Skin Lesion Segmentation with C-UNet.

Malignant melanoma is one of the leading cancers around the world. It is critical to timely diagnose and treat melanoma to improve patient survival. This paper proposes a deep learning model C-UNet for skin lesion segmentation. The C-UNet incorporates the Inception-like convolutional block, the recurrent convolutional block and dilated convolutional layers. We also apply a finetune technique using Dice loss after training the model with commonly used cross-entropy loss. The conditional random field was used to further smooth predicted label maps. Experiment results show that the proposed method achieves better accuracy and more robust segmentation results than UNet.

From Deep Learning Towards Finding Skin Lesion Biomarkers.

Melanoma is a type of skin cancer with the most rapidly increasing incidence. Early detection of melanoma using dermoscopy images significantly increases patients' survival rate. However, accurately classifying skin lesions by eye, especially in the early stage of melanoma, is extremely challenging for the dermatologists. Hence, the discovery of reliable biomarkers will be meaningful for melanoma diagnosis. In recent years, the value of deep learning empowered computer-assisted diagnose has been shown in biomedical imaging-based decision making. However, much deep learning research focuses on improving disease detection accuracy but not understanding the features deep learning use to determine the evidence of pathology. We aim to make sure the features used by deep learning methods are the reasonable clinical features for skin lesions diagnosis, rather than artifacts. Further, we aim to discover new biomarkers, which may not have been included in clinical criteria but do make sense to the dermatologists. Our proposed pipeline can find biomarkers for identifying different lesions. The patterns are agreed with dermatologists. Surprisingly, we find surround skins also can be used as evidence for skin lesion diagnosis, which has not been included in traditional diagnosis rules. The biomarkers discovered from deep learning classifier can be significant and useful to guide clinical diagnosis.

A role for bacterial urease in gut dysbiosis and Crohn's disease.

Gut dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn's disease and found an association between disease severity, gut dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using 15N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gut microbiota where it was used for amino acid synthesis. Inoculation of a conventional murine host (pretreated with antibiotics and polyethylene glycol) with commensal Escherichia coli engineered to express urease led to dysbiosis of the gut microbiota, resulting in a predominance of Proteobacteria species. This was associated with a worsening of immune-mediated colitis in these animals. A potential role for altered urease expression and nitrogen flux in the development of gut dysbiosis suggests that bacterial urease may be a potential therapeutic target for inflammatory bowel diseases.

EUS-guided liver biopsy provides diagnostic samples comparable with those via the percutaneous or transjugular route.

BACKGROUND AND AIMS: Liver biopsy (LB) traditionally has been performed via a percutaneous (PC), transjugular (TJ), or surgical approach. EUS-guided LB (EUS-LB) is an emerging method that has shown promise in terms of tissue yield and procedural safety. Comparison of histologic yield of EUS-LB with other methods of LB has not been done. This study aimed to compare tissue yield of different LB methods. METHODS: EUS-LB, TJ-LB, and PC-LB were identified retrospectively. EUS-LB was obtained via transgastric and transduodenal biopsy, or via transgastric (left lobe) biopsy alone using a 19-gauge FNA needle (non-Trucut). TJ-LB specimens were obtained with an 18- or 19-gauge needle, and PC-LB specimens with an 18- or 20-gauge needle. Stained slides were digitized on a whole slide scanner, and the total specimen length (TSL) and the count of complete portal triads (CPTs) were determined. Comparisons of TSL and CPT among the 3 groups were done with Wilcoxon rank sum tests. RESULTS: Wilcoxon rank sum tests indicated that EUS-LB of both liver regions produced significantly more tissue in terms of both TSL and CPTs compared with a PC-LB (P = .0000 and .0006). EUS-LB produced significantly longer TSL than TJ-LB (P = .01) and similar CPTs (P = .22). Those EUS-LB cases in which the left lobe only was sampled were not statistically different compared with PC-LB and TJ-LB. CONCLUSION: EUS-guided-LB produces specimens at least comparable to, and in some cases better than, PC-LB or TJ-LB. Widely separated liver regions can be easily sampled, which may have some benefit. The role of EUS-LB is likely to increase in the future.

Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.

