bluuebunny/crossref_metadata_2025 huggingface dataset:
Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection
Authors: Perez-Gomez A , Vitalle J , Gasca-Capote MC , Gutierrez-Valencia A , Trujillo-Rodriguez M , Serna-Gallego A , Muñoz-Muela E , Jimenez-Leon MR , Rafii-El-Idrissi Benhnia M , Rivas-Jeremias I , Sotomayor C , Roca-Oporto C , Espinosa N , Infante-Dominguez C , Crespo-Rivas JC , Fernández-Villar A , Pérez-González A , Lopez-Cortes LF , Poveda E , Ruiz-Mateos E
Published: March 2021

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and non-hospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers as CD86 and CD4 were only restored in previously non-hospitalized patients while integrin β7 and indoleamine 2,3- dyoxigenase (IDO) no restoration was observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19.
Exploitation of the genetic variability in the genotype of Egyptian Wheat by studding Molecular Markers, Molecular Docking and Nano Composites. Regulation of leaf and stem rust
Authors: Omar Hanaa S. , Sedeek Mohamed S. , Shamkh Israa M. , Reyad Nour El-Houda A.
Published: March 2021

This manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Prevalence and determinants of serum antibodies to SARS-CoV-2 in the general population of the Gardena Valley
Authors: Melotti Roberto , Scaggiante Federica , Falciani Michela , Weichenberger Christian X. , Foco Luisa , Lombardo Stefano , Grandi Alessandro De , Laer Dorothee von , Mahlknecht Angelika , Pramstaller Peter P. , Pagani Elisabetta , Meier Horand , Gaertner Timon , Troi Christina , Mascalzoni Deborah , Pattaro Cristian , Mian Michael
Published: March 2021

Background

Community-based studies are essential to quantify the spread of SARS-CoV-2 infection and for unbiased characterization of its determinants and outcomes. We conducted a cross-sectional study in the Gardena valley, a major Alpine touristic destination which was struck in the expansion phase of the COVID-19 pandemic over the winter 2020.

Methods

We surveyed 2244 representative study participants who underwent swab and serum antibody tests. We made multiple comparisons among the Abbott and Diasorin bioassays and serum neutralization titers. Seroprevalence accounted for the stratified design, non-response and test accuracy. Determinants and symptoms predictive of infection were analyzed by weighted multiple logistic regression.

Results

SARS-CoV-2 seroprevalence was 26.9% (95% confidence interval: 25.2%, 28.6%) by June 2020. The serum antibody bioassays had modest agreement with each other. Receiver operating characteristic curve analysis on the serum neutralizing capacity showed better performance of the Abbott test at lower than the canonical threshold. Socio-demographic characteristics showed no clear evidence of association with seropositivity, which was instead associated with place of residence and economic activity. Loss of taste or smell, fever, difficulty in breathing, pain in the limbs, and weakness were the most predictive symptoms of positive antibody test results. Fever and weakness associations were age-dependent.

Conclusion

The Gardena valley had one of the highest SARS-CoV-2 infection prevalence in Europe. The age-dependent risk associated with COVID-19 related symptoms implies targeted strategies for screening and prophylaxis planning.
Cancer services during the COVID-19 pandemic: systematic review of patients’ and caregivers’ experiences
Authors: Dhada Symran , Stewart Derek , Cheema Ejaz , Hadi Muhammed Abdul , Paudyal Vibhu
Published: March 2021

Background

Cancer patients have faced intersecting crises in the face of COVID-19 pandemic. This review aimed to examine patients’ and caregivers’ experiences of accessing cancer services during the COVID-19 pandemic and perceived impact of the pandemic on their psychological wellbeing.

Methods

A protocol-led (CRD42020214906) systematic review was conducted by searching six databases including EMBASE, MEDLINE and CINAHL for articles published in English-language between 1/2020-12/2020. Data were extracted using a pilot-tested, structured data extraction form. Thematic synthesis of data was undertaken and reported as per the PRISMA guideline.

Results

A total of 1110 articles were screened of which 19 studies met the inclusion criteria. Studies originated from 10 different countries including the US, UK, India and China. Several themes were identified which were categorised into seven categories. Postponement and delays in cancer screening and treatment, drug shortages and inadequate nursing care were commonly experienced by patients. Hospital closures, resource constraints, national lockdowns and patient reluctance to use health services because of infection worries contributed to the delay. Financial and social distress, isolation; and spiritual distress due to the uncertainty of rites as well as fulfilment of last wishes were also commonly reported. Caregivers felt anxious about infecting cancer patients with COVID-19.

Conclusions

Patients and caregivers experienced extensive impact of COVID-19 on cancer screening, treatment and care, and their own psychological wellbeing. Patient and caregiver views and preferences should be incorporated in ensuring resilient cancer services that can minimise the impact of ongoing and future pandemic on cancer care and mitigate patient fears.

Protocol Registration

Published protocol registered with Centre for Review and Dissemination CRD42020214906 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=214906)
MRSD: a novel quantitative approach for assessing suitability of RNA-seq in the clinical investigation of mis-splicing in Mendelian disease
Authors: Rowlands Charlie F. , Taylor Algy , Rice Gillian , Whiffin Nicola , Hall Hildegard Nikki , Newman William G. , Black Graeme C.M. ,   kConFab Investigators, O’Keefe Raymond T. , Hubbard Simon , Douglas Andrew G.L. , Baralle Diana , Briggs Tracy A. , Ellingford Jamie M.
Published: March 2021

Background

RNA-sequencing of patient biosamples is a promising approach to delineate the impact of genomic variants on splicing, but variable gene expression between tissues complicates selection of appropriate tissues. Relative expression level is often used as a metric to predict RNA-sequencing utility. Here, we describe a gene- and tissue-specific metric to inform the feasibility of RNA-sequencing, overcoming some issues with using expression values alone.

Results

We derive a novel metric, Minimum Required Sequencing Depth (MRSD), for all genes across three human biosamples (whole blood, lymphoblastoid cell lines (LCLs) and skeletal muscle). MRSD estimates the depth of sequencing required from RNA-sequencing to achieve user-specified sequencing coverage of a gene, transcript or group of genes of interest. MRSD predicts levels of splice junction coverage with high precision (90.1-98.2%) and overcomes transcript region-specific sequencing biases. Applying MRSD scoring to established disease gene panels shows that LCLs are the optimum source of RNA, of the three investigated biosamples, for 69.3% of gene panels. Our approach demonstrates that up to 59.4% of variants of uncertain significance in ClinVar predicted to impact splicing could be functionally assayed by RNA-sequencing in at least one of the investigated biosamples.

Conclusions

We demonstrate the power of MRSD as a metric to inform choice of appropriate biosamples for the functional assessment of splicing aberrations. We apply MRSD in the context of Mendelian genetic disorders and illustrate its benefits over expression-based approaches. We anticipate that the integration of MRSD into clinical pipelines will improve variant interpretation and, ultimately, diagnostic yield.
Agreement of parent- and child-reported wheeze: are they associated with FeNO and lung function?
Authors: Mozun Rebeca , Ardura-Garcia Cristina , Pedersen Eva S. L. , Goutaki Myrofora , Usemann Jakob , Singer Florian , Latzin Philipp , Moeller Alexander , Kuehni Claudia E.
Published: March 2021

In epidemiological studies, childhood asthma is usually assessed with questionnaires directed at parents or children, and these may give different answers. We studied how well parents and children agreed when asked to report symptoms of wheeze and investigated whose answers were closer to measurable traits of asthma.

LuftiBus in the schoolis a cross-sectional survey of respiratory health among Swiss schoolchildren aged 6-17 years. We applied questionnaires to parents and children asking about wheeze and exertional wheeze in the past year. We assessed agreement between parent-child answers with Cohen’s kappa (k), and associations of answers from children and parents with physiological measurements (i.e. FeNO and FEV1/FVC), using quantile regression.

We received questionnaires from 3079 children and their parents. Agreement was poor for reported wheeze (k=0.37) and exertional wheeze (k=0.36). Median FeNO varied when wheeze was reported by children (19 ppb, IQR: 9-44), parents (22 ppb, IQR: 12-46), both (31 ppb, IQR: 16-55) or neither (11 ppb, IQR: 7-19). Median absolute FEV1/FVC was the same when wheeze was reported by children (84%, IQR: 78-89) and by parents (84%, IQR: 78-89), lower when reported by both (82%, IQR: 78-87) and higher when reported by neither (87%, IQR: 82-91). For exertional wheeze findings were similar. Results did not differ by age or sex.

Our findings suggest that surveying both parents and children and combining their responses can help us to better identify children with measurable asthma traits.

Take home message

There is poor agreement between schoolchildren and their parents when reporting current wheeze. However, wheeze correlates best with lung function and FeNO when reported by both children and parents.
Invariant representation of physical stability in the human brain
Authors: Pramod R.T. , Cohen M. , Tenenbaum J. , Kanwisher N.
Published: March 2021

Successful engagement with the world requires the ability to predict what will happen next. Here we investigate how the brain makes the most basic prediction about the physical world: whether the situation in front of us is stable, and hence likely to stay the same, or unstable, and hence likely to change in the immediate future. Specifically, we ask if judgements of stability can be supported by the kinds of representations that have proven to be highly effective at visual object recognition in both machines and brains, or instead if the ability to determine the physical stability of natural scenes may require generative algorithms that simulate the physics of the world. To find out, we measured responses in both convolutional neural networks (CNNs) and the brain (using fMRI) to natural images of physically stable versus unstable scenarios. We find no evidence for generalizable representations of physical stability in either standard CNNs trained on visual object and scene classification (ImageNet), or in the human ventral visual pathway, which has long been implicated in the same process. However, in fronto-parietal regions previously implicated in intuitive physical reasoning we find both scenario-invariant representations of physical stability, and higher univariate responses to unstable than stable scenes. These results demonstrate abstract representations of physical stability in the dorsal but not ventral pathway, consistent with the hypothesis that the computations underlying stability entail not just pattern classification but forward physical simulation.
The inhibitory effects of toothpaste and mouthwash ingredients on the interaction between the SARS-CoV-2 spike protein and ACE2, and the protease activity of TMPRSS2,in vitro
Authors: Tateyama-Makino Riho , Abe-Yutori Mari , Iwamoto Taku , Tsutsumi Kota , Tsuji Motonori , Morishita Satoru , Kurita Kei , Yamamoto Yukio , Nishinaga Eiji , Tsukinoki Keiichi
Published: March 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells when the viral spike protein is cleaved by transmembrane protease serine 2 (TMPRSS2) after binding to the host angiotensin-converting enzyme 2 (ACE2). Since ACE2 and TMPRSS2 are expressed in the mucosa of the tongue and gingiva, the oral cavity seems like it is an entry point for SARS-CoV-2. Daily oral care using mouthwash seems to play an important role in preventing SARS-CoV-2 infection. However, the relationship between daily oral care and the mechanisms of virus entry into host cells is unclear. In this study, we evaluated the inhibitory effects of ingredients that are generally contained in toothpaste and mouthwash on the interaction between the spike protein and ACE2 and on the serine protease activity of TMPRSS2 using an enzyme-linked immunosorbent assay andin vitroenzyme assay, respectively. Both assays detected inhibitory effects of sodium tetradecene sulfonate, sodium N-lauroyl-N-methyltaurate, sodium N-lauroylsarcosinate, sodium dodecyl sulfate, and copper gluconate. Molecular docking simulations suggested that these ingredients could bind to the inhibitor-binding site of ACE2. In addition, tranexamic acid and 6-aminohexanoic acid, which act as serine protease inhibitors, exerted inhibitory effects on TMPRSS2 protease activity. Further experimental and clinical studies are needed to further elucidate these mechanisms. Our findings support the possibility that toothpaste and mouthwash contain ingredients that inhibit SARS-CoV-2 infection.
Multiomics Interrogation into HBV (Hepatitis B Virus)-Host Interaction Reveals Novel Coding potential in Human Genome, and Identifies Canonical and Non-canonical Proteins as Host Restriction Factors against HBV
Authors: Yuan Shilin , Liao Guanghong , Zhang Menghuan , Zhu Yuanfei , Xiao Weidi , Wang Kun , Jia Caiwei , Deng Qiang , Zhang Jian , Xu Ping , Hu Ronggui
Published: March 2021

Hepatitis B Virus constitutes a major threat to global public health. Current understanding of HBV-host interaction is yet limited. Here, ribosome profiling, quantitative mass spectrometry and RNA-sequencing are conducted on a recently established HBV replication system. We have identified multiomic DEGs (differentially expressed genes) that HBV orchestrated to remodel host proteostasis networks. Our multiomics interrogation revealed that HBV induced significant changes in both transcription and translation of 35 canonical genes including PPP1R15A, PGAM5 and SIRT6, as well as the expression of at least 15 non-canonical ORFs including ncPON2 and ncGRWD1, thus revealing an extra coding potential of human genome. Overexpression of these five genes but not the enzymatically deficient SIRT6 mutants suppressed HBV replication while knockdown SIRT6 had opposite effect. Furthermore, the expression ofSIRT6was down-regulated in patients, cells or animal models of HBV infection. Mechanistic study further indicated that SIRT6 directly binds to mini-chromosome and deacetylates histone H3 lysine 9 (H3K9ac) and histone H3 lysine 56 (H3K56ac), and chemical activation of endogenous SIRT6 with MDL800 suppressed HBV infectionin vitroandin vivo. By generating the first multiomics landscape of host-HBV interaction, our work is thus opening a new avenue to facilitate therapeutic development against HBV infection.
Two-pore channel 2 is a key regulator of adipocyte differentiation via the cAMP signaling pathway with calpain as downstream effector
Authors: Zhang Yuxuan , Chan Lai-Hing , Tunn Ruth , Ruas Margarida , Gay David , Todorcevic Marijana , Christodoulides Costas , Parrington John
Published: March 2021

We investigated whether the endolysosomal two-pore channel TPC2 is a mediator of adipocyte differentiation. We show thatTpcn2mRNA is expressed transiently during induction of C3H10T1/2 mesenchymal stem cells to differentiate into adipocytes, and that this expression is triggered by cAMP. This is the first demonstration of a cell signaling pathway that can regulate TPC gene expression. We also identified an important functional role for TPC2 in adipocyte differentiation. First, ectopic TPC2 expression in C3H10T1/2 cells partially rescued the block to adipocyte differentiation caused by cAMP absence. Second, inhibition of endogenous TPC2 expression in primary preadipocytes substantially reduced their ability to differentiate into adipocytes. Finally, genetic variation at theTpcn2locus is associated with increased upper-body fat distribution in women concomitant with reducedTpcn2expression in abdominal adipose tissue. Our findings implicate TPC2 as an important mediator of adipogenesis and may aid identification of new drug targets for treatment of obesity.
Unbiased transcriptomic analysis of chondrocyte differentiation in a high-density cell culture model
Authors: Kruger Claudia , Limpach Aimee , Kappen Claudia
Published: March 2021

In the developing vertebrate skeleton, cartilage is an important precursor to the formation of bones. Cartilage is produced by chondrocytes, which derive from embryonic mesoderm and undergo a stereotypical program of differentiation and maturation. Here we modeled this processin vitro, using primary fetal mouse rib chondrocytes in a high-density cell culture model of cartilage differentiation, and performed genome-wide gene expression profiling over the course of culture. The overarching goal of this study was to characterize the molecular pathways involved in cartilage differentiation and maturation. Our results also enable a comprehensive appraisal of distinctions between commonin vitromodels for cartilage differentiation, and of differences in their molecular resemblance to cartilage formationin vivo.
The lifetime cost of reproductive potential – who spends the most?
Authors: Fuchs Shai , Goldenfeld Miki , Dviri Michal , Librach Clifford , Baum Micha
Published: March 2021

Objectives

To determine who spends more energy over a lifetime on maintaining their reproductive potential: men or women?

Design

As a model and energetic equivalent, we set the mass of gametes supported over time from birth until exhaustion of fertility. We calculated gender-specific dynamics of gamete pool mass over time. To this purpose we collated data from existing literature, accounting for gamete volume over stages of development, time in each stage, mass density, and count. Our model generates the integral, or area under the curve (AUC) of the gamete pool mass over a lifetime as a proxy to energetic requirements.

Main outcome measures

The area under gamete mass curve over a lifetime in men and women.

Results

The number of gametes over a lifetime is 600,000 in women and close to 1 trillion in men. Accounting for mass and time, women invest approximately 100 gram*days in maintaining the female oocyte pool. Women reach 50% of lifetime AUC by age 10, and 90% by age 25. Men invest approximately 30 Kg*days over a lifetime (300-fold more), reaching 50% of lifetime AUC at age 37 and 90% at age 62 years old.

Conclusions

The study quantifies for the first time the area under gamete mass in men and women through a nuanced calculation accounting for all components of post-natal gamete dynamics. We found a 300-fold excess is supported male gamete mass over a lifetime (100g*days vs. 30 Kg*days in females vs. males, respectively). Our methodology offers a framework for assessing other components of the reproductive system in a similar quantitative manner.
Heightened virulence ofYersiniais associated with decreased function of the YopJ protein
Authors: Mares Chris A. , Lugo Fernando P. , Albataineh Mohammad , Goins Beth A. , Newton Irene G. , Isberg Ralph R. , Bergman Molly A.
Published: March 2021

Despite the maintenance of YopP/J alleles throughout the human-pathogenicYersinialineage, the benefit of YopP/J-induced phagocyte death forYersiniapathogenesis in animals is not obvious. To determine how sequence divergence of YopP/J has impactedYersiniavirulence, we examined protein polymorphisms in this Type III secreted effector protein across 17Yersiniaspecies, and tested the consequences of polymorphism in a murine model of sub-acute systemic yersiniosis. Our evolutionary analysis revealed that codon 177 has been subjected to positive selection - theY. enterocoliticaresidue had been altered from a leucine to a phenylalanine in nearly allY. pseudotuberculosisandY. pestisstrains examined. Despite being a minor change, as both leucine and phenylalanine have hydrophobic side chains, reversion of YopJF177to the ancestral YopJL177variant yielded aY. pseudotuberculosisstrain with enhanced cytotoxicity towards macrophages, consistent with previous findings. Surprisingly, expression of YopJF177Lin the mildly attenuatedksgA-background rendered the strain completely avirulent in mice. Consistent with this hypothesis that YopJ activity indirectly relates toYersiniapathogenesisin vivo,ksgA-strains lacking functional YopJ failed to kill macrophages but actually regained virulence in animals. Also, treatment with the anti-apoptosis drug suramin prevented YopJ-mediated macrophage cytotoxicity and enhancedY. pseudotuberculosisvirulencein vivo. Our results demonstrate thatYersinia-induced cell death is detrimental for bacterial pathogenesis in this animal model of illness, and indicate that positive selection has driven YopJ/P andYersiniaevolution towards diminished cytotoxicity and increased virulence, respectively.
Label-free screening of brain tissue myelin content using phase imaging with computational specificity (PICS)
Authors: Fanous Michael , Shi Chuqiao , Caputo Megan P. , Rund Laurie A. , Johnson Rodney W. , Das Tapas , Kuchan Matthew J. , Sobh Nahil , Popescu Gabriel
Published: March 2021

Inadequate myelination in the central nervous system is associated with neurodevelopmental complications. Thus, quantitative, high spatial resolution measurements of myelin levels are highly desirable. We used spatial light interference microcopy (SLIM), a highly sensitive quantitative phase imaging (QPI) technique, to correlate the dry mass content of myelin in piglet brain tissue with dietary changes and gestational size. We combined SLIM micrographs with an AI classifying model that allows us to discern subtle disparities in myelin distributions with high accuracy. This concept of combining QPI label-free data with AI for the purpose of extracting molecular specificity has recently been introduced by our laboratory as phase imaging with computational specificity (PICS). Training on nine thousand SLIM images of piglet brain tissue with the 71-layer transfer learning model Xception, we created a two-parameter classification to differentiate gestational size and diet type with an accuracy of 82% and 80%, respectively. To our knowledge, this type of evaluation is impossible to perform by an expert pathologist or other techniques.
Targeting tau mitigates mitochondrial fragmentation and oxidative stress in amyotrophic lateral sclerosis
Authors: Petrozziello Tiziana , Bordt Evan A. , Mills Alexandra N. , Kim Spencer E. , Sapp Ellen , Devlin Benjamin A. , Obeng-Marnu Abigail A. , Farhan Sali M.K. , Amaral Ana C. , Dujardin Simon , Dooley Patrick M. , Henstridge Christopher , Oakley Derek H. , Neueder Andreas , Hyman Bradley T. , Spires-Jones Tara L. , Bilbo Staci D. , Vakili Khashayar , Cudkowicz Merit E. , Berry James D. , DiFiglia Marian , Silva M. Catarina , Haggarty Stephen J. , Sadri-Vakili Ghazaleh
Published: March 2021

Understanding the mechanisms underlying amyotrophic lateral sclerosis (ALS) is crucial for the development of new therapies. Recent evidence suggest that tau may be involved in ALS pathogenesis. Here, we demonstrated that hyperphosphorylated tau (pTau-S396) is mis-localized to synapses in human post-mortem motor cortex (mCTX) across ALS subtypes. Treatment with ALS synaptoneurosomes (SNs) derived from post-mortem mCTX, enriched in pTau-S396, increased oxidative stress, induced mitochondrial fragmentation, and altered mitochondrial connectivityin vitro. Furthermore, our findings revealed that pTau-S396 interacts with the pro-fission dynamin-related protein (DRP1), and similar to pTau-S396, DRP1 accumulated in ALS SNs across ALS subtypes. Lastly, reducing tau with a specific bifunctional degrader, QC-01-175, prevented ALS SNs-induced mitochondrial fragmentation and oxidative stressin vitro. Collectively, our findings suggest that increases in pTau-S396 may lead to mitochondrial fragmentation and oxidative stress in ALS and decreasing tau may provide a novel strategy to mitigate mitochondrial dysfunction in ALS.

Graphical abstract

pTau-S396 mis-localizes to synapses in ALS.

ALS synaptoneurosomes (SNs), enriched in pTau-S396, increase oxidative stress and induce mitochondrial fragmentationin vitro.

pTau-S396 interacts with the pro-fission GTPase DRP1 in ALS.

Reducing tau with a specific degrader, QC-01-175, mitigates ALS SNs-induced mitochondrial fragmentation and increases in oxidative stressin vitro.
Microbiome Maps: Hilbert Curve Visualizations of Metagenomic Profiles
Authors: Valdes Camilo , Stebliankin Vitalii , Ruiz-Perez Daniel , Park Ji In , Lee Hajeong , Narasimhan Giri
Published: March 2021

Motivation

Abundance profiles from metagenomic sequencing data synthesize information from billions of sequenced reads coming from thousands of microbial genomes. Analyzing and understanding these profiles can be a challenge since the data they represent are complex. Particularly challenging is their visualization, as existing techniques are inadequate when the taxa number is in the thousands. We present a technique, and accompanying software, for the visualization of metagenomic abundance profiles using a space-filling curve that transforms a profile into an interactive 2D image.

Results

We created Jasper, an easy to use tool for the visualization and exploration of metagenomic profiles from DNA sequencing data. It orders taxa using a space-filling Hilbert curve, and creates a “Microbiome Map”, where each position in the image represents the abundance of a single taxon from a reference collection. Jaspercan order taxa in multiple ways, and the resultingmicrobiome mapscan highlight “hot spots” of microbes that are dominant in taxonomic clades or biological conditions.

We use Jasperto visualize samples from a variety of microbiome studies, and discuss ways in whichmicrobiome mapscan be an invaluable tool to visualize spatial, temporal, disease, and differential profiles. Our approach can create detailedmicrobiome mapsinvolving hundreds of thousands of microbial reference genomes with the potential to unravel latent relationships (taxonomic, spatio-temporal, functional, and other) that could remain hidden using traditional visualization techniques. The maps can also be converted into animated movies that bring to life the dynamicity of microbiomes.

Availability

Jasperis freely available atmicrobiomemaps.organd viabiorg.cs.fiu.edu/jasper

Contact

cvaldes2@unl.edu;giri@fiu.edu

Supplementary information

Supplementary materials are available atmicrobiomemaps.org
Brain kernel: a new spatial covariance function for fMRI data
Authors: Wu Anqi , Nastase Samuel A. , Baldassano Christopher A. , Turk-Browne Nicholas B. , Norman Kenneth A. , Engelhardt Barbara E. , Pillow Jonathan W.
Published: March 2021

A key problem in functional magnetic resonance imaging (fMRI) is to estimate spatial activity patterns from noisy high-dimensional signals. Spatial smoothing provides one approach to regularizing such estimates. However, standard smoothing methods ignore the fact that correlations in neural activity may fall off at different rates in different brain areas, or exhibit discontinuities across anatomical or functional boundaries. Moreover, such methods do not exploit the fact that widely separated brain regions may exhibit strong correlations due to bilateral symmetry or the network organization of brain regions. To capture this non-stationary spatial correlation structure, we introduce thebrain kernel, a continuous covariance function for whole-brain activity patterns. We define the brain kernel in terms of a continuous nonlinear mapping from 3D brain coordinates to a latent embedding space, parametrized with a Gaussian process (GP). The brain kernel specifies the prior covariance between voxels as a function of the distance between their locations in embedding space. The GP mapping warps the brain nonlinearly so that highly correlated voxels are close together in latent space, and uncorrelated voxels are far apart. We estimate the brain kernel using resting-state fMRI data, and we develop an exact, scalable inference method based on block coordinate descent to overcome the challenges of high dimensionality (10-100K voxels). Finally, we illustrate the brain kernel’s usefulness with applications to brain decoding and factor analysis with multiple task-based fMRI datasets.
Optical and magnetic properties of particles containing guanine in strong basic solution
Authors: Iwasaka Masakazu
Published: March 2021

Guanine based particle is one of very efficient material to control light especially near the surface of animal body. Past studies reported that platelets of anhydrous guanin crystal are utilized by living creatures, and they can change their colour and light reflection intensity when the arrangement of platelets. Guanine has relatively high reflective index and its particle can exhibit a unique optical property. Under higher pH which can be provided by a high concentration of NaOH aqueous solution, guanine molecules formed a sodium salt particle which contain guanine. Here this work presents that particles containing guanine in basic aqueous solution with NaOH exhibited very strong shining and light reflection switching by magnetic fields. In addition, adding an extracted solution of a fish iridophore enhanced the formation of intensively light reflecting guanine particles floating in a strong basic solution.
Sensitivity and resolution improvement for in-vivo magnetic resonance current density imaging (MRCDI) of the human brain
Authors: Göksu Cihan , Scheffler Klaus , Gregersen Fróði , Eroğlu Hasan H. , Heule Rahel , Siebner Hartwig R. , Hanson Lars G. , Thielscher Axel
Published: March 2021

Purpose

Magnetic resonance current density imaging (MRCDI) combines MR brain imaging with the injection of time-varying weak currents (1-2 mA) to assess the current flow pattern in the brain. However, the utility of MRCDI is still hampered by low measurement sensitivity and poor image quality.

Methods

We recently introduced a multi-gradient-echo-based MRCDI approach that has the hitherto best documented efficiency. We now advanced our MRCDI approach in three directions and performed phantom and in-vivo human brain experiments for validation: First, we verified the importance of enhanced spoiling and optimize it for imaging of the human brain. Second, we improved the sensitivity and spatial resolution by using acquisition weighting. Third, we added navigators as a quality control measure for tracking physiological noise. Combining these advancements, we tested our optimized MRCDI method by using 1 mA transcranial electrical stimulation (TES) currents injected via two different electrode montages in five subjects.

Results

For a session duration of 4:20 min, the new MRCDI method was able to detect magnetic field changes caused by the TES current flow at a sensitivity level of 84 pT, representing in a twofold increase relative to our original method. Comparing both methods to current flow simulations based on personalized head models demonstrated a consistent increase in the coefficient of determination of ΔR2=0.12 for the current-induced magnetic fields and ΔR2=0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite of the strongly improved measurement quality. This suggests that MRCDI can reveal useful information for the improvement of head models used for current flow simulations.

Conclusion

The advanced method strongly improves the sensitivity and robustness of MRCDI and is an important step from proof-of-concept studies towards a broader application of MRCDI in clinical and basic neuroscience research.
Toward developing a sustainable regeneration framework for urban industrial heritage
Authors: Arbab Parsa , Alborzi Gelareh
Published: March 2021

Purpose

Regeneration of industrial heritage aims to display the patrimony assets by launching measures to convert them into cultural spaces associated with sustainable initiatives for satisfying environmental, social and economic demands in the city. The adaptive transformation and reusing process of industrial heritage constitutes a crucial cultural objective and consequently must be identified in a way that simultaneously integrates preservation with conversion and conservation with refurbishment. Hence, this paper explores to develop a framework for the sustainable regeneration of industrial heritage in cities.

Design/methodology/approach

By reviewing the current literature, research and experiences on urban industrial heritage, including existing approaches, frameworks, and case studies, this study brings a theoretical and conceptual approach to sustainable regeneration of industrial heritage, which is a fundamental start point for conducting further research and performing practical projects.

Findings

Three key phases of the Initiation as decision context, including understand the characteristics and assess the significance, the Planning as decision problem, including study the feasibility, develop a policy, and prepare a proposed reuse plan, and the Execution as decision output, including implement the plan, monitor the results and review the plan should be considered regarding the sustainable regeneration of urban industrial heritage.

Originality/value

The suggested framework considers sustainable regeneration of industrial heritage in cities as a decision-making process, which requires defining the decision context, analyzing the decision problem, and finally, results in the decision output. Accordingly, it seems to help bridge the gap between various discourses and planning perspectives and make all stakeholders' involvement easier, more effective and efficient regarding the sustainable regeneration of industrial heritage in cities.
Dupilumab shows slow, steady effectiveness for intractable prurigo in patients with atopic dermatitis
Authors: Takeuchi Satoshi , Inoue Keiichi , Kuretake Keisuke , Kiyomatsu‐Oda Mari , Furue Masutaka
Published: March 2021

Prurigo lesions in atopic dermatitis are intractable. This single‐center, retrospective study examined dupilumab’s clinical effects on intractable prurigo. Twenty adult atopic dermatitis patients (12 with prurigo, eight without) were administrated dupilumab. Its effects on itching and disease severity were examined with Numerical Rating Scale–Itch (NRS‐I), Eczema Area and Severity Index (EASI), and Investigator Global Assessment (IGA) scores; body surface areas (BSA); and thymus‐ and activation‐regulated chemokine (TARC), total immunoglobulin (Ig)E, and eosinophil levels. NRS‐I scores, EASI scores, TARC levels, and total IgE levels before dupilumab treatment were not statistically different between the prurigo and non‐prurigo groups. With dupilumab treatment, NRS‐I scores, EASI scores, IGA scores, BSA, TARC levels, and total IgE levels were significantly reduced from baseline in both groups at 1–2 months and onward, but skin symptom improvement in the prurigo group was slower than in the non‐prurigo group, as evidenced by significantly higher EASI scores, BSA, and TARC levels at several time points during the 12 months of dupilumab treatment. Prurigo patients were slower in EASI‐50 achievement and significantly lower in EASI‐90 achievement at 12 months than non‐prurigo patients. Adherence to dupilumab was not different, but total equivalent amounts of concomitant therapeutic agents (corticosteroids and tacrolimus) used during dupilumab treatment were significantly higher in the prurigo group (median, 56.2 g/week) than in the non‐prurigo group (median, 33.7 g/week). There were 2.2 adverse events per patient on average; ocular complaints were most frequent. Dupilumab was effective in treating intractable prurigo, but despite significantly greater concomitant therapeutic agent use, skin symptom improvement was slower in prurigo patients than in non‐prurigo patients.
C4‐dicarboxylates and l‐aspartate utilization by Escherichia coli K‐12 in the mouse intestine: l‐aspartate as a major substrate for fumarate respiration and as a nitrogen source
Authors: Schubert Christopher , Winter Maria , Ebert‐Jung Andrea , Kierszniowska Sylwia , Nagel‐Wolfrum Kerstin , Schramm Thorben , Link Hannes , Winter Sebastian , Unden Gottfried
Published: March 2021

C4‐dicarboxylates, such as fumarate, l‐malate and l‐aspartate represent substrates for anaerobic growth of Escherichia coli by fumarate respiration. Here, we determined whether C4‐dicarboxylate metabolism, as well as fumarate respiration, contribute to colonization of the mammalian intestinal tract. Metabolite profiling revealed that the murine small intestine contained high and low levels of l‐aspartate and l‐malate respectively, whereas fumarate was nearly absent. Under laboratory conditions, addition of C4‐dicarboxylate at concentrations corresponding to the levels of the C4‐dicarboxylates in the small intestine (2.6 mmol kg−1 dry weight) induced the dcuBp‐lacZ reporter gene (67% of maximal) in a DcuS‐DcuR‐dependent manner. In addition to its role as a precursor for fumarate respiration, l‐aspartate was able to supply all the nitrogen required for anaerobically growing E. coli. DcuS‐DcuR‐dependent genes were transcribed in the murine intestine, and mutants with defective anaerobic C4‐dicarboxylate metabolism (dcuSR, frdA, dcuB, dcuA and aspA genes) were impaired for colonizing the murine gut. We conclude that l‐aspartate plays an important role in providing fumarate for fumarate respiration and supplying nitrogen for E. coli in the mouse intestine.
Effects of alcohol sensitivity on alcohol‐induced blackouts and passing out: An examination of the alcohol sensitivity questionnaire among underage drinkers
Authors: Davis Christal N. , Piasecki Thomas M. , Bartholow Bruce D. , Slutske Wendy S.
Published: March 2021

Background

The role of alcohol sensitivity in the experience of blacking out and passing out has not been well established. Here, we examined the relation between individual differences in alcohol sensitivity (i.e., numbers of drinks required to experience various effects of alcohol) and reports of blacking out and passing out in the past year.

Methods

Participants (925 healthy, underage college student drinkers) completed the Alcohol Sensitivity Questionnaire (ASQ) and reported on their past year blacking out and passing out experiences.

Results

The fit of the ASQ’s 2‐factor structure was fair (CFI = 0.90, RMSEA = 0.09) in this sample of underage drinkers. In unadjusted models, higher ASQ scores (i.e., requiring more drinks to experience effects, indicating lower alcohol sensitivity) were associated with experiencing more blackouts (IRR = 1.68 [1.31–2.15]) and passing out (IRR = 2.25 [1.59–3.18]) in the past year. After controlling for typical consumption, however, higher ASQ scores were associated with fewer past‐year blackouts (IRR = 0.76 [0.60–0.98]). Total ASQ scores moderated the relationship between typical alcohol consumption and blackout occurrence (interaction IRR = 0.96 [0.93–0.98]), but not passing out occurrence (interaction IRR = 0.95 [0.89–1.01]), with the quantity of alcohol consumed more strongly associated with blackout occurrence among higher‐sensitivity than lower‐sensitivity drinkers.

Conclusions

These findings are consistent with prior work suggesting that low sensitivity may act as a paradoxical risk factor for certain heavy drinking effects, contributing to higher levels of alcohol consumption and more frequent negative consequences while also conferring protection (relative to high‐sensitivity peers) at a given level of alcohol exposure.
CEO pay disparity, takeover premiums and bidder performance in Australia: efficient contracting or managerial power?
Authors: Luong Hoa , Duong Lien , Evans John
Published: March 2021

We compare acquiring firms’ CEO pay with that of the highest‐paid non‐CEO director and investigate the influence of CEO pay disparity on takeover premiums and bidder performance. Based on a takeover sample of Australian listed targets and bidders during the 2002–2015 period, we find that takeover premiums are significantly higher if the deals are processed by acquiring firms with higher CEO pay disparity. Although these firms do not receive favourable immediate market responses to their takeover announcements, they outperform in the long run. We find no evidence that offering a large takeover premium harms shareholders’ wealth. Overall, our findings largely support efficient contracting theory in the Australian M&A context.
Revised guidelines for the endodontic education of dentistry students in Australia and New Zealand (FEBRUARY 2021)
Authors: Sadr Atieh , Rossi‐Fedele Giampiero , Love Robert M. , George Roy , Parashos Peter , Wu Morgan C‐Y , Friedlander Lara , Peters Ove , Moule Alex J. , Zimet Phillippe , Abbott Paul V.
Published: March 2021

These revised guidelines for contemporary endodontic education in Australia and New Zealand (version 2021) propose the minimum criteria for the training of dentistry students. The document contains a definition of endodontics and a description of the scope of endodontics. It proposes a general outline for education programmes in endodontics as part of general dental practice.
The ability of reciprocating glide path instruments to reach the full root canal working length
Authors: Campos Daniel Souza , Rodrigues Evaldo Almeida , Bueno Carlos Eduardo da Silveira , Fontana Carlos Eduardo , da Silva Emmanuel João Nogueira Leal , de Lima Carolina Oliveira , De Martin Alexandre Sigrist
Published: March 2021

This study evaluated the ability of reciprocating glide path instruments to reach the full working length (RFWL). Thirty mesial roots of mandibular molars were matched into 2 groups (n = 15 teeth, 30 root canals), according to the system used for glide path: WaveOne Gold Glider (WOGG) and R‐Pilot. The samples with fractured instruments or when it was not possible to RFWL were scanned using micro‐computed tomography. Fractured instruments were also visualised through a scanning electron microscopy to verify the type of fracture. The parameters were compared statistically by Fisher's and chi‐square tests (P < 0.05). No instrument fractures were observed in the R‐pilot, while 2 fractures occurred in the WOGG group (P > 0.05). RFLW was achieved in 29 canals (96.66%) and 28 canals (93.33%) with R‐pilot and WOGG instruments, respectively (P > 0.05). The instruments are able to RFWL in mesial canals of mandibular molars. WOGG showed two fractures while no R‐Pilot instruments fractured.
Shortening the Early Treatment Diabetic Retinopathy Study visual acuity test utilizing a novel computer software: reproducibility in control and patient eyes
Authors: Cohen Amir D. N. , Mimouni Michael , El‐Yaniv Ran , Blumenthal Eytan Z.
Published: March 2021

Purpose

To describe and compare a method of computerized visual acuity (VA) testing software to the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

Methods

Setting: Single tertiary institution. Study Population: Prospective study including right eyes of volunteers (N = 109) and patients (N = 126). Intervention: Subjects were tested in a random order twice with the ETDRS chart and twice with the VA software. For ETDRS, we calculated the final VA separately for each run, using four different test termination criteria (1‐miss in a row, 2‐miss in a row, 50% miss and per‐letter). For software testing, we calculated final VA with a variety of number of letters presented. Main Outcome Measures: The main outcome measures were reproducibility and number of letters required to exceed ETDRS reproducibility.

Results

For ETDRS, the average number of letters presented was 55.1 ± 9, 54.3 ± 10, 53.1 ± 10 and 70 for the 1‐miss, 2‐miss, 50% termination and per‐letter criterion. The test–retest variability (TRV) of ETDRS was 0.29, 0.42, 0.17 and 0.141 for the 1‐miss in a row, 2‐miss in a row, 50% and per‐letter termination criteria. For the software VA test, TRV was 0.202, 0.138 and 0.112 after presenting 6, 11 and 20 letters. The reproducibility of the software was equal to the ETDRS at 11 letters and thereafter surpassed. Similar results were achieved in the patient group.

Conclusions

This study demonstrates that by utilizing a VA testing software, based on advanced threshold testing algorithms we were able to duplicate, and surpass, the reproducibility of the ETDRS chart while presenting much fewer letters.
Rotational alignment of corneal endothelial grafts and risk of graft detachment after Descemet membrane endothelial keratoplasty: a double‐masked pseudo‐randomized study
Authors: Fritz Marianne , Grewing Viviane , Gruber Markus , Wagner Helena , Zander Daniel , Lapp Thabo , Lang Stefan J. , Heinzelmann‐Mink Sonja , Maier Philip C. , Reinhard Thomas , Wacker Katrin
Published: March 2021

Purpose

The posterior cornea is rotationally asymmetric, and Descemet membrane endothelial keratoplasty (DMEK) grafts preferentially scroll vertically. This prospective study assessed whether graft attachment after DMEK differed depending on the rotational alignment of the donor graft in the recipient eye.

Methods

Pseudo‐randomization and blinding of the graft orientation in the recipient’s eye were possible by procedural separation: (1) The eye bank recorded the position of an orientation marker in the donor cornea; (2) the surgeon preparing the DMEK graft recorded an upside‐down marker relative to the eye bank marker; and (3) the surgeon assessed the position of the upside‐down marker in the recipient after DMEK. Surgeons were masked towards the eye bank marker. Using mixed‐effects models, we assessed graft attachment relative to the rotational alignment of the donor graft.

Results

Postoperatively, the graft was not fully attached in 59 of 179 eyes (33%). A second air fill (rebubbling) was performed in 11%. The graft axis was in line with the recipient cornea axis in 40%, oblique in 28% and orthogonal in 32%. We did not detect an elevated risk of incomplete attachment (odds ratio [OR], 1.16; 95% CI, 0.61–2.20), risk of rebubbling (OR, 1.25; 95% CI, 0.47–3.31) or larger areas of graft detachment in non‐aligned grafts compared to aligned grafts.

Conclusion

Rotational alignment was not strongly associated with the risk of incomplete graft attachment, although modestly elevated risks cannot be ruled out. Efforts are needed to reduce the need for rebubbling after DMEK and to identify modifiable risk factors for graft detachment.