 Gy) retarded irradiated tumor growth without affecting on the growth of nonirradiated tumors. Notably, the combination therapy of RT and Erb-(IL10)2 not only additively inhibited irradiated tumor growth, but also induced abscopal antitumor responses. In vivo depletion of CD8+ T cells abrogated the combinational antitumor effects, while blockade of lymphocyte trafficking by FTY720 treatment abolished the abscopal antitumor responses without affecting the antitumor effects on the irradiated tumor sites. Conclusion: This study provides evidences for the radio-sensitivity role of Erb-(IL10)2 in B16-EGFR-OVA tumor model. Our findings suggest a novel strategy to elicit abscopal antitumor effects of RT through combining tumor-targeted therapy of IL10.

Variants in HNRNPU have been reported in patients with epileptic encephalopathy, early infantile 54 (OMIM 602869). We hereby describe two children from different families with autosomal dominance early-onset epileptic encephalopathy, and summarize the genotype and phenotype of reported individuals. Whole exome sequencing analysis was applied to the patients. De novo frameshift variants in the HNRNPU, c.143_149del7 (p.G48Afs*11) and c.1282delC(p.G429Afs*53) were identified respectively. This is the first time to report Chinese patients with early infantile epileptic encephalopathy causing by HNRNPU variants, and so far, these variants have not been reported in population gene database. The present study expands our knowledge of HNRNPU variants and emphasizes the importance of early gene diagnosis.

Background Hemiconvulsion–hemiplegia–epilepsy (HHE) syndrome is a rare syndrome characterized by childhood onset partial motor convulsions, hemiplegia, and epilepsy in sequence. Exact pathogenesis is not clear. Case presentation: We present a girl with global developmental delay with history and brain MRI consistent with the diagnosis of HHE syndrome. The cytogenetic microarray (CMA) showed 9.1 Mb deletion in 5q33.3q34 region. Along with HHE syndrome, the patient also had global developmental delay. Clinical phenotype of this microdeletion region has not been described in association with HHE syndrome in the literature. We compared the patient’s phenotype with other patients in 5 previously published papers of a common region of deletion spanning 157501989–164166203. GABRA1, GABRB2, GABRG2, CYFIP2, THG1 are the important genes in the present deleted region, which may be responsible for the fever sensitivity and global developmental delay. Conclusions This is the first case of HHE syndrome in which CMA showed a microdeletion of 5q33.3q34 region. This case report links HHE syndrome and global developmental delay to microdeletions of 5q33.3q34, which has never been reported in literature. Cause of HHE syndrome remains unexplained in present case and HHE may be a causal or chance co-occurrence.

In recent years, the rapid innovation of computer technology has brought profound changes to all walks of life. The electronic information industry permeates every aspect of daily life and has been developing vigorously in our country. However, some problems have emerged in recent years. This paper starts from the analysis of the basic status of electronic information engineering, points out some of its problems, and how to use computer technology to solve the present dilemma.

The authors have requested that this preprint be removed from Research Square.

Many of the sustainable urban development issues, such as human heath, energy consumption, carbon emission, are related to the climate of cities. As a result, research insights gained in urban climate study can be applied to improve urban sustainability. Although the Local Climate Zones (LCZ) scheme was originally proposed to provide a standardized classification of landscapes to study urban air temperature, its use was not limited to the study of urban heat islands. This study explores the applications of LCZ scheme in various research domains by conducting a bibliometric analysis in CiteSpace on over 800 articles that cites the original article of LCZ. These articles cover a wide range of research categories including meteorology, atmospheric science, environmental science, remote sensing, building technology, civil engineering, ecology, urban studies, etc. The LCZ scheme facilitates urban climate data collection by refining monitoring network, providing reasonable modelling input, and improving database documentation. In addition to the study of urban heat islands, the LCZ scheme was applied in studies of urban thermal comfort, human health, building energy consumption, and carbon emission. The diffusion of the LCZ scheme to other research domains offers an example that the development of urban climate research advances sustainable urban development. This review provides insights of multidisciplinary studies related to urban climate for policy-makers, urban specialists, architects, ecologists, and others.

When the first computer was born, after half a century or so, electronic information technology with its unique influence and vitality has quickly become the global science and technology history of the most extensive impact on human beings in a field. In the new era, higher vocational colleges attach great importance to cultivating students’ electronic information technology. In this context, higher vocational colleges continue to reform and innovate the teaching system and mode, but no matter how to reform, electronic information experiment teaching will always be the most important part. Electronic information experimental teaching department can only enable students to master electronic information knowledge, but also conducive to the development of students in electronic information innovation spirit, practical operation ability and the ability to analyze practical problems and solve problems, it has an irreplaceable role.

