bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural geochemical markers reveal environmental history and population connectivity of common cuttlefish in the Atlantic Ocean and Mediterranean Sea
Authors: Rooker Jay R. , Wells R. J. David , Addis Piero , Arrizabalaga Haritz , Baptista Miguel , Bearzi Giovanni , Dance Michael A. , Fraile Igaratza , Lacoue-Labarthe Thomas , Lee Jessica M. , Megalofonou Persefoni , Rosa Rui , Sobrino Ignacio , Sykes António V. , Villanueva Roger
Published: July 2020

Natural markers (δ
13
C and δ
18
O stable isotopes) in the cuttlebones of the European common cuttlefish (
Sepia officinalis
) were determined for individuals collected across a substantial portion of their range in the Northeast Atlantic Ocean (NEAO) and Mediterranean Sea. Cuttlebone δ
13
C and δ
18
O were quantified for core and edge material to characterize geochemical signatures associated with early (juvenile) and recent (sub-adult/adult) life-history periods, respectively. Regional shifts in cuttlebone δ
13
C and δ
18
O values were detected across the 12 sites investigated. Individuals collected from sites in the NEAO displayed more enriched δ
13
C and δ
18
O values relative to sites in the Mediterranean Sea, with the latter also showing salient differences in both markers among western, central and eastern collection areas. Classification success based on cuttlebone δ
13
C and δ
18
O values to four geographical regions (NEAO, western, central and eastern Mediterranean Sea) was relatively high, suggesting that environmental conditions in each region were distinct and produced area-specific geochemical signatures on the cuttlebones of
S. officinalis
. A modified δ
13
C and δ
18
O baseline was developed from sites proximal to the Strait of Gibraltar in both the NEAO and Mediterranean Sea to assess potential mixing through this corridor. Nearly, all (95%) of δ
13
C and δ
18
O signatures of
S. officinalis
collected in the area of the NEAO closest to the Strait of Gibraltar (Gulf of Cadiz) matched the signatures of specimens collected in the western Mediterranean, signifying potential movement and mixing of individuals through this passageway. This study extends the current application of these geochemical markers for assessing the natal origin and population connectivity of this species and potentially other taxa that inhabit this geographical area.
A new perspective for mitigation of SARS-CoV-2 infection: priming the innate immune system for viral attack
Authors: Kolodny Oren , Berger Michael , Feldman Marcus W. , Ram Yoav
Published: July 2020

The course of infection by SARS-CoV-2 frequently includes a long asymptomatic period, followed in some individuals by an immune dysregulation period that may lead to complications and immunopathology-induced death. This course of disease suggests that the virus often evades detection by the innate immune system. We suggest a novel therapeutic approach to mitigate the infection's severity, probability of complications and duration. We propose that priming an individual's innate immune system for viral attack shortly before it is expected to occur may allow pre-activation of the preferable trajectory of immune response, leading to early detection of the virus. Priming can be carried out, for example, by administering a standard vaccine or another reagent that elicits a broad anti-viral innate immune response. By the time that the expected SARS-CoV-2 infection occurs, activation cascades will have been put in motion and levels of immune factors needed to combat the infection will have been elevated. The infection would thus be cleared faster and with less complication than otherwise, alleviating adverse clinical outcomes at the individual level. Moreover, priming may also mitigate population-level risk by reducing need for hospitalizations and decreasing the infectious period of individuals, thus slowing the spread and reducing the impact of the epidemic. In view of the latter consideration, our proposal may have a significant epidemiological impact even if applied primarily to low-risk individuals, such as young adults, who often show mild symptoms or none, by shortening the period during which they unknowingly infect others. The proposed view is, at this time, an unproven hypothesis. Although supported by robust bio-medical reasoning and multiple lines of evidence, carefully designed clinical trials are necessary.
Descriptive epidemiology of 16,780 hospitalized COVID-19 patients in the United States
Authors: Chawla Devika , Rizzo Shemra , Zalocusky Kelly , Keebler Daniel , Chia Jenny , Lindsay Lisa , Yau Vincent , Kamath Tripthi , Tsai Larry
Published: July 2020

1.

Background

Despite the significant morbidity and mortality caused by the 2019 novel coronavirus disease (COVID-19), our understanding of basic disease epidemiology remains limited. This study aimed to describe key patient characteristics, comorbidities, treatments, and outcomes of a large U.S.-based cohort of patients hospitalized with COVD-19 using electronic health records (EHR).

Methods

We identified patients in the Optum De-identified COVID-19 EHR database who had laboratory-confirmed COVID-19 or a presumptive diagnosis between 20 February 2020 and 6 June 2020. We included hospitalizations that occurred 7 days prior to, or within 21 days after, COVID-19 diagnosis. Among hospitalized patients we describe the following: vital statistics and laboratory results on admission, relevant comorbidities (using diagnostic, procedural, and revenue codes), medications (NDC, HCPC codes), ventilation, intensive care unit (ICU) stay, length of stay (LOS), and mortality.

Findings

We identified 76,819 patients diagnosed with COVID-19, 16,780 of whom met inclusion criteria for COVID-related hospitalization. Over half the cohort was over age 50 (74.5%), overweight or obese (77.2%), or had hypertension (56.6%). At admission, 30.3% of patients presented with fever (>38° C) and 32.3% had low oxygen saturation (<90%). Among the 16,099 patients with complete hospital records, we observed that 58.9% had hypoxia, 23.4% had an ICU stay during hospitalization, 18.1% were ventilated, and 16.2% died. The median LOS was 6 days (IQR: 4, 11).

