An Improved Anchor-Free Nodule Detection System Using Feature Pyramid Network.

Lung cancer (LC) is the leading cause of cancer death. Detecting LC at the earliest stage facilitates curative treatment options and will improve mortality rates. Computer-aided detection (CAD) systems can help improve LC diagnostic accuracy. In this work, we propose a deep-learning-based lung nodule detection method. The proposed CAD system is a 3D anchor-free nodule detection (AFND) method based on a feature pyramid network (FPN). The deep learning-based CAD system has several novel properties: (1) It achieves region proposal and nodule classification in a single network, forming a one-step detection pipeline and reducing operation time. (2) An adaptive nodule modelling method was designed to detect nodules of various sizes. (3) The proposed AFND also establishes a novel center point selection mechanism for better classification. (4) Based on the new nodule model, a composite loss function integrating cosine similarity (CS) loss and SmoothL1loss was designed to further improve the nodule detection accuracy. Experimental results show that the AFND outperforms other similar nodule detection systems on the LUNA 16 dataset.

Microcystis spp. and phosphorus in aquatic environments: A comprehensive review on their physiological and ecological interactions.

Cyanobacterial blooms caused by eutrophication have become a major environmental problem in aquatic ecosystems worldwide over the last few decades. Phosphorus is a limiting nutrient that affects the growth of cyanobacteria and plays a role in dynamic changes in algal density and the formation of cyanobacterial blooms. Therefore, identifying the association between phosphorus sources and Microcystis, which is the most representative and harmful cyanobacteria, is essential for building an understanding of the ecological risks of cyanobacterial blooms. However, systematic reviews summarizing the relationships between Microcystis and phosphorus in aquatic environments are rare. Thus, this study provides a comprehensive overview of the physiological and ecological interactions between phosphorus sources and Microcystis in aquatic environments from the following perspectives: (i) the effects of phosphorus source and concentration on Microcystis growth, (ii) the impacts of phosphorus on the environmental behaviors of Microcystis, (iii) mechanisms of phosphorus-related metabolism in Microcystis, and (iv) role of Microcystis in the distribution of phosphorus sources within aquatic environments. In addition, relevant unsolved issues and essential future investigations (e.g., secondary ecological risks) have been highlighted and discussed. This review provides deeper insights into the relationship between phosphorus sources and Microcystis and can serve as a reference for the evaluation, monitoring, and effective control of cyanobacterial blooms.

Molten-Volcanic-Ash-Phobic Thermal Barrier Coating based on Biomimetic Structure.

Volcanic ash is a major threat to aviation safety. The softening/melting temperatures of volcanic ash lie far below typical aero-engine operating temperatures. Thus, molten ash can accelerate the failure of thermal barrier coatings (TBCs). Here, inspired by natural superhydrophobic surfaces (e.g., the lotus leaf), a molten-volcanic-ash-phobic TBC, which provides a large possibility to eliminate molten ash issues of TBCs, is developed. A hierarchically structured surface is first prepared on a (Gd0.9 Yb0.1 )2 Zr2 O7 (GYbZ) pellet by ultrafast laser direct writing technology, aiming to confirm the feasibility of the biomimetic microstructure to repel molten volcanic ash wetting. Then biomimetic-structured GYbZ TBCs are successfully fabricated using plasma spray physical vapor deposition, which reveals "silicate" phobicity at high temperatures. The exciting molten-volcanic-ash-phobic attribute of the designed surfaces is attributed to the lotus-leaf-like dual-scale microstructure, emulating in particular the existence of nanoparticles. These findings may be an important step toward the development of next-generation aviation engines with greatly reduced vulnerability to environmental siliceous debris.

Subpopulation-specific machine learning prognosis for underrepresented patients with double prioritized bias correction.

