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Mechanisms of improving coastal saline-alkali soil by periphyton
Ye  Zhu
Tianyun  Shao

Ye Zhu

and 5 more

January 20, 2021
Periphyton plays an indispensable role in coastal saline-alkali land, but its function is poorly understood. Soil physical and chemical properties (pH value, salinity, soil organic matter), enzyme activity and microbial diversity (based on 16s rDNA, ITS and functional genes) were measured in periphyton formed on rice-growing coastal saline-alkali soil modified by a new type of soil conditioner. The results showed that the content of organic matter and catalase activity in periphyton were significantly higher than in the unplanted control soil. Soil pH and salinity were decreased in periphyton compared to the unplanted control soil. Based on the relative abundance, bacterial genera Desulfomicrobium, Rhodobacter, cyanobacterium_scsio_T−2, Gemmatimonas, and Salinarimonas as well as fungal genus Fusarium were more abundant in periphyton than the unplanted control soil. In terms of functional genes, the cbbM and cbbL sequencing showed higher abundance of Hydrogenophaga, Rhodovulum, Magnetospira, Leptothrix, and Thiohalorhabdus, whereas the nifH sequencing indicated higher abundance of Cyanobacteria in the periphyton compared to the unplanted soil. The relative abundance and community structure of soil microorganisms were improved by periphyton, thus reducing soil salinity and pH, increasing soil organic matter and enzyme activity. This indicated that the periphyton can improve the conditions and offer a suitable environment for plant growth in coastal saline-alkali soil.
A Multicenter Study of Three-dimensional Echocardiographic Evaluation of Normal Pedia...
Pei-Ni Jone
Lisa Le

Pei-Ni Jone

and 10 more

January 20, 2021
Background: Three-dimensional echocardiography (3DE) evaluation of left ventricular (LV) volume and function in pediatrics compares favorably with cardiac magnetic resonance imaging. The aim of this study was to establish from a multicenter, normal pediatric z-score values of 3DE left ventricular volumes and function. Methods: Six hundred and ninety-eight healthy children (ages 0 to 18 years) were recruited from five centers. LV 3DE was acquired from the 4-chamber view. A vendor independent software analyzed end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using semi-automated quantification. Body surface area (BSA) based z-scores were generated. Intraobserver and interobserver variability were calculated using intraclass correlation (ICC) and repeatability coefficient (RC). Results: Z-scores were generated for ESV, EDV, and SV. The ICC for intraobserver variability for EDV, ESV, and SV were 0.99, 0.99, and 0.99 respectively. The ICC for interobserver variability for EDV, ESV, and SV were 0.98, 0.94, and 0.98 respectively. The RC for intraobserver and interobserver variability for LV EF was 4.39% (95% CI: 3.01, 5.59) and interobserver was 7.08% (95%CI: 5.51, 8.42). Conclusions: We report pediatric Z-scores for normal LV volumes using the semi-automated method from five centers, enhancing its generalizability. 3DE evaluation of LV volumes and EF in pediatric patients is highly reproducible.
Treatment of Recalcitrant Plantar Wart Unresponsive to Cryotherapy with Acupuncture a...
Soo Bo Shim
Hye Lim Lee

Soo Bo Shim

and 2 more

January 20, 2021
This study presents the case of a 9-year-old girl for whom complete resolution of recalcitrant warts was achieved with acupuncture and moxibustion treatment. This result suggests that acupuncture and moxibustion could be effective therapeutic strategies for plantar warts in the paediatric patient population.
Multiple coping strategies maintain stability of a small mammal population in resourc...
Anne Polyakov
William Tietje

