bluuebunny/crossref_metadata_2025 huggingface dataset:
Corneal Total and Epithelial Thickness Measured by Sonogage Ultrasound Pachometry and High-resolution Optical Coherence Tomography
Authors: Swarbrick Helen A. , Kang Pauline , Peguda Rajini
Published: May 2020

SIGNIFICANCE

This research questions the validity of using the Sonogage ultrasound (US) pachometer to measure corneal epithelial thickness and coincidentally provides confirmation for the conventional view of the mechanism of orthokeratology (OK) based on central epithelial thinning.

PURPOSE

The Sonogage (Corneo-Gage Plus 1) pachometer uses A-scan US to measure total corneal thickness. It is claimed that this instrument can also measure corneal epithelial thickness. We sought to validate this claim by comparing total and epithelial thickness measurements with the Sonogage with those obtained with high-resolution optical coherence tomography (OCT).

METHODS

Fourteen non–contact lens wearers and 14 subjects who had worn Paragon CRT OK lenses overnight for greater than 1 month were recruited. Three OCT and five US measurements were taken in one eye of each subject. Depending on normality of data, paired t tests or Wilcoxon tests were used to compare total and epithelial thicknesses measured with the Sonogage pachometer and the Tomey Casia OCT. Pearson or Spearman correlation analyses were used to examine relationships between measurements obtained with the two instruments.

RESULTS

There was a significant difference in total corneal thickness measurements between the two instruments. Although a significant correlation was found (r = 0.916, P < .001), the Sonogage consistently measured greater total corneal thickness than did the OCT (+19.5 ± 9.2 μm; P < .001). Epithelial thickness using the Sonogage showed little variation (range, 46.4 to 50.0 μm), whereas epithelial thickness using the OCT ranged from 30.7 to 54.7 μm. There was no significant correlation between epithelial thicknesses obtained with the two instruments (r = −0.135, P = .49). Epithelial thickness measured by OCT was significantly thinner in OK wearers (35.8 ± 2.8 μm) than in nonlens wearers (46.7 ± 4.5 μm, P < .001).

CONCLUSIONS

The Sonogage is not able to measure epithelial thickness in vivo, returning essentially identical measurements over a range of epithelial thicknesses. Optical coherence tomography measurements confirm the conventional view of the mechanism of OK based on central epithelial thinning.
Baseline and Clinical Factors Associated with Response to Amblyopia Treatment in a Randomized Clinical Trial
Authors: Birch Eileen E. , Jost Reed M. , Kelly Krista R. , Leffler Joel N. , Dao Lori , Beauchamp Cynthia L.
Published: May 2020

SIGNIFICANCE

We sought to identify baseline and clinical factors that were predictive of the response to amblyopia treatment. We report that binocular amblyopia treatment may be especially effective for moderate amblyopia in orthotropic children.

PURPOSE

We previously reported results from the primary cohort (n = 28) enrolled in a randomized clinical trial (NCT02365090), which found that binocular amblyopia treatment was more effective than patching. Enrollment of an additional 20 children was pre-planned to provide the opportunity to examine factors that may be predictive of response to amblyopia treatment.

METHODS

Forty-eight children (4 to 10 years old) were enrolled, with 24 randomized to contrast-rebalanced binocular game treatment (1 hour a day, 5 days a week) and 24 to patching treatment (2 hours a day, 7 days a week). The primary outcome was change in amblyopic eye best-corrected visual acuity at the 2-week visit. Baseline factors examined were age at enrollment, visual acuity, stereoacuity, and suppression. Clinical factors were etiology, age at diagnosis, prior treatment, and ocular alignment.

RESULTS

At 2 weeks, visual acuity improvement was significantly greater with the binocular game than patching. Children with moderate amblyopia and orthotropia had more visual acuity improvement with binocular game play than did those with severe amblyopia. In addition, children who spent more time playing the binocular game had more improvement. We were not able to confidently identify any baseline or clinical factors that were associated with response to patching treatment.

CONCLUSIONS

Binocular amblyopia treatment was more effective among orthotropic children with moderate amblyopia than among children with microtropia or severe amblyopia.
Timely Delivery of Discharge Medications to Patients’ Bedsides: A Patient-centered Quality Improvement Project
Authors: Katz Daphna T. , Fernandez-Sanchez Josaura V. , Loeffler Leah A. , Chang Simone M. , Puertolas-Lopez Mora V. , Ramdial Faizal R. , Fisher Gabrielle R. , Gutierrez Susan A. , Mahajan Neha , Keerthy Divya R. , Cavallaro Stephania P. , Landaeta Claudia E. , Pascall Akilah S. , Acevedo Kristina T. , Chan-Poon Kwai T. , Abraham Benjamin R. , Siri Matthew , Reynolds Kimberly L. , Van Kirk Kendra , Bayes Santos Liz Y.
Published: May 2020

Introduction:

Patients who are unable to fill prescriptions after discharge are at risk of hospital readmission. Ensuring that patients have prescriptions in hand at the time of discharge is a critical component of a safe and effective discharge process. Using a “Meds to Beds” program, we aimed to increase the percentage of patients discharged from Holtz Children’s Hospital with medications in hand from 49% to 80%, reduce turnaround time (TAT) from electronic prescription signature to bedside delivery from 4.9 hours (±2.6 hours) to 2 hours, and increase caregiver satisfaction.