Background: Many clinical datasets are intrinsically imbalanced, dominated by overwhelming majority groups. Off-the-shelf machine learning models that optimize the prognosis of majority patient types (e.g., healthy class) may cause substantial errors on the minority prediction class (e.g., disease class) and demographic subgroups (e.g., Black or young patients). In the typical one-machine-learning-model-fits-all paradigm, racial and age disparities are likely to exist, but unreported. In addition, some widely used whole-population metrics give misleading results. Methods: We design a double prioritized (DP) bias correction technique to mitigate representational biases in machine learning-based prognosis. Our method trains customized machine learning models for specific ethnicity or age groups, a substantial departure from the one-model-predicts-all convention. We compare with other sampling and reweighting techniques in mortality and cancer survivability prediction tasks. Results: We first provide empirical evidence showing various prediction deficiencies in a typical machine learning setting without bias correction. For example, missed death cases are 3.14 times higher than missed survival cases for mortality prediction. Then, we show DP consistently boosts the minority class recall for underrepresented groups, by up to 38.0%. DP also reduces relative disparities across race and age groups, e.g., up to 88.0% better than the 8 existing sampling solutions in terms of the relative disparity of minority class recall. Cross-race and cross-age-group evaluation also suggests the need for subpopulation-specific machine learning models. Conclusions: Biases exist in the widely accepted one-machine-learning-model-fits-all-population approach. We invent a bias correction method that produces specialized machine learning prognostication models for underrepresented racial and age groups. This technique may reduce potentially life-threatening prediction mistakes for minority populations.

Influence of the Magnitude of Ferroelectric Domain Polarization on the Photochemical Reactivity of BaTiO3.

The spontaneous polarization of domains in ferroelectric materials has been used to spatially separate photogenerated electrons and holes, reducing recombination and thereby improving the efficiency of photochemical reactions. Here, the influence of the magnitude of the polarization on photochemical reactivity is investigated. The magnitude of the out-of-plane component of the polarization was characterized by scanning Kelvin probe force microscopy (KFM). By examining crystals with orientations that deviate by only a few degrees from (001), two types of domains were identified: those with polarization vectors nearly perpendicular to the surface and those with polarization vectors nearly parallel to the surface. The photochemical reactivity was measured using topographic atomic force microscopy to determine the amount of Ag+ (Pb2+) that was photochemically reduced (oxidized) to Ag (PbO2) on the surface. For the reduction reaction, the reactivities of domains with polarizations nearly perpendicular to the surface were only about 3 times greater than the reactivities of the domains with polarizations nearly parallel to the surface, indicating that, for this reaction, the magnitude of the out-of-plane polarization is less important than its sign. For the oxidation of lead, only the domains with polarizations nearly perpendicular to the surface were reactive, indicating that for this reaction, both the sign and magnitude of the polarization are important.

Wetting and Spreading of Molten Volcanic Ash in Jet Engines.

A major hazard to jet engines posed by volcanic ash is linked to the wetting and spreading of molten ash droplets on engine component surfaces. Here, using the sessile drop method, we study the evolution of the wettability and spreading of volcanic ash. We employ rapid temperature changes up to 1040-1450 °C, to replicate the heating conditions experienced by volcanic ash entering an operating jet engine. In this scenario, samples densify as particles coalesce under surface tension until they form a large system-sized droplet (containing remnant gas bubbles and crystals), which subsequently spreads on the surface. The data exhibit a transition from a heterogeneous to a homogeneous wetting regime above 1315 °C as crystals in the drops are dissolved in the melt. We infer that both viscosity and microstructural evolution are key controls on the attainment of equilibrium in the wetting of molten volcanic ash droplets.

Preparation and Properties of Hydrogels Based on PEGylated Lignosulfonate Amine.

Sodium lignosulfonate (SLS) was aminated to obtain a lignin amine (LA) compound, which was subsequently crosslinked with poly(ethylene glycol) diglycidyl ether (PEGDGE) to obtain hydrogels. The chemical structure of the resulting LA-derived hydrogel (LAH) was characterized by Fourier transform infrared (FTIR) spectroscopy, solid-state 13C NMR spectroscopy, and elemental analysis, and the interior morphology of the freeze-dried hydrogel was examined by scanning electron microscopy. NMR and FTIR spectroscopy results indicated that the amino groups of LA reacted with PEGDGE in the crosslinking reaction. The lignin content in the resulting hydrogel increased with an increase in the LA/PEGDGE weight ratio in the reaction, approaching a maximum (∼71 wt %) and leveling off. The hydrogel with such a composition happened to be the same as the one prepared by reacting the primary amines of LA and epoxy groups of PEGDGE in equal stoichiometry. These results strongly suggest that the formation of the hydrogel network structure was largely dictated by the reactions between the primary amines and epoxy groups. The gels with lignin contents at this level exhibited a superior swelling capacity, viscoelasticity, and shear properties.

Volcanic ash melting under conditions relevant to ash turbine interactions.