Ann Polyakov

and 5 more

January 20, 2021
In semi-arid environments, aperiodic rainfall pulses determine cycles of plant production and resource availability for higher trophic levels, creating strong bottom-up regulation. The influence of climatic factors on population vital rates often shapes the dynamics of small mammal populations in such resource-restricted environments. Using a 21-year biannual capture–recapture dataset (1993 to 2014), we examined the impacts of climatic factors on the population dynamics of the brush mouse (Peromyscus boylii) in semi-arid oak woodland of coastal-central California. We applied Pradel’s temporal symmetry model to estimate capture probability (p), apparent survival (φ), recruitment (f), and realized population growth rate (λ) of the brush mouse, and examined the effects of temperature, rainfall, and El Niño on these demographic parameters. The population was stable during the study period with a monthly realized population growth rate of 0.993 ± SE 0.032, but growth varied over time from 0.680 ± 0.054 to 1.450 ± 0.083. Monthly survival estimates averaged 0.817 ± 0.005 and monthly recruitment estimates averaged 0.175 ± 0.038. Survival probability and realized population growth were positively correlated with rainfall and negatively correlated with temperature. In contrast, recruitment was negatively correlated with rainfall and positively correlated with temperature. Brush mice maintained their population through multiple coping strategies, investing in high recruitment during warmer and drier periods and allocating more energy towards survival during cooler and wetter conditions. Although climatic change in coastal-central California will favor recruitment over survival, varying strategies may serve as a mechanism by which brush mice maintain resilience in the face of climate change. Our results indicate that rainfall and temperature are both important drivers of brush mouse population dynamics and will play a significant role in predicting the future viability of brush mice under a changing climate.
Factors associated with suggestive of pulmonary hypertension measured by echocardiogr...
Dong Geum  Shin
Min-Kyung Kang

Dong Geum Shin

and 7 more

January 20, 2021
Background: Ultrasound techniques are generally not used as a primary tool in the evaluation of mediastinal tumors and cysts. This study aimed to identify factors associated with pulmonary hypertension (PH) measured by transthoracic echocardiography (TTE) in patients with a mediastinal tumor. Methods: This retrospective, observational study was performed from January 2015 to December 2020. Fifty-five patients (mean age, 62 ± 13 years; 31 [56%] women) who had a mediastinal tumor and underwent TTE were included. Patients were classified as with PH or without PH. We analyzed clinical factors and echocardiographic parameters. Results: PH was found in 21 (38%) patients. Twenty-two patients were asymptomatic, and none had symptoms associated with PH. Forty-seven (86%) patients underwent surgery, and 23 (42%) patients were diagnosed with malignant tumors. The presence of PH was not related with malignancy. Patients with PH were older than those without PH (67 ± 10 versus [vs.] 59 ± 14 years, p = 0.017). Small left ventricular (LV) systolic dimension (29.4 ± 3.6 vs. 31.6 ± 3.6 mm, p = 0.040) and dimension (4.2 ± 0.3 vs. 4.5 ± 0.3 mm, p = 0.004) and hyperdynamic LV ejection fraction (EF, 69 ± 6 vs. 65 ± 5%, p = 0.019) were associated with PH. Among them, older age, small LV dimension, and high EF were independently associated with PH. Conclusion: The presence of PH had no significant effect on patients’ clinical manifestation or malignancy.
Effects of high-fat diet and CYP2B6 mutants on the pharmacokinetics of bupropion and...
Hui Ma
Xiao Ying Yang

Hui Ma

and 7 more

January 20, 2021
Aims To provide evidence for the clinically rational administration of bupropion (BUP), the effects of high-fat diet and CYP2B6 mutants on BUP and hydroxybupropion (HBUP) among 44 healthy Chinese subjects. Methods The concentrations of BUP and HBUP in plasma were determined with a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. Genotypes were ascertained after amplified by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results The maximum plasma concentration (Cmax) and time to Cmax (tmax) of BUP as well as the concentration–time curve (AUC(0→96)) and Cmax of HBUP all increased by 1.18-, 1.41-, 1.38-, and 1.33-fold in the feeding group relative to the fasting group, respectively. Interestingly, the Cmax and terminal half-life (t1/2) of BUP increased by 1.33- and 1.39-fold among those subjects carrying the CYP2B6*1/*1 genotype in the feeding group relative to those in the fasting group. Similarly, the apparent volume of distribution (Vd) and clearance (CL) of HBUP increased by 1.38- and 1.59-fold, respectively, while the Cmax and AUC(0→96) of HBUP decreased by 1.44- and 1.49-fold among those subjects carrying the CYP2B6*1/*1 genotype in the feeding group relative to those in the fasting group. Concliusion These data suggest that high-fat diet and CYP2B6 mutants can influence the pharmacokinetic parameters of BUP and HBUP, thereby offering clear evidence for the rational administration of BUP among Chinese subjects in clinical settings.
Factors influencing participation rates in clinical late effect studies of childhood...
Anne Sophie Helligsoe
Louise Henriksen

Anne Sophie Helligsoe

and 5 more

January 20, 2021
Introduction: Several studies on late effects of childhood cancer have been conducted during the past decades. To ensure external validation of a study population, the participation rate must be high. This study investigated demographic data in late effect studies and potential factors impacting on participation rates such as cancer type, time since diagnosis and duration of clinical examinations. Procedure: By searching the databases PubMed, Embase and Web of Science and by contacting researchers and clinicians, we identified studies including an invitation to a clinical examination for late effects after childhood cancer. Studies conducted from January 2010 - March 2020 in the Nordic countries were included. Results: We found 80 published studies originating from 16 cohorts. The overall participation rates ranged between 27 and 100%. The majority of studies (eleven studies) were conducted more than ten years after the cancer diagnosis and primarily on hematologic malignancies (seven studies). The highest participation rates were seen in studies of survivors with solid tumors (92%) and the lowest in survivors with hematologic malignancies (67%) and central nervous system tumors (73%). Neither duration of the clinical examination nor time since diagnosis seemed to affect the participation rate. Conclusion: A trend of lower participation rates when recruiting survivors of hematologic malignancies and central nervous system tumors was found. We encourage future studies to describe the recruitment process more thouroughly to improve understanding of the factors influencing participation rates.
Shannon, R\’enyi, Tsallis entropies of 1s$^2$-State Atomic System
swe uer

suw swe

January 20, 2021
A document by swe uer. Click on the document to view its contents.
Mutualism disruption by an invasive ant reduces carbon fixation for a foundational Ea...
Patrick Milligan
Timothy Martin

Patrick Milligan

and 6 more

January 20, 2021
Invasive ants shape assemblages and interactions of native species, but their effect on fundamental ecological processes is poorly understood. In East Africa, Pheidole megacephala ants have invaded monodominant stands of the ant-tree Acacia drepanolobium, extirpating native ant defenders and rendering trees vulnerable to canopy damage by vertebrate herbivores. We used experiments and observations to quantify direct and interactive effects of invasive ants and large herbivores on A. drepanolobium photosynthesis over a 2-year period. Trees that had been invaded for ≥ 5 years exhibited 69% lower whole-tree photosynthesis during key growing seasons, resulting from interaction between invasive ants and vertebrate herbivores that caused leaf- and canopy-level photosynthesis declines. We also surveyed trees shortly before and after invasion, finding that recent invasion induced only minor changes in leaf physiology. Our results from individual trees likely scale up, highlighting the potential of invasive species to alter ecosystem-level carbon fixation and other biogeochemical cycles.
Presence of hypothyroidism and thyroiditis does not improve the performance of ultras...
Gabriel Gimenez-Perez
Assumpta Recasens

Gabriel Gimenez-Perez

and 5 more

January 20, 2021
Purpose: It has been suggested, on a theoretical basis, that ultrasound screening of thyroid nodules in obese patients with additional risk factors (family history, thyroiditis or high thyrotropin) might be cost-effective for the early detection and treatment of thyroid cancer. The present study evaluates if this approach can be validated in a real clinical setting. Methods: Patients with obesity attended in hospital-based clinics were evaluated for risk factors of thyroid cancer and ultrasound screened for thyroid nodularity. Detected nodules were evaluated according to current guidelines. Results: A total of 429 patients were evaluated (70.2% women, mean age 49.1±11.0, mean body mass index 42.6±5.8 kg/m2). Risk factors were present in 129 (30.1%) patients. Thyroid nodules with indication for fine needle aspiration biopsy were detected in 69 (16.1%). We did not find differences in the risk of harbouring thyroid nodules according to the presence of risk factors (no risk factors 16.6%, risk factors 14.1%, p = 0.64). No single risk factor conferred an increased risk for thyroid nodules During the screening procedure 4 cases of thyroid cancer were detected, none of them with the evaluated risk factors. Conclusion: The present study, has been unable to demonstrate that the use of known risk factors for thyroid cancer is helpful to discriminate obese patients with higher risk of harbouring thyroid nodules.
Unstable Angina and Renal Colic in a Patient with Ankylosing Spondylitis -- A Challen...
Azhar Sayyed
Jibril Khalil

Azhar Sayyed

and 3 more

January 20, 2021
Ankylosing spondylitis (AS) a seronegative inflammatory disease that often presents with co-existing issues like bilateral hip replacements, nephrolithiasis, skin lesions, peripheral vascular disease and coronary artery disease.. We describe a patient with ankylosing spondylitis with bilateral hip replacements in the past who was waiting for an elective coronary artery bypass grafting (CABG) but needed urgent admission with renal colic and unstable angina. In the current COVID pandemic in order to reduce hospital stay and risk of hospital acquired COVID infection we decided to perform simultaneous CABG and removal of ureteric stone. In this case report we discuss the issues in relation to management of patients with coronary artery disease and ankylosing spondylitis.
Unbounded generalization of logarithmic representation of infinitesimal generators
Yoritaka Iwata

Yoritaka Iwata

January 20, 2021
The logarithmic representation of infinitesimal generators is generalized to the cases when the evolution operator is unbounded. The generalized result is applicable to the representation of infinitesimal generators of unbounded evolution operators, where unboundedness of evolution operator is an essential ingredient of nonlinear analysis. In conclusion a general framework for the identification between the infinitesimal generators with evolution operators is established. A mathematical framework for such an identification is indispensable to the rigorous treatment of nonlinear transforms: e.g., transforms appearing in the theory of integrable systems.
Azithromycin alleviates the severity of rheumatoid arthritis via targeting UPR compon...
Yongli Zhang
Luna Ge

Yongli Zhang

and 10 more

January 20, 2021
Background and Purpose: Azithromycin (AZM) is a macrolide antibiotic with well-described anti-inflammatory properties. This study aimed to substantiate its treatment potential in rheumatoid arthritis (RA). Experimental Approach: Gene expression profiles were collected by RNA-sequencing and the effects of AZM were assessed in functional assays. In vitro and vivo assays for examining the blockade of glucose-regulated protein 78 (GRP78) actions by AZM: assays for defining the anti-inflammatory activity of AZM using fibroblast-like synoviocytes (FLSs) from RA patients as well as collagen-induced arthritis (CIA) in DBA/1 mice. Identification and characterization of the binding of AZM to GRP78 using drug affability responsive target stability assay, proteomics and cellular thermal shift assay. Detect AZM inhibition of GRP78 and dependence of AZM’s anti-arthritis activity on GRP78. Key Results: AZM reduced pro-inflammatory factor production, cell migration, invasion and chemo-attractive potential, enhanced apoptosis, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. AZM ameliorated the severity of CIA lesions. Transcriptional analyses implied that AZM treatment causes impairments in signaling cascades associated with cholesterol and lipid biosynthetic process. GRP78 was isolated as a novel target of AZM. AZM-mediated activation of unfolded protein response (UPR) via inhibiting GRP78 activity is required not only for inducing the expression of C/EBP-homologous protein (CHOP), but also for activation of sterol-regulatory element binding protein (SREBP) and its targeted genes involved in cholesterol and lipid biosynthetic process. Further, deletion of GRP78 abolished AZM’s anti-arthritis activity. Conclusion and Implications: These findings confirmed that AZM is an anti-arthritis therapeutic drug for RA treatment.
A novel mast cell-dependent allergic peritonitis model
Hadas Pahima
Pier Giorgio Puzzovio

Hadas Pahima

and 2 more

January 20, 2021
Background: Typical murine models of allergic inflammation are induced by the combination of ovalbumin and aluminum hydroxide. However, accumulating evidence indicates that, in models of asthma and atopic dermatitis, allergic inflammation can be generated in the absence of aluminum hydroxide. Moreover, co-administration of S. aureus enterotoxin B with ovalbumin can enhance inflammation. Objective: The objective of this study was to establish a rapid and mast cell-dependent murine model of allergic inflammation by inducing allergic peritonitis using ovalbumin and S. aureus enterotoxin B. Methods: Allergic peritonitis was induced in C57BL/6 mice by subcutaneous sensitization and intraperitoneal challenge with ovalbumin and S. aureus enterotoxin B. Disease characteristics were assessed by flow cytometry, ELISA, Trypan Blue exclusion and colorimetric assays. Results: Time course of the allergic peritonitis revealed a peak of peritoneal inflammation 48h after challenge, as assessed by total cells and eosinophil counts. Decrease of cell numbers started 96h post challenge with complete clearance within 168h. Moreover, significantly higher levels of tryptase and increased vascular permeability were found 30 min following challenge. Allergic inflammation induction by ovalbumin and S. aureus enterotoxin B was impaired in mast cells deficient mice and partially restored by mice reconstitution with bone marrow derived mast cells, indicating the mast cell role in this model. Conclusion: We present a novel model of allergic peritonitis that is mast cell-dependent, simple and robust. Moreover, the use of S. aureus enterotoxin B better resembles human allergic inflammation, which is known to be characterized by the colonization of Staphylococcus aureus.
Inhaled bacteriophage therapy in a porcine model of ventilator-associated pneumonia c...
Antoine Guillon
Jeoffrey Pardessus

Antoine Guillon

and 15 more

January 20, 2021
Background and Purpose. Pseudomonas aeruginosa is a main cause of ventilator-associated pneumonia (VAP) with drug-resistant bacteria. Bacteriophage therapy has experienced resurgence to compensate for the limited development of novel antibiotics. However, phage therapy is limited to a compassionate use so far, resulting from lack of adequate studies in relevant pharmacological models. We used a pig model of VAP caused by P. aeruginosa that recapitulates essential features of human disease to study the antimicrobial efficacy of nebulized-phage therapy. Experimental Approach. (i) Lysis kinetic assays were performed to evaluate in vitro phage antibacterial efficacy against P. aeruginosa and select relevant combinations of lytic phages. (ii) The efficacy of the phage combinations was investigated in vivo (murine model of P. aeruginosa lung infection). (iii) We determined the optimal conditions to ensure efficient phage delivery by aerosol during mechanical ventilation. (iv) Lung antimicrobial efficacy of inhaled-phage therapy was evaluated in pigs, which were anesthetized, mechanically ventilated and infected with P. aeruginosa. Key Results. By selecting an active phage cocktail and optimizing aerosol delivery conditions, we were able to deliver high phage concentrations in the lungs, which resulted in a rapid and marked reduction in P. aeruginosa density (1.5 Log reduction, p<0.001). No phage was detected in the sera and urines throughout the experiment. Conclusion and Implications. Our findings demonstrated: (i) the feasibility of delivering large amounts of active phages by nebulization during mechanical ventilation, (ii) rapid control of in situ infection by inhaled bacteriophage in an experimental model of VAP with high translational value.
Multiple Intracardiac Masses as the Primary Presentation of a Systemic Inflammatory D...
Zahra Khajali
Bahar Galeshi

Zahra Khalaji

and 4 more

January 20, 2021
Antiphospholipid syndrome (APS) classically presents with venous or arterial thrombosis and pregnancy morbidity. Although clinical manifestations with fever of unknown origin and intracardiac masses are unusual, in a patient with prolonged fever and multiple intracardiac thrombi, systemic inflammatory diseases such as APS should be considered.
ALMOST BS-COMPACT OPERATORS AND DOMINATION PROBLEM
Mohamed Hajji

Mohamed Hajji

January 20, 2021
Let X and Y be two Banach spaces. A bounded operator T : X −→ Y is said to be a BS-compact operator whenever T sends Banach-Saks subsets of X onto norm compact sets of Y ([20]). In this paper, our central focus is upon introducing the class of almost BS-compact operators. The paper rests essentially on two parts. The first is devoted to the connection of this new class of operators with classical notions of operators, such as BS-compact operators, AM-compact operators, and Dunfort-Pettis operators. The second part is dedicated to the domination problem within the framework of (almost) BS-compact operators. Mathematics Subject Classification. 46B42, 47B60, 47B65.
Giving-up diversity (GUDiv): top-down effects of foraging decisions on local, landsca...
Jana Eccard
Clara Ferreira

Jana Eccard

and 3 more

January 20, 2021
Foraging by consumers has direct effects on the community of their resource species, and may serve as a biotic filtering mechanism of diversity. Determinants of foraging behaviour may thus have cascading effects on abundance, diversity, and functional trait composition of the resource community. Here we propose giving-up diversity (GUDiv) as a novel concept and simple measure to quantify community effects of foraging at multiple spatial diversity scales. GUDiv provides a framework linking theories of adaptive foraging behaviour with community ecology. In experimental resource landscapes we showcase effects of patch residency of foraging wild rodents on α-GUDiv, ß-GUDiv and γ- GUDiv, and on functional trait composition of resources. Using GUDiv allows for prediction-based investigation of cascading indirect predation effects (ecology of fear) across multiple trophic levels, of feedbacks between functional trait composition of resource and consumer communities, and of effects of inter-individual differences among foragers on the diversity of resource communities.
Uncovering the influence of diet and gut microbiota in human serum metabolome
David Obeso Montero
Elisa  Zubeldia-Varela

David Obeso Montero

and 2 more

January 20, 2021
Article type: News and Views: Groundbreaking Discoveries in ImmunologyTitle: Uncovering the influence of diet and gut microbiota in human serum metabolomeAuthors: David Obeso1,2‡, Elisa Zubeldia-Varela1,2‡ and Alma Villaseñor11Instituto de Medicina Molecular Aplicada (IMMA), Departamento de Ciencias Médicas Básicas. Facultad de Medicina. Universidad San Pablo-CEU, CEU Universities, Madrid, España.2Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Madrid, España.‡: These Authors have equally contributedCorrespondence: Alma Villaseñor, Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Madrid, EspañaEmail address:alma.villasenor@ceu.esKeywords: Metabolomics, Diet, Microbiota, Allergy, Serum, MetabolomeAbbreviations: MS, mass spectrometry; LC, liquid chromatography; short chain fatty acids (SCFA)Acknowledgement: We would like to thank Anna Głobińska for her assistance in generating the graphical figure. AV Gratefully acknowledges the Martín-Carbajo family for supporting her scientific development through the X Mario Martín Velamazán award.Author contributions: D.O., E.Z-V. and A.V contributed to the writing of the manuscript and have given approval to the manuscript. A.V. supervised the final version.
Syncope in Acute Pulmonary Embolism. Importance of Early Recognition of Recurrent Syn...
Ksawalha
Shoaib  Khan

Khalid Sawalha

and 3 more

January 20, 2021
A 43-year-old female patient presented with large bilateral pulmonary emboli. During patient's stay, a fleeting episodes of bradycardia and hypotension with drop in systolic pressure over 40mmHg on slight movements were noted.Being in a rural hospital, patient was transferred in which following that she was pronounced dead relating her presentation.
Lymphomatoid granulomatosis of the central nervous system (CNS-LYG), immune thrombocy...
Mohsin Soleja
Jesse Jaso

Mohsin Soleja

and 8 more

January 20, 2021
We describe a case of isolated primary CNS lymphomatoid granulomatosis and a discordant low-grade B-cell lymphoma involving the bone marrow causing chronic immune thrombocytopenia. Clinical course was complicated with disseminated zoster and sub-massive pulmonary embolism. Our patient was successfully managed with a combination radioimmunotherapy strategy with rituximab and radiation therapy.
Spontaneous disappearance of common bile duct stones after the use of a new dumbbell-...
Yuto Ishizaki
Mitsuru Sugimoto

Yuto Ishizaki

and 15 more

January 20, 2021
Endoscopic stone removal becomes challenging owing to a distal common bile duct stricture. A new dumbbell-shaped covered self-expanding metallic stent is efficient in removing the common bile duct stones with common bile duct strictures that occur due to chronic pancreatitis.
Deep Imputation on Large-Scale Drug Discovery Data
Benedict Irwin
Thomas Whitehead

Benedict Irwin

and 5 more

January 27, 2021
More accurate predictions of the biological properties of chemical compounds would guide the selection and design of new compounds in drug discovery and help to address the enormous cost and low success-rate of pharmaceutical R&D. However this domain presents a significant challenge for AI methods due to the sparsity of compound data and the noise inherent in results from biological experiments. In this paper, we demonstrate how data imputation using deep learning provides substantial improvements over quantitative structure-activity relationship (QSAR) machine learning models that are widely applied in drug discovery. We present the largest-to-date successful application of deep-learning imputation to datasets which are comparable in size to the corporate data repository of a pharmaceutical company (678,994 compounds by 1166 endpoints). We demonstrate this improvement for three areas of practical application linked to distinct use cases; i) target activity data compiled from a range of drug discovery projects, ii) a high value and heterogeneous dataset covering complex absorption, distribution, metabolism and elimination properties and, iii) high throughput screening data, testing the algorithm’s limits on early-stage noisy and very sparse data. Achieving median coefficients of determination, R2, of 0.69, 0.36 and 0.43 respectively across these applications, the deep learning imputation method offers an unambiguous improvement over random forest QSAR methods, which achieve median R2 values of 0.28, 0.19 and 0.23 respectively. We also demonstrate that robust estimates of the uncertainties in the predicted values correlate strongly with the accuracies in prediction, enabling greater confidence in decision-making based on the imputed values.
Case finding of early pregnancies at risk of preeclampsia using maternal blood leptin...
Qianyang Huang
Shiying Hao

Qianyang Huang

and 20 more

January 20, 2021
Objective To evaluate whether longitudinal measurements of serological adipokines and sphingolipids can predict preeclampsia early in gestation. Design Retrospective multi-omics discovery and longitudinal validation. Setting Maternity units in two US hospitals. Methods A multi-omics approach integrating genomic and lipidomic discoveries was employed to identify leptin (Lep) and ceramide (Cer) as novel PE early gestational biomarkers. The levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-1), Lep, and Cer in maternal sera were then determined by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays. Main outcome measures Interval from positive prediction to confirmative diagnosis. Results Genomic meta-analysis compiled six PE placental cohorts with 78 PE and 95 non-PE control placentas. The Testing Cohort included sera from 7 non-PE and 8 PE women collected at confirmatory diagnosis. The Validation Cohort included sera from 20 non-PE and 20 PE women collected longitudinally through gestation. Our findings revealed a marked elevation of maternal serum Leptin/Ceramide (d18:1/25:0) ratio from early gestation (a median of 23 weeks) when comparing later PE-complicated with uncomplicated pregnancies. The maternal Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting PE for sensitivity (85% vs. 40%), positive predictive value (89% vs. 42%), and AUC (0.92 vs. 0.52) from 5 to 25 weeks of gestation. Conclusions Non-invasive longitudinal assessment by serological evaluation of Lep/Cer (d18:1/25:0) ratio can case find early pregnancies at risk of preeclampsia, outperforming sFlt-1/PlGF ratio test. Tweetable abstract Non-invasive longitudinal assessment by serological evaluation of Lep and Cer ratio can predict preeclampsia early in gestation.
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