Abnormal composition of intestinal bacteria--"dysbiosis"-is characteristic of Crohn's disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn's disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments.

Endoscopic ultrasound-guided liver biopsy: a multicenter experience.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided (EUS) liver biopsy (LB) is proposed as a newer method that offers several advantages over existing techniques for sampling liver tissue. This study evaluated the diagnostic yield of EUS-LB as the primary outcome measure. In addition, the safety of the technique in a large patient cohort was assessed. PATIENTS AND METHODS: Patients undergoing EUS for evaluation of elevated liver enzymes or hepatic disease were included in this prospective, non-randomized, multicenter study. EUS-LB was performed with EUS-fine needle aspiration (FNA; 19-gauge needle). Tissue was formalin-fixed and stained with hematoxylin and eosin, and trichrome. Using a microscope micrometer, specimen length was measured and the number of complete portal triads (CPTs) were counted. The main outcome measure was to assess the diagnostic yield of EUS-LB, and to monitor for any procedure-related complications. RESULTS: Patients (110; median age, 53 years; 62 women) underwent EUS-LB at eight centers. The indication was abnormal liver enzymes in 96 patients. LB specimens sufficient for pathological diagnosis were obtained in 108 of 110 patients (98 %). The overall tissue yield from 110 patients was a median aggregate length of 38 mm (range, 0 - 203), with median of 14 CPTs (range, 0 - 68). There was no statistical difference in the yield between bilobar, left lobe only, or right lobe only biopsies. There was one complication (0.9 %) where self-limited bleeding occurred in a coagulopathic and thrombocytopenic patient. This complication was managed conservatively. CONCLUSIONS: EUS-guided LB was a safe technique that yields tissue adequate for diagnosis among 98 % of patients evaluated.

Comparative Effectiveness of Nutritional and Biological Therapy in North American Children with Active Crohn's Disease.

BACKGROUND: Therapeutic targets in pediatric Crohn's disease include symptoms, quality of life (QOL), and mucosal healing. Although partial enteral nutrition (PEN), exclusive enteral nutritional (EEN), and anti-tumor necrosis factor alpha (anti-TNF) therapy all improve symptoms, the comparative effectiveness of these approaches to improve QOL and achieve mucosal healing has not been assessed prospectively. METHODS: In a prospective study of children initiating PEN, EEN, or anti-TNF therapy for Crohn's disease, we compared clinical outcomes using the Pediatric Crohn's Disease Activity Index (PCDAI), QOL (IMPACT score), and mucosal healing as estimated by fecal calprotectin (FCP). PCDAI, IMPACT, FCP, and diet (prompted 24-h recall) were measured at baseline and after 8 weeks of therapy. RESULTS: We enrolled 90 children with active Crohn's disease (PCDAI, 33.7 ± 13.7; and FCP, 976 ± 754), of whom 52 were treated with anti-TNF, 22 with EEN, and 16 with PEN plus ad lib diet. Clinical response (PCDAI reduction ≥15 or final PCDAI ≤10) was achieved by 64% on PEN, 88% EEN, and 84% anti-TNF (test for trend P = 0.08). FCP ≤250 µg/g was achieved with PEN in 14%, EEN 45%, and anti-TNF 62% (test for trend P = 0.001). Improvement in overall QOL was not statistically significantly different between the 3 groups (P = 0.86). However, QOL improvement was the greatest with EEN in the body image (P = 0.03) domain and with anti-TNF in the emotional domain (P = 0.04). CONCLUSIONS: Although PEN improved clinical symptoms, EEN and anti-TNF were more effective for decreasing mucosal inflammation and improving specific aspects of QOL.

Genome wide nucleosome mapping for HSV-1 shows nucleosomes are deposited at preferred positions during lytic infection.