The ingestion of volcanic ash by jet engines is widely recognized as a potentially fatal hazard for aircraft operation. The high temperatures (1,200-2,000 °C) typical of jet engines exacerbate the impact of ash by provoking its melting and sticking to turbine parts. Estimation of this potential hazard is complicated by the fact that chemical composition, which affects the temperature at which volcanic ash becomes liquid, can vary widely amongst volcanoes. Here, based on experiments, we parameterize ash behaviour and develop a model to predict melting and sticking conditions for its global compositional range. The results of our experiments confirm that the common use of sand or dust proxy is wholly inadequate for the prediction of the behaviour of volcanic ash, leading to overestimates of sticking temperature and thus severe underestimates of the thermal hazard. Our model can be used to assess the deposition probability of volcanic ash in jet engines.

Evaluation of Evidence-based Nursing Pain Management Practice.

It is important to ensure that cancer pain management is based on the best evidence. Nursing evidence-based pain management can be examined through an evaluation of pain documentation. The aim of this study was to modify and test an evaluation tool for nursing cancer pain documentation, and describe the frequency and quality of nursing pain documentation in one oncology unit via the electronic medical system. A descriptive cross-sectional design was used for this study at an oncology unit of an academic medical center in the Pacific Northwest. Medical records were examined for 37 adults hospitalized during April and May 2013. Nursing pain documentations (N = 230) were reviewed using an evaluation tool modified from the Cancer Pain Practice Index to consist of 13 evidence-based pain management indicators, including pain assessment, care plan, pharmacologic and nonpharmacologic interventions, monitoring and treatment of analgesic side effects, communication with physicians, and patient education. Individual nursing documentation was assigned a score ranging from 0 (worst possible) to 13 (best possible), to reflect the delivery of evidence-based pain management. The participating nurses documented 90% of the recommended evidence-based pain management indicators. Documentation was suboptimal for pain reassessment, pharmacologic interventions, and bowel regimen. The study results provide implications for enhancing electronic medical record design and highlight a need for future research to understand the reasons for suboptimal nursing documentation of cancer pain management. For the future use of the data evaluation tool, we recommend additional modifications according to study settings.

Identification of high risk DISC1 protein structural variants in patients with bipolar spectrum disorder.

In a large Scottish pedigree, a balanced translocation t (1;11)(q42.1;q14.3) disrupting the DISC1 and DISC2 genes segregates with major mental illness, including schizophrenia and depression. A frame-shift carboxyl-terminal deletion was reported in DISC1 in an American family with schizophrenia, but subsequently found in two controls. Herein, we test one hypothesis utilizing a large scale case-control mutation analysis: uncommon DISC1 variants are associated with high risk for bipolar spectrum disorder. We have analyzed the regions of likely functional significance in the DISC1 gene in 504 patients with bipolar spectrum disorder and 576 ethnically similar controls. Five patients were heterozygous for ultra-rare protein structural variants not found in the 576 controls (p=0.02, one-sided Fisher's exact test) and shown to be ultra-rare by their absence in a pool of 10,000 control alleles. In our sample, ultra-rare (private) protein structural variants in DISC1 are associated with an estimated attributable risk of about 0.5% in bipolar spectrum disorder. These data are consistent with: (i) the high frequency of depression in the large Scottish family with a translocation disrupting DISC1; (ii) linkage disequilibrium analysis demonstrating haplotypes associated with relatively small increases in risk for bipolar disorder (<3-fold odds ratio). The data illustrate how low/moderate risk haplotypes that might be found by the HapMap project can be followed up by resequencing to identify protein structural variants with high risk, low frequency and of potential clinical utility.

Missense mutations in the MEFV gene are associated with fibromyalgia syndrome and correlate with elevated IL-1beta plasma levels.

