Using DUCK-Net for polyp image segmentation.

This paper presents a novel supervised convolutional neural network architecture, "DUCK-Net", capable of effectively learning and generalizing from small amounts of medical images to perform accurate segmentation tasks. Our model utilizes an encoder-decoder structure with a residual downsampling mechanism and a custom convolutional block to capture and process image information at multiple resolutions in the encoder segment. We employ data augmentation techniques to enrich the training set, thus increasing our model's performance. While our architecture is versatile and applicable to various segmentation tasks, in this study, we demonstrate its capabilities specifically for polyp segmentation in colonoscopy images. We evaluate the performance of our method on several popular benchmark datasets for polyp segmentation, Kvasir-SEG, CVC-ClinicDB, CVC-ColonDB, and ETIS-LARIBPOLYPDB showing that it achieves state-of-the-art results in terms of mean Dice coefficient, Jaccard index, Precision, Recall, and Accuracy. Our approach demonstrates strong generalization capabilities, achieving excellent performance even with limited training data.

Peptide mediated, enhanced toxicity of a bacterial pesticidal protein against southern green stink bug.

The damage caused by stink bugs that feed on agricultural crops accounts for such significant losses that transgenic plant resistance to stink bugs would be highly desirable. As the level of toxicity of the Bacillus thuringiensis-derived, ETX/Mtx2 pesticidal protein Mpp83Aa1 is insufficient for practical use against the southern green stink bug Nezara viridula, we employed two disparate approaches to isolate peptides NvBP1 and ABP5 that bind to specific proteins (alpha amylase and aminopeptidase N respectively) on the surface of the N. viridula gut. Incorporation of these peptides into Mpp83Aa1 provided artificial anchors resulting in increased gut binding, and enhanced toxicity. These peptide-modified pesticidal proteins with increased toxicity provide a key advance for potential future use against N. viridula when delivered by transgenic plants to mitigate economic loss associated with this important pest.

The Benefits of Enhanced Recovery After Surgery Programs and Their Application in Cardiothoracic Surgery.

The perioperative care of the surgical patient is undergoing a paradigm shift. Enhanced Recovery After Surgery (ERAS) programs are becoming the standard of care and best practice in many surgical specialties throughout the world. ERAS is a multimodal, multidisciplinary, evidence-based approach to care of the surgical patient that aims to optimize perioperative management and outcomes. Implementation, however, has been slow because it challenges traditional surgical doctrine. The key elements of ERAS Pathways strive to reduce the response to surgical stress, decrease insulin resistance, and maintain anabolic homeostasis to help the patient return to baseline function more quickly. Data suggest that these pathways have produced not only improvements in clinical outcome and quality of care but also significant cost savings. Large trials reveal an increase in 5-year survival and a decrease in immediate complication rates when strict compliance is maintained with all pathway components. Years of success using ERAS in colorectal surgery have helped to establish a body of evidence through a number of randomized controlled trials that encourage application of these pathways in other surgical specialties.

Enhanced recovery after thoracic surgery reduces discharge on highly dependent narcotics.

BACKGROUND: There is large prescription drug epidemic in United States. We want to determine if ERATS (enhanced recovery after thoracic surgery) program can reduce discharge on highly dependent narcotics. METHODS: We performed a retrospective analysis of prospectively collected data on patients who underwent lung resection and foregut procedures on thoracic surgery service over an 8-month time period. Patients underwent preoperative conditioning instructions, multimodal non-narcotic pharmaceutical usage, total intravenous anesthesia (TIVA) and minimizing highly addictive narcotics during the post-operative period. We gathered information on demographics, indication and type of surgery, morbidity, mortality and length of stay. We also recorded the type of pain medication patients were given as a prescription based on the Drug Enforcement Agency's classification schedule. RESULTS: Fifty-two patients underwent lung resection and 54 patients underwent foregut surgery. There were no mortalities in either group. Ten percent of patients after lung surgery and 6% after foregut surgery had a greater than grade II complication. The median length of stay after lung resection was 2 days and foregut surgery was 1 day. Only 10% of patients went home after lung resection and 2% after foregut surgery with a prescription for schedule II narcotics. We found that patients who were on schedule II narcotics prior to surgery all went home with schedule II narcotics. CONCLUSIONS: We found that ERATS program for thoracic surgical cases can reduce the number of patients going home with highly dependent narcotics. This strategy will decrease the availability of highly addictive prescription drugs in the community.

Crystal structure of dicamba monooxygenase: a Rieske nonheme oxygenase that catalyzes oxidative demethylation.

Dicamba (3,6-dichloro-2-methoxybenzoic acid) is a widely used herbicide that is efficiently degraded by soil microbes. These microbes use a novel Rieske nonheme oxygenase, dicamba monooxygenase (DMO), to catalyze the oxidative demethylation of dicamba to 3,6-dichlorosalicylic acid (DCSA) and formaldehyde. We have determined the crystal structures of DMO in the free state, bound to its substrate dicamba, and bound to the product DCSA at 2.10-1.75 A resolution. The structures show that the DMO active site uses a combination of extensive hydrogen bonding and steric interactions to correctly orient chlorinated, ortho-substituted benzoic-acid-like substrates for catalysis. Unlike other Rieske aromatic oxygenases, DMO oxygenates the exocyclic methyl group, rather than the aromatic ring, of its substrate. This first crystal structure of a Rieske demethylase shows that the Rieske oxygenase structural scaffold can be co-opted to perform varied types of reactions on xenobiotic substrates.