HSV is a large double stranded DNA virus, capable of causing a variety of diseases from the common cold sore to devastating encephalitis. Although DNA within the HSV virion does not contain any histone protein, within 1 h of infecting a cell and entering its nucleus the viral genome acquires some histone protein (nucleosomes). During lytic infection, partial micrococcal nuclease (MNase) digestion does not give the classic ladder band pattern, seen on digestion of cell DNA or latent viral DNA. However, complete digestion does give a mono-nucleosome band, strongly suggesting that there are some nucleosomes present on the viral genome during the lytic infection, but that they are not evenly positioned, with a 200 bp repeat pattern, like cell DNA. Where then are the nucleosomes positioned? Here we perform HSV-1 genome wide nucleosome mapping, at a time when viral replication is in full swing (6 hr PI), using a microarray consisting of 50mer oligonucleotides, covering the whole viral genome (152 kb). Arrays were probed with MNase-protected fragments of DNA from infected cells. Cells were not treated with crosslinking agents, thus we are only mapping tightly bound nucleosomes. The data show that nucleosome deposition is not random. The distribution of signal on the arrays suggest that nucleosomes are located at preferred positions on the genome, and that there are some positions that are not occupied (nucleosome free regions -NFR or Nucleosome depleted regions -NDR), or occupied at frequency below our limit of detection in the population of genomes. Occupancy of only a fraction of the possible sites may explain the lack of a typical MNase partial digestion band ladder pattern for HSV DNA during lytic infection. On average, DNA encoding Immediate Early (IE), Early (E) and Late (L) genes appear to have a similar density of nucleosomes.

Nonhematopoietically derived DNA is shorter than hematopoietically derived DNA in plasma: a transplantation model.

BACKGROUND: Plasma DNA is predominantly hematopoietic in origin. The size difference between maternal- and fetal-derived DNA in maternal plasma prompted us to investigate whether there was any discrepancy in molecular size between hematopoietically and nonhematopoietically derived DNA in plasma. METHODS: Plasma DNA samples from 6 hematopoietic stem cell transplant recipients and 1 liver transplant recipient were analyzed by massively parallel paired-end sequencing. The size of each fragment was deduced from the alignment positions of the paired reads. In sex-mismatched transplant recipients, the reads from chromosome Y were used as markers for the male donor/recipient. For other transplant recipients, the reads of the donor- and recipient-specific alleles were identified from the single-nucleotide polymorphism genotypes. RESULTS: In male patients receiving female hematopoietic stem cells, more chromosome Y-derived DNA molecules (nonhematopoietically derived) were ≤150 bp than the autosome-derived ones (mainly hematopoietically derived) (median difference, 9.9%). In other hematopoietic stem cell transplant recipients, more recipient-specific DNA molecules (nonhematopoietically derived) were ≤150 bp than the donor-specific ones (hematopoietically derived) (median difference, 14.8%). In the liver transplant recipient, more donor-derived DNA molecules (liver derived) were ≤150 bp than the recipient-derived ones (mainly hematopoietically derived) (difference, 13.4%). The nonhematopoietically derived DNA exhibited a reduction in a 166-bp peak compared with the hematopoietically derived DNA. A 10-bp periodicity in size distribution below approximately 143 bp was observed in both DNA populations. CONCLUSIONS: Massively parallel sequencing is a powerful tool for studying posttransplantation chimerism. Plasma DNA molecules exhibit a distinct fragmentation pattern, with the nonhematopoietically derived molecules being shorter than the hematopoietically derived ones.

SFRS7-mediated splicing of tau exon 10 is directly regulated by STOX1A in glial cells.

BACKGROUND: In this study, we performed a genome-wide search for effector genes bound by STOX1A, a winged helix transcription factor recently demonstrated to be involved in late onset Alzheimer's disease and affecting the amyloid processing pathway. METHODOLOGY/PRINCIPAL FINDINGS: Our results show that out of 218 genes bound by STOX1A as identified by chromatin-immunoprecipitation followed by sequencing (ChIP-Seq), the serine/arginine-rich splicing factor 7 (SFRS7) was found to be induced, both at the mRNA and protein levels, by STOX1A after stable transfection in glial cells. The increase in SFRS7 was followed by an increase in the 4R/3R ratios of the microtubule-associated protein tau (MAPT) by differential exon 10 splicing. Secondly, STOX1A also induced expression of total tau both at the mRNA and protein levels. Upregulation of total tau expression (SFRS7-independent) and tau exon 10 splicing (SFRS7-dependent), as shown in this study to be both affected by STOX1A, is known to have implications in neurodegeneration. CONCLUSIONS: Our data further supports the functional importance and central role of STOX1A in neurodegeneration.