Interpretation

To our knowledge, this is the largest descriptive study of patients hospitalized with COVID-19 in the United States. We report summary statistics of key clinical outcomes that provide insights to better understand COVID-19 disease epidemiology.
Prophylaxis with tetracyclines in ARDS: Potential therapy for COVID-19-induced ARDS?
Authors: Byrne James D. , Shakur Rameen , Collins Joy E. , Becker Sarah , Young Cameron C. , Boyce Hannah , Traverso Giovanni
Published: July 2020

There is an immediate need for therapies related to coronavirus disease 2019 (COVID-19), especially candidate drugs that possess anti-inflammatory and immunomodulatory effects with low toxicity profiles. We hypothesized the application of pleiotropic tetracyclines as potential therapeutic candidates. Here, we present a retrospective multi-institutional cohort study evaluating ventilatory status in patients who had taken a tetracycline antibiotic within a year prior to diagnosis of acute respiratory distress syndrome (ARDS). The primary outcomes were the need for mechanical ventilation and duration of mechanical ventilation. The secondary outcome was the duration of intensive care unit (ICU) stay. Data was evaluated using logistic regression and treatment effects regression models. Minocycline or doxycycline treatment within a year prior to ARDS diagnosis was associated with a 75% reduced likelihood for mechanical ventilation during hospital stay. Furthermore, tetracycline antibiotic therapy corresponded to significant reductions in duration of mechanical ventilation and ICU stay in ARDS patients. These data suggest tetracyclines may provide prophylactic benefit in reducing ventilatory support for ARDS patients and support further evaluation in a randomized prospective trial.
A Retrospective Study on Efficacy and Safety of Guduchi Ghan Vati for Covid-19 Asymptomatic Patients
Authors: Kumar Abhimanyu , Prasad Govind , Srivastav Sanjay , Gautam Vinod Kumar , Sharma Neha
Published: July 2020

Background
Coronavirus disease 2019 (Covid-19) has been declared global emergency with immediate safety, preventative and curative measures to control the spread of virus. Confirmed cases are treated with clinical management as they are diagnosed but so far, there is no effective treatment or vaccine yet for Covid-19. Ayurveda has been recommended by preventative and clinical management guidelines in India and several clinical trials are ongoing. But there is no study to assess impact of Ayurveda on Covid-19.
Methods
Objective of present study was to evaluate the clinical outcome in Covid-19 confirmed asymptomatic to mild symptomatic patients who had received Ayurveda and compare with control (who has not received Ayurveda or any support therapy). Patients having Ayurveda intervention (Guduchi Ghan Vati-extract of Tinospora cordifolia) were included from Jodhpur Covid Care Centre and non-recipients were taken from Jaipur Covid Care Centre between May 15 to June 15, 2020. Total 91 patients, who were asymptomatic at the time of hospital admission and between 18 -75 years of age, were included in the study to analyse retrospectively.
Results
In control group, 11.7% developed mild symptoms after average 1.8 days and none in Ayurveda group reported any symptoms. Significant difference was reported between the group of patients taking Guduchi Ghan Vati (n=40) and patients in standard care (n=51) in terms of virologic clearance at day-7 (97.5% vs 15.6% respectively; p=0.000), at day 14 (100% vs 82.3%) days to stay in hospital ( 6.4 vs 12.8 respectively; p< 0.0001) .
Conclusion
Results of the study suggest that Guduchi Ghan Vati, a common and widely used Ayurveda preparation, could benefit treating asymptomatic Covid-19 patients. Larger, randomised controlled Trials are required to confirm the findings.

Keywords: Ayurveda, Guduchi Ghan
Identifying Sepsis Subphenotypes via Time-Aware Multi-Modal Auto-Encoder
Authors: Yin Changchang , Liu Ruoqi , Zhang Dongdong , Zhang Ping
Published: July 2020

Sepsis is a heterogeneous clinical syndrome that is the leading cause of mortality in hospital intensive care units (ICUs). Identification of sepsis subphenotypes may allow for more precise treatments and lead to more targeted clinical interventions. Recently, sepsis subtyping on electronic health records (EHRs) has attracted interest from healthcare researchers. However, most sepsis subtyping studies ignore the temporality of EHR data and suffer from missing values. In this paper, we propose a new sepsis subtyping framework to address the two issues. Our subtyping framework consists of a novel Time-Aware Multi-modal auto-Encoder (TAME) model which introduces time-aware attention mechanism and incorporates multi-modal inputs (e.g., demographics, diagnoses, medications, lab tests and vital signs) to impute missing values, a dynamic time wrapping (DTW) method to measure patients’ temporal similarity based on the imputed EHR data, and a weighted k-means algorithm to cluster patients. Comprehensive experiments on real-world datasets show TAME outperforms the baselines on imputation accuracy. After analyzing TAME-imputed EHR data, we identify four novel subphenotypes of sepsis patients, paving the way for improved personalization of sepsis management.

CCS CONCEPTS

•Applied computing → Health informatics; • Social and professional topics → Medical records; • Mathematics of computing → Time series analysis.

ACM Reference Format

Changchang Yin, Ruoqi Liu, Dongdong Zhang, and Ping Zhang. 2020. Identifying Sepsis Subphenotypes via Time-Aware Multi-Modal Auto-Encoder.
Accounting for small-study effects using a bivariate trim and fill meta-analysis procedure
Authors: Luo Chongliang , Marks-Anglin Arielle , Duan Rui , Lin Lifeng , Hong Chuan , Chu Haitao , Chen Yong
Published: July 2020

In meta-analyses, small-study effects (SSE) refer to the phenomenon that smaller studies show different, often larger, treatment effects than larger studies, which may lead to incorrect, commonly optimistic estimates of treatment effects. Visualization tools such as funnel plots have been widely used to investigate the SSE in univariate meta-analyses. The trim and fill procedure is a non-parametric method to identify and adjust for SSE and is widely used in practice due to its simplicity. However, most visualization tools and SSE bias correction methods have been focusing on univariate outcomes. For a meta-analysis with multiple outcomes, the estimated number of trimmed studies by trim and fill for different outcomes may be different, leading to inconsistent conclusions. In this paper, we propose a bivariate trim and fill procedure to account for SSE in a bivariate meta-analysis. Based on a recently developed visualization tool of bivariate meta-analysis, known as the galaxy plot, we develop a sensible data-driven imputation algorithm for SSE bias correction. The method relies on the symmetry of the galaxy plot and assumes that some studies are suppressed based on a linear combination of outcomes. The studies are projected along a particular direction and the univariate trim and fill method is used to estimate the number of trimmed studies. Compared to the univariate method, the proposed method yields consistent conclusion about SSE and trimmed studies. The proposed approach is validated using simulated data and is applied to a meta-analysis of efficacy and safety of antidepressant drugs.
A rapid and sensitive method to detect SARS-CoV-2 virus using targeted-mass spectrometry
Authors: Singh Praveen , Chakraborty Rahul , Marwal Robin , V S Radhakrishan , Bhaskar Akash kumar , Vashisht Himanshu , Dhar Mahesh S , Pradhan Shalini , Ranjan Gyan , Imran Mohamed , Raj Anurag , Sharma Uma , Singh Priyanka , Lall Hemlata , Dutta Meena , Garg Parth , Ray Arjun , Dash Debasis , Sivasubbu Sridhar , Gogia Hema , Madan Preeti , Kabra Sandhya , Singh Sujeet K , Agrawal Anurag , Rakshit Partha , Kumar Pramod , Sengupta Shantanu
Published: July 2020

In the last few months, there has been a global catastrophic outbreak of severe acute respiratory syndrome disease caused by the novel corona virus SARS-CoV-2 affecting millions of people worldwide. Early diagnosis and isolation is key to contain the rapid spread of the virus. Towards this goal, we report a simple, sensitive and rapid method to detect the virus using a targeted mass spectrometric approach, which can directly detect the presence of virus from naso-oropharyngeal swabs. Using a multiple reaction monitoring we can detect the presence of two peptides specific to SARS-CoV-2 in a 2.3 minute gradient run with 100% specificity and 90.4 % sensitivity when compared to RT-PCR. Importantly, we further show that these peptides could be detected even in the patients who have recovered from the symptoms and have tested negative for the virus by RT-PCR highlighting the sensitivity of the technique. This method has the translational potential of in terms of the rapid diagnostics of symptomatic and asymptomatic COVID-19 and can augment current methods available for diagnosis of SARS-CoV-2.
Evaluating the neuroprotective impact of senolytic drugs on human vision
Authors: El-Nimri Nevin W. , Moore Spencer M. , Zangwill Linda M. , Proudfoot James A. , Weinreb Robert N. , Skowronska-Krawczyk Dorota , Baxter Sally L.
Published: July 2020

Glaucoma, a chronic neurodegenerative disease of retinal ganglion cells (RGCs), is a leading cause of irreversible blindness worldwide. Its management currently focuses on lowering intraocular pressure to slow disease progression. However, disease-modifying, neuroprotective treatments for glaucoma remain a major unmet need. Recently, senescent cells have been observed in glaucomatous eyes, exposing a potential pathway for alternative glaucoma therapies. Prior studies demonstrated that targeting senescent RGCs for removal (i.e., a senolytic approach) protected healthy RGCs and preserved visual function in a mouse ocular hypertension model. However, the effects of senolytic drugs on vision in human patients are unknown. Here, we used existing clinical data to conduct a retrospective cohort study in 28 human glaucoma patients who had been exposed to senolytics. Senolytic exposure was not associated with decreased visual acuity, elevated intraocular pressure, or documentation of senolytic-related adverse ocular effects by treating ophthalmologists. Additionally, patients exposed to senolytics (n=9) did not exhibit faster progression of glaucomatous visual field damage compared to matched glaucoma patients (n=26) without senolytic exposure. These results suggest that senolytic drugs do not carry significant ocular toxicity and provide further support for additional evaluation of the potential neuroprotective effects of senolytics on glaucoma and other neurodegenerative diseases.
Mutational analysis unveils the temporal and spatial distribution of G614 genotype of SARS-CoV-2in different Indian states and its association with case fatality rate of COVID-19
Authors: Kumar Ballamoole Krishna , Venkatraja Bakilapadavu , Prithvisagar Kattapuni Suresh , Rai Praveen , Rohit Anusha , Hegde Madhura Nagesh , Karunasagar Indrani , Karunasagar Iddya
Published: July 2020