To evaluate efficacy of internet-based intensive weight management or exenatide treatment on weight loss and metabolism in overweight/obese patients with polycystic ovary syndrome(PCOS). The study recruited 50 overweight/obese patients with PCOS into intensive lifestyle intervention group(ILI) for internet-based intensive weight management, which characterized with strict-energy and low-carbohydrate diets(1100-1400 kcal of total energy and less than 50g of carbohydrates per day), nutritional meal-replacement diets for lunch and dinner, online reporting followed by nutrionists, exercises, behavioral intervention and medication(metformin, 500mg Tid), for 3 months. 50 BMI matched subjects assigned to 3 months of exenatide injection (10μg bid)in our previous study were recruited as control group (EXE group). Oral glucose tolerance test were performed to assess glucose tolerance and insulin sensitivity. Anthropometric, glycolipid metabolic markers, sex hormone level and inflammatory state were measured and compared between two intervention. After 3 months of intervention, decreases of weight(ILI group 10.02 ± 3.06 kg vs. EXE group 6.15 ± 2.28 kg), BMI (ILI group 3.98±1.26 kg/m2 vs. EXE group 2.54±1.05 kg/m2), HOMA-IR(2.60 ± 2.37 vs. 1.06 ± 2.04), WC, FBG, FINS, TG and UA in ILI group were more statistically significant than EXE group. There were no significant differences in decreases of 2hPBG, 2hINS, testosterone and hs-CRP between two groups(P> 0.05). There were no statistically differences in improvements of total cholesterol, LDL-C, ALT, and AST in both groups (P> 0.05). It is suggested that internet-based intensive weight management in overweight/obese PCOS can significantly reduce weight, improve central obesity and insulin resistance. These effects were significantly better than exenatide treatment. However there were no significant differences in improvements of testosterone level and inflammatory state. Disclosure S. Zheng: None. Y. Zhang: None. R. Li: None. J. Xue: None. H. Shen: None.

Objective To summarize and extend the phenotypic characterization of Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome, and to discuss genotype-phenotype correlations. Methods Collecting clinical information of 17 patients with pathogenic variants in PIGN, PIGA, and PIGT. Genetic studies were performed on all patients. Results There were 7 patients with 15 PIGN mutations (one patient carrying 3 mutations), 8 patients with 8 PIGA mutations, and 2 patients with 5 PIGT mutations (one patient carrying 3 mutations). All patients had epilepsy and developmental delay, with 71% of them showed hypotonia. And among these patients’ various seizure types, the focal seizure was the most common one. Eighty-two percent patients showed a significant relationship between seizures and fever. Serum ALP was elevated in one patient with PIGN mutations and in two patients with PIGA mutations. Brain MRI showed enlarged subarachnoid space in 56% of patients. Some other different characteristics had also been found in our patients: First, atypical absence seizures presented in three patients with PIGN mutations; Second, diffuse slow waves mixed with focal or multifocal discharges of interictal EEG in 88% cases with PIGA-deficient; Third, phenotypes of seven out of eight patients with PIGA mutations were difficult to be classified as severe or less severe group; Last, mild neurological symptoms and developmental status rather than severe conditions occurred in one patient with PIGT mutations. Conclusion With epilepsy, developmental delay, and/or hypotonia as common features, the knowledge of MCAHS in terms of phenotype and genotype has been expanded. In cases with PIGN-deficient, we expanded the types of atypical absence seizures, and described one patient with elevated serum ALP. Focal seizures with diffuse slow waves mixed with focal or multifocal discharges on EEG rather than infantile spasms with hypsarrhythmia, which as previously reported were often seen in our patients with PIGA mutations. The classifications of phenotypes caused by PIGA mutations should be more continuous than discrete. The mild phenotype of one patient with PIGT mutations expanded the clinical presentation of MCAHS3.

In this paper, a nano Voxel X-ray 3D microscope is used to scan the long flame coal samples and to reconstruct the 3D pore structure by the use of microscopic computed tomography. With image segmentation technique, a model of micro-pore structure of coal is obtained from the reconstructed coal. With different planes selected as seepage inlets, a numerical simulation of low-pressure water seepage is conducted. Studies show that water pressure gradually decreases along the direction of water seepage and reaches the maximum at the pore-pipes with good connectivity near the inlet. Due to the difference between the structure and development direction of pores in the three dimensions, there is an optimal seepage outlet that is most appropriately corresponding to each seepage inlet. When different planes are selected as seepage inlets, the velocity of each seepage outlet is positively correlated with the seepage mass flow rate at the outlet.

The pharmacokinetic properties of vitacoxib have not been established completely; current dosage recommendations are based on clinical experiences. The primary objective of this study was to describe plasma concentrations and characterize the pharmacokinetics of vitacoxib formulation following oral administrations in horses. Also, the effect of the state of stomach contents on the absorption of vitacoxib was investigated in fed/fasted horses. Blood samples were collected prior to and at various times up to 72 hr post-administration. Drug concentrations were measured using ultra high-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated using Non-Compartmental Analysis Model 200 in WinNonlin™ software. No complications resulting from the vitacoxib administration were noted. All procedures were tolerated well by the horses throughout the study. Cmax was 17.5 ± 9.36 ng/ml (fasted) and 9.47 ± 3.53 ng/ml (fed) following oral administrations. AUClast was 173.7 ± 137.9 ng hr/ml (fasted) and 113.2 ± 70.8 ng h/ml (fed). No significant differences in pharmacokinetic parameters were noted and the results from the pharmacokinetic analysis were similar between the studies, regardless of precision of dosage and fasted and fed conditions. The study extends previous studies describing the pharmacokinetics of vitacoxib following p.o. administration to the horses. Further studies investigating the pharmacokinetics/pharmacodynamics of vitacoxib are necessary to establish adequate therapeutic protocols (optimal dosage and frequency of administration) in horses.