Dicamba resistance: enlarging and preserving biotechnology-based weed management strategies.

The advent of biotechnology-derived, herbicide-resistant crops has revolutionized farming practices in many countries. Facile, highly effective, environmentally sound, and profitable weed control methods have been rapidly adopted by crop producers who value the benefits associated with biotechnology-derived weed management traits. But a rapid rise in the populations of several troublesome weeds that are tolerant or resistant to herbicides currently used in conjunction with herbicide-resistant crops may signify that the useful lifetime of these economically important weed management traits will be cut short. We describe the development of soybean and other broadleaf plant species resistant to dicamba, a widely used, inexpensive, and environmentally safe herbicide. The dicamba resistance technology will augment current herbicide resistance technologies and extend their effective lifetime. Attributes of both nuclear- and chloroplast-encoded dicamba resistance genes that affect the potency and expected durability of the herbicide resistance trait are examined.

In vivo and in vitro anaerobic mating in Candida albicans.

Candida albicans cells of opposite mating types are thought to conjugate during infection in mammalian hosts, but paradoxically, the mating-competent opaque state is not stable at mammalian body temperatures. We found that anaerobic conditions stabilize the opaque state at 37 degrees C, block production of farnesol, and permit in vitro mating at 37 degrees C at efficiencies of up to 84%. Aerobically, farnesol prevents mating because it kills the opaque cells necessary for mating, and as a corollary, farnesol production is turned off in opaque cells. These in vitro observations suggest that naturally anaerobic sites, such as the efficiently colonized gastrointestinal (GI) tract, could serve as niches for C. albicans mating. In a direct test of mating in the mouse GI tract, prototrophic cells were obtained from auxotrophic parent cells, confirming that mating will occur in this organ. These cells were true mating products because they were tetraploid, mononuclear, and prototrophic, and they contained the heterologous hisG marker from one of the parental strains.

Mechanism of 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate synthase, a key enzyme in the methanopterin biosynthetic pathway.

The first committed step in methanopterin biosynthesis is catalyzed by 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate (RFA-P) synthase. Unlike all known phosphoribosyltransferases, beta-RFA-P synthase catalyzes the unique formation of a C-riboside instead of an N-riboside in the condensation of p-aminobenzoic acid (pABA) and 5-phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) to produce 4-(beta-D-ribofuranosyl)aminobenzene 5'-phosphate (beta-RFA-P), CO(2), and inorganic pyrophosphate (PP(i)). Here we report the successful cloning, active overexpression in Escherichia coli, and purification of this homodimeric enzyme containing two 36.2-kDa subunits from the methanogen Methanococcus jannaschii. Steady-state initial velocity and product inhibition kinetic studies indicate an ordered Bi-Ter mechanism involving binding of PRPP, then pABA, followed by release of the products CO(2), then beta-RFA-P, and finally PP. The Michaelis parameters are as follows: K(m)pABA, 0.15 mm; K(m)PRPP, 1.50 mm; V(max), 375 nmol/min/mg; k(cat), 0.23 s(-1). CO(2) showed uncompetitive inhibition, K(i) = 0.990 mm, under varied PRPP and saturated pABA, and a mixed type of inhibition, K(1) = 1.40 mm and K = 3.800 mm, under varied pABA and saturated PRPP. RFA-P showed uncompetitive inhibition, K(i) = 0.210 mm, under varied PRPP and saturated pABA, and again uncompetitive, K(i) = 0.300 mm, under saturated PRPP and varied pABA. PP(i) exhibits competitive inhibition, K(i) = 0.320 mm, under varied PRPP and saturated pABA, and a mixed type of inhibition, K(1) = 0.60 mm and K(2) = 1.900 mm, under saturated PRPP and varied pABA. Synthase lacks any chromogenic cofactor, and the presence of pyridoxal phosphate and the mechanistically related pyruvoyl cofactors has been strictly excluded.

Targeting methanopterin biosynthesis to inhibit methanogenesis.

This paper describes the design, synthesis, and successful employment of inhibitors of 4-(beta-D-ribofuranosyl)aminobenzene-5'-phosphate (RFA-P) synthase, which catalyzes the first committed step in the biosynthesis of methanopterin, to specifically halt the growth of methane-producing microbes. RFA-P synthase catalyzes the first step in the synthesis of tetrahydromethanopterin, a key cofactor required for methane formation and for one-carbon transformations in methanogens. A number of inhibitors, which are N-substituted derivatives of p-aminobenzoic acid (pABA), have been synthesized and their inhibition constants with RFA-P synthase have been determined. Based on comparisons of the inhibition constants among various inhibitors, we propose that the pABA binding site in RFA-P synthase has a relatively large hydrophobic pocket near the amino group. These enzyme-targeted inhibitors arrest the methanogenesis and growth of pure cultures of methanogens. Supplying pABA to the culture relieves the inhibition, indicating a competitive interaction between pABA and the inhibitor at the cellular target, which is most likely RFAP synthase. The inhibitors do not adversely affect the growth of pure cultures of the bacteria (acetogens) that play a beneficial role in the rumen. Inhibitors added to dense ruminal fluid cultures (artificial rumena) halt methanogenesis; however, they do not inhibit volatile fatty acid (VFA) production and, in some cases, VFA levels are slightly elevated in the methanogenesis-inhibited cultures. We suggest that inhibiting methanopterin biosynthesis could be considered in strategies to decrease anthropogenic methane emissions, which could have an environmental benefit since methane is a potent greenhouse gas.