bluuebunny/crossref_metadata_2025 huggingface dataset:
THE USE OF LOW-DOSE CT WITH ADAPTIVE STATISTICAL ITERATIVE RECONSTRUCTION FOR THE DIAGNOSIS OF URINARY CALCULI
Authors: Xie Yingdi , Tao Jingshan , Liu Hailing , Zang Xiaojin , Zhang Zhengming , Guo Guangjie , Liu Bin
Published: June 2020

This study aimed to explore the diagnosis of urinary calculi through utilisation of low-dose computed tomography (LDCT) with adaptive statistical iterative reconstruction (ASIR). Data from 140 patients that had undergone pathological or operative diagnosis with urinary calculi were analysed. Patients were divided into two groups based on whether they received conventional-dose computed tomography (CDCT) or LDCT, respectively, followed by filtered back projection or ASIR. Average CDCT radiation doses were roughly 4-fold higher than LDCT doses. Despite this difference, there were no significant differences between groups with respect to stone size or location, image quality (P = 0.261), image noise (P = 0.153) and diagnostic efficacy (P = 0.371). LDCT is an effective approach to urinary calculi diagnosis, performing to ASIR while decreasing the effective radiation dose, improving the safety of this procedure.
Neurocognitive underpinnings of cross-cultural differences in risky decision making
Authors: Chen Xing-Jie , Ba Lan , Kwak Youngbin
Published: June 2020

Culture permeates across human mind and behavior. Cultural influence is reported even in economic decision making, which involves basic cognitive process, once believed to be invariant across all humans. The current study investigated the neurocognitive processes underlying economic decision making in East Asians and European Americans, with an aim to understand the cross-cultural differences in the discrete mental processes of decision making. Participants performed a risky gambling task that captures the gain maximizing and loss minimizing strategies, while electroencephalography was simultaneously collected. Event-related potentials (ERPs) associated with spontaneous emotional arousal (P2) and effortful attentional allocation (P3) were examined to determine the cultural effects on mental processes during pre-decisional and post-decisional stages. Behaviorally, Americans showed greater loss minimization than Asians. ERPs demonstrated significant cultural differences during post-decisional evaluation of outcomes, but not during pre-decisional processes. In Asians’, ERP associated with emotional arousal (P2) was strongly modulated by gains, while in Americans’, ERP associated with attentional allocation (P3) was strongly modulated by losses. These results suggest that Americans make conscious efforts to be self-reliant when facing financial losses, whereas Asians are more emotionally aroused by financial gains, which invites a refinement to the current theoretical propositions about cultural influence on decision making.
Family Foundations in Switzerland
Authors: Peter Natalie
Published: June 2020

At a governmental level, the introduction of a Swiss law on trusts is currently being reviewed. One of the arguments is that Switzerland does not provide for a suitable instrument to be used for estate planning or asset protection purposes. Many scholars and practitioners take the view, though, that a common law trust is not a suitable instrument and that therefore it would be more advisable to review the existing instruments, such as the Swiss family foundation or the fiducie (Treuhand), and to amend them accordingly. This article shall shed some light on the Swiss family foundation, on its use and limits and how it could be used de lege ferenda in the future if its legal limits were finally to be released.
Prone Positioning for Pregnant Women With Hypoxemia Due to Coronavirus Disease 2019 (COVID-19)
Authors: Tolcher Mary Catherine , McKinney Jennifer R. , Eppes Catherine S. , Muigai David , Shamshirsaz Amir , Guntupalli Kalpalatha K. , Nates Joseph L.
Published: June 2020

The coronavirus disease 2019 (COVID-19) pandemic has prompted expanded use of prone positioning for refractory hypoxemia. Clinical trials have demonstrated beneficial effects of early prone positioning for acute respiratory distress syndrome (ARDS), including decreased mortality. However, pregnant women were excluded from these trials. To address the need for low-cost, low-harm interventions in the face of a widespread viral syndrome wherein hypoxemia predominates, we developed an algorithm for prone positioning of both intubated and nonintubated pregnant women. This algorithm may be appropriate for a wide spectrum of hypoxemia severity among pregnant women. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is responsible for the clinical manifestations of COVID-19. This syndrome can manifest as severe pneumonia complicated by hypoxemia and ARDS. Given the current global COVID-19 pandemic, with a large number of ARDS cases, there is renewed interest in the use of prone positioning to improve oxygenation in moderate or severe hypoxemia. Among the populations who can benefit from prone positioning are pregnant women experiencing severe respiratory distress, as long as the physiologic changes and risks of pregnancy are taken into account.
Unusual Circumstances and Additional Procedures for Fetal Evaluation in Labor
Authors: RICHARDS DOUGLAS S.
Published: June 2020

This chapter describes several circumstances in which the interpretation of the intrapartum fetal heart rate pattern falls outside the usual frame of reference. This includes a more extensive discussion of causes of tachycardia and bradycardia. Ways in which a fetal dysrhythmia may manifest itself in the context of heart rate monitoring are described. Finally, the chapter reviews technological innovations designed to clarify the fetal status when compromise is suspected from the fetal heart rate pattern.
Blood pressure variability and microvascular dysfunction: the Maastricht Study
Authors: Zhou Tan Lai , Rensma Sytze P. , van der Heide Frank C.T. , Henry Ronald M.A. , Kroon Abraham A. , Houben Alfons J.H.M. , Jansen Jacobus F.A. , Backes Walter H. , Berendschot Tos T.J.M. , Schouten Jan S.A.G. , van Dongen Martien C.J.M. , Eussen Simone J.P.M. , Dagnelie Pieter C. , Webers Carroll A.B. , Schram Miranda T. , Schalkwijk Casper G. , van Sloten Thomas T. , Stehouwer Coen D.A.
Published: June 2020

Background:

Microvascular dysfunction (MVD) contributes to stroke, dementia, depression, retinopathy and chronic kidney disease. However, the determinants of MVD are incompletely understood. Greater blood pressure variability (BPV) may be one such determinant.