Objective To investigate high-frequency oscillations (HFOs) in epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) with different etiologies. Methods Twenty-one CSWS patients treated with methylprednisolone were divided into structural group and genetic/unknown group. Comparisons were made between the two etiological groups: selected clinical variables including gender, age parameters, seizure frequencies and antiepileptic drugs; distribution of HFOs in pre-methylprednisolone electroencephalography (EEG) and percentage changes of HFOs and spikes after methylprednisolone treatment. Results There were 7 patients (33%) in structural group and 14 patients (68%) in genetic/unknown group. No significant difference was found between the two groups regarding selected clinical variables. HFOs were found in 12 patients in pre-methylprednisolone EEG. The distribution of HFOs was focal and accordant with lesions in 5 of structural group, and it was also focal but in different brain regions in 7 of genetic/unknown group. The percentage reduction of total HFOs and spikes was 81% (158/195) and 19% (1956/10,037) in structural group, while 98% (315/323) and 55% (6658/12,258) in genetic/unknown group after methylprednisolone treatment. Conclusion The etiologies had no distinct correlation with some clinical characteristics in CSWS. HFOs recorded on scalp EEG might not only be used as makers of seizure-onset zone (SOZ), but also have association with functional disruption of brain networks. Both HFOs and spikes reduced more in genetic/unknown patients than that in structural patients after methylprednisolone treatment and HFOs were more sensitive to treatment than spikes.

Purpose/Objective(s) With the increasing numbers of haploidentical hematopoietic stem cell transplants (Haplo-HSCT), the roles affecting transplant outcomes of anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are currently being evaluated. Patients with high levels of DSAs were desensitized with plasmapheresis, immunoglobulin and rituximab prior to transplantation. However, the therapies were not very effective, probably because the source of DSA production was not controlled effectively. Rescue splenectomy has been used with short-term success by establishing source control for the DSA-producing plasmablasts in renal transplantation patients. Splenic irradiation was also proved to be effective in these patients. Herein, we describe the first reported use of splenic irradiation as adjunct therapy for patients with high level of DSAs prior to haplo-HSCT. Materials/Methods 14 haplo-HSCT patients were involved, including 3 males and 11 females. The median age was 45 years (26-55). Before transplantation, 9 patients were tested positive of HLA-I DSA, and 6 patients were positive of HLA-II DSA, including 1 patient which was tested positive for both HLA-I and II. 12 patients were diagnosed with acute patients and were in complete remission before transplantation, and the other 2 patients with myelodysplastic syndrome received no treatment before transplantation. Modified busulfan/ cyclophosphamide (BU/CY) protocol was processed in all 14 patients. All patients received DSA desensitization treatments as below: spleen irradiation (before transplant, 200cGY in total, 50cGY/d × 4 days), plasmapheresis (before transplant, 40ml/kg × 2 doses), rituximab (before transplant, 375mg/m2 × 1 dose), immunoglobulin (before transplant, transplant day, 0.4g/kg). Results The average of median fluorescence intensity (MFI) were tested significantly decreased after transplantation (15628 vs 6889, P Conclusion Spleen irradiation combined with plasmapheresis, rituximab and immunoglobulin therapy can reduce the levels of anti-HLA DSAs, improving engraftment and survival after haplo-HSCT. No excess toxicity is observed. This protocol can help to improve the prognosis of DSA-positive haplo-HSCT patients, but further study proving the efficacy is still needed.

Objective To investigate the general characteristics and the category of myoclonic epilepsy in infancy (MEI) with or without afebrile generalized tonic-clonic seizures (GTCS). Methods Thirty-three children were retrospectively recruited from approximately 42,814 video-electroencephalogram (VEEG) recordings monitored in our department over last nearly 10 years. Myoclonic seizures (MS) must be identified by VEEG in all patients. The clinical, EEG features and outcome were analyzed among these patients. Results The 33 patients (25 boys and 8 girls) were divided into three groups: 11 patients with typical MEI; 16 patients with MEI experienced afebrile GTCS before MS onset; and 6 patients with MEI presented afebrile GTCS occurring concurrently with MS. No significant differences were found among the three groups, including gender distribution, family history, personal history of febrile seizures, the age at seizure onset and control, the duration of MS, the interval between age at onset and seizure control, the age at EEG normalization, the interval between seizure onset age and EEG normalization age and normal psychomotor development at the end of follow-up. More patients in group two and group three were controlled by two or three kinds of antiepileptic drugs compared with those in group one. Conclusions In this study, three groups of patients had similar clinical, EEG features and outcome. Afebrile GTCS was associated with a stronger cortical hyperexcitability. It was worth considering whether MEI with preceding or concurrent afebrile GTCS should be recognized as subgroups or different epileptic syndromes independent of MEI.

Creating a favorable thermal environment in an outdoor space is essential for attracting more occupants to outdoor areas and vitalizing a city. It is possible to study occupants’ needs in an outdoor thermal environment by observing their attendance and behaviors, since people may exhibit certain adaptive measures, such as seeking shade, using parasols, etc., “vote with their feet”, or even leave the space, if they feel uncomfortable. In order to investigate the influence of thermal environment on attendance and adaptive behaviors in outdoor spaces, in this study we carried out field campaigns in a university campus in a cold-climate city. The thermal environment was monitored, while surveys of thermal perceptions and observations of attendance and adaptive behaviors were conducted. Through the data analyses, it was found that the thermal environment had a great impact on the attendance of optional activities, but necessary activities were not influenced. The greatest influence on attendance came from air temperature. The influences of wind and humidity on attendance were found to be coupled with that of air temperature. Adaptive behaviors, such as seeking shade, using parasols, changing clothes, and changing the lengths of stay, were also greatly influenced by air temperature.

A numerical simulation research was carried out on vortex and sound pressure level of the butterfly valve in the flow process based on FLUENT, which analyzed the variation of the vorticity and sound pressure level at different opening angles. There was an inverse pressure gradient in the orifice formed by the butterfly plate and pipe, which caused partial particle reflux on the back of butterfly plate in flowing, thus formed the vortex. The vortex formed on the back of the butterfly plate was decreased gradually, with the increasing opening angle of the valve in opening process. The noise was generated by the vortex separated and rupture in flowing. And the sound pressure level on the back of butterfly plate was decreased with the increasing opening angle. At the same time, the vorticity and the maximum sound pressure level position moved from the center to the rotation center of butterfly plate in opening process. The expanding orifice formed by butterfly plate upstream and the pipe and the tapered orifice formed by butterfly plate downstream and the pipe had the different throttling action to the fluid, which made the sound pressure level of upstream was higher than that of downstream in symmetrical position. The vortex generated by the separation of boundary layer would cause vortex excited vibration between plate and fluid, and then resonance occurred. The studies were carried out in the vorticity and the sound pressure level on the downstream of butterfly plate, and the changing law of those was found. It would provide a basis theory for reducing noise and avoiding vortex vibration of butterfly valve.

Objective To elucidate the characteristics of the myoclonic seizures alone, or predominant myoclonus combined with generalized tonic-clonic seizures (GTCS) and/or absences, in early childhood, and discuss its classification. Methods Forty-two children were retrospectively recruited between January 2006 and June 2015. Results The mean age of seizure onset was 40.5 months. They were divided into 4 groups: myoclonic seizures alone; predominant myoclonus combined with GTCS; predominant myoclonus combined with absences; predominant myoclonus combined with both GTCS and absences. Interictal EEG showed generalized spike- or polyspike-wave discharges at 2–4 Hz. Seizures were controlled in 22 patients at a mean age of 60.5 months. The psychomotor development was normal (30/37) or mildly delayed (7/37). Conclusions We reported a cohort of patients with early childhood myoclonic epilepsy (ECME), with the following characteristics: Seizures started below 5 years old in otherwise normal children; Seizure types included myoclonic seizures alone or combined with GTCS and/or absences; Febrile or afebrile GTCS might appear firstly; Interictal EEG showed generalized spike- or polyspike-wave; Seizures usually were in remission before adolescence with normal development or mild cognitive or behavioral deficits in most. Significance ECME might be an independent epileptic syndrome not established by International League Against Epilepsy (ILAE) previously.

Objective To study the atonic elements combined or uncombined with epileptic spasms in infantile spasms. Methods The demographic data, clinical characteristics, electroencephalogram (EEG), and polyelectromyography (PEMG) features were analyzed in 12 infantile spasm patients with atonic elements. Results A total of 29 EEGs were recorded. Hypsarrhythmia or hypsarrhythmia variants were identified during interictal EEG. Insular or clustered epileptic spasms occurred in all. Three subtypes of atonic elements combined or uncombined with epileptic spasms (spasm-atonic, pure atonic, and atonic-spasm seizures) were observed electroclinically, which could present insularly or in cluster or altered with epileptic spasms in the same cluster. The ictal EEG showed generalized high-amplitude slow waves presenting alone or combined with other patterns. The corresponding PEMG showed an obvious electrical silence alone or preceding or following a crescendo-decrescendo pattern generated from myoelectric burst. Conclusions Atonic elements combined or uncombined with epileptic spasms was a newly noticed phenomenon in infantile spasms, which was artificially divided into three subtypes here. It might be a variant of epileptic spasms or a unique seizure type. Significance Atonic elements combined or uncombined with epileptic spasms was a previously ignored phenomenon in infantile spasms, which should be seriously considered in clinical practice.

Purpose: To evaluate the effects of a single oral dose of pyridoxine on lysine metabolites including α-aminoadipic semialdehyde (a-AASA), piperideine-6-carboxylate (P6C), the sum of AASA and P6C (AASA-P6C), pipecolic acid (PA), and α-aminoadipic acid (α-AAA) in PDE patients. Methods: The lysine metabolites of 15 patients with molecularly confirmed PDE were detected before and 4 h after taking a single oral dose of pyridoxine, respectively, using liquid chromatography-mass spectrometry (LC-MS/MS) method. Five types of samples were freshly prepared, including plasma, serum, dried blood spots (DBS), urine, and dried urine spots (DUS). Results: All the patients had been treated with long-term oral pyridoxine for several months to years, with doses of 30–360 mg/d. The concentrations of a-AASA, P6C, AASA-P6C, PA, and a-AAA before and after taking a single oral dose of pyridoxine for the same analyte detected in the same type of sample varied among patients. The mean concentrations increased in almost all the metabolites after taking an oral dose of pyridoxine, with or without statistical significance. Whereas, the metabolites concentrations might increase or decrease among different patients, or in different samples of the same patient, without a regular tendency. There was no statistical correlation between the concentrations before and after taking pyridoxine in the same type of sample for most metabolites. Conclusions: No obvious relationship between the metabolite levels or concentration differences and the age, pyridoxine dose (a single oral dose and long-term maintenance dose), duration of treatment, or neurodevelopmental phenotype was found at present study. The large individual differences among patients, probably affected by various genotypes, leading to quite different effects of pyridoxine on the change degree of metabolites concentrations. Our study suggested that long-term pyridoxine treatment could control seizures rather than getting toxic lysine metabolites such as a-AASA and P6C back to normal. In the future, more therapies should be focused to alleviate the metabolites accumulation and further improve the prognosis of PDE.

Background and purpose The aim was to determine the electroclinical findings in benign childhood focal epilepsy with vertex spikes (BEVS) with epileptic negative myoclonus (ENM) restricted to the lower limbs. Methods The electroencephalogram database of Peking University First Hospital and medical records of patients with BEVS and ENM restricted to the lower limbs were reviewed. Results Twenty-seven patients with BEVS had ENM restricted to the lower limbs. Twelve started as ENM restricted to the lower limbs. The age at seizure onset ranged from 1.5 to 4.8 years. During the course, half of the 12 patients developed focal sensorimotor seizures and then were diagnosed as benign childhood epilepsy with centrotemporal spikes (BECTS), with BEVS (four cases) and without BEVS (two cases). Five of them had electrical status epilepticus during sleep (ESES) and met the diagnostic criteria of atypical benign partial epilepsy (ABPE). Fifteen of the 27 patients had ENM restricted to the lower limbs during the course. The age at seizure onset ranged from 1.3 to 9.8 years. All had ESES and were diagnosed as ABPE, 11 as ABPE with BEVS and four as ABPE evolving into BEVS. Conclusions Benign childhood focal epilepsy with vertex spikes (BEVS) might represent a specific epileptic syndrome of the continuum of benign childhood focal epilepsy. ENM restricted to the lower limbs was a special phenomenon in BEVS. BEVS could overlap with BECTS or evolve into BECTS and further into ABPE and vice versa. Ignorance of vertex spikes with associated ENM restricted to the lower limbs might lead to a misunderstanding of BEVS, a specific type of benign childhood focal epilepsy.

223 Background: Definitive or palliative chemoradiation therapy has been employed in the management of esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitor has improved outcomes in metastatic stage IV pts. Here we report the addition of KN046, a PD-L1/CTLA-4 bispecific antibody, to concurrent chemoradiation (CRT) therapy to determine the safety and efficacy of this approach (ChiCTR2000031544). Methods: Pts with recurrent or metastatic ESCC, not been treated by CRT or other systemic treatment within 6 months, were recruited and received palliative CRT consisting of cisplatin (75 mg/m2 IV Q3W for 4~6 cycles), paclitaxel (135~175 mg/m2 IV Q3W for 4-6 cycles) and radiation (SBRT or conventional and dose are determined at the investigator’s discretion according to institutional standard). KN046 at ascending doses of 1, 3 and 5 mg/kg Q3W was added within 7-14 days after the completion of radiation therapy (RT) and concurrently with chemotherapy, followed by KN046 Q2W maintenance. Dose limiting toxicities (DLTs) were assessed for the first treatment cycle of KN046. Anti-tumor activity was assessed according to RECIST 1.1 every 6 weeks within the first year, and every 12 weeks thereafter. Results: As of June 30, 2020, 18 subjects were enrolled and received KN046 treatment (1mg/kg, n = 3; 3mg/kg, n = 11; 5mg/kg, n = 4). The median KN046 exposure was 11.5 weeks. No DLT was reported. 3 (16.7%) subjects experienced Grade 3, KN046 related adverse events (1 Grade 3 pneumonitis and 2 Grade 3 colitis recovered after steroid and antibiotic Tx). For 18 evaluable subjects, the disease control rate and objective response rate were 94.4% and 44.4%, respectively. DOR and PFS were not matured yet as of cutoff date. At 3 mg/kg, objective response was observed in 5 out of 9 subjects (55.6%) with measurable disease and disease control rate was 100%; 7/9 (77.8%) subjects experienced further tumor reduction after initiation of KN046 treatment. It is worth to note that, 2 subjects at 3mg/kg achieved complete response after receiving KN046 treatment. Conclusions: The addition of KN046 to CRT was well tolerated and showed promising efficacy signal in recurrent or metastatic ESCC. This pilot study enables further investigation of a new treatment modality of KN046 with CRT in this detrimental disease with poor prognosis. Clinical trial information: 2000031544.

The optimization of installation of baffles in a UV rector is investigated. The flow field is obtained by solving continuity and momentum equations. The radiation intensity is solved by a radiative transfer equation. The UV dosage is obtained by coupling the Lagrangian particle tracking approach with the solved radiation intensity. One unbaffled reactor and two baffled reactors are simulated. The baffled UV reactor A has the longest residence time and the lowest UV dosage while the baffled UV reactor B has the relatively longer residence time and the highest UV dosage. The unbaffled reactor performs between the two baffled reactors considering residence time and UV dosage. The baffled UV reactor B enables the best disinfection of microorganisms. The results demonstrate that optimization should consider flow field and radiation intensity simultaneously.

Purpose Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder caused by mutations of the ALDH7A1 gene. We aimed to analyze the relations between the clinical diagnosis and treatment of PDE and ALDH7A1 gene mutations in Chinese PDE patients. Methods The clinical manifestations, diagnosis and treatment were observed in a cohort of PDE patients with early onset of seizure. Video-electroencephalogram (VEEG) and magnetic resonance imaging (MRI) were performed. The mutation of ALDH7A1 gene was analyzed. Results Of eight patients, six were males and two were females. Age of seizure onset ranged from 1 to 100 days and 75% patients presented with seizures in the neonatal period. All patients showed different degrees of developmental delay. EEGs showed focal or multifocal discharges, or were normal. Molecular analysis revealed 10 ALDH7A1 mutations, including 2 splice site mutations. Five patients had mutation at IVS11+1G>A site, six patients had missense mutations, one with nonsense mutation and another patient had 9-bp genomic deletion mutation. Among them, two mutations were first time reported. Conclusions Seizure onset was in neonatal or early infantile period in our PDE patients. Early recognition and diagnosis of the disease is necessary for early intervention and improve cognitive development in the later life. In this study, on the molecular level, we also identified the splice site mutation IVS11+1G>A as a high prevalence mutation site with a frequency of 31.25% (5 of 16 alleles) in Chinese PDE patients.

The development of renewable energy (RE), due to the ever-growing increase in energy demand and the negative impact of fossil fuels on the environment, has become an increasingly important development area at present, with broad prospects. However, compared with traditional energy projects, RE projects often involve long life cycles, complex uncertainties, and they exert for-reaching impacts on risk management. The Citespace software was used to systematically summarize the research hotspots development, and frontiers of researches on the risk management in renewable energy projects in China from 1997 to 2018. Results show that the overall evolutionary trend of risk management in renewable energy field is from RM practice to technology driven integration system. Based on the trend, knowledge gaps and future research directions were found out and discussed.

Objective In this study, we observed the effects of one-time exhaustive exercise on the grip strength, the time of grabbing, and the changes of the electromyography (EMG) of the hind limb flexor muscles and the flexor elbow muscles of the forelimbs, and revealed the effects of exercise fatigue on the peripheral motor drive level. Methods Male SD rats finished exhaustive fatigue exercise. A one-time exhaustive treadmill exercise fatigue model was established after one-week adaptive training in rats. The model was established by the modified Bedford incremental load motion program of the laboratory. The load is divided into 3 levels: the first stage movement speed 8.2 m/min, exercise time 15 min; second stage speed 15 m/min, exercise time 15 min; third stage speed at 20 m/min, exercise to exhaustion. At the same time, a miniature wireless acceleration sensor (18g) was worn in the tail of the rat to monitor the acceleration change of the running direction of the rat while running on the running platform. Three consecutive parallel experiments were performed using a rat grip tester (BioSEB GS3) to measure and compare the maximal muscle strength changes of the limbs before and after exercise fatigue in rats. Compared the static contraction of the rat muscle before and after exercise fatigue to overcome the length of time and gravity of the rod, and evaluated the muscle endurance after training the rats to learn to grab the rod. The EMG,square root amplitude (maxRMS), frequency domain analysis of EMG median frequency (MDF) and mean frequency (MPF) of the hind limb flexor and the forelimb flexor muscles (EMG) was measured by the Italian BTS FREEEMG ultra-miniature wireless surface electromyography tester to predict peripheral muscle tone and drive level. Results 1) The maximum holding force of the rat in resting state was 68.53 N/Kg, and the gripping force was significantly decreased (p

This study describes the pharmacokinetics of vitacoxib in healthy rabbits following administration of 10 mg/kg intravenous (i.v.) and 10 mg/kg oral. Twelve New Zealand white rabbits were randomly allocated to two equally sized treatment groups. Blood samples were collected at predetermined times from 0 to 36 hr after treatment. Plasma drug concentrations were determined using UPLC-MS/MS. Pharmacokinetic analysis was completed using noncompartmental methods via WinNonlin™ 6.4 software. The mean concentration area under curve (AUClast ) for vitacoxib was determined to be 11.0 ± 4.37 μg hr/ml for i.v. administration and 2.82 ± 0.98 μg hr/ml for oral administration. The elimination half-life (T1/2λz ) was 6.30 ± 2.44 and 6.30 ± 1.19 hr for the i.v. and oral route, respectively. The Cmax (maximum plasma concentration) and Tmax (time to reach the observed maximum (peak) concentration at steady-state) following oral application were 189 ± 83.1 ng/ml and 6.58 ± 3.41 hr, respectively. Mean residence time (MRTlast ) following i.v. injection was 6.91 ± 3.22 and 11.7 ± 2.12 hr after oral administration. The mean bioavailability of oral administration was calculated to be 25.6%. No adverse effects were observed in any rabbit. Further studies characterizing the pharmacodynamics of vitacoxib are required to develop a formulation of vitacoxib for rabbits.

Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included “generalized tonic-clonic seizures (GTCS)” in 15, “partial secondarily GTCS (PGTCS)” in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

The aim of this paper was to develop a model that can characterize the actual micropore structures in coal and gain an in-depth insight into water’s seepage rules in coal pores under different pressure gradients from a microscopic perspective. To achieve this goal, long-flame coals were first scanned by an X-ray 3D microscope; then, through a representative elementary volume (REV) analysis, the optimal side length was determined to be 60 μm; subsequently, by using Avizo software, the coal’s micropore structures were acquired. Considering that the porosity varies in the same coal sample, this study selected four regions in the sample for an in-depth analysis. Moreover, numerical simulations on water’s seepage behaviors in coal under 30 different pressure gradients were performed. The results show that (1) the variation of the simulated seepage velocity and pressure gradient accorded with Forchheimer’s high-velocity nonlinear seepage rules; (2) the permeability did not necessarily increase with the increase of the effective porosity; (3) in the same model, under different pressure gradients, the average seepage pressure decreased gradually, while the average seepage velocity and average mass flow varied greatly with the increase of the seepage length; and (4) under the same pressure gradient, the increase of the average mass flow from the inlet to the outlet became more significant under a higher inlet pressure.

A 2.5 GHz direct digital frequency synthesizer (DDS) in 0.18 μm CMOS is presented. This DDS has a 32 bit phase word and uses an optimized excess-four Coordinated Rotation Digital Computer (CORDIC) arithmetic to achieve phase to amplitude conversion (SFDR as 113 dB). A time interleaved architecture is used to achieve 2.5 GHz high speed. Fundamental principle of CORDIC and four practical considerations in circuit implementation are also presented. This 2.5 GHz DDS (with an embedded 14 bit current steering DAC) is implemented in a 0.18 μm CMOS technology, occupies 4.6 mm × 4.2 mm including bond pads. Measured performance is SFDR >58 dB (spur cancelled) and narrowband SFDR >84 dB for output signal frequencies up to 1 GHz.

Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant and free radical scavenger that may have therapeutic applications for the treatment of many disorders. Radiation therapy is widely used for the treatment of various types of cancers; however, radiation-induced skin injury remains a serious concern. EGCG has not yet been reported as protecting skin cells against ionizing radiation. In the present study, we investigated whether EGCG confers cytoprotection against ionizing radiation. We found that, compared with the control, pretreatment with EGCG significantly enhanced the viability of human skin cells that were irradiated with X-rays, and decreased apoptosis induced by X-ray irradiation. Mito-Tracker assay showed that EGCG suppressed the damage to mitochondria induced by ionizing radiation via upregulation of SOD2. Reactive oxygen species (ROS) in HaCaT cells were significantly reduced when pretreated with EGCG before irradiation. Radiation-induced γH2AX foci, which are representative of DNA double-strand breaks, were decreased by pretreatment with EGCG. Furthermore, EGCG induced the expression of the cytoprotective molecule heme oxygenase-1 (HO-1) in a dose-dependent manner via transcriptional activation. HO-1 knockdown or treatment with the HO-1 inhibitor tin protoporphyrin (SnPPIX) reversed the protective role of EGCG, indicating an important role for HO-1. These results suggest that EGCG offers a new strategy for protecting skin against ionizing radiation.

To analyze the clinical and genetic characteristics of Chinese patients with pyridox(am)ine-5'-phosphate oxidase (PNPO) deficiency. The clinical presentations and the responses to treatments were analyzed in 4 patients. Blood and urinary metabolic screenings, electroencephalogram (EEG), brain magnetic resonance imaging (MRI) and epilepsy-related genes detection were performed in all patients. Patient 1 and 2 were identical twin brothers, who were born at 35+5 w gestation with a sign of encephalopathy. Their seizures started within the first day and could not be controlled by pyridoxine or pyridoxal-5'-phosphate (PLP) completely. Patient 3 presented seizures at 5 months, responding well to pyridoxine. Seizures in patient 4 began at 40 days after birth and were controlled by valproic acid and topiramate. EEG showed atypical hypsarrhythmia or multifocal epileptiform discharges in 3 patients, and showed normality in patient 4. MRI showed nonspecific abnormality or normality. Blood metabolic screening showed multiple amino acids level abnormalities in all cases. Urinary metabolic screening showed vanillactic acid prominently elevated in 3 patients. Genetic analysis revealed 5 mutations of PNPO, three of which were novel. The mutation c.445_448del was carried by the twins and patient 3. Assessment of psychomotor development indicated severe delay in 3 patients and borderline to mild delay in patient 3. This is the first time to report patients with PNPO deficiency diagnosed by gene analysis in China. The novel clinical characteristics and novel mutations found here expanded the phenotypes and genotypes of this disease. Further, the frameshift mutation c.445_448del might be high prevalence in PNPO deficiency in Chinese patients.

Infantile spasms (IS) was an epileptic disease with varied treatment widely among clinicians. Here, we aimed to compare and analyze the clinical characteristics of IS response to pyridoxine or topiramate monotherapy (TPM control IS). The clinical manifestations, treatment processes and outcomes were analyzed in 11 pyridoxine responsive IS and 17 TPM-control IS. Of the 11 patients with pyridoxine responsive IS, nine were cryptogenic/idiopathic. Age of seizure onset was 5.36 ± 1.48 months. Spasms were controlled within a week in most of the patients. At the last follow-up, EEG returned to normal in 8. Psychomotor development was normal in 6, mild delay in 3, severe delay in 2. Of the 17 patients with TPM-control IS, 10 were cryptogenic/idiopathic. The age of seizure onset was 5.58 ± 2.09 months. All patients were controlled within a month. At the last follow-up, EEG was normal in 10. Psychomotor development was normal in 8, mild delay in 5, severe delay in 4. Genetic analysis did not show any meaningful results. The clinical characteristics and disease courses of pyridoxine responsive IS and TPM-control IS were similar, which possibly clued for a same pathogenic mechanism. Pyridoxine should be tried first in all IS patients, even in symptomatic cases. If patients were not responsive to pyridoxine, TPM could be tried.

Immunization policy strives to promote vaccination coverage in population-wide social network of community by encouraging vaccination for a group of vulnerable population and accelerating health awareness diffusion in the personal networks of vaccinators. In order to determine the relative prognostic importance of the various factors predisposing to vaccination decision-making of individual and analyze diffusion of innovation in immunization policy adoption on overall social network architecture, this paper carries out an agent-based modeling (ABM) approach to construct a pandemic immunization simulation model for providing insights into immunization behavior modification of individual during social interaction in community. Simulation results give decision support to assess the relative impact of healthcare services for pandemic control and suggest that reasonable immunization policies tend to promote individual immunization behavior. Moreover, propagation path of immunization awareness inside the community can be reviewed in depth in the simulation result.

To predict the survival of appendiceal mucinous adenocarcinoma (AMA) by prognostic nomogram. A total of 3234 patients with AMA were collected from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2015. Univariate and multivariate Cox proportional hazards (PH) regression analyses were used to generate independent prognostic factors. These variables were included in the nomogram to predict overall survival (OS) and disease-specific survival (DSS) at 1-, 3-, and 5- years. These data are validated both internally and externally. The consistency index (C-index) and calibration chart were used to estimate the accuracy of the nomogram. The study cohort was randomly divided into the training (n = 2155) and validation group (n = 1799). According to univariate and multivariate analyses, age at diagnosis, marital status, sex, histological differentiation, SEER extent of disease, number of local lymph nodes examined, whether they were positive, and surgical methods were independent prognostic factors for OS and DSS. These factors were incorporated into the nomogram. Internal validation in the training cohort showed that the C-index values for nomogram predictions of OS and DSS were 0.73 (95% CI 0.70–0.76) and 0.77 (95% CI 0.73–0.81), respectively. Similarly, the corresponding C-index values in the external validation cohort were 0.76 (95% CI 0.70–0.81) and 0.75 (95% CI 0.71–0.80). The Calibration plots revealed that the actual survival and nomogram prediction had a good consistency. Build a nomogram in the SEER database to predict OS and DSS in patients with AMA. It can provide accurate and personalised survival prediction for clinicians and patients.

Objective Hyperphosphatasia mental retardation syndrome (Mabry syndrome) is an autosomal recessive disorder. We aim to analyze two Chinese patients diagnosed as Mabry syndrome. Methods The clinical manifestations, diagnosis and treatment were observed in two patients. Genetic analysis including PIGV and PIGO was examined. Results Two patients were diagnosed as Mabry syndrome clinically and genetically. Developmental delay, hyperphosphatasia and seizures were presented in both of them. Typical facial dysmorphism and hypoplastic terminal phalanges were only found in one. Some novel presentations including congenital laryngeal cartilage softening, inguinal hernia, broken palmprint, optic atrophy and skeleton dysplasia such as carpal age delay and metaphysis anomalies were observed in two patients. Molecular genetic analysis revealed compound heterozygous mutations of PIGV or PIGO in our patients, including c.615C>G (p.Asn205Lys) and c.854A>G (p.Tyr285Cys) of PIGV in patient 1, and c.458T>C (p.Phe153Ser) and c.1355_1356del (p.Ala452Glyfs*52) of PIGO in patient 2. Additionally, a heterozygous c.2926G>A (Asp976Asn) of PCDH19 was identified in patient with PIGV mutations, the causative gene of Epilepsy and mental retardation limited to females (EFMR). Conclusion To our best knowledge, this is the first time to report Chinese patients diagnosed as Mabry syndrome. For the PCDH19 mutation in our patient carrying PIGV mutations, due to lacking characteristics of EFMR and the ambiguity results in pathogenicity analysis, we were not sure how much pathogenic role PCDH19 mutation shared with PIGV mutations in this disease. The novel mutations of PIGV and PIGO, and novel clinical manifestations reported here might expand the genotype and phenotype spectrum of Mabry syndrome.

Nowadays, time series prediction is a hot issue in machine learning, however, how to predict time series fast and accurately remains extremely challengeable. In this paper, we proposed an Improved Error Minimized Extreme Learning Machine (IEM-ELM) algorithm which has better accuracy and prediction on change in direction (POCID) compared with Error Minimized Extreme Learning Machine (EM-ELM) for stock price prediction, meanwhile we implement the Online Sequential algorithm based on IEM-ELM (OSIEM-ELM) which fully inherits the merits of IEM-ELM. The performance of IEM-ELM and OSIEM-ELM are evaluated and compared with EM-ELM and OSEM-ELM respectively, and the experiments are carried out on three stock datasets, experimental results show that IEM-ELM and OSIEM-ELM produces better POCID performance than EM-ELM and OSEM-ELM at fast learning speed.

This paper presents a new method for monocular position-pose measurement, which is based on the circular and linear features. The method improves the single circle based monocular position-pose measurement by recognizing the detectable circular structure and linear edge of target. First, according to the projection of the circle on the image, two sets of position-pose solutions are calculated, which do not contain the roll angle. Then, the roll angle is solved by utilizing the linear feature. The upper endpoint of the linear edge is selected as a reference point to eliminate the ambiguity. Finally, the simulation model and physical experimental platform are established to verify the validity and accuracy of the proposed method. Experimental results indicate that the proposed method can obtain the roll angle accurately and eliminate the ambiguity effectively. In case of noise and detection error, the results still remain accurate, which indicates that the proposed method is robust and has great application value in monocular position-pose measurement.