BACKGROUND: Fibromyalgia syndrome (FMS), a common, chronic, widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, has both genetic and environmental contributions. Patients and their parents have high plasma levels of the chemokines MCP-1 and eotaxin, providing evidence for both a genetic and an immunological/inflammatory origin for the syndrome (Zhang et al., 2008, Exp. Biol. Med. 233: 1171-1180). METHODS AND FINDINGS: In a search for a candidate gene affecting inflammatory pathways, among five screened in our patient samples (100 probands with FMS and their parents), we found 10 rare and one common alleles for MEFV, a gene in which various compound heterozygous mutations lead to Familial Mediterranean Fever (FMF). A total of 2.63 megabases of genomic sequence of the MEFV gene were scanned by direct sequencing. The collection of rare missense mutations (all heterozygotes and tested in the aggregate) had a significant elevated frequency of transmission to affecteds (p = 0.0085, one-sided, exact binomial test). Our data provide evidence that rare missense variants of the MEFV gene are, collectively, associated with risk of FMS and are present in a subset of 15% of FMS patients. This subset had, on average, high levels of plasma IL-1beta (p = 0.019) compared to FMS patients without rare variants, unaffected family members with or without rare variants, and unrelated controls of unknown genotype. IL-1beta is a cytokine associated with the function of the MEFV gene and thought to be responsible for its symptoms of fever and muscle aches. CONCLUSIONS: Since misregulation of IL-1beta expression has been predicted for patients with mutations in the MEFV gene, we conclude that patients heterozygous for rare missense variants of this gene may be predisposed to FMS, possibly triggered by environmental factors.

Identification of high risk DISC1 structural variants with a 2% attributable risk for schizophrenia.

The causes of schizophrenia remain elusive. In a large Scottish pedigree, a balanced translocation t(1;11) (q42.1;q14.3) disrupting the DISC1 and DISC2 genes segregates with major mental illness, including schizophrenia and unipolar depression. A frame-shift carboxyl-terminal deletion was reported in DISC1 in an American family, but subsequently found in two controls. A few common structural variants have been associated with less than a 2-fold increased risk for schizophrenia, but replication has not been uniform. No large scale case-control mutation study has been performed. We have analyzed the regions of likely functional significance in the DISC1 gene in 288 patients with schizophrenia and 288 controls (5 megabases of genomic sequence analyzed). Six patients with schizophrenia were heterozygous for ultra-rare missense variants not found in the 288 controls (p=0.015) and shown to be ultra-rare by their absence in a pool of 10,000 control alleles. We conclude that ultra-rare structural variants in DISC1 are associated with an attributable risk of about 2% for schizophrenia. In addition, we confirm that two common structural variants (Q264R and S704C) elevate the risk for schizophrenia slightly (odds ratio 1.3, 95% CI: 1.0-1.7). DISC1 illustrates how common/moderate risk alleles suggested by the HapMap project might be followed up by resequencing to identify genes with high risk, low frequency alleles of clinical relevance.

A mouse model for nonsense mutation bypass therapy shows a dramatic multiday response to geneticin.

Aminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT). Initial results demonstrate the need for more potent drugs and an in vivo model system for quantitative assessment of TBT. Herein, we present an in vivo system for evaluating the efficacy of premature stop codon management therapies: in vivo quantitative stop codon management repli-sampling TBT efficacy assay (IQSCMaRTEA). Application of IQSCMaRTEA reveals that geneticin is much more efficacious in vivo than gentamicin. Treatment with geneticin elicits a multiday response, and residual F9 antigen can be detected after 3 weeks. These data demonstrate the utility of IQSCMaRTEA for evaluating drugs that bypass nonsense mutations. In addition, IQSCMaRTEA may be helpful for testing inhibitors of nonsense-mediated decay, as stop codon management therapy will sometimes require inhibition of nonsense-mediated decay and translational bypass of the nonsense mutation. Furthermore, geneticin, its metabolites, or better tolerated analogues should be evaluated as a general treatment with multiday response for severe genetic disease caused by nonsense mutation.

Toward a fluorescent single-strand conformation polymorphism technique that detects all mutations: F-DOVAM-S.

Although DOVAM-S (detection of virtually all mutations-SSCP) in effect detects all mutations and is less costly than direct sequencing, the technique currently requires the use of radioactivity. F-DOVAM-S (fluorescent DOVAM-S) was developed to replace the isotopic label with fluorescence and to increase throughput via dye color multiplexing. As proof of principle, two multitemperature slab gel electrophoresis conditions were evaluated through the blinded analysis of mutations in the factor IX (FIX) genes of 88 hemophilia B (HB) patients and 7 wild-type controls. Using only two conditions, it was determined that F-DOVAM-S had a detection sensitivity of 97%. It is anticipated that when three or four optimized conditions are employed, F-DOVAM-S will detect all mutations. Three patient samples were multiplexed per well using three different fluorescent dyes (6FAM, VIC, and NED), demonstrating that it is possible to analyze up to 44 kb of diploid, color-coded amplification product per gel lane. This value corresponds to a throughput of approximately 4 Mb of DNA analyzed per 96-well gel, which is approximately triple that of conventional radiolabeled DOVAM-S. Throughput is further enhanced by the rapidity at which the fluorescent signal can be captured and the resultant multicolor chromatograms analyzed. Given these data, F-DOVAM-S has the potential to be a particularly powerful technology for clinical diagnosis because it allows the mutation analysis of multiple patients to be performed within 24h.