Methods and results:

We used cross-sectional data of The Maastricht Study (n = 2773, age 59.9 years; 51.9% men) to investigate whether greater very short- to mid-term BPV is associated with various MVD measures. We standardized and averaged within-visit, 24-h and 7-day BPV into a systolic and a diastolic BPV composite score. MVD measures included a composite score of MRI cerebral small vessel disease (CSVD) features (total brain parenchymal volume, white matter hyperintensity volume, lacunar infarcts and cerebral microbleeds), a composite score of flicker light-induced retinal arteriolar and venular dilation response, albuminuria, heat-induced skin hyperemia and a composite score of plasma biomarkers of MVD (sICAM-1, sVCAM-1, sE-selectin and von Willebrand Factor). We used linear regression adjusted for age, sex, glucose metabolism status, mean 24-h systolic or DBP, cardiovascular risk factors and antihypertensive medication. We found that higher systolic and diastolic BPV composite scores (per SD) were associated with higher albuminuria [higher ratio, 1.04 (95% CI 1.00–1.08) and 1.07 (1.03–1.11), respectively], but not with other measures of MVD tested.

Conclusion:

Greater systolic and diastolic BPV was associated with higher albuminuria, but not with CSVD features, flicker light-induced retinal arteriolar and venular dilation response, heat-induced skin hyperemia and plasma biomarkers of MVD. This suggests that the microvasculature of the kidneys is most vulnerable to the detrimental effects of greater BPV.
Baloxavir Marboxil Single-dose Treatment in Influenza-infected Children
Authors: Baker Jeffrey , Block Stanley L. , Matharu Balpreet , Burleigh Macutkiewicz Laura , Wildum Steffen , Dimonaco Sophie , Collinson Neil , Clinch Barry , Piedra Pedro A.
Published: June 2020

Background:

Baloxavir marboxil (baloxavir) is a novel, cap-dependent endonuclease inhibitor that has previously demonstrated efficacy in the treatment of influenza in adults and adolescents. We assessed the safety and efficacy of baloxavir in otherwise healthy children with acute influenza.

Methods:

MiniSTONE-2 (Clinicaltrials.gov: NCT03629184) was a double-blind, randomized, active controlled trial enrolling children 1–<12 years old with a clinical diagnosis of influenza. Children were randomized 2:1 to receive either a single dose of oral baloxavir or oral oseltamivir twice daily for 5 days. The primary endpoint was incidence, severity and timing of adverse events (AEs); efficacy was a secondary endpoint.

Results:

In total, 173 children were randomized and dosed, 115 to the baloxavir group and 58 to the oseltamivir group. Characteristics of participants were similar between treatment groups. Overall, 122 AEs were reported in 84 (48.6%) children. Incidence of AEs was similar between baloxavir and oseltamivir groups (46.1% vs. 53.4%, respectively). The most common AEs were gastrointestinal (vomiting/diarrhea) in both groups [baloxavir: 12 children (10.4%); oseltamivir: 10 children (17.2%)]. No deaths, serious AEs or hospitalizations were reported. Median time (95% confidence interval) to alleviation of signs and symptoms of influenza was similar between groups: 138.1 (116.6–163.2) hours with baloxavir versus 150.0 (115.0–165.7) hours with oseltamivir.

Conclusions:

Oral baloxavir is well tolerated and effective at alleviating symptoms in otherwise healthy children with acute influenza. Baloxavir provides a new therapeutic option with a simple oral dosing regimen.
Familial macro thrombocytopenia: role of genetics where morphology fails
Authors: Chaudhary Himanshi , Jindal Ankur , Guleria Sandesh , Sharma Saniya , Sachdeva Man U.S. , Ahluwalia Jasmina
Published: June 2020

Myosin heavy chain 9 (MYH9)-related disorders are rare inherited platelet disorders that are accompanied by a wide variety of systemic abnormalities. The persistent thrombocytopenia is usually asymptomatic and these patients are often misdiagnosed and treated as immune thrombocytopenia. MYH9 gene has been studied in association with solid organ malignancies. We report a young girl with family history of thrombocytopenia and hearing loss who presented with kidney dysfunction and later developed acute lymphoblastic leukemia. She lacked the characteristic inclusion bodies in her blood granulocytes, however a diagnosis of MYH9-related Epstein syndrome was confirmed on genetic testing. In the background of known causal association of MYH9 gene in solid organ malignancies, the role of MYH9 gene variant in malignant transformation in the index case remains conjectural.
Early Delays in Insurance Coverage and Long-term Use of Home-based Peritoneal Dialysis
Authors: Lin Eugene , Chertow Glenn M. , Bhattacharya Jay , Lakdawalla Darius
Published: June 2020

Background:

Uninsured patients with end-stage renal disease face barriers to peritoneal dialysis (PD), a type of home dialysis that is associated with improved quality of life and reduced Medicare costs. Although uninsured patients using PD at dialysis start receive retroactive Medicare coverage for required predialysis services, coverage only applies for the calendar month of dialysis start. Thus, initiating dialysis later in the month yields longer retroactive coverage.

Objectives:

To examine whether differences in retroactive Medicare were associated with decreased long-term PD use.

Research Design:

We exploited the dialysis start date using a regression discontinuity design on a national cohort from the US Renal Data System.

Subjects:

36,256 uninsured adults starting dialysis between January 1, 2006 and December 31, 2014.

Measures:

PD use at dialysis days 1, 90, 180, and 360.

Results:

Starting dialysis on the first versus last day of the calendar month was associated with an absolute decrease in PD use of 2.7% [95% confidence interval (CI), 1.5%–3.9%], or a relative decrease of 20% (95% CI, 12%–27%) at dialysis day 360. The absolute decrease was 5.5% (95% CI, 3.5%–7.2%) after Medicare established provider incentives for PD in 2011 and 7.2% (95% CI, 2.5%–11.9%) after Medicaid expansion in 2014. Patients were unlikely to switch from hemodialysis to PD after the first month of dialysis (probability of 6.9% in month 1, 1.5% in month 2, and 0.9% in month 4).

Conclusions:

Extending retroactive coverage for preparatory dialysis services could increase PD use and reduce overall Medicare spending in the uninsured.
Diagnostic performance of F-18 fluciclovine PET/CT in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen level ≤0.5 ng/mL
Authors: Teyateeti Ajalaya , Khan Bilal , Teyateeti Achiraya , Chen Bo , Bridhikitti Jidapa , Pan Tinsu , Peng Wei , Macapinlac Homer A. , Lu Yang
Published: June 2020

Purpose

The aim of the study was to assess the diagnostic performance of fluciclovine positron emission tomography (PET)/computerized tomography (CT) in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen (PSA) ≤0.5 ng/mL, and identify the associated predictive factors of positive studies.

Patients and methods

From 30 June 2017 to 9 August 2019, patients with post-radical prostatectomy prostate cancer who underwent F-18 fluciclovine PET/CT and had PSA level within 2-week interval (PSAPET) ≤0.5 ng/mL were enrolled into this single-institution retrospective study. Data on tumor characteristics, including Gleason scores, extra-prostatic extension, seminal vesicle invasion, surgical margin and nodal metastasis, PSA after radical prostatectomy, previous hormonal therapy, PSA doubling time (PSADT), scanner type, PSAPET and site of recurrence were collected. Comparison of these factors between groups of positive and negative fluciclovine PET/CT was done by using Mann–Whitney U-test and Fisher’s exact test.

Results

Of 94 eligible patients with post-radical prostatectomy prostate cancer, 10 patients had positive studies (10.6%). Detection rate at PSAPET 0.1, 0.2, 0.3, 0.4 and 0.5 ng/mL were 0% (0/11), 0% (0/15), 20% (6/30), 4% (1/25) and 23.1% (3/13), respectively. Upon multivariate analysis of clinical factors, only a PSADT <3 months (P = 0.023) was shown to have a statistically significant correlation with a positive study.

Conclusion

In post-radical prostatectomy prostate cancer patients with rising PSA 0.1–0.5 ng/mL, the sensitivity of F-18 fluciclovine PET/CT for identifying tumor recurrence/metastases is poor with an overall detection rate of 10.6%. Larger prospective studies are required to validate these findings.
The Cascade of Care From Routine Point-of-Care HIV Testing at Birth: Results From an 18-Months Pilot Program in Eswatini
Authors: Khumalo Philisiwe Ntombenhle , Sacks Emma , Chouraya Caspian , Tsabedze Bhekisisa , Masuku Thembie , Nyoni Gcinile , Zikalala Tandzile , Nhlabatsi Bonisile , Mthethwa Nobuhle , Cohn Jennifer
Published: June 2020

Background:

HIV testing at birth may improve early treatment, but concerns remain about feasibility and retention of infants in care. In 2017, point-of-care (POC) HIV birth testing was introduced into routine care at 3 high-volume maternity health facilities in Eswatini.

Methods:

POC birth testing was offered to HIV-exposed infants (HEI) born at, or presenting to, 3 maternities within 3 days of birth. Data were collected from a project-specific EID test request form and routine registers on all tests conducted from August 1, 2017 to November 30, 2018, including retesting at 6–8 weeks for infants testing negative at birth and six-month retention in HIV care and viral load suppression among infants testing HIV-positive at birth.

Results:

Of 4322 eligible HEI, 3311 (76.6%) were tested. Twenty-six HIV-infected infants were identified (positivity rate 0.8%) and 25 initiated on antiretroviral therapy (ART) (96.1%). The median time from sample collection to ART initiation was 20.50 days (IQR 14–45). Twenty-one (84%) ART-initiated infants were on ART at 6 months after initiation. Nineteen infants (90.5%) had viral load test information at 6 months and 16 (84.2%) were virally suppressed. Of 3126 HEI testing negative at birth, 3004 (96.1%) were linked to laboratory databases and 2744 (91.3%) were retested at 6–8 weeks, with 9 (0.3%) additional infants testing HIV-positive.

Conclusions:

Uptake of POC birth testing was high in Eswatini with low HIV positivity. Almost all infants identified HIV-positive at birth were initiated on ART, with high retention in care and viral suppression. Birth testing did not seem to significantly reduce subsequent 6–8-week testing.
The Regimen of Computed Tomography Screening for Lung Cancer
Authors: Henschke Claudia I. , Yip Rowena , Shaham Dorith , Zulueta Javier J. , Aguayo Samuel M. , Reeves Anthony P. , Jirapatnakul Artit , Avila Ricardo , Moghanaki Drew , Yankelevitz David F.
Published: June 2020

We learned many unanticipated and valuable lessons since we started planning our study of low-dose computed tomography (CT) screening for lung cancer in 1991. The publication of the baseline results of the Early Lung Cancer Action Project (ELCAP) in Lancet 1999 showed that CT screening could identify a high proportion of early, curable lung cancers. This stimulated large national screening studies to be quickly started. The ELCAP design, which provided evidence about screening in the context of a clinical program, was able to rapidly expand to a 12-institution study in New York State (NY-ELCAP) and to many international institutions (International-ELCAP), ultimately working with 82 institutions, all using the common I-ELCAP protocol. This expansion was possible because the investigators had developed the ELCAP Management System for screening, capturing data and CT images, and providing for quality assurance. This advanced registry and its rapid accumulation of data and images allowed continual assessment and updating of the regimen of screening as advances in knowledge and new technology emerged. For example, in the initial ELCAP study, introduction of helical CT scanners had allowed imaging of the entire lungs in a single breath, but the images were obtained in 10 mm increments resulting in about 30 images per person. Today, images are obtained in submillimeter slice thickness, resulting in around 700 images per person, which are viewed on high-resolution monitors. The regimen provides the imaging acquisition parameters, imaging interpretation, definition of positive result, and the recommendations for further workup, which now include identification of emphysema and coronary artery calcifications. Continual updating is critical to maximize the benefit of screening and to minimize potential harms. Insights were gained about the natural history of lung cancers, identification and management of nodule subtypes, increased understanding of nodule imaging and pathologic features, and measurement variability inherent in CT scanners. The registry also provides the foundation for assessment of new statistical techniques, including artificial intelligence, and integration of effective genomic and blood-based biomarkers, as they are developed.
Giant Mixed Tumor of the Skin Affecting the Hemiface
Authors: Sung Kun-Yong , Lee Seung-Koo , Jeong Yeon-Jin , Lee Sang-Yeul
Published: June 2020

Mixed tumor of the skin (MTS) is a rare skin adnexal neoplasm occurring in sweat glands. It is usually benign, measures 0.5 to 3 cm, and presents as a slowly growing, painless, firm nodule commonly in the head and neck regions. Owing to its rarity and lack of distinctive clinical manifestations, confirmative diagnosis is made on the basis of its pathologic features. Malignant MTS also develops de novo or from preexisting benign MTS even though they occur rarely. It should be excised completely to exclude malignant potentials. Herein, we report a 35-year history of a giant MTS of eccrine type measuring approximately 10.5 × 6.5 cm on the right hemiface of a 91-year-old woman, which is the largest facial MTS reported in the literature so far, to the best of our knowledge.
Evolution of reduced minimum critical size as a response to selection for rapid pre-adult development inDrosophila melanogaster
Authors: Sharma Khushboo , Mishra Nalini , Shakarad Mallikarjun N.
Published: June 2020

Adult body size in holometabolus insects is directly proportional to the time spent during the larval period. The larval duration can be divided into two parts: (i) pre-critical duration—time required to attain a critical size/critical weight that would result in successful completion of development and metamorphosis even under non-availability of nutrition beyond the time of attainment of critical size, and (ii) post-critical duration—the time duration from the attainment of critical size till pupation. It is of interest to decipher the relative contribution of the two larval growth phases (from the hatching of the egg to the attainment of critical size, and from the attainment of critical size to pupation) to the final adult size. Many studies usingDrosophila melanogasterhave shown that selecting populations for faster development results in the emergence of small adults. Some of these studies have indirectly reported the evolution of smaller critical size. Using two kinds ofD. melanogasterpopulations, one of which is selected for faster/accelerated pre-adult development and the other their ancestral control, we demonstrate that the final adult size is determined by the time spent as larvae post the attainment of critical size despite having increased growth rate during the second larval instar. Our populations under selection for faster pre-adult development are exhibiting adaptive bailout due to intrinsic food limitation as against extrinsic food limitation in the yellow dung fly.
Contributions of modern network science to the cognitive sciences: revisiting research spirals of representation and process
Authors: Castro Nichol , Siew Cynthia S. Q.
Published: June 2020

Modelling the structure of cognitive systems is a central goal of the cognitive sciences—a goal that has greatly benefitted from the application of network science approaches. This paper provides an overview of how network science has been applied to the cognitive sciences, with a specific focus on the two research ‘spirals’ of cognitive sciences related to therepresentationandprocessesof the human mind. For each spiral, we first review classic papers in the psychological sciences that have drawn on graph-theoretic ideas or frameworks before the advent of modern network science approaches. We then discuss how current research in these areas has been shaped by modern network science, which provides the mathematical framework and methodological tools for psychologists to (i) represent cognitive network structure and (ii) investigate and model the psychological processes that occur in these cognitive networks. Finally, we briefly comment on the future of, and the challenges facing, cognitive network science.
Chryseobacterium vaccae sp. nov., isolated from raw cow's milk
Authors: Lee Ju-Eun , Yoon Sung-Hee , Lee Gi-Yong , Lee Do-Hoon , Huh Chul-Sung , Kim Geun-Bae
Published: June 2020

Strain CA7T, a Gram-stain-negative, non-motile, non-spore-forming, aerobic and rod-shaped bacterial strain, was isolated from raw cow’s milk collected from a farm affiliated with Chung-Ang University, Anseong, Korea, and characterized by a polyphasic approach. Optimal growth of strain CA7T was observed on tryptic soy agar at 30 °C and pH 7.0 with 0 % NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain CA7T belonged to the genus

Chryseobacterium

. The most closely related strains (16S rRNA gene sequence similarity indicated in parentheses), based on the phylogenetic analysis, were

Chryseobacterium rhizosphaerae

KCTC 22548T (98.08 %),

Chryseobacterium nakagawai

CCUG 60563T (98.61 %),

Chryseobacterium jejuense

KACC 12501T (97.85 %) and

Chryseobacterium aurantiacum

KCTC 62135T (97.78 %). Whole genome sequencing indicated that the genome size was 5 125 723 bp and had a DNA G+C content of 37.4 mol%. Average nucleotide identity values for strain CA7T with

C. rhizosphaerae

,

C. nakagawai

,

C. jejuense

,

C. aurantiacum

, and the type species of the genus Chryseobacterium, C. gleum, were 80.2, 79.8, 79.8, 79.6 and 80.4 %, respectively. The digital DNA–DNA hybridization values of CA7T compared to

C. rhizosphaerae

,

C. nakagawai

,

C. jejuense

,

C. aurantiacum

and

C. gleum

were 24.1, 23.9, 23.9, 23.7 and 24.3 %, respectively. The major fatty acids were iso-C15 : 0, summed feature 9 (iso-C17 : 1
ω9c and/or C16 : 0 10-methyl), iso-C17 : 0 3-OH and summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1
ω7c). Menaquinone-6 was the only respiratory quinone. The major polar lipid was phosphatidylethanolamine. Based on this polyphasic taxonomic study, strain CA7T represents a novel species of the genus

Chryseobacterium

for which the name Chryseobacterium vaccae sp. nov. is proposed. The type strain is CA7T (=KACC 21402T=JCM 33749T).
The status of the species Lactobacillus fornicalis Dicks et al. 2000. Request for an opinion
Authors: Ribeiro Teresa Gonçalves , Rocha Joana , Ksiezarek Magdalena , Perovic Svetlana Ugarcina , Grosso Filipa , Peixe Luísa
Published: June 2020

During a recent study on members of the genus

Lactobacillus

we realized that cultures of

Lactobacillus fornicalis

TV 1018T (=DSM 13171T=ATCC 700934T) are no longer available from the online catalogue of the German Collection of Microorganisms and Cell Cultures GmbH, being displayed as

Lactobacillus plantarum

at the American Type Culture Collection. Based on data currently available, the organism deposited as ATCC 700934T is a member of the species

Lactobacillus plantarum

subs. plantarum. Therefore, the type strain of

Lactobacillus fornicalis

cannot be included in any further scientific comparative study. This matter is referred to the Judicial Commission, asking for an opinion on the status of the species.
Microglial trogocytosis and the complement system regulate axonal pruningin vivo
Authors: Lim Tony K.Y. , Ruthazer Edward S.
Published: June 2020

Partial phagocytosis—called trogocytosis—of axons by microglia has been documented inex vivopreparations but has not been directly observedin vivo. The mechanisms that modulate microglial trogocytosis of axons and its function in neural circuit development remain poorly understood. Here we directly observe axon trogocytosis by microgliain vivoin the developingXenopus laevisretinotectal circuit. We show that microglia regulate pruning of retinal ganglion cell axons and are important for proper behavioral response to dark and bright looming stimuli. We identify amphibian regulator of complement activation 3, a homolog of human CD46, as a neuronally-expressed synapse-associated complement inhibitory molecule that inhibits trogocytosis and axonal pruning. Using a membrane-bound complement C3 fusion protein, we demonstrate that enhancing complement activity enhances axonal pruning. Our results support the model that microglia remodel axons via trogocytosis and that neurons can control this process through expression of complement inhibitory proteins.
Comparative transcriptomics reveal conserved modules of plant defence against different pathogens in Strawberry
Authors: Badmi Raghuram , Sheikh Arsheed Hussain
Published: June 2020

Strawberry (Fragaria×ananassa)is an economically important high-value crop that is susceptible to three most devastating pathogens with different lifestyles – a necrotrophic fungusBotrytis cinereacausing grey mold, a hemibiotrophic oomycetePhytophthora cactorumcausing crown/root rot, and a biotrophic fungusPodosphaera aphaniscausing powdery mildew. Studies on individual plant-pathogen interactions are only sufficient for developing disease resistant strawberry varieties to a particular pathogen. However, each of these pathogens have the potential to co-infect strawberry at a given point of time. Therefore, understanding how these pathogens manipulate strawberry’s defences and how it responds to these pathogens is essential for developing broad-spectrum disease resistant varieties. Here, in the diploid modelFragaria vesca, we performed comparative transcriptome analysis between each of these pathogen infections to identify 501CommonResponsive (CoRe) genes targeted against these pathogens. Furthermore, about 80% of these CoRe set are upregulated upon infection by all three pathogens indicating a similar transcriptional response ofF. vescaindependent of pathogen’s lifestyle. These upregulated CoRe set include genes from well-known defence responsive pathways such as calcium and MAP kinase signalling, WRKY transcription factors, pathogenesis-related allergen genes and hormone and terpene biosynthetic genes. These novel insights intoF. vesca’s defences might serve as a basis for engineering plants with broad spectrum resistance.
Long-lasting event-related beta synchronizations of electroencephalographic activity in response to support-surface perturbations during upright stance
Authors: Nakamura Akihiro , Suzuki Yasuyuki , Milosevic Matija , Nomura Taishin
Published: June 2020

Movement related beta band cortical oscillations, including beta rebound after execution and/or suppression of movement, have drawn attention in upper extremity motor control literature. However, fewer study focused on beta band oscillations during postural control in upright stance. Here, we examined beta rebound and other components of electroencephalogram (EEG) activity during perturbed upright stance to investigate supraspinal contributions to postural stabilization. Particularly, we aimed to clarify the timing and duration of beta rebound within a non-sustained, but long-lasting, postural recovery process that occurs more slowly compared to upper extremities. To this end, EEG signals were acquired from nine healthy young adults in response to a support-surface perturbation, together with the center of pressure (CoP) and mass (CoM) and electromyogram (EMG) activities of ankle muscles. Event-related potentials (ERPs) and event-related spectral perturbations were computed from EEG data using the perturbation-onset as a triggering event. After short-latency (< 0.3 s) ERPs, our results showed high-beta band power decrease (event-related desynchronization), which was followed by an event-related synchronization at high-beta band and theta band desynchronization. Specifically, beta synchronization (beta rebound) was sustained for as long as three seconds. EMGs of the ankle muscles and the ankle and hip joint torques remained activated in the first half period of the beta rebound. They returned to the steady-state in the remaining phase, where the CoP/CoM were in their final approach to the equilibrium. We propose possible mechanistic causes of the long-lasting beta rebound, which may be related to underlying intermittent control strategy in upright stance.

New & Noteworthy

Beta rebound cortical activity was identified during postural recovery from a perturbed upright stance. Contrary to upper extremities, it was initiated before the recovery of motion was completed, and sustained for as long as three seconds. Those novel characteristics of the beta rebound might be caused by slow dynamics of the upright posture and by selections of on/off switching in an intermittent feedback controller, which was shown to stabilize upright posture.
Structure Basis for Inhibition of SARS-CoV-2 by the Feline Drug GC376
Authors: Luan Xiaodong , Shang Weijuan , Wang Yifei , Yin Wanchao , Jiang Yi , Feng Siqin , Wang Yiyang , Liu Meixi , Zhou Ruilin , Zhang Zhiyu , Wang Feng , Cheng Wang , Gao Minqi , Wang Hui , Wu Wei , Tian Ran , Tian Zhuang , Jin Ye , Jiang Hualiang , Zhang Leike , Xu H. Eric , Zhang Shuyang
Published: June 2020

The pandemic of SARS-CoV-2 coronavirus disease-2019 (COVID-19) caused by SARS-COV-2 continues to ravage many countries in the world. Mpro is an indispensable protein for viral translation in SARS-CoV-2 and a potential target in high-specificity anti-SARS-CoV-2 drug screening. In this study, to explore potential drugs for treating COVID-19, we elucidated the structure of SARS-CoV-2 Mpro and explored the interaction between Mpro and GC376, an antiviral drug used to treat a range of coronaviruses in Feline via inhibiting Mpro. The availability and safety of GC376 were proved by biochemical and cell experiments in vitro. We determined the structure of an important protein, Mpro, in SARS-CoV-2, and revealed the interaction of GC376 with the viral substrate and inhibition of the catalytic site of SARS-CoV-2 Mpro.
Insights on long-distance dispersal, ecological and morphological evolution in the fern genusMicrogrammafrom phylogenetic inferences
Authors: Almeida Thaís Elias , Salino Alexandre , Dubuisson Jean-Yves , Hennequin Sabine
Published: June 2020

The epiphytic fern genusMicrogramma(Polypodiaceae) comprises 30 species occurring mainly in the Neotropics with one species in Africa, being an example of trans-Atlantic disjunction. Morphologically and ecologically,Microgrammapresents a wide variation that is not seen in its closest related genera. Recent works changed the circumscription ofMicrogrammato better conform with phylogenetic evidence, but no comprehensively sampled study has addressed the evolution of this lineage. This study aimed to investigate phylogenetic relationships, ecological and morphological evolution withinMicrogramma, as well as test the role of long-distant dispersal in the history of the genus. Sequences from five plastid regions were used to infer the phylogenetic relationships and estimate divergence times. Our results show five clades inMicrogrammathat do not corroborate any infrageneric classification system proposed. Several morphological traits seem to be homoplastic, such as leaf dimorphism. Tuber-like myrmecodomatia are suggested to be synapomorphic for one clade, although ant-plant association appears in two distinct lineages.Microgramma lycopodioidesandM. mauritianaare not closely related, with the African species nested within an Atlantic Forest clade, indicating a long-distance dispersal event estimated to have occurred around 15 Ma from South America to Africa, followed by speciation.
In vitroendoderm emergence and self-organisation in the absence of extraembryonic tissues and embryonic architecture
Authors: Vianello Stefano , Lutolf Matthias P.
Published: June 2020

The endoderm is the cell lineage which gives rise in the embryo to the organs of the respiratory and gastrointestinal system. Uniquely, endodermal tissue does not just derive from descendants of the embryo proper (the epiblast) but instead arises from their gradual incorporation into an extraembryonic substrate (the visceral endoderm). Given the configuration of the early embryo, such a paradigm requires epiblast endodermal progenitors to negotiate embryonic compartments with very diverse epithelial character, a developmental contingency reflected by the fact that key early endodermal markers such asFoxa2andSox17have been consistently found to be embedded within gene programmes involved in epithelialisation.

To explore the underlying cell biology of embryonic endoderm precursors, and to explore the relationship between endoderm development, epithelial identity, and extraembryonic mixing, we leveraged Gastruloids,in vitromodels of early development. These self-organising three-dimensional aggregates of mouse embryonic stem cells do not possess an extraembryonic component, nor do they appear to display typical tissue architecture. Yet, they generate cells expressing endodermal markers. By tracking these cells throughoutin vitrodevelopment, we highlight a persistent and uninterrupted pairing between epithelial and endodermal identity, with FoxA2+/Sox17+ endoderm progenitors never transitioning through mesenchymal intermediates and never leaving the epithelial compartment in which they arise. We also document the dramatic morphogenesis of these progenitors into a macroscopic epithelial primordium extending along the entire anterior-posterior axis of the Gastruloid. Finally, we find that this primordium correctly patterns into broad domains of gene expression, and matures cells with anterior foregut, midgut, and hindgut identities within 7 days of culture. We thus postulate that Gastruloids may serve as a potential source of endodermal types difficult to obtain through classical 2D differentiation protocols.
Socio-demographic determinants associated with Blastocystis infection in Arequipa, Peru
Authors: Salazar-Sánchez Renzo S. , Ascuña-Durand Kasandra , Cartillo-Neyra Ricardo , Vásquez-Huerta Victor , Martínez-Barrios Elí , Ballón-Echegaray Jorge
Published: June 2020

Blastocystis is one of the most common protozoa in the human gut and is a zoonotic parasite related to unhealthy living conditions. This parasite shows a broad distribution, unclear symptomatology, and undefined pathogenicity. In Peru, studies report the presence of Blastocystis in many regions, but the highest prevalence levels are reported in Arequipa. The aim of this study was to link Blastocystis infection with social determinants of health. We recruited and survey 232 participants from infected and uninfected homes. All samples were analyzed by direct microscopy and confirmed with methylene-stained stool smear. We found a human Blastocystis prevalence of 51.3% in the study sample. We also found statistical associations between Blastocystis infection and the use of alternative non-domiciliary water supplies as well as the use of latrine for body-waste disposal, suggesting these are risk factors for human Blastocystis infection.
Eye-movement related brain potentials during assisted navigation in real-world
Authors: Wunderlich Anna , Gramann Klaus
Published: June 2020

Conducting neuroscience research in the real world remains challenging because of movement- and environment-related artifacts as well as missing control over stimulus presentation. The present study demonstrated that it is possible to investigate the neuronal correlates underlying visuo-spatial information processing during real-world navigation. Using mobile EEG allowed for extraction of saccade- and blink-related potentials as well as gait-related EEG activity. In combination with source-based cleaning of non-brain activity and unfolding of overlapping event-related activity, brain activity of naturally behaving humans was revealed even in a complex and dynamic city environment.
Model-based prediction of muscarinic receptor function from auditory mismatch negativity responses
Authors: Schöbi Dario , Jung Fabienne , Frässle Stefan , Endepols Heike , Moran Rosalyn J. , Friston Karl J. , Tittgemeyer Marc , Heinzle Jakob , Stephan Klaas Enno
Published: June 2020

Abstract

Drugs affecting neuromodulation, for example by dopamine or acetylcholine, take centre stage among therapeutic strategies in psychiatry. These neuromodulators can change both neuronal gain and synaptic plasticity and therefore affect electrophysiological measures. An important goal for clinical diagnostics is to exploit this effect in the reverse direction, i.e., to infer the status of specific neuromodulatory systems from electrophysiological measures.

In this study, we provide proof-of-concept that the functional status of cholinergic (specifically muscarinic) receptors can be inferred from electrophysiological data using generative (dynamic causal) models. To this end, we used epidural EEG recordings over two auditory cortical regions during a mismatch negativity (MMN) paradigm in rats. All animals were treated, across sessions, with muscarinic receptor agonists and antagonists at different doses. Together with a placebo condition, this resulted in five levels of muscarinic receptor status. Using a dynamic causal model - embodying a small network of coupled cortical microcircuits - we estimated synaptic parameters and their change across pharmacological conditions. The ensuing parameter estimates associated with (the neuromodulation of) synaptic efficacy showed both graded muscarinic effects and predictive validity between agonistic and antagonistic pharmacological conditions.

This finding illustrates the potential utility of generative models of electrophysiological data as computational assays of muscarinic function. In application to EEG data of patients from heterogeneous spectrum diseases, e.g. schizophrenia, such models might help identify subgroups of patients that respond differentially to cholinergic treatments.

SignificanceStatement

In psychiatry, the vast majority of pharmacological treatments affect actions of neuromodulatory transmitters, e.g. dopamine or acetylcholine. As treatment is largely trial-and-error based, one of the goals for computational psychiatry is to construct mathematical models that can serve as “computational assays” and infer the status of specific neuromodulatory systems in individual patients. This neuro-modelling strategy has great promise for electrophysiological data in particular but requires careful validation. The present study demonstrates that the functional status of cholinergic (muscarinic) receptors can be inferred from electrophysiological data using dynamic causal models of neural circuits. While accuracy needs to be enhanced and our results must be replicated in larger samples, our current results provide proof-of-concept for computational assays of muscarinic function using EEG.
Hitchhiking on condensed chromatin promotes plasmid persistence in yeast without perturbing chromosome function
Authors: Prajapati Hemant Kumar , Kumar Deepanshu , Yang Xian-Mei , Ma Chien-Hui , Mittal Priyanka , Jayaram Makkuni , Ghosh Santanu K.
Published: June 2020

Equipartitioning by chromosome hitchhiking and copy number correction by DNA amplification are at the heart of the evolutionary success of the selfish yeast 2-micron plasmid. The present analysis reveals plasmid presence near centromeres and telomeres in mitotic cells, with a preference towards the latter. The observed correlation of plasmid missegregation with non-disjunction of rDNA and telomeres under Cdc14 inactivation, higher plasmid missegregation upon induced missegregation of chromosome XII but not chromosome III, requirement of condensin for plasmid stability and the interaction of the condensin subunit Brn1 with the plasmid partitioning system lend functional credence to condensed chromatin being favored for plasmid tethering. By homing to condensed/quiescent chromosome locales, and not over-perturbing genome homeostasis, the plasmid may minimize fitness conflicts with its host. Analogous persistence strategies may be utilized by other extrachromosomal selfish genomes, for example, episomes of mammalian viruses that also hitchhike on host chromosomes for their stable maintenance.
SUMO orchestrates multiple alternative DNA-protein crosslink repair pathways
Authors: Serbyn Nataliia , Bagdiul Ivona , Michel Agnès H. , Suhandynata Raymond T. , Zhou Huilin , Kornmann Benoît , Stutz Françoise
Published: June 2020

Several endogenous metabolites, environmental agents, and therapeutic drugs promote formation of covalent DNA-protein crosslinks (DPCs). Persistent DPCs pose a serious threat to genome integrity and are eliminated by multiple repair pathways. Aberrant Top1 crosslinks to DNA, or Top1ccs, are processed by Tdp1 and Wss1 functioning in parallel pathways inSaccharomyces cerevisiae.It remains obscure how cells choose between these diverse mechanisms of DPC repair. Here we show that several SUMO biogenesis factors - Ulp1, Siz2, Slx5, Slx8 - control repair of Top1cc or an analogous DPC lesion. Genetic analysis reveals that SUMO promotes Top1cc processing in the absence of Tdp1 but has an inhibitory role if cells additionally lack Wss1. In thetdp1Δ wss1Δmutant, the E3 SUMO ligase Siz2 stimulates sumoylation in the vicinity of the DPC, but not SUMO conjugation to Top1. This Siz2-dependent sumoylation delays DPC repair when cells progress through S and G2 phases. Our findings suggest that SUMO tunes available repair pathways to facilitate faithful DPC repair.
Neuromodulation Exerts Feedback and Feedforward Control of Action Selection
Authors: Diao Fengqiu , Peabody Nathan , White Benjamin H.
Published: June 2020

To be effective, behavioral choices must result in actions that are appropriate to an animal’s needs and environmental circumstances. In addition, the actions must be ones the animal can sustain until its needs are met. This aligning of goals, action, and motivation requires the coordinated activity of multiple brain circuits, but how such coordination is achieved is poorly understood. Here, we show how the insect hormone Bursicon coordinates the selection and sustains execution of a behavior in newly emerged adultDrosophila.Such flies must expand and harden their wings after metamorphosis, but they choose to delay expansion in confined conditions. We show that the decision to expand is mediated by an environmentally-sensitive, positive feedback loop in which Bursicon promotes its own sustained release. Released Bursicon then modulates motor neurons to promote wing expansion behavior. Bursicon thus exerts feedforward and feedback control to coordinately select and motivate a goal-directed action.
Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives
Authors: Tandon Ritesh , Sharp Joshua S. , Zhang Fuming , Pomin Vitor H. , Ashpole Nicole M. , Mitra Dipanwita , Jin Weihua , Liu Hao , Sharma Poonam , Linhardt Robert J.
Published: June 2020

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. Currently there is no vaccine, effective therapeutic or prophylactic. Like other betacoronaviruses, attachment and entry of SARS-CoV-2 is mediated by the spike glycoprotein (SGP). In addition to its well-documented interaction with its receptor, human angiotensin converting enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we pseudotyped SARS-CoV-2 SGP on a third generation lentiviral (pLV) vector and tested the impact of various sulfated polysaccharides on transduction efficiency in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high titers on HEK293T cells. Various sulfated polysaccharides potently neutralized pLV-S pseudotyped virus with clear structure-based differences in anti-viral activity and affinity to SGP. Concentration-response curves showed that pLV-S particles were efficiently neutralized by a range of concentrations of unfractionated heparin (UFH), enoxaparin, 6-O-desulfated UFH and 6-O-desulfated enoxaparin with an IC50of 5.99 µg/L, 1.08 mg/L, 1.77 µg/L, and 5.86 mg/L respectively. The low serum bioavailability of intranasally administered UFH, along with data suggesting that the nasal epithelium is a portal for initial infection and transmission, suggest that intranasal administration of UFH may be an effective and safe prophylactic treatment.