bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Parallel Acquisition Technology on the Robustness of Magnetic Resonance Imaging Radiomic Features
Authors: Hu Kui , Deng Wenyou , Li Ning , Cai Qian , Yuan Zilong , Li Ling , Liu Yulin
Published: June 2022

Objective

The aim of this study was to investigate the impact of integrated parallel acquisition technology (iPAT) on the robustness of magnetic resonance imaging radiomic features.

Methods

A phantom and 6 healthy volunteers were scanned on a clinical 3-T system using T1-weighted (S1), T1-weighted fluid-attenuated (S2), T2-weighted fluid-attenuated (S3), and T2-weighted (S4); 2 iPAT flavors (generalized autocalibration partially parallel acquisitions and modified sensitivity encoding [mSENSE]) and their different acceleration factors R. Radiomic features were extracted, and their robustness was assessed using coefficient of variation (CV), and differences between sequences and region of interest (ROI) were evaluated using the χ
2 test.

Results

One volunteer was excluded because of movement during imaging acquisition. Generalized autocalibration partially parallel acquisitions provided more radiomic features with excellent robustness than mSENSE. Radiomic features with excellent robustness, unaffected by iPAT across different sequences and ROIs, in 92 radiomic features for phantom and healthy volunteers are 6.5% and 2.2%. For phantom, difference in the robustness degree between 4 sequences/P-ROIs was significant according to χ
2 test; S2 and S3 could provide more excellent robust radiomic features than S1 and S4, and P-ROI3 filled with the biggest polystyrene particles could provide the most radiomic features with excellent robustness than the other P-ROIs. For healthy volunteers, only the difference in the degree of robustness between the 4 V-ROIs was significant, and V-ROI3 in white matter region of the left frontal lobe, which was located at periphery in image, could provide the most robust radiomic features compared with other V-ROIs.

Conclusions

Integrated parallel acquisition technology had a significant impact on the robustness of radiomic features. Generalized autocalibration partially parallel acquisitions delivered a more robust substrate for radiomic analyses than mSENSE.
COVID-19 Infection With the Omicron SARS-CoV-2 Variant in a Cohort of Kidney and Kidney Pancreas Transplant Recipients: Clinical Features, Risk Factors, and Outcomes
Authors: Wong Germaine , Rowlandson Matthew , Sabanayagam Dharshana , Ginn Andrew N. , Kable Kathy , Sciberras Frederika , Au Eric , Draper Jenny , Arnott Alicia , Sintchenko Vitali , Dwyer Dominic E. , Chen Sharon C.A. , Kok Jen
Published: June 2022

Background.

Since November 2021, a new variant of concern (VOC), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.1.529 (Omicron) has emerged as the dominant coronavirus disease 2019 (COVID-19) infection worldwide. We describe the clinical presentation, risk factors, and outcomes in a cohort of kidney and kidney pancreas transplant recipients with COVID-19 caused by Omicron infection.

Methods.

We included all kidney and kidney pancreas transplant recipients diagnosed with SARS-CoV-2 Omicron infections between December 26, 2021, and January 14, 2022, in a single transplant center in Australia. Identification of the VOC Omicron was confirmed using phylogenetic analysis of SARS-CoV-2 sequences.

Results.

Forty-one patients with kidney (6 living and 33 deceased) and kidney pancreas transplants were diagnosed with the VOC Omicron (lineage B.1.1.529/BA.1) infection during the study period. The mean age (SD) at the time of diagnosis was 52 (11.1) y; 40 (out of 41) (98%) had received at least 2 doses of COVID-19 vaccine. Cough was the most frequent symptom (80.5%), followed by myalgia (70.7%), sore throat (63.4%), and fever (58.5%). After a follow-up time of 30 d, 1 (2.4%) patient died, 2 (4.9%) experienced multiorgan failure, and 5 (12.2%) had respiratory failure; 11 (26.8%) patients developed other superimposed infections. Compared with recipients who did not receive sotrovimab antibody therapy, the odds ratio (95% confidence interval) for hospitalization among patients who received sotrovimab was 0.05 (0.005-0.4).

Conclusions.

Despite double or triple dose vaccination, VOC Omicron infections in kidney and kidney pancreas transplant recipients are not necessarily mild. Hospitalization rates remained high (around 56%), and sotrovimab use may prevent hospitalization.
Assessment of Factors Associated with Morbidity and Textbook Outcomes of Laparoscopic Liver Resection in Obese Patients: A French Nationwide Study
Authors: Genser Laurent , Lim Chetana , Barbier Louise , Regimbeau Jean-Marc , Hobeika Christian , Goumard Claire , Laurent Alexis , Fuks David , Chiche Laurence , Vibert Eric , Scatton Olivier ,   for the AFC-LLR-2018 Study Group
Published: June 2022

BACKGROUND:

Liver surgeons need to know the expected outcomes of laparoscopic liver resection (LLR) in obese patients.

OBJECTIVE:

The purpose of the present study is to assess morbidity, mortality and textbook outcomes (TO) after LLR in obese patients.

METHODS:

This is a French multicenter study of patients undergoing LLR between 1996 and 2018. Obesity was defined by a BMI at or above 30 kg/m2. Short-term outcomes and TO were compared between obese (ob) and nonobese (non-ob) patients. Factors associated with severe morbidity and TO were investigated.

RESULTS:

Of 3,154 patients included, 616 (19.5%) were obese. Ob-group patients had significantly higher American Society of Anesthesiologists (ASA) score and higher incidence of metabolic syndrome and chronic liver disease and were less likely to undergo major hepatectomy. Mortality rates were similar between ob and non-ob groups (0.8 vs 1.1%; p = 0.66). Overall morbidity and hospital stay were significantly increased in the ob group compared with the non-ob group (39.4 vs 34.7%, p = 0.03; and 9.5 vs 8.6 days, p = 0.02), whereas severe 90-day morbidity (at or above Clavien–Dindo grade III) was similar between groups (8% in both groups; p = 0.90). TO rate was significantly lower for the ob group than the non-ob group (58.3 vs 63.7%; p = 0.01). In multivariate analysis, obesity did not emerge as a risk factor for severe 90-day morbidity but was associated with a lower TO rate after LLR (odds ratio = 0.8, 95% CI 0.7–1.0; p = 0.03).

CONCLUSIONS:

LLR in obese patients is safe and effective with acceptable mortality and morbidity. Obesity had no impact on severe morbidity but was a factor for failing to achieve TO after LLR.
PriorVAE: encoding spatial priors with variational autoencoders for small-area estimation
Authors: Semenova Elizaveta , Xu Yidan , Howes Adam , Rashid Theo , Bhatt Samir , Mishra Swapnil , Flaxman Seth
Published: June 2022

Gaussian processes (GPs), implemented through multivariate Gaussian distributions for a finite collection of data, are the most popular approach in small-area spatial statistical modelling. In this context, they are used to encode correlation structures over space and can generalize well in interpolation tasks. Despite their flexibility, off-the-shelf GPs present serious computational challenges which limit their scalability and practical usefulness in applied settings. Here, we propose a novel, deep generative modelling approach to tackle this challenge, termed PriorVAE: for a particular spatial setting, we approximate a class of GP priors through prior sampling and subsequent fitting of a variational autoencoder (VAE). Given a trained VAE, the resultant decoder allows spatial inference to become incredibly efficient due to the low dimensional, independently distributed latent Gaussian space representation of the VAE. Once trained, inference using the VAE decoder replaces the GP within a Bayesian sampling framework. This approach provides tractable and easy-to-implement means of approximately encoding spatial priors and facilitates efficient statistical inference. We demonstrate the utility of our VAE two-stage approach on Bayesian, small-area estimation tasks.
Experimental approaches to assess the effect of composition of abrasives in the cause of dental microwear
Authors: Mihlbachler Matthew C. , Rusnack Frances , Beatty Brian Lee
Published: June 2022

Dental microwear is used to investigate feeding ecology. Animals ingest geological material in addition to food. The full effect of geological abrasives on tooth wear is unknown. To evaluate mineralogical abrasives as tooth wear agents, rats were fed food manufactured with quartz silt, diatomaceous earth, and calcium carbonate. Rats were assigned to treatments and fed for 15 days. Molars were scanned with a Sensofar Plu Neox confocal microscope and evaluated using ISO-25178-2 parameters and traditional microwear variables using light microscopy. Using a pellet-diet as the control, all treatments had influence on microwear and discriminant function analyses indicated that unique surface textures had been produced. ISO variables with high discriminatory values were correlated to scratch and pit frequencies, but more ISO parameters identified changes associated with numbers of scratches than changes associated with pits. The microwear changes associated with the abrasive inclusions were co-dependent on the type of diet that the abrasives had been added to. The abrasives had less effect with pellets but produced more modified and more differentiated microwear when added to the transgenic dough. Although abrasives produce distinctive surface textures, some knowledge of the properties of food with the abrasives is needed to identify the abrasive agent.
Personality and predictability in farmed calves using movement and space-use behaviours quantified by ultra-wideband sensors
Authors: Occhiuto Francesca , Vázquez-Diosdado Jorge A. , Carslake Charles , Kaler Jasmeet
Published: June 2022

Individuals within a population often show consistent between individual differences in their average behavioural expression (personality), and consistent differences in their within individual variability of behaviour around the mean (predictability). Where correlations between different personality traits and/or the predictability of traits exist, these represent behavioural or predictability syndromes. In wild populations, behavioural syndromes have consequences for individuals' survival and reproduction and affect the structure and functioning of groups and populations. The consequences of behavioural syndromes for farm animals are less well explored, partly due to the challenges in quantifying behaviour of many individuals across time and context in a farm setting. Here, we use ultra-wideband location sensors to provide precise measures of movement and space use for 60 calves over 40–48 days. We are the first livestock study to demonstrate consistent within and between individual variation in movement and space use with repeatability values of up to 0.80 and CVp values up to 0.49. Our results show correlations in personality and predictability, indicating the existence of ‘exploratory’ and ‘active’ personality traits in farmed calves. We consider the consequences of such individual variability for cattle behaviour and welfare and how such data may be used to inform management decisions in farm animals.
Land reversion and zoonotic spillover risk
Authors: Vinson John E. , Gottdenker Nicole L. , Chaves Luis Fernando , Kaul RajReni B. , Kramer Andrew M. , Drake John M. , Hall Richard J.
Published: June 2022

Deforestation alters wildlife communities and modifies human–wildlife interactions, often increasing zoonotic spillover potential. When deforested land reverts to forest, species composition differences between primary and regenerating (secondary) forest could alter spillover risk trajectory. We develop a mathematical model of land-use change, where habitats differ in their relative spillover risk, to understand how land reversion influences spillover risk. We apply this framework to scenarios where spillover risk is higher in deforested land than mature forest, reflecting higher relative abundance of highly competent species and/or increased human–wildlife encounters, and where regenerating forest has either very low or high spillover risk. We find the forest regeneration rate, the spillover risk of regenerating forest relative to deforested land, and how rapidly regenerating forest regains attributes of mature forest determine landscape-level spillover risk. When regenerating forest has a much lower spillover risk than deforested land, reversion lowers cumulative spillover risk, but instaneous spillover risk peaks earlier. However, when spillover risk is high in regenerating and cleared habitats, landscape-level spillover risk remains high, especially when cleared land is rapidly abandoned then slowly regenerates to mature forest. These results suggest that proactive wildlife management and awareness of human exposure risk in regenerating forests could be important tools for spillover mitigation.
A sampling-based approach for information-theoretic inspection management
Authors: Bull Lawrence A. , Dervilis Nikolaos , Worden Keith , Cross Elizabeth J. , Rogers Timothy J.
Published: June 2022

A partially supervised approach to Structural Health Monitoring is proposed, to manage the cost associated with expert inspections and maximize the value of monitoring regimes. Unlike conventional data-driven procedures, the monitoring classifier is learnt online while making predictions—negating the requirement for complete data before a system is in operation (which are rarely available). Most critically, periodic inspections are replaced (or enhanced) by anautomaticinspection regime, which only queries measurements that appear informative to the evolving model of the damage-sensitive features. The result is a partially supervised Dirichlet process clustering that manages expert inspections online given incremental data. The method is verified on a simulated example and demonstrated onin situbridge monitoring data.
Confined helium, density dependence of the inelastic electron and photon scattering cross-sections and the optical oscillator strength
Authors: Pyper N. C. , Whelan Colm T.
Published: June 2022

The electron and photon excitation of confined and compressed atoms is discussed. It is shown that the optical oscillator strength, the inelastic X-ray and electron impact cross-sections are all density-dependent.
Ab-initio
electronic structure calculations are presented for the

1

s
2

→
1
s
2
p

(
1

P
)

transition in helium, which predict that the amplitudes for the inelastic scattering of electrons, optical absorption and the excitation energy are all significantly increased in bulk condensed phases of pure helium compared to those of an isolated atom. The enhancements increase with atomic density but are very similar for bcc and fcc structured bulk phases of the same density. These enhancements need to be incorporated into the analysis of scanning transmission electron microscope studies of helium nano bubbles embedded in different materials. The excitation energy and cross-section enhancements with increasing density arise from the contraction of the

2
p

orbital on entering a condensed phase. For the bulk phases, but not the bubbles, the close agreement between the experimental and computed values of the energy shifts can be well described by a simple relationship.
The influence of demographic and meteorological factors on temporal patterns of rotavirus infection in Dhaka, Bangladesh
Authors: Asare Ernest O. , Al-Mamun Mohammad A. , Sarmin Monira , Faruque A. S. G. , Ahmed Tahmeed , Pitzer Virginia E.
Published: June 2022

To quantify the potential impact of rotavirus vaccines and identify strategies to improve vaccine performance in Bangladesh, a better understanding of the drivers of pre-vaccination rotavirus patterns is required. We developed and fitted mathematical models to 23 years (1990–2012) of weekly rotavirus surveillance data from Dhaka with and without incorporating long-term and seasonal variation in the birth rate and meteorological factors. We performed external model validation using data between 2013 and 2019 from the regions of Dhaka and Matlab. The models showed good agreement with the observed age distribution of rotavirus cases and captured the observed shift in seasonal patterns of rotavirus hospitalizations from biannual to annual peaks. The declining long-term trend in the birth rate in Bangladesh was the key driver of the observed shift from biannual to annual winter rotavirus patterns. Meteorological indices were also important: a 1°C, 1% and 1 mm increase in diurnal temperature range, surface water presence and degree of wetness were associated with a 19%, 3.9% and 0.6% increase in the transmission rate, respectively. The model demonstrated reasonable predictions for both Dhaka and Matlab, and can be used to evaluate the impact of rotavirus vaccination in Bangladesh against changing patterns of disease incidence.
Insect cross-tolerance to freezing and drought stress: role of metabolic rearrangement
Authors: Hůla Petr , Moos Martin , Des Marteaux Lauren , Šimek Petr , Koštál Vladimír
Published: June 2022

The accumulation of trehalose has been suggested as a mechanism underlying insect cross-tolerance to cold/freezing and drought. Here we show that exposing diapausing larvae of the drosophilid fly,Chymomyza costatato dry conditions significantly stimulates their freeze tolerance. It does not, however, improve their tolerance to desiccation, nor does it significantly affect trehalose concentrations. Next, we use metabolomics to compare the complex alterations to intermediary metabolism pathways in response to three environmental factors with different ecological meanings: environmental drought (an environmentalstressorcausing mortality), decreasing ambient temperatures (an acclimationstimulusfor improvement of cold hardiness), and short days (an environmentalsignalinducing diapause). We show that all three factors trigger qualitatively similar metabolic rearrangement and a similar phenotypic outcome—improved larval freeze tolerance. The similarities in metabolic response include (but are not restricted to) the accumulation of typical compatible solutes and the accumulation of energy-rich molecules (phosphagens). Based on these results, we suggest that transition to metabolic suppression (a state in which chemical energy demand is relatively low but need for stabilization of macromolecules is high) represents a common axis of metabolic pathway reorganization towards accumulation of non-toxic cytoprotective compounds, which in turn stimulates larval freeze tolerance.
On the prediction of arginine glycation using artificial neural networks
Authors: Que-Salinas Ulices , Martinez-Peon Dulce , Reyes-Figueroa A. D. , Ibarra Ivonne , Scheckhuber Christian Quintus
Published: June 2022

One of the hallmarks of diabetes is an increased modification of cellular proteins. The most prominent type of modification stems from the reaction of methylglyoxal with arginine and lysine residues, leading to structural and functional impairments of target proteins. For lysine glycation, several algorithms allow a prediction of occurrence, thus making it possible to pinpoint likely targets. However, according to our knowledge, no approaches have been published for predicting the likelihood of arginine glycation. There are indications that arginine and not lysine is the most prominent target for the toxic dialdehyde. One of the reasons why there is no arginine glycation predictor is the limited availability of quantitative data. Here we used a recently published high-quality dataset of arginine modification probabilities to employ an artificial neural network strategy. Despite the limited data availability, our results achieve an accuracy of about 75% of correctly predicting the exact value of the glycation probability of an arginine-containing peptide without setting thresholds upon whether it is decided if a given arginine is modified or not. This contribution suggests a possible solution for predicting arginine glycation. Our approach will greatly aid researchers in narrowing down possible glycation sites in protein targets. This strategy could improve the structural and functional characterization of proteins of interest.
Forecasting hospital-level COVID-19 admissions using real-time mobility data
Authors: Klein Brennan , Zenteno Ana C. , Joseph Daisha , Zahedi Mohammadmehdi , Hu Michael , Copenhaver Martin , Kraemer Moritz U.G. , Chinazzi Matteo , Klompas Michael , Vespignani Alessandro , Scarpino Samuel V. , Salmasian Hojjat
Published: June 2022

For each of the COVID-19 pandemic waves, hospitals have had to plan for deploying surge capacity and resources to manage large but transient increases in COVID-19 admissions. While a lot of effort has gone into predicting regional trends in COVID-19 cases and hospitalizations, there are far fewer successful tools for creating accurate hospital-level forecasts. At the same time, anonymized phone-collected mobility data proved to correlate well with the number of cases for the first two waves of the pandemic (spring 2020, and fall-winter 2021). In this work, we show how mobility data could bolster hospital-specific COVID-19 admission forecasts for five hospitals in Massachusetts during the initial COVID-19 surge. The high predictive capability of the model was achieved by combining anonymized, aggregated mobile device data about users’ contact patterns, commuting volume, and mobility range with COVID hospitalizations and test-positivity data. We conclude that mobility-informed forecasting models can increase the lead-time of accurate predictions for individual hospitals, giving managers valuable time to strategize how best to allocate resources to manage forthcoming surges.
Assessing the completeness of reporting of exercise-based interventions in cardiovascular trials
Authors: Freccia Guilherme Weiss , dos Santos Rafaella Zulianello , de Lucca Leonardo , Korbes Andrea Schaefer , de Carvalho Tales
Published: June 2022

Study Objective: In cardiology, the reporting of interventions is insufficiently detailed to elicit replication. Specifically for cardiovascular rehabilitation (CVR) trials, the quality of the description of its exercise-based interventions (EBI) is poorly known. Our primary objective is to estimate the adherence of EBI of CVR trials to TIDieR reporting guideline. Secondarily, we tested whether the CVR setting would be associated with a better reporting, also exploring whether transparency and methodological characteristics could be related. Design and Setting: This cross-sectional study analyzed 96 trials with EBI published within CVR literature. For our primary objective, TIDieR reporting guideline was accounted as a reference to assess overall adherence of eligible RCTs. For our secondary objectives we used generalized estimating equations to point out (a) if intervention setting (eg, home-based vs. centre-based) was associated with intervention reporting, and (b) if trials transparency and methodological characteristics would be associated with intervention reporting. Results: On average, arms adequately reported 4.8/12 (SD=2.4) TIDieR items. 65.07% of our EBI arms failed to adequately report ≥ 6 TIDieR items. Three of 146 (2.05%) arms adhered to all 12 TIDieR items. Additionally, intervention setting was not associated with a better description. Conclusions: We concluded that EBIs in CVR lack to report fundamental aspects of the interventions to be replicated by third parties based on their reports.
The L. pneumophila effector PieF modulates mRNA stability through association with eukaryotic CCR4-NOT
Authors: Mount Harley O’Connor , Zangari Francesco , Gingras Anne-Claude , Ensminger Alexander W.
Published: June 2022

The eukaryotic CCR4-NOT deadenylase complex is a highly conserved regulator of mRNA metabolism that influences the expression of the complete transcriptome, representing a prime target for a generalist bacterial pathogen. We show that a translocated bacterial effector protein, PieF (Lpg1972) of L. pneumophila Str. Philadelphia-1, interacts specifically with the CNOT7/8 nuclease module of CCR4-NOT, with a dissociation constant in the low nanomolar range. PieF inhibits the catalytic deadenylase subunit CNOT7 of the CCR4-NOT complex in a stoichiometric, dose-dependent manner in vitro. In transfected cells, PieF can silence reporter gene expression and reduce mRNA steady-state levels when artificially tethered. PieF demonstrates molecular similarities to another family of CNOT7-associated factors but demonstrates divergence concerning the interaction interface with CNOT7. In addition, we show that PieF overexpression changes the subcellular localization of CNOT7 and displaces the CNOT6/6L nucleases from CCR4-NOT. Finally, PieF expression phenocopies knockout of the CNOT7 ortholog in S. cerevisiae, resulting in 6-azauracil sensitivity. Collectively, this work suggests that L. pneumophila targets host mRNA stability and expression through a highly conserved host pathway not previously associated with Legionella pathogenesis.
NtcA, LexA and heptamer repeats involved in the multifaceted regulation of DNA repair genes recF, recO and recR in the cyanobacterium Nostoc PCC7120
Authors: Pradhan Mitali , Kumar Arvind , Kirti Anurag , Pandey Sarita , Rajaram Hema
Published: June 2022

Regulation of DNA repair genes in cyanobacteria is an unexplored field despite some of them exhibit high radio-resistance. With the RecF pathway speculated to be the major double strand break repair pathway in Nostoc sp. strain PCC7120, the regulation of recF, recO and recR genes was investigated. Bioinformatic approach-based identification of promoter and regulatory elements was validated using qRT-PCR analysis, reporter gene and DNA binding assays. Different deletion constructs of the upstream regulatory regions of these genes were analysed in host Nostoc as well as heterologous system Escherichia coli. Studies revealed: (1) Positive regulation of all three genes by NtcA, (2) Negative regulation by LexA, (3) Involvement of contiguous heptamer repeats with/without its yet to be identified interacting partner in regulating (i) binding of NtcA and LexA to recO promoter and its translation, (ii) transcription or translation of recF, (4) Translational regulation of recF and recO through non-canonical and distant S.D. sequence and of recR through a rare initiation codon. Presence of NtcA either precludes binding of LexA to AnLexA-Box or negates its repressive action resulting in higher expression of these genes under nitrogen-fixing conditions in Nostoc. Thus, in Nostoc, expression of recF, recO and recR genes is intricately regulated through multiple regulatory elements/proteins. Contiguous heptamer repeats present across the Nostoc genome in the vicinity of start codon or promoter is likely to have a global regulatory role. This is the first report on the involvement of NtcA and heptamer repeats in regulation of DNA repair genes in any organism.
Cortical synapses of the world’s smallest mammal: an FIB/SEM study in the Etruscan shrew
Authors: Alonso-Nanclares Lidia , Rodríguez J. Rodrigo , Merchan-Perez Ángel , González-Soriano Juncal , Plaza-Alonso Sergio , Cano-Astorga Nicolás , Naumann Robert K. , Brecht Michael , DeFelipe Javier
Published: June 2022

The main aim of the present study was to determine if synapses from the exceptionally small brain of the Etruscan shrew show any peculiarities compared to the much larger human brain. This study constitutes the first description of the Etruscan shrew synaptic characteristics using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM). We analyzed the synaptic density and a variety of structural characteristics of 7,239 3D reconstructed synapses, obtaining the following major results: (i) cortical synaptic density was very high, particularly in layer I; (ii) the vast majority of synapses were excitatory, with the highest proportion found in layer I; (iii) excitatory synapses were larger than inhibitory synapses in all layers except in layer VI; and (iv) synapses were either randomly distributed in space or showed a slight tendency to be organised in a regular arrangement. Some of these general synaptic characteristics are remarkably similar to those found in the human cerebral cortex. However, the cortical volume of the human brain is about 50,000 times larger than the cortical volume of the Etruscan shrew, while the total number of cortical synapses in human is only 20,000 times the number of synapses in the shrew, and synaptic junctions are 35% smaller in the Etruscan shrew. Thus, the differences in the number and size of synapses cannot be attributed to a brain size scaling effect but rather to adaptations of synaptic circuits to particular functions. The present work provides a quantitative dataset from the Etruscan shrew synapses — not only contributing to the knowledge of the ultrastructure of the mammalian cortex, but also identifying common and differing principles of synaptic organization.
Microglial STAT1-sufficiency is required for resistance to toxoplasmic encephalitis
Authors: Cowan M.N. , Kovacs M.A. , Sethi I. , Babcock I.W. , Still K. , Batista S.J. , O’Brien C.A. , Thompson J.A. , Sibley L.A. , Labuzan S. A. , Harris T.H.
Published: June 2022

Toxoplasma gondiiis a ubiquitous intracellular protozoan parasite that establishes a life-long chronic infection largely restricted to the central nervous system (CNS). Constant immune pressure, notably IFN-γ-STAT1 signaling, is required for preventing fatal pathology duringT. gondiiinfection. Here, we report that abrogation of STAT1 signaling in microglia, the resident immune cells of the CNS, is sufficient to induce a loss of parasite control in the CNS and susceptibility to toxoplasmic encephalitis during the early stages of chronic infection. Using a microglia-specific genetic labeling and targeting system that discriminates microglia from blood-derived myeloid cells that infiltrate the brain during infection, we find that, contrary to previousin vitroreports, microglia do not express inducible nitric-oxide synthase (iNOS) duringT. gondiiinfectionin vivo. Instead, transcriptomic analyses of microglia reveal that STAT1 regulates both (i) a transcriptional shift from homeostatic to “disease-associated microglia” (DAM) phenotype conserved across several neuroinflammatory models, includingT. gondiiinfection, and (ii) the expression of anti-parasitic cytosolic molecules that are required for eliminatingT. gondiiin a cell-intrinsic manner. Further, genetic deletion ofStat1from microglia duringT. gondiichallenge leads to fatal pathology despite largely equivalent or enhanced immune effector functions displayed by brain-infiltrating immune populations. Finally, we show that microglial STAT1-deficiency results in the overrepresentation of the highly replicative, lytic tachyzoite form ofT. gondii, relative to its quiescent, semi-dormant bradyzoite form typical of chronic CNS infection. Our data suggest an overall protective role of CNS-resident microglia againstT. gondiiinfection, illuminating (i) general mechanisms of CNS-specific immunity to infection (ii) and a clear role for IFN-STAT1 signaling in regulating a microglial activation phenotype observed across diverse neuroinflammatory disease states.
Protein-protein interaction (PPI) network analysis reveals important hub proteins and sub-network modules for root development in rice (Oryza sativa)
Authors: Wimalagunasekara Samadhi , Tirimanne Shamala , Fernando Pasan Chinthana
Published: June 2022

The root system is vital to plant growth and survival. Therefore, genetic improvement of the root system is beneficial for developing stress-tolerant and improved plant varieties. This requires the identification of proteins that significantly contributes to root development. Analyzing protein-protein interaction (PPI) networks is vastly beneficial in studying developmental phenotypes, such as root development because a phenotype is an outcome of several interacting proteins. PPI networks can be analyzed to identify modules and get a global understanding of important proteins governing the phenotypes. PPI network analysis for root development in rice has not been performed before and has the potential to yield new findings to improve stress tolerance. Therefore, in this research, the network module for the root development was extracted from a PPI network retrieved from the STRING database. Novel protein candidates were predicted, and hub proteins and sub-modules were identified from the extracted module. The validation of the predictions yielded 75 novel candidate proteins, 6 sub-modules, 20 intramodular hubs, and 2 intermodular hubs. These results show how the PPI network module is organized for root development and can be used for future wet-lab studies for producing improved rice varieties.
Hallucinating structure-conditioned antibody libraries for target-specific binders
Authors: Mahajan Sai Pooja , Ruffolo Jeffrey A. , Frick Rahel , Gray Jeffrey J.
Published: June 2022

Antibodies are widely developed and used as therapeutics to treat cancer, infectious disease, and inflammation. During development, initial leads routinely undergo additional engineering to increase their target affinity. Experimental methods for affinity maturation are expensive, laborious, and time-consuming and rarely allow the efficient exploration of the relevant design space. Deep learning (DL) models are transforming the field of protein engineering and design. While several DL-based protein design methods have shown promise, the antibody design problem is distinct, and specialized models for antibody design are desirable. Inspired by hallucination frameworks that leverage accurate structure prediction DL models, we propose the FvHallucinator for designing antibody sequences, especially the CDR loops, conditioned on an antibody structure. Such a strategy generates targeted CDR libraries that retain the conformation of the binder and thereby the mode of binding to the epitope on the antigen. On a benchmark set of 60 antibodies, FvHallucinator generates sequences resembling natural CDRs and recapitulates perplexity of canonical CDR clusters. Furthermore, the FvHallucinator designs amino acid substitutions at the VH-VL interface that are enriched in human antibody repertoires and therapeutic antibodies. We propose a pipeline that screens FvHallucinator designs to obtain a library enriched in binders for an antigen of interest. We apply this pipeline to the CDR H3 of the Trastuzumab-HER2 complex to generate in silico designs improving upon the binding affinity and interfacial properties of the original antibody. Thus, the FvHallucinator pipeline enables generation of inexpensive, diverse, and targeted antibody libraries enriched in binders for antibody affinity maturation.
The Brain/MINDS Marmoset Connectivity Atlas: exploring bidirectional tracing and tractography in the same stereotaxic space
Authors: Skibbe Henrik , Rachmadi Muhammad Febrian , Nakae Ken , Gutierrez Carlos Enrique , Hata Junichi , Tsukada Hiromichi , Poon Charissa , Doya Kenji , Majka Piotