An Efficient Cervical Whole Slide Image Analysis Framework Based on Multi-scale Semantic and Spatial Deep Features

Digital gigapixel whole slide image (WSI) is widely used in clinical diagnosis, and automated WSI analysis is key for computer-aided diagnosis. Currently, analyzing the integrated descriptor of probabilities or feature maps from massive local patches encoded by ResNet classifier is the main manner for WSI-level prediction. Feature representations of the sparse and tiny lesion cells in cervical slides, however, are still challengeable for the under-promoted upstream encoders, while the unused spatial representations of cervical cells are the available features to supply the semantics analysis. As well as patches sampling with overlap and repetitive processing incur the inefficiency and the unpredictable side effect. This study designs a novel inline connection network (InCNet) by enriching the multi-scale connectivity to build the lightweight model named You Only Look Cytopathology Once (YOLCO) with the additional supervision of spatial information. The proposed model allows the input size enlarged to megapixel that can stitch the WSI without any overlap by the average repeats decreased from $10^3\sim10^4$ to $10^1\sim10^2$ for collecting features and predictions at two scales. Based on Transformer for classifying the integrated multi-scale multi-task features, the experimental results appear $0.872$ AUC score better and $2.51\times$ faster than the best conventional method in WSI classification on multicohort datasets of 2,019 slides from four scanning devices.Comment: 16 pages, 8 figures, already submitted to Medical Image Analysi

A Single Multi-Task Deep Neural Network with a Multi-Scale Feature Aggregation Mechanism for Manipulation Relationship Reasoning in Robotic Grasping

Grasping specific objects in complex and irregularly stacked scenes is still challenging for robotics. Because the robot is not only required to identify the object's grasping posture but also needs to reason the manipulation relationship between the objects. In this paper, we propose a manipulation relationship reasoning network with a multi-scale feature aggregation (MSFA) mechanism for robot grasping tasks. MSFA aggregates high-level semantic information and low-level spatial information in a cross-scale connection way to improve the generalization ability of the model. Furthermore, to improve the accuracy, we propose to use intersection features with rich location priors for manipulation relationship reasoning. Experiments are validated in VMRD datasets and real environments, respectively. The experimental results demonstrate that our proposed method can accurately predict the manipulation relationship between objects in the scene of multi-object stacking. Compared with previous methods, it significantly improves reasoning speed and accuracy

Genetic Engineering of Starch Biosynthesis in Maize Seeds for Efficient Enzymatic Digestion of Starch during Bioethanol Production

Maize accumulates large amounts of starch in seeds which have been used as food for human and animals. Maize starch is an importantly industrial raw material for bioethanol production. One critical step in bioethanol production is degrading starch to oligosaccharides and glucose by alpha-amylase and glucoamylase. This step usually requires high temperature and additional equipment, leading to an increased production cost. Currently, there remains a lack of specially designed maize cultivars with optimized starch (amylose and amylopectin) compositions for bioethanol production. We discussed the features of starch granules suitable for efficient enzymatic digestion. Thus far, great advances have been made in molecular characterization of the key proteins involved in starch metabolism in maize seeds. The review explores how these proteins affect starch metabolism pathway, especially in controlling the composition, size and features of starch. We highlight the roles of key enzymes in controlling amylose/amylopectin ratio and granules architecture. Based on current technological process of bioethanol production using maize starch, we propose that several key enzymes can be modified in abundance or activities via genetic engineering to synthesize easily degraded starch granules in maize seeds. The review provides a clue for developing special maize cultivars as raw material in the bioethanol industry

Tumor microenvironment in pancreatic ductal adenocarcinoma: Implications in immunotherapy

Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers. Surgical resection is the only curable treatment option, but it is available for only a small fraction of patients at the time of diagnosis. With current therapeutic regimens, the average 5-year survival rate is less than 10% in pancreatic cancer patients. Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage. However, its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer. Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer. In this review, we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer

Differentiation of canine distemper virus isolates in fur animals from various vaccine strains by reverse transcription-polymerase chain reaction-restriction fragment length polymorphism according to phylogenetic relations in china

In order to effectively identify the vaccine and field strains of Canine distemper virus (CDV), a new differential diagnostic test has been developed based on reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). We selected an 829 bp fragment of the nucleoprotein (N) gene of CDV. By RFLP analysis using BamHI, field isolates were distinguishable from the vaccine strains. Two fragments were obtained from the vaccine strains by RT-PCR-RFLP analysis while three were observed in the field strains. An 829 nucleotide region of the CDV N gene was analyzed in 19 CDV field strains isolated from minks, raccoon dogs and foxes in China between 2005 and 2007. The results suggest this method is precise, accurate and efficient. It was also determined that three different genotypes exist in CDV field strains in fur animal herds of the north of China, most of which belong to Asian type. Mutated field strains, JSY06-R1, JSY06-R2 and JDH07-F1 also exist in Northern China, but are most closely related to the standard virulent strain A75/17, designated in Arctic and America-2 genetype in the present study, respectively

4,10-Bis(pyridin-2-ylmeth­yl)-1,7-dithia-4,10-diazo­niacyclo­dodecane bis(perchlorate)

The asymmetric unit of the title compound C20H30N4S2 +. 2ClO4 − comprises one macrocyclic cation and two perchlorate anions. In the cation, one of the protonated H atoms bound to the amide N atom is involved in an intra­molecular N—H⋯N hydrogen bond. The O atoms in the two perchlorate anions are disordered over two sets of sites with occupancy ratios of 0.65 (3):0.35 (3) and 0.640 (15):0.360 (15)

Development of Diagnostic SCAR Markers for Genomic DNA Amplifications in Breast Carcinoma by DNA Cloning of High-GC RAMP-PCR Fragments

Cancer is genetically heterogeneous regarding to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers, including DNA markers, is used in determining genomic instability, molecular subtype determination and disease prognosis, and estimating sensitivity to different drugs in clinical practice. In a previous study, we developed highly effective DNA markers using improved random amplified polymorphic DNA (RAPD) with high-GC primers, which is a valuable approach for the genetic authentication of medicinal plants. In this study, we applied this effective DNA marker technique to generate genetic fingerprints that detect genomic alterations in human breast cancer tissues and then developed sequence-characterized amplified region (SCAR) markers. Three SCAR markers (BC10-1, BC13-4 and BC31-2) had high levels of genomic DNA amplification in breast cancer. The PHKG2 and RNF40 genes are either overlapping or close to the sequences of SCAR marker BC13-4, while SCAR marker BC10-1 is in the intron and overlap the DPEP1 gene, suggesting that alterations in the expression of these genes could contribute to cancer progression. Screening of breast cancer cell lines showed that the mRNA expression levels for the PHKG2 and DPEP1 were lower in non-tumorigenic mammary epithelial cell MCF10A, but elevated in other cell lines. The DPEP1 mRNA level in invasive ductal carcinoma specimens was significantly higher than that of the adjacent normal tissues in women. Taken together, high-GC RAMP-PCR provides greater efficacy in measuring genomic DNA amplifications, deletion or copy number variations. Furthermore, SCAR markers BC10-1 and BC13-4 might be useful diagnostic markers for breast cancer carcinomas

Newborn Screening for Methylmalonic Acidemia in a Chinese Population: Molecular Genetic Confirmation and Genotype Phenotype Correlations

Background: Methylmalonic acidemia (MMA) incidence was evaluated based on newborn screening in Xuzhou from November 2015 to December 2017, and the clinical, biochemical and molecular characteristics of patients with MMA harboring MMACHC and MUT mutations were summarized.Methods: During the study, 236,368 newborns were screened for MMA by tandem mass spectrometry (MS/MS) in the Maternity and Child Health Care Hospital of Xuzhou. C3, C3/C2 and methionine, and tHcy if necessary, were measured during the first screening. Blood samples from the infants and/or their family members were used for DNA analysis. The entire coding regions of the MMACHC and MUT genes associated with MMA were sequenced by DNA MassARRAY and next-generation sequencing (NGS).Results: Eleven patients with MMACHC mutations and three with MUT mutations were identified among the 236,368 screened newborns; the estimated total incidence of MMA was 1:16,883. Among the MMA patients, two died of infection-triggered metabolic crisis approximately 3 months after birth. All the patients identified had two mutant alleles except for one individual with early-onset disease. The most common MMACHC mutation was c.609G > A. The laboratory levels of C3 and C3/C2 were elevated in MMA individuals compared to other infants. Importantly, we demonstrate that accelerated C2 degradation is related to air temperature and humidity.Conclusion: Our study reports the clinical characteristics of MMA and diagnosis through MS/MS and NGS. There was a higher incidence of MMA with homocysteinemia than of isolated MMA in Xuzhou. Insight from this study may help explain the high false-positive rate of MMA in summer