High frequency of neurexin 1beta signal peptide structural variants in patients with autism.

Neuroligins are postsynaptic membrane cell-adhesion molecules which bind to beta-neurexins, a family of proteins that act as neuronal cell surface receptors. To explore the possibility that structural variants in the beta-neurexin genes predispose to autism, the coding regions and associated splice junctions of three beta-neurexin genes were scanned with detection of virtually all mutations-SSCP (DOVAM-S) in 72 Caucasian patients with autism. In addition, segments of the neurexin 1beta gene were sequenced in 131 additional Caucasian and 61 Afro-American patients with autism from South Carolina and the Midwest. Two putative missense structural variants were identified in the neurexin 1beta gene in four Caucasian patients with autism and not in 535 healthy Caucasian controls (4/203 vs. 0/535, P=0.0056). Initial family data suggest that incomplete penetrance may occur. In addition, no structural variant was found in the neurexin 2beta gene and the neurexin 3beta gene. In the context of all available data, we conclude that mutations of the neurexin 1beta gene may contribute to autism susceptibility.

[Associations of Bsm1 polymorphism of the vitamin D receptor gene and blood lead, zinc protoporphyrin, and physical development in 476 environmental lead-exposed children].

The associations of the Bsm1 polymorphism of vitamin D receptor gene and blood lead, zinc protoporphyrin and physical development in 476 environmental lead-exposed children were studied. After blood lead level, age, sex and education level of the patients were adjusted by analysis of covariance, the children with B allele had larger head circumference than those with bb genotype(P = 0.02). While the subjects were stratified by blood lead level and sex, the statistically significant difference in head circumference between different Bsm1 genotypes was found only in high-blood-lead subgroup and in male subgroup. No significant influence of Bsm1 polymorphism on blood lead level, zinc protoporphyrin, height and weight was found, suggesting that the Bsm1 polymorphism of VDR gene may modify the effect of lead on the skull development of children highly exposed to lead.

[A molecular epidemiological study of childhood lead poisoning in lead-polluted environment].

OBJECTIVE: The relationship between polymorphisms of ALAD and VDR genes and individual susceptibility of lead poisoning was investigated in children highly-exposed to lead. METHOD: Four hundred and sixty-nine children were recruited into this study and the blood lead, ZPP, hemoglobin as well as three physical developmental indexes (head circumference, height and weight) were measured. VDR and ALAD gene polymorphisms were analyzed by the methods of PCR-RFLP. RESULTS: The subjects with ALAD2 allele had higher ZPP level (10.12 micro mol/L vs 12.87 micro mol/L) (P = 0.017). The subjects with B allele has larger head circumference than only with b allele (51.19 cm vs 50.75 cm) (P = 0.028). CONCLUSIONS: It was suggested that the ALAD gene polymorphism modified the relationship between blood lead and ZPP and the VDR gene variants influenced the skull development in children living under lead-polluted environment. The polymorphism of ALAD and VDR genes might serve as the molecular inherited factors modifying the susceptibility of lead poisoning.

[The relationship between hemoglobin adducts of trinitrotoluene and exposed level].

OBJECTIVE: To explore the biomarkers for monitoring trinitrotoluene (TNT) exposure, the relationship between TNT hemoglobin adducts and TNT exposed level. METHOD: Hemoglobin adducts (4A-Hb and 2A-Hb) were determined by GC-MS in 25 TNT exposed workers. TNT exposed level was evaluated by determining skin contaminated and inhaled TNT levels. The correlation between hemoglobin adducts level and TNT exposed level was analyzed. RESULTS: There was a correlation between total TNT exposure level, especially skin exposure level, and 4A-Hb or 2A-Hb content. No significant difference was found between the slopes and intercepts of lin ear equation of (4A-Hb) vs TNT exposed level and linear equation of (4A-Hb +2A-Hb) vs TNT exposed level (P > 0.05). CONCLUSION: Skin contamination is the major role of TNT exposure. TNT exposed level can be evaluated by determining the content of both 4A-Hb and 2A-Hb, and 4A-Hb is more suitable for monitoring TNT exposure.