Pan genomic analysis of the global SARS-CoV-2 isolates has resulted in the identification of several regions of increased genetic variation but there is absence of research on its association with the clinical outcome. The present study fills the vacuum and does mutational analysis of genomic sequence of Indian SARS-CoV-2 isolates. Results reveal the existence of non-synonymous G614 spike protein mutation in 61.45% of the total study genome along with three other mutations. Further, temporal variation in the frequencies of G614 genotype in the country is observed. The examination of the probable association of G614 genotype with COVID-19 severity shows that CFR G614 genotype in India is positively and strongly correlated. It appears that the clinical outcome of the COVID-19 cases in India are significantly and adversely affected by the increasing trend in the G614 genotype; which needs to be addressed combining both laboratory experiments and epidemiological investigations.
Mineralisation of theCallorhinchusvertebral column (Holocephali; Chondrichthyes)
Authors: Pears Jacob , Johanson Zerina , Trinajstic Kate , Dean Mason , Boisvert Catherine
Published: July 2020

Chondrichthyes (Elasmobranchii and Holocephali) are distinguished by their largely cartilaginous endoskeleton that comprises an uncalcified core overlain by a mineralised layer; in the Elasmobranchii (sharks, skates, rays) this mineralisation takes the form of calcified polygonal tiles known as tesserae. In recent years, these skeletal tissues have been described in ever increasing detail in sharks and rays but those of Holocephali (chimaeroids) have been less well-described, with conflicting accounts as to whether or not tesserae are present. During embryonic ontogeny in holocephalans, cervical vertebrae fuse to form a structure called the synarcual. The synarcual mineralises early and progressively, anteroposteriorly and dorsoventrally, and therefore presents a good skeletal structure in which to observe mineralised tissues in this group. Here we describe the development and mineralisation of the synarcual in an adult and stage 36 elephant shark embryo (Callorhinchus milii). Small, discrete, but irregular blocks of cortical mineralisation are present in stage 36, similar to what has been described recently in embryos of other chimaeroid taxa such asHydrolagus, while inCallorhinchusadults, the blocks of mineralisation have become more irregular, but remain small. This differs from fossil members of the holocephalan crown group (Edaphodon), as well as from stem group holocephalans (e.g., Symmorida,Helodus, Iniopterygiformes), where tessellated cartilage is present, with tesserae being notably larger than inCallorhinchusand showing similarities to elasmobranch tesserae, for example with respect to polygonal shape.
A CRISPR/Cas9 vector system for neutrophil-specific gene disruption in zebrafish
Authors: Wang Yueyang , Hsu Alan Y. , Walton Eric M. , Syahirah Ramizah , Wang Tianqi , Zhou Wenqing , Ding Chang , Lemke Abby Pei , Tobin David M. , Deng Qing
Published: July 2020

Tissue-specific knockout techniques are widely applied in biological studies to probe the tissue-specific roles of specific genes in physiology, development, and disease. CRISPR/Cas9 is a widely used technology to perform fast and efficient genome editing in vitro and in vivo. Here, we report a robust CRISPR-based gateway system for tissue-specific gene inactivation in zebrafish. A transgenic fish line expressing Cas9 under the control of a neutrophil-restricted promoter was constructed. As proof of principle, we transiently disruptedrac2orcdk2in neutrophils using plasmids driving the expression of sgRNAs from U6 promoters. Loss of therac2orcdk2gene in neutrophils resulted in significantly decreased cell motility, which could be restored by re-expressing Rac2 or Cdk2 in neutrophils in the corresponding knockout background. The subcellular location of Rac activation and actin structure and stress in the context of neutrophil migration was determined in both the wild-type andrac2knockout neutrophilsin vivo. In addition, we evaluated an alternative approach where the Cas9 protein is ubiquitously expressed while the sgRNA is processed by ribozymes and expressed in a neutrophil-restricted manner. Cell motility was also reduced uponrac2sgRNA expression. Together, our work provides a potent tool that can be used to advance the utility of zebrafish in identification and characterization of gene functions in neutrophils.
The ABCD Stop Signal Data: Response to Bissett et al.
Authors: Garavan H , Chaarani B , Hahn S , Allgaier N , Juliano A , Yuan DK , Orr C , Watts R , Wager TD , Ruiz de Leon O , Hagler DJ , Potter A
Published: July 2020

This paper responds to a recent critique by Bissett and colleagues (Bissett et al., eLife, In Press) of the fMRI Stop task being used in the Adolescent Brain Cognitive DevelopmentSMStudy (ABCD Study®). The critique focuses primarily on a design feature of the task that the authors contend lead to a violation of race model assumptions (i.e., that the Go and Stop processes are fully independent) which are relevant to the calculation of the Stop Signal Reaction Time, a measure of the inhibition process. Bissett and colleagues also raise a number of secondary concerns. In this response we note that satisfying race model assumptions is a pernicious challenge for Stop task designs but also that the race model is quite robust against violations of its assumptions. Most importantly, while Bissett et al. raise conceptual concerns with the task we focus here on analyses of both the performance and the neuroimaging data and we conclude that the concerns appear to have minimal impact on the neuroimaging data (the validity of which do not rely on race model assumptions) and have far less of an impact on the performance data than the critique suggests. We note that Bissett et al. did not apply any performance-based exclusions to the data they analyzed, that a number of the trial coding errors that they flagged were already identified and corrected in the ABCD annual data releases, that a number of the secondary concerns reflect sensible design decisions and, indeed, that their own computational modeling of the ABCD Stop task suggests the problems they identify have just a modest impact on the rank ordering of individual differences in subject performance. In this paper, we list some adjustments that have been made to the task and some new flags that are now added to the annual, curated data releases. We stress that the ABCD data are fully available to the scientific community who are empowered to apply whatever inclusion and exclusion criteria they deem appropriate for their analyses and we conclude that the ABCD Stop task yields valuable data that researchers can use to track adolescent neurodevelopment.
Altered Thalamocortical Signaling in a Mouse Model of Parkinson’s Disease
Authors: Swanson Olivia K. , Richard David , Maffei Arianna
Published: July 2020

Activation of the primary motor cortex (M1) is important for the execution of skilled movements and motor learning, and its dysfunction contributes to the pathophysiology of Parkinson’s disease (PD). A well accepted idea in PD research, albeit not tested experimentally, is that loss of midbrain dopamine leads to decreased activation of M1 by the motor thalamus (Mthal). Here, we report that midbrain dopamine loss reduced Mthal input in a laminar- and cell type-specific fashion and induced laminar-specific changes in intracortical synaptic transmission. As a result, M1 activation by Mthal was decreased, but M1 output was increased. Our results demonstrate that loss of midbrain dopaminergic neurons alters thalamocortical activation of M1, and provide novel insights into circuit mechanisms for motor cortex dysfunction in a mouse model of PD.
Proteomic and Transcriptomic Analyses of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Cases
Authors: Leitner Dominique F. , Mills James D. , Pires Geoffrey , Faustin Arline , Drummond Eleanor , Kanshin Evgeny , Nayak Shruti , Askenazi Manor , Verducci Chloe , Chen Bei Jun , Janitz Michael , Anink Jasper J. , Baayen Johannes C. , Idema Sander , van Vliet Erwin A. , Devore Sasha , Friedman Daniel , Diehl Beate , Scott Catherine , Thijs Roland , Wisniewski Thomas , Ueberheide Beatrix , Thom Maria , Aronica Eleonora , Devinsky Orrin
Published: July 2020

Sudden unexpected death in epilepsy (SUDEP) is the leading type of epilepsy-related death. Severely depressed brain activity in these cases may impair respiration, arousal, and protective reflexes, occurring as a prolonged postictal generalized EEG suppression (PGES) and resulting in a high-risk for SUDEP. In autopsy hippocampus and cortex, we observed no proteomic differences between SUDEP and epilepsy cases, contrasting our previously reported robust differences between epilepsy and controls. Transcriptomics in hippocampus and cortex from surgical epilepsy cases segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 lncRNAs, three pending) in hippocampus. Overall, the SUDEP proteome and high-risk SUDEP transcriptome largely reflected other epilepsy cases in the brain regions analyzed, consistent with diverse epilepsy syndromes and comorbidities associated with SUDEP. Thus, studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions may identify molecular mechanisms of SUDEP.
Multicolor structured illumination microscopy and quantitative control of polychromatic coherent light with a digital micromirror device
Authors: Brown Peter T. , Kruithoff Rory , Seedorf Gregory J. , Shepherd Douglas P.
Published: July 2020

Structured illumination microscopy (SIM) is a broadly applicable super-resolution microscopy technique which does not impose photophysics requirements on fluorescent samples. Multicolor SIM implementations typically rely on liquid crystal on silicon (LCoS) spatial light modulators (SLM’s) for precise patterning of the excitation light, but digital micromirror devices (DMD’s) are a promising alternative, owing to their lower cost, increased imaging rate, and simplified experimental timings. Given these advantages, why do existing DMD SIM implementations either rely on incoherent projection, resulting in an order of magnitude lower signal-to-noise, or utilize coherent light at only a single wavelength? The primary obstacle to realizing a multicolor coherent DMD SIM microscope is the lack of an efficient approach for dealing with the blazed grating effect. To address this challenge, we developed quantitative tools applicable to a single DMD acting as a polychromatic diffractive optic. These include a closed form solution of the blaze and diffraction conditions, a forward model of DMD diffraction, and a forward model of coherent pattern projection. We applied these to identify experimentally feasible configurations using a single DMD as a polychromatic diffractive optic for combinations of three and four common fluorophore wavelengths. Based on these advances, we constructed a DMD SIM microscope for coherent light which we used to validate these models, develop a high-resolution optical transfer function measurement technique, and demonstrate SIM resolution enhancement for calibration samples, fixed cells, and live cells. This low-cost setup opens the door to applying DMD’s in polychromatic applications which were previously restricted to LCoS SLM’s.
Sensitive detection of SARS-CoV-2 seroconversion by flow cytometry reveals the presence of nucleoprotein-reactive antibodies in unexposed individuals
Authors: Egia-Mendikute Leire , Bosch Alexandre , Prieto-Fernández Endika , Lee So Young , Jiménez-Lasheras Borja , del Río Ana García , Antoñana-Vildosola Asier , Bruzzone Chiara , Bizkarguenaga Maider , Embade Nieves , Gil-Redondo Rubén , Martínez-Chantar María Luz , López-Hoyos Marcos , Abrescia Nicola G A , Mato Jose M. , Millet Oscar , Palazón Asís
Published: July 2020

There is an ongoing need of developing sensitive and specific methods for the determination of SARS-CoV-2 seroconversion. For this purpose, we have developed a multiplexed flow cytometric bead array (C19BA) that allows the identification of IgG and IgM antibodies against three immunogenic proteins simultaneously: the spike receptor-binding domain (RBD), the spike protein subunit 1 (S1) and the nucleoprotein (N). Using different cohorts of samples collected before and after the pandemic, we show that this assay is more sensitive than ELISAs performed in our laboratory. The combination of three viral antigens allows for the interrogation of full seroconversion. Importantly, we have detected N-reactive antibodies in COVID-19-negative individuals. Here we present an immunoassay that can be easily implemented and has superior potential to detect low antibody titers compared to current gold standard serology methods.
A Speedy Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors
Authors: Yang Kai S. , Ma Xinyu R. , Ma Yuying , Alugubelli Yugendar R. , Scott Danielle A. , Vatansever Erol C. , Drelich Aleksandra K. , Sankaran Banumathi , Geng Zhi Z. , Blankenship Lauren R. , Ward Hannah E. , Sheng Yan J. , Hsu Jason C. , Kratch Kaci C. , Zhao Baoyu , Hayatshahi Hamed S. , Liu Jin , Li Pingwei , Fierke Carol A. , Tseng Chien-Te K. , Xu Shiqing , Liu Wenshe Ray
Published: July 2020

The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2MPro) to digest two of its translated polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replication in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1MPro), we have designed and synthesized a series of SC2MPro inhibitors that contain β-(S-2-oxopyrrolidin-3-yl)-alaninal (Opal) for the formation of a reversible covalent bond with the SC2MPro active site cysteine C145. All inhibitors display high potency with IC50 values at or below 100 nM. The most potent compound MPI3 has as an IC50 value as 8.5 nM. Crystallographic analyses of SC2MPro bound to 7 inhibitors indicated both formation of a covalent bond with C145 and structural rearrangement from the apoenzyme to accommodate the inhibitors. Virus inhibition assays revealed that several inhibitors have high potency in inhibiting the SARS-CoV-2-induced cytopathogenic effect in both Vero E6 and A549 cells. Two inhibitors MP5 and MPI8 completely prevented the SARS-CoV-2-induced cytopathogenic effect in Vero E6 cells at 2.5-5 μM and A549 cells at 0.16-0.31 μM. Their virus inhibition potency is much higher than some existing molecules that are under preclinical and clinical investigations for the treatment of COVID-19. Our study indicates that there is a large chemical space that needs to be explored for the development of SC2MPro inhibitors with extreme potency. Due to the urgent matter of the COVID-19 pandemic, MPI5 and MPI8 may be quickly advanced to preclinical and clinical tests for COVID-19.
Biological control of chili damping off disease, caused byPythium myriotylum
Authors: Hyder Sajjad , Gondal Amjad Shahzad , Rizvi Zarrin Fatima , Sajjad Haider Muhammad Irtaza , Inam-ul-Haq Muhammad
Published: July 2020

Pythium myriotylumis a notorious soil-borne oomycete causes post-emergence damping off in chilli pepper. Of various disease management strategies, utilization of plant growth promoting rhizobacteria (PGPR) in disease suppression and plant growth promotion is eye catching strategy. The present study was performed to isolate and characterize PGPR indigenous to chili rhizosphere in Pakistan, and to test their potential to suppress damping off and plant growth promotion in chilli. Out of total 28 antagonists, 8 bacterial isolates (4a2, JHL-8, JHL-12, 1C2, RH-24, 1D, 5C and RH-87) significantly suppressed the colony growth ofP. myriotylumin dual culture experiment. All the tested bacterial isolates were characterized for biochemical attributes, and 16S rRNA sequence based phylogenetic analysis identified these isolates asFlavobacteriumspp.,Bacillus megaterium, Pseudomonas putida, Bacillus cereusandPseudomonas libanensis. All the tested bacterial isolates showed positive test results for ammonia production, starch hydrolase (except 4a2), and hydrogen cyanide production (except 4a2 and 1D). All the tested antagonists produced indole-3-acetic acid (13.4-39.0 μg ml−1), solubilized inorganic phosphate (75–103 μgml-1) and produced siderophores (17.1–23.7%) in vitro. All the tested bacterial isolates showed varied level of susceptibility and resistance response against different antibiotics and all these bacterial isolates were found non-pathogenic to chill seeds and notably enhanced percentage seed germination, plumule, redical length and vigor index over un-inoculated control. Additionally, under pathogen pressure, bacterization increased the defense related enzymes (PO, PPO and PAL) activates. Moreover, chilli seeds treatment with these bacterial isolates significantly suppressed damping-off caused byP. myriotylum, and improved PGP traits as compared to control. In addition, a positive correlation was noticed between shoot, root length and dry shoot and root weigh and a negative correlation was seen between dry shoot, root weight and seedling percentage mortality. These results showed that native PGPR possess multiple traits beneficial to the chilli plants and can be used to develop eco-friendly and effective seed treatment formulation as an alternative to synthetic chemical fungicides.
Increased influence of prior choices on perceptual decisions in autism
Authors: Feigin Helen , Shalom-Sperber Shir , Zachor Ditza A. , Zaidel Adam
Published: July 2020

Autism spectrum disorder (ASD) manifests sensory and perceptual atypicalities. Recent theories suggest that these may reflect a reduced influence of prior information in ASD. Some studies have found reduced adaptation to recent sensory stimuli in ASD. However, the effects of prior stimuli and prior perceptual choices can counteract one-another. Here, we investigated this using two different tasks (in two different cohorts): (i) visual location discrimination, and (ii) multisensory (visual-vestibular) heading discrimination. We fit the data using a logistic regression model to dissociate the specific effects of prior stimuli and prior choices. In both tasks perceptual decisions were biased toward recent choices. Notably, the ‘attractive’ effect of prior choices was significantly larger in ASD (in both tasks and cohorts), while there was no difference in the influence of prior stimuli. These results challenge theories of reduced priors in ASD, and rather suggest an increased consistency bias for perceptual decisions in ASD.
Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism
Authors: Jacob Fadi , Pather Sarshan R. , Huang Wei-Kai , Wong Samuel Zheng Hao , Zhou Haowen , Zhang Feng , Cubitt Beatrice , Chen Catherine Z. , Xu Miao , Pradhan Manisha , Zhang Daniel Y. , Zheng Wei , Bang Anne G. , Song Hongjun , de a Torre Juan Carlos , Ming Guo-li
Published: July 2020

Neurological complications are common in patients with COVID-19. While SARS-CoV-2, the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function are not well understood, and experimental models using human brain cells are urgently needed. Here we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found modest numbers of infected neurons and astrocytes, but greater infection of choroid plexus epithelial cells. We optimized a protocol to generate choroid plexus organoids from hiPSCs, which revealed productive SARS-CoV-2 infection that leads to increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our results provide evidence for SARS-CoV-2 neurotropism and support use of hiPSC-derived brain organoids as a platform to investigate the cellular susceptibility, disease mechanisms, and treatment strategies for SARS-CoV-2 infection.
CyAn: A MATLAB toolbox for image and data analysis of cyanobacteria
Authors: Tay Jian Wei , Cameron Jeffrey C.
Published: July 2020

Studies of photosynthetic cyanobacteria are often carried out by growing the bacteria in large volume cultures. However, this results in an uneven amount of light received by the cells due to cell-cell shading. Fluorescence microscopy solves this issue as cells can be grown in a single layer, eliminating shading issues. However, microscopy brings its own challenge as hundreds of cells are imaged at the same time, making it difficult to analyze the resulting data by hand. Here we present CyAn, a toolbox to process and analyze microscope images of cyanobacteria. The toolbox automates cyanobacteria identification in microscope images, tracks moving and dividing cells, and computes relevant biological data such as growth rates. As proof-of-principle, we demonstrate that wild type and mutants can be grown on the same slide and identified using the software, allowing a much more accurate probe into photosynthetic processes that are often masked due to cellular heterogeneity or those requiring precise light control to prevent cell-cell shading.
ZmMTOPVIBis essential for double-strand break formation and bipolar spindle assembly during maize meiosis
Authors: Jing Ju-Li , Zhang Ting , Kao Yu-Hsin , Huang Tzu-Han , Wang Chung-Ju Rachel , He Yan
Published: July 2020

The programmed formation of DNA double-strand breaks (DSBs) during early meiosis is catalyzed by SPO11, a conserved ortholog to the A subunit of an archaeal topoisomerase VI (TopoVI) which functions as a hetero-tetramer comprising two A and two B subunits. An essential role of the meiotic TopoVI B subunit (TopVIB) in DSB formation has been reported in mouse, Arabidopsis and rice. Very recently, riceMTopVIBwas revealed to have an unexpected role in meiotic bipolar spindle assembly, highlighting multiple functions ofMTopVIBduring rice meiosis. In this work, the meioticTopVIBin maize (ZmMTOPVIB) was characterized. TheZmmtopVIBmutant plants exhibited normal vegetative growth but male and female sterility. DSB formation is abolished in mutant meiocytes. Despite normal assembly of axial elements, synapsis was severely affected and homologous pairing was disrupted in mutants. Importantly, we showed that bipolar spindle assembly was also affected inZmmtopVIB, resulting in triad and polyad formation. Overall, our results demonstrate thatZmMTOPVIBplays critical roles in DSB formation and homologous recombination. In addition, the newly-discovered function ofMTOPVIBin bipolar spindle assembly is likely conserved across different monocots.

One-sentence summary

The dual roles ofMTOPVIBin regulating meiotic DSB formation and bipolar spindle assembly are evolutionarily conserved in monocot plants.
Accounting for the “uncounted” workers: a dialectical view of accounting through Rancière
Authors: Yang Da , Dumay John , Tweedie Dale
Published: July 2020

Purpose

This paper examines how accounting either contributes to or undermines worker resistance to unfair pay, thereby enhancing our current understanding of the emancipatory potential of accounting.

Design/methodology/approach

We apply Jacques Rancière's concept of politics and build on recent calls to introduce Rancière's work to accounting by analysing a case based on workers in an Australian supermarket chain who challenged their employer Coles over wage underpayments.

Findings

We find that in this case, accounting is, in part, a means to politics and a part of the police in Rancière's sense. More specifically, accounting operated within the established order to constrain the workers, but also provided workers with a resource for their political acts that enabled change.

Originality/value

This empirical research adds to Li and McKernan (2016) and Brown and Tregidga (2017) conceptual work on Rancière. It also contributes more broadly to emancipatory accounting research by identifying radical possibilities for workers' accounting to bring about change.
Effect of organizational identification on organizational innovativeness in universities and higher education institutions of Iran, mediated by risk-taking capability
Authors: Khorshid Seddigheh , Mehdiabadi Amir
Published: July 2020

Purpose

This study explores the effect of organizational identification (OID) on organizational innovativeness (OINN) in universities and higher education institutions (HEIs) of Iran, mediated by organizational risk-taking capability (ORTC).

Design/methodology/approach

A questionnaire was designed and distributed in universities and HEIs in three geographical regions of Iran. The sample includes deans of faculties, their assistants, and heads of departments, and heads, assistants, and employees of research and education offices. The authors determined the reliability and validity of the scales and used structural equation modeling to develop the conceptual model and to test hypothesized relationships.

Findings

The results show that the OID has a positive impact on the ORTC and OINN in universities and HEIs of Iran. Furthermore, the ORTC played a partially mediating role between the OID and OINN.

Research limitations/implications

This study can lead to a theory of the effect of the OID on the OINN in higher education (HE) system, mediated by the ORTC. It can support practitioners working in the HE system as they create a climate that welcomes uncertainties, ambiguities, failures and mistakes in a risk-taking spirit and develop an innovation culture open to new things and generate ideas. Such a culture is rooted in a distinct organizational identity. The researchers recommend that the promising results of this study be pursued in a larger sample and also in universities and HEIs of other countries.

Originality/value

This study develops an understanding of the role of the OID with the university in fostering, enhancing and embedding the ORTC into university, and as a result, promoting its innovativeness culture.
Structure and complexity in six supply chains of the Brazilian wind turbine industry
Authors: Adami Vivian Sebben , Verschoore Jorge Renato , Sellitto Miguel Afonso
Published: July 2020

Purpose

The purpose of this article is to compare design choices and assess the structural complexity of six manufacturing supply chains (SCs) of the Brazilian wind turbine industry.

Design/methodology/approach

The research method is quantitative modeling. This study adopts the social network perspective to provide a broad set of network metrics for comparative analysis and characterization of the structural configuration and complexity of SCs. Transaction costs and the risk of disruption supported the metrics employed in the study. Network size, network density, core-size and centralization metrics stem from transaction costs, whereas constraint and betweenness centrality stem from risk of disruption.

Findings

The main conclusion is that, in the Brazilian wind manufacturing industry, increasing the SC structural complexity by adding redundant ties to minimize disruption risks, even implying higher transaction costs, increases the capacity to win orders.

Research limitations/implications

Only the Brazilian wind turbine industry was studied. Therefore, findings are not general, but specific, to the case.

Practical implications

Managers and practitioners of the Brazilian wind turbine industry should focus on increasing the complexity of their SCs, even if it increases transaction costs, to ensure due dates compliance in orders.

Originality/value

To the best of the available knowledge, there is no commonly accepted or shared measurement for SC complexity, and this study proposed an alternative approach to bridge this research gap, the structural perspective of social networks. Traditional measures were complemented by new metrics, and the power of the application of social network analysis to SC investigations was empirically demonstrated in different levels of analysis.
Optimized deep belief network and entropy-based hybrid bounding model for incremental text categorization
Authors: Srilakshmi V. , Anuradha K. , Bindu C. Shoba
Published: July 2020

Purpose

This paper aims to model a technique that categorizes the texts from huge documents. The progression in internet technologies has raised the count of document accessibility, and thus the documents available online become countless. The text documents comprise of research article, journal papers, newspaper, technical reports and blogs. These large documents are useful and valuable for processing real-time applications. Also, these massive documents are used in several retrieval methods. Text classification plays a vital role in information retrieval technologies and is considered as an active field for processing massive applications. The aim of text classification is to categorize the large-sized documents into different categories on the basis of its contents. There exist numerous methods for performing text-related tasks such as profiling users, sentiment analysis and identification of spams, which is considered as a supervised learning issue and is addressed with text classifier.

Design/methodology/approach

At first, the input documents are pre-processed using the stop word removal and stemming technique such that the input is made effective and capable for feature extraction. In the feature extraction process, the features are extracted using the vector space model (VSM) and then, the feature selection is done for selecting the highly relevant features to perform text categorization. Once the features are selected, the text categorization is progressed using the deep belief network (DBN). The training of the DBN is performed using the proposed grasshopper crow optimization algorithm (GCOA) that is the integration of the grasshopper optimization algorithm (GOA) and Crow search algorithm (CSA). Moreover, the hybrid weight bounding model is devised using the proposed GCOA and range degree. Thus, the proposed GCOA + DBN is used for classifying the text documents.

Findings

The performance of the proposed technique is evaluated using accuracy, precision and recall is compared with existing techniques such as naive bayes, k-nearest neighbors, support vector machine and deep convolutional neural network (DCNN) and Stochastic Gradient-CAViaR + DCNN. Here, the proposed GCOA + DBN has improved performance with the values of 0.959, 0.959 and 0.96 for precision, recall and accuracy, respectively.

Originality/value

This paper proposes a technique that categorizes the texts from massive sized documents. From the findings, it can be shown that the proposed GCOA-based DBN effectively classifies the text documents.