Methods:

We formed a multidisciplinary team and implemented 4 patient-centered interventions through iterative plan-do-study-act cycles. Statistical process control charts were used to understand the impact of the interventions over 10 months. Hospital length of stay and discharges before 2:00 pm were used as balancing measures. We measured caregiver satisfaction using a telephone survey administered by pediatric residents within 7 days after discharge.

Results:

The mean percentage of patients discharged with medications in hand increased to 76%. TAT decreased to 3.5 hours (±1.8 hours). Length of stay did not significantly increase, whereas the percentage of patients discharged before 2:00 pm did. Caregivers of patients who had prescriptions delivered to their bedside reported high levels of satisfaction.

Conclusions:

Using a “Meds to Beds” program, we increased the percentage of patients discharged with medications in hand, decreased TAT with reduced variability, and achieved high levels of caregiver satisfaction. Importantly, there was a shift in the culture of the institution toward improved medication access for patients.
Segnochrobactrum spirostomi gen. nov., sp. nov., isolated from the ciliate Spirostomum yagiui and description of a novel family, Segnochrobactraceae fam. nov. within the order Rhizobiales of the class Alphaproteobacteria
Authors: Akter Sumi , Shazib Shahed Uddin Ahmed , Shin Mann Kyoon
Published: May 2020

A bacterial strain, designated Sp-1T, was isolated from the heterotrich ciliate Spirostomum yagiui collected from a reservoir located in Ulsan, Republic of Korea. Cells of Sp-1T were Gram stain-negative, rod-shaped, non-spore-forming, non-motile and contained poly-β-hydroxybutyrate granules. Phylogenetic analyses based on 16S rRNA gene sequences indicated that Sp-1T constituted a distinct phylogenetic lineage within different families in the order

Rhizobiales

with a pairwise sequence similarity of 95 % to the species of the genus Ochrobactrum: Ochrobactrum anthropi ATCC 49188T and

Ochrobactrum cytisi

ESC1T (family

Brucellaceae

). The major cellular fatty acids were C19 : 0 cyclo ω8c (44.4 %) and C16 : 0 (32.1 %). The identified sole isoprenoid quinone was ubiquinone-10 (Q-10). The major polar lipids produced were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminolipid, two unidentified phospholipids and three unidentified lipids. The genome size was about 5.4 Mbp and the DNA G+C content was 68.2 mol%. Sp-1T exhibited the highest average nucleotide identity value of 76.6 % and in silico DNA–DNA hybridization value of 22.1 % with

Pseudoxanthobacter soli

DSM 19599T (family Xanthobacteraeae). This strain is distinguishable from closely related members of the order

Rhizobiales

by its differential phenotypic, chemotaxonomic, genomic and phylogenetic characteristics. On the basis of evidence from polyphasic taxonomic analysis, we concluded that Sp-1T represents a novel species in a novel genus within the order

Rhizobiales

, for which the name Segnochrobactrum spirostomi gen. nov., sp. nov. is proposed. The type strain is Sp-1T (=KCTC 62036T=JCM 32162T). We also describe a novel family, Segnochrobactraceae fam. nov., to encompass the proposed novel genus and species.
Chest Computed Tomography Findings in Asymptomatic Patients with COVID-19
Authors: Chang Min Cheol , Hur Jian , Park Donghwi
Published: May 2020

Background: Little is known about the damage to the respiratory system in asymptomatic patients with coronavirus disease (COVID-19).
Objective: Herein, we evaluated the findings of chest computed tomography (CT) and radiography in patients with COVID-19 who were asymptomatic.
Methods: We retrospectively investigated patients with a confirmed diagnosis of COVID-19 but who did not show any symptoms. Among the 139 patients with COVID-19 who were hospitalized, 10 (7.2%) were asymptomatic. Their chest CT and radiographic findings were analyzed.
Results: In the results, all patients (100%) had ground glass opacity (GGO) on chest CT. Further, the GGO lesions were predominantly distributed peripherally and posteriorly in all patients. In 9 (90%) patients, the GGO lesions were combined with reticular opacity. Air-bronchogram due to bronchiolectasis surrounded by GGO was observed in 8 patients (80%). Additionally, the lung lesions were dominant on the right side in all patients.
Conclusions: In conclusion, considering our results that the lung is affected in asymptomatic patients, it will be necessary to extend the indications of COVID-19 testing for effective management of COVID-19 during the pandemic.
Impact of COVID-19 infection on maternal and neonatal outcomes: a review of 287 pregnancies
Authors: Azarkish Fatemeh , Janghorban Roksana
Published: May 2020

Pregnant women are vulnerable group in viral outbreaks especially in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this review was to identify maternal and neonatal outcomes in available articles on pregnancies affected by COVID-19. The articles that had assessed outcomes of pregnancy and perinatal of women with COVID-19 between Oct 2019 and Apr 30, 2020 without language limitation were considered. All kinds of studies such as case report, case series, retrospective cohort, case control were included. We searched databases, selected relevant studies and extracted data regarding maternal and neonatal outcomes from each article. Data of 287 pregnant women with COVID-19 of 6 countries were assessed from 28 articles between December 8, 2019 and April 6, 2020. Most pregnant women reported in their third trimester, 102 (35.5%) cases were symptomatic at the time of admission. Common onset symptoms, abnormal laboratory findings, and chest computed tomography pattern were fever (51.5%), lymphocytopenia (67.9%), and multiple ground-glass opacities (78.5%) respectively. 93% of all deliveries were done through cesarean section. No maternal mortality and 3 % ICU admission were reported. Vertical transmission was not reported but its possibility was suggested in three neonates. One neonatal death, one stillbirth, and one abortion were reported. All newborns were not breastfed. This review showed fewer adverse maternal and neonatal outcomes in pregnant women with COVID-19 in comparison with previous coronavirus outbreak infection in pregnancy. Limited data are available regarding possibility of virus transmission in utero, during vaginal childbirth and breastfeeding. Effect of COVID-19 on first and second trimester and ongoing pregnancy outcomes in infected mothers is still questionable.
Medical overuse in the Iranian healthcare system: a systematic scoping review and practical recommendations for decreasing medical overuse during unexpected COVID-19 pandemic opportunity
Authors: Pezeshki Mohammad Zakaria , Janati Ali , Arab-Zozani Morteza
Published: May 2020

Background: Overuse of medical care is a major problem across health systems as well as in Iran. By our knowledge, this is the first scoping review in which medical overuse in the Iranian healthcare system was investigated.
Objective: To perform an inclusive search for original studies that report medical overuse in the Iranian healthcare system.
Methods: A systematic search of the literature conducted in bibliographic databases including PubMed, Embase, Scopus, Web of Sciences, Cochrane and Scientific Information Database using a comprehensive search strategy without time limit until the end of 2018, accomplished by reference tracking, author contacting and expert consultation to identify studies on the overuse of medical care.
Results: We reviewed 4124 published articles based on predetermined inclusion criteria. The authors consensus included a total of 40 articles. Of these, 31 were in English and 9 in Farsi, published between 19975-2018. The result categorized into two distinct clinical areas: treatment (17 articles), and diagnostic (23 articles) services. Almost all of the studies only described the magnitude of unnecessary overuse. Unnecessary overuse of Antibiotics, MRI and CT-scan were the most reported topics. The ranges of their overuse proportion were as follows; Antibiotic (31 to 97%); MRI (33 to 88%), and CT-scan (19 to 50%).
Conclusions: Our review showed, even so, the magnitude of unnecessary overuse of medical services is high but there are only a few interventional studies in clinical and administrative level for finding effective methods for decreasing these unnecessary services. Researchers should be encouraged to conducting interventional studies. We suggest the ministry of health to use the golden opportunity of COVID-19 epidemic for designing Iran national policy and action plan for controlling and preventing unnecessary health care services and including a section for Interventional Research in the action plan.
Quantitative faecal immunochemical test for patients with high risk bowel symptoms: a prospective cohort study
Authors: Laszlo Helga E , Seward Edward , Ayling Ruth , Lake Jenny , Malhi Aman , Hackshaw Allan , Stephens Clare , Pritchard-Jones Kathy , Chung Donna , Machesney Michael
Published: May 2020

Objectives: To evaluate whether quantitative measurement of faecal haemoglobin (f-Hb) using faecal immunochemical testing (FIT) can be used to rule out colorectal cancer (CRC) for patients who present to primary care with high risk symptoms defined by national guidelines for urgent referral for suspected cancer (NICE NG12).

Design: Prospective cohort study carried out between April 2017 and March 2019.

Setting: 59 GP practices in London and 24 hospitals in England.

Participants: Symptomatic patients in England referred to the urgent CRC pathway who provided a faecal sample for FIT in addition to standard investigations for cancer.

Main outcome measures: CRC was confirmed by established clinical and histopathology procedures. f-Hb (microgr per gram of stool) was measured in a central laboratory blinded to cancer outcome. We calculated sensitivity (percentage of patients with CRC who have f-Hb exceeding specified cut-offs); false-positive rate [FPR] (percentage of patients without CRC whose f-Hb exceeds the same cut-offs); and positive predictive value [PPV] (percentage of all patients with f-Hb above the cut-offs who have CRC).

Results: 4676 patients were recruited of whom 3596 patients were included (had a valid FIT test and a known definitive diagnosis). Among the 3596, median age was 67 years, 53% were female and 78% had colonoscopy. 90 patients were diagnosed with CRC, 7 with other cancers, and 3499 with no cancer found. f-Hb did not correlate with age, sex or ethnicity. Using f-Hb greater than or equal to 4 microgr/g (lowest limit of detection), sensitivity, FPR and PPV were 87.8%, 27.0% and 7.7% respectively. Using f-Hb greater than or equal to 10 microgr/g, the corresponding measures were 83.3%, 19.9% and 9.7%. 15 patients with CRC had f-Hb below 10 microgr/g. If FIT had been used at thresholds of 10 microg/gr or 4 microgr/g, 1 in 6 or 1 in 8 patients with cancer respectively would have been missed. If the absence of anaemia or abdominal pain is used alongside f-Hb 10 microgr/g, only 1 in 18 cancers would be missed but 56% of people without CRC could potentially avoid further investigations including colonoscopies.

Conclusions: In our study, if FIT alone had been used to determine urgent referral for patients with high risk symptoms for definitive cancer investigation, some patients with bowel cancer would not have been diagnosed. If used in conjunction with clinical features, particularly in the absence of anaemia, the efficacy of FIT is significantly improved. With appropriate safety netting, FIT could be used to focus secondary care diagnostic capacity on patients most at risk of CRC.
Pre-existing Cardiovascular Disease in United States Population at High Risk for Severe COVID-19 Infection
Authors: Qureshi Adnan I
Published: May 2020

Background and Purpose
There is increasing recognition of a relatively high burden of pre-existing cardiovascular disease in Corona Virus Disease 2019 (COVID 19) infected patients. We determined the burden of pre-existing cardiovascular disease in persons residing in United States (US) who are at risk for severe COVID-19 infection.
Methods
Age (60 years or greater), presence of chronic obstructive pulmonary disease, diabetes, mellitus, hypertension, and/or malignancy were used to identify persons at risk for admission to intensive care unit, or invasive ventilation, or death with COVID-19 infection. Persons were classified as low risk (no risk factors), moderate risk (1 risk factor), and high risk (two or more risk factors present) using nationally representative sample of US adults from National Health and Nutrition Examination Survey 2017 and 2018 survey.
Results
Among a total of 5856 participants, 2386 (40.7%) were considered low risk, 1325 (22.6%) moderate risk, and 2145 persons (36.6%) as high risk for severe COVID-19 infection. The proportion of patients who had pre-existing stroke increased from 0.6% to 10.5% in low risk patients to high risk patients (odds ratio [OR]19.9, 95% confidence interval [CI]11.6-34.3). The proportion of who had pre-existing myocardial infection (MI) increased from 0.4% to 10.4% in low risk patients to high risk patients (OR 30.6, 95% CI 15.7-59.8).
Conclusions
A large proportion of persons in US who are at risk for developing severe COVID 19 infection are expected to have pre-existing cardiovascular disease. Further studies need to identify whether targeted strategies towards cardiovascular diseases can reduce the mortality in COVID-19 infected patients.
Assisting Scalable Diagnosis Automatically via CT Images in the Combat against COVID-19
Authors: Liu Bohan , Liu Pan , Dai Lutao , Yang Yanlin , Xie Peng , Tan Yiqing , Du Jicheng , Shan Wei , Zhao Chenghui , Zhong Qin , Lin Xixiang , Guan Xizhou , Xing Ning , Sun Yuhui , Wang Wenjun , Zhang Zhibing , Fu Xia , Fan Yanqing , Li Meifang , Zhang Na , Li Lin , Liu Yaou , Xu Lin , Du Jingbo , Zhao Zhenhua , Hu Xuelong , Fan Weipeng , Wang Rongpin , Wu Chongchong , Nie Yongkang , Cheng Liuquan , Ma Lin , Li Zongren , Jia Qian , Liu Minchao , Guo Huayuan , Huang Gao , Shen Haipeng , An Weimin , Li Hao , Zhou Jianxin , He Kunlun
Published: May 2020

Introductory paragraph

The pandemic of coronavirus Disease 2019 (COVID-19) caused enormous loss of life globally. 1-3 Case identification is critical. The reference method is using real-time reverse transcription PCR (rRT-PCR) assays, with limitations that may curb its prompt large-scale application. COVID-19 manifests with chest computed tomography (CT) abnormalities, some even before the onset of symptoms. We tested the hypothesis that application of deep learning (DL) to the 3D CT images could help identify COVID-19 infections. Using the data from 920 COVID-19 and 1,073 non-COVID-19 pneumonia patients, we developed a modified DenseNet-264 model, COVIDNet, to classify CT images to either class. When tested on an independent set of 233 COVID-19 and 289 non-COVID-19 patients. COVIDNet achieved an accuracy rate of 94.3% and an area under the curve (AUC) of 0.98. Application of DL to CT images may improve both the efficiency and capacity of case detection and long-term surveillance.
Comparative analyses revealed reduced spread of COVID-19 in malaria endemic countries
Authors: Muneer Azhar , Kumari Kiran , Tripathi Manish , Srivastava Rupesh , Mohmmed Asif , Rathore Sumit
Published: May 2020

In late 2019, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection started in Hubei province of China and now it has spread like a wildfire in almost all parts of the world except some. WHO named the disease caused by SARS-CoV-2 as COVID-19 (CoronaVirus Disease-2019). It is very intriguing to see a mild trend of infection in some countries which could be attributed to mitigation efforts, lockdown strategies, health infrastructure, demographics and cultural habits. However, the lower rate of infection and death rates in mostly developing countries, which are not placed at higher levels in terms of healthcare facilities, is a very surprising observation. To address this issue, we hypothesize that this lower rate of infection is majorly been observed in countries which have a higher transmission/prevalence of protozoan parasite borne disease, malaria. We compared the COVID-19 spread and malaria endemicity of 108 countries which have shown at least 200 cases of COVID-19 till 18th April 2020. We found that the number of COVID-19 cases per million population correlates negatively with the malaria endemicity of respective countries. The malaria free countries not only have higher density of COVID-19 infections but also the higher case fatality rates as compared to highly malaria endemic countries. We also postulate that this phenomenon is due to natural immune response against malaria infection, which is providing a heterologous protection against the virus. Unfortunately, there is no licensed vaccine against SARS-CoV-2 yet, but this information will be helpful in design of future strategies against fast spreading COVID-19 disease.
Estimating and forecasting COVID-19 attack rates and mortality
Authors: Ketcheson David I. , Ombao Hernando C. , Moraga Paula , Ballal Tarig , Duarte Carlos M.
Published: May 2020

{We describe a model for estimating past and current infections
as well as future deaths due to the ongoing COVID-19 pandemic. The model does not use confirmed case numbers and is based instead on recorded
numbers of deaths and on the age-specific population distribution.
A regularized deconvolution technique is used to infer past infections from
recorded deaths.
Forecasting is based on a compartmental SIR-type model, combined
with a probability distribution for the time from infection to death.
The effect of non-pharmaceutical interventions (NPIs) is
modelled empirically, based on recent trends in the death rate. The model can
also be used to study counterfactual scenarios based on hypothetical NPI
policies.
Proposed Clinical Indicators for Efficient Screening and Testing for COVID-19 Infection from Classification and Regression Trees (CART) Analysis
Authors: Zimmerman Richard K , Nowalk Mary Patricia , Bear Todd , Taber Rachel , Sax Theresa M , Eng Heather , Balasubramani Goundappa K
Published: May 2020

Background: The introduction and rapid transmission of SARS CoV2 in the United States resulted in implementation of methods to assess, mitigate and contain the resulting COVID-19 disease based on limited knowledge. Screening for testing has been based on symptoms typically observed in inpatients, yet outpatient symptom complexes may differ.
Methods: Classification and regression trees (CART) recursive partitioning created a decision tree classifying enrollees into laboratory-confirmed cases and non-cases. Demographic and symptom data from patients ages 18-87 years who were enrolled from March 29-April 26, 2020 were included. Presence or absence of SARSCoV2 was the target variable.
Results: Of 736 tested, 55 were positive for SARS-CoV2. Cases significantly more often reported chills, loss of taste/smell, diarrhea, fever, nausea/vomiting and contact with a COVID-19 case, but less frequently reported shortness of breath and sore throat. A 7-terminal node tree with a sensitivity of 96% and specificity of 53%, and an AUC of 78% was developed. The positive predictive value for this tree was 14% while the negative predictive value was 99%. Almost half (44%) of the participants could be ruled out as likely non-cases without testing.
Discussion: Among those referred for testing, negative responses to three questions could classify about half of tested persons with low risk for SARS-CoV2 and would save limited testing resources. These questions are: was the patient in contact with a COVID-19 case? Has the patient experienced 1) a loss of taste or smell; or 2) nausea or vomiting? The outpatient symptoms of COVID-19 appear to be broader than the well-known inpatient syndrome.
Haplotype-based analysis distinguishes maternal-fetal genetic contribution to pregnancy-related outcomes
Authors: Srivastava Amit K. , Juodakis Julius , Sole-Navais Pol , Chen Jing , Bacelis Jonas , Teramo Kari , Hallman Mikko , Njølstad Pal R. , Evans David M. , Jacobsson Bo , Muglia Louis J. , Zhang Ge
Published: May 2020

Abstract

Genotype-based approaches for the estimation of SNP-based narrow-sense heritabilityhave limited utility in pregnancy-related outcomes due to confounding by the shared alleles between mother and child. Here, we propose a haplotype-based approach to estimate the genetic variance attributable to three haplotypes – maternal transmitted, maternal non-transmittedand paternal transmittedin mother-child pairs. We show through extensive simulations that our haplotype-based approach outperforms the conventional and contemporary approaches for resolving the contribution of maternal and fetal effects, particularly when m1 and p1 have different effects in the offspring. We apply this approach to estimate the explicit and relative maternal-fetal genetic contribution to the phenotypic variance of gestational duration and gestational duration adjusted fetal size measurements at birth in 10,375 mother-child pairs. The results reveal that variance of gestational duration is mainly attributable to m1 and m2 (= 17.3%, S. E. = 5.2%;= 12.2%, S. E. = 5.2%;= 0.0%, S. E. = 5.0%). In contrast, variance of fetal size measurements at birth are mainly attributable to m1 and p1 (= 18.6 − 36.4%,= 0.0 − 5.2% and= 4.4 − 13.6%). Our results suggest that gestational duration and fetal size measurements are primarily genetically determined by the maternal and fetal genomes, respectively. In addition, a greater contribution of m1 as compared to m2 and p1to birth length and head circumference suggests a substantial influence of correlated maternal-fetal genetic effects on these traits. Our newly developed approach provides a direct and robust alternative for resolving explicit maternal and fetal genetic contributions to the phenotypic variance of pregnancy-related outcomes.
A normative account of confirmation bias during reinforcement learning
Authors: Lefebvre Germain , Summerfield Christopher , Bogacz Rafal
Published: May 2020

Reinforcement learning involves updating estimates of the value of states and actions on the basis of experience. Previous work has shown that in humans, reinforcement learning exhibits a confirmatory bias: when updating the value of a chosen option, estimates are revised more radically following positive than negative reward prediction errors, but the converse is observed when updating the unchosen option value estimate. Here, we simulate performance on a multi-arm bandit task to examine the consequences of a confirmatory bias for reward harvesting. We report a paradoxical finding: that confirmatory biases allow the agent to maximise reward relative to an unbiased updating rule. This principle holds over a wide range of experimental settings and is most influential when decisions are corrupted by noise. We show that this occurs because on average, confirmatory biases lead to overestimating the value of more valuable bandits, and underestimating the value of less valuable bandits, rendering decisions overall more robust in the face of noise. Our results show how apparently suboptimal learning policies can in fact be reward-maximising if decisions are made with finite computational precision.
Rewiring of peatland plant-microbe networks outpaces species turnover
Authors: Robroek Bjorn J.M. , Martí Magalí , Svensson Bo H. , Dumont Marc G. , Veraart Annelies J. , Jassey Vincent E.J.
Published: May 2020

Enviro-climatological changes are thought to be causing alterations in ecosystem processes through shifts in plant and microbial communities; however, how links between plant and microbial communities change with enviro-climatological change is likely to be less straightforward but may be fundamental for many ecological processes. To address this, we assessed the composition of the plant community and the prokaryotic community –using amplicon-based sequencing– of three European peatlands that were distinct in enviro-climatological conditions. Bipartite networks were used to construct site-specific plant-prokaryote co-occurrence networks. Our data show that between sites, plant and prokaryotic communities differ and that turnover in interactions between the communities was complex. Essentially, turnover in plant-microbial interactions is much faster than turnover in the respective communities. Our findings suggest that network rewiring does largely result from novel associations between species that are common and shared across the networks. Turnover in network composition is largely driven by novel interactions between a core community of plants and microorganisms. Taken together our results indicate that plant-microbe associations are context dependent, and that changes in enviro-climatological conditions will likely lead to network rewiring. Integrating turnover in plant-microbe interactions into studies that assess the impact of enviro-climatological change on peatland ecosystems is essential to understand ecosystem dynamics and must be combined with studies on the impact of these changes on ecosystem processes.
Key traits and genes associate with salinity tolerance independent from vigor in cultivated sunflower (Helianthus annuusL.)
Authors: Temme Andries A. , Kerr Kelly L. , Masalia Rishi R. , Burke John M. , Donovan Lisa A.
Published: May 2020

With rising food demands, crop production on salinized lands is increasingly necessary. Sunflower, a moderately salt tolerant crop, exhibits a trade-off where more vigorous, high-performing genotypes have a greater proportional decline in biomass under salinity stress. Prior research has found deviations from this relationship across genotypes; the magnitude and direction of these deviations provides a useful metric of tolerance. Here, we identified the traits and genomic regions underlying variation in this expectation-deviation tolerance. We grew a diversity panel under control and salt-stressed conditions and measured a suite of morphological (growth, allocation, plant and leaf morphology) and leaf ionomic traits. The genetic basis of variation in these traits and their plasticity was investigated via genome-wide association studies, which also enabled the identification of genomic regions (i.e., haplotypic blocks) influencing multiple traits. We found that the magnitude of plasticity in whole root mass fraction, fine root mass fraction, and chlorophyll content, as well as leaf Na and K content under saline conditions, were the traits most strongly correlated with expectation-deviation tolerance. Additionally, we identified multiple genomic regions underlying these traits as well as a single gene directly associated with this tolerance metric. Our results show that, by taking the vigor-salinity effect trade-off into account, we can identify unique traits and genes associated with salinity tolerance. Since these traits and genomic regions are distinct from those associated with high vigor (i.e., growth in benign conditions), they provide an avenue for increasing salinity tolerance in high-performing sunflower genotypes without compromising vigor.

Single sentence summary

Despite a trade-off between vigor and salinity-induced decline in biomass, distinct traits and genomic regions exist that could modulate this trade-off in cultivated sunflower.
Investigating the role of N-terminal domain in phosphodiesterase 4B-inhibition by molecular dynamics simulation
Authors: Sharma Vidushi , Wakode Sharad
Published: May 2020

Phosphodiesterase 4B (PDE4B) is a potential therapeutic target for the inflammatory respiratory diseases such as congestive obstructive pulmonary disease (COPD) and asthma. The sequence identity of ∼88% with its isoform PDE4D is the key barrier in developing selective PDE4B inhibitors which may help to overcome associated side effects. Despite high sequence identity, both isoforms differ in few residues present in N-terminal (UCR2) and C-terminal (CR3) involved in catalytic site formation. Previously, we designed and tested specific PDE4B inhibitors considering N-terminal residues as a part of the catalytic cavity. In continuation, current work thoroughly presents an MD simulation-based analysis of N-terminal residues and their role in ligand binding. The various parameters viz. root mean square deviation (RMSD), radius of gyration (Rg), root mean square fluctuation (RMSF), principal component analysis (PCA),dynamical cross-correlation matrix(DCCM) analysis, secondary structure analysis, and residue interaction mapping were investigated to establish rational. Results showed that UCR2 reduced RMSF values for the metal binding pocket (31.5±11 to 13.12±6 Å2) and the substrate-binding pocket (38.8±32 to 17.3±11 Å2). UCR2 enhanced anti-correlated motion at the active site region that led to the improved ligand-binding affinity of PDE4B from −24.57±3 to −35.54±2 kcal/mol. Further, the atomic-level analysis indicated that T-pi and π-π interactions between inhibitors and residues are vital forces that regulate inhibitor association to PDE4B with high affinity. In conclusion, UCR2, the N-terminal domain, embraces the dynamics of PDE4B active site and stabilizes PDE4B inhibitor interactions. Therefore the N-terminal domain needs to be included by designing next-generation, selective PDE4B-inhibitors as potential anti-inflammatory drugs.
Differential myoblast and tenoblast affinity to collagen, fibrin and mixed threads in the prospect of muscle-tendon junction modelisation
Authors: Rieu Clément , Rose Nicolas , Taleb Anissa , Mosser Gervaise , Haye Bernard , Coradin Thibaud , Le Grand Fabien , Trichet Léa
Published: May 2020

The myotendinous junction transfers forces from muscle to tendon. As such, it must hold two tissues of completely different biological and cellular compositions as well as mechanical properties (kPa-MPa to MPa-GPa) and is subject to frequent stresses of high amplitude. This region remains a weak point of the muscle-tendon unit and is involved in frequent injuries. We here produce fibrin (40 mg/mL, E0 =0.10 ± 0.02 MPa) and collagen (60 mg/mL, E0=0.57 ± 0.05 MPa) threads as well as mixed collagen:fibrin threads (3:2 in mass, E0 = 0.33 ± 0.05 MPa) and investigate the difference of affinity between primary murine myoblasts and tenoblasts. We demonstrate a similar behavior of cells on mixed and fibrin threads with high adherence of tenoblasts and myoblasts, in comparison to collagen threads that promote high adherence and proliferation of tenoblasts but not of myoblasts. Besides, we show that myoblasts on threads differentiate but do not fuse, on the contrary to 2D control substrates, raising the question of the effect of substrate curvature on the ability of myoblasts to fusein vitro.
Evolution of body size and wing shape trade-offs in arsenurine silkmoths
Authors: Hamilton Chris A. , Winiger Nathalie , Rubin Juliette J. , Breinholt Jesse , Rougerie Rodolphe , Kitching Ian J. , Barber Jesse R. , Kawahara Akito Y.
Published: May 2020

Abstract

One of the key objectives in biological research is understanding how evolutionary processes have produced Earth’s biodiversity. These processes have led to a vast diversity of wing shapes in insects; an unanswered question especially pronounced in moths. As one of the major predators of nocturnal moths, bats are thought to have been involved in a long evolutionary arms race with their prey. In response, moths are thought to have evolved many counter strategies, such as diverse wing shapes and large body sizes. However, the tradeoffs between body size and wing shape are not well understood. Here we examined the evolution of wing shape in the wild silkmoth subfamily Arsenurinae (Saturniidae). By using phylogenomics and geometric morphometrics, we established the framework to evaluate potential evolutionary relationships between body size and wing shape. The phylogeny was inferred based on 781 loci from target capture data of 42 arsenurine species representing all 10 recognized genera.

We found there are evolutionary trade-offs between body size, wing shape, and the interaction of fore- and hindwing shape. Namely, body size decreases with increasing hindwing length, but increases as forewing shape becomes more complex. Additionally, hindwing shape has a significant effect on forewing shape complexity. The complex wing shapes that make Arsenurinae, and silkmoths as a whole, so charismatic are likely driven by the strong forces of natural selection and genomic constraints.

One other important outcome was discovering within our data one of the most vexing problems in phylogenetic inference – a region of a tree that possesses short branches and no “support” for relationships (i.e., a polytomy). These parts of the Tree of Life are often some of the most interesting from an evolutionary standpoint. To investigate this problem, we used reciprocal illumination to determine the most probable generic relationships within the Arsenurinae by inspecting differing phylogenetic inferences, alternative support values, quartets, and phylogenetic networks to reveal hidden phylogenetic signal.
Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear
Authors: Ma Cassandra , Jean-Richard-dit-Bressel Philip , Roughley Stephanie , Vissel Bryce , Balleine Bernard W. , Killcross Simon , Bradfield Laura A.
Published: May 2020

Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsion and compulsive disorders. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented instrumental conditioned punishment learning in a manner that could not be attributed to differences in Pavlovian conditioned fear. We then showed that increasing the frequency of punishing outcomes allowed mOFC-lesioned animals to overcome their initial deficit. Our second experiment demonstrated that the retrieval of instrumental punishment is also mOFC-dependent, as mOFC lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent the re-acquisition of conditioned punishment that was learned prior to lesions being administered. Together, these results reveal that the mOFC does indeed regulate punishment learning and retrieval in a manner that is disassociated from any role in Pavlovian fear learning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.
The Genomic Landscape of Prostate Cancer Brain Metastases
Authors: Rodriguez Antonio , Gallon John , Akhoundova Dilara , Maletti Sina , Ferguson Alison , Cyrta Joanna , Amstutz Ursula , Garofoli Andrea , Paradiso Viola , Tomlins Scott A. , Hewer Ekkehard , Genitsch Vera , Fleischmann Achim , Rushing Elisabeth J. , Grobholz Rainer , Fischer Ingeborg , Jochum Wolfram , Cathomas Gieri , Bubendorf Lukas , Moch Holger , Ng Charlotte K.Y. , Sommer Silke Gillessen , Piscuoglio Salvatore , Rubin Mark A.
Published: May 2020

Lethal prostate cancer commonly metastasizes to bone, lymph nodes, and visceral organs but with more effective therapies, there is an increased frequency of metastases to the brain. Little is known about the genomic drivers of prostate cancer brain metastases (PCBM). To address this, we conducted a comprehensive multi-regional, genomic, and targeted transcriptomic analysis of PCBM from 28 patients. We compared whole-exome and targeted RNA sequencing with matched primary tumors when available (n = 10) and with publicly available genomic data from non-brain prostate cancer metastases (n = 416). In addition to common alterations inTP53,AR,RB1, andPTEN, we identified highly significant enrichment of mutations inNF1(25% cases (6/28),q= 0.049, 95% CI = 2.38 – 26.52, OR = 8.37) andRICTOR(17.9% cases (5/28),q= 0.01, 95% CI = 6.74 – 480.15, OR = 43.7) in PCBM compared to non-brain prostate cancer metastases, suggesting possible activation of the druggable pathways RAS/RAF/MEK/ERK and PI3K/AKT/mTOR, respectively. Compared to non-brain prostate cancer metastases, PCBM were almost three times as likely to harbor DNA homologous repair (HR) alterations (42.9% cases (12/28), p =0.016, 95% CI = 1.17 – 6.64, OR = 2.8). When considering the combination of somatic mutations, copy number alteration, and Large-scale State Transitions, 64.3% of patients (18/28) were affected. HR alterations may be critical drivers of brain metastasis that potentially provide cancer cells a survival advantage during re-establishment in a special microenvironment. We demonstrate that PCBM have genomic dependencies that may be exploitable through clinical interventions including PARP inhibition.
Construction of mutant heparinase I with significantly increased specific activity
Authors: Kalinina A.N. , Borschevskaya L.N. , Gordeeva T.L. , Patrusheva E. , Sineokiy S.P.
Published: May 2020

The cleavage of heparin by heparin lyases showed great potential as a cost-effective and innoxious method for producing heparin with low molecular weight (LMWH). One of the most studied and sought heparin lyase is heparinase I (HepI). However, the industrial use of HepI was largely hampered by its low specific activity and thermal stability. In this article we describe increasing in specific heparinase I activity by stepwise site-directed mutagenesis. Thus after two cycles of mutagenesis, we obtained mutant heparinase I Flavobacterium heparinum with significantly increased specific activity (25%).
Stress-primed secretory autophagy drives extracellular BDNF maturation
Authors: Martinelli Silvia , Anderzhanova Elmira A. , Wiechmann Svenja , Dethloff Frederik , Weckmann Katja , Bajaj Thomas , Hartmann Jakob , Hafner Kathrin , Pöhlmann Max L. , Jollans Lee , Maccarrone Giuseppina , Hausch Felix , Turck Christoph W , Philipsen Alexandra , Schmidt Mathias V. , Kuster Bernhard , Gassen Nils C
Published: May 2020

The stress response is an essential mechanism that strives to maintain homeostasis, and its disruption is implicated in several psychiatric disorders. As a cellular response to stressors, autophagy is activated to regulate homeostasis through protein degradation and recycling. Secretory autophagy is a recently described pathway where autophagosomes fuse with the plasma membrane rather than lysosomes. In this study, we demonstrate that glucocorticoid-mediated stress enhances secretory autophagy, via the stress-responsive co-chaperone FK506-binding protein 51. We identified the matrix metalloproteinase 9 (MMP9) as one of the stress-induced secreted proteins. Using cellular assays andin vivomicrodialysis, we further found that stress-enhanced MMP9 secretion increases the cleavage of pro-brain derived neurotrophic factor (proBDNF) to its mature form. BDNF is essential for adult synaptic plasticity and its pathway is associated with major depression and posttraumatic stress disorder. These findings unravel a novel mechanistic link between stress, stress adaptation and the development of psychiatric disorders, with possible therapeutic implications.
Data-Driven Modeling of Resource Distribution in Honeybee Swarms
Authors: Fard Golnar Gharooni , Bradley Elizabeth , Peleg Orit
Published: May 2020

Trophallaxis is the mutual exchange and direct transfer of liquid food among eusocial insects such as ants, termites, wasps, and bees. This process allows efficient dissemination of nutrients and is crucial for the colony’s survival. In this paper, we present a data-driven agent-based model and use it to explore how the interactions of individual bees, following simple, local rules, affect the global food distribution. We design the rules in our model using laboratory experiments on honeybees. We validate its results via comparisons with the movement patterns in real bees. Using this model, we demonstrate that the efficiency of food distribution is affected by the density of the individuals, as well as the rules that govern their behavior: e.g., how they move and whether or not they aggregate. Specifically, food is distributed more efficiently when donor bees do not always feed their immediate neighbors, but instead prioritize longer motions, sharing their food with more-distant bees. This non-local pattern of food exchange enhances the overall probability that all of the bees, regardless of their position in the colony, will be fed efficiently. We also find that short-range attraction improves the efficiency of the food distribution in the simulations. Importantly, this model makestestablepredictions about the effects of different bee densities, which can be validated in experiments. These findings can potentially contribute to the design of local rules for resource sharing in swarm robotic systems.
Dynamics of transposable elements in recently diverged fungal pathogens: lineage-specific transposable element content and efficiency of genome defences
Authors: Lorrain Cécile , Feurtey Alice , Möller Mareike , Haueisen Janine , Stukenbrock Eva
Published: May 2020

Transposable elements (TEs) impact genome plasticity, architecture and evolution in fungal plant pathogens. The wide range of TE content observed in fungal genomes reflects diverse efficacy of host-genome defence mechanisms that can counter-balance TE expansion and spread. Closely related species can harbour drastically different TE repertoires, suggesting variation in the efficacy of genome defences. The evolution of fungal effectors, which are crucial determinants of pathogenicity, has been linked to the activity of TEs in pathogen genomes. Here we describe how TEs have shaped genome evolution of the fungal wheat pathogenZymoseptoria triticiand four closely related species. We comparedde novoTE annotations and Repeat-Induced Point mutation signatures in thirteen genomes from theZymoseptoriaspecies-complex. Then, we assessed the relative insertion ages of TEs using a comparative genomics approach. Finally, we explored the impact of TE insertions on genome architecture and plasticity. The thirteen genomes ofZymoseptoriaspecies reflect different TE dynamics with a majority of recent insertions. TEs associate with distinct genome compartments in allZymoseptoriaspecies, including chromosomal rearrangements, genes showing presence/absence variation and effectors. EuropeanZ. triticiisolates have reduced signatures of Repeat-Induced Point mutations compared to Iranian isolates and closely related species. Our study supports the hypothesis that ongoing but moderate TE mobility inZymoseptoriaspecies shapes pathogen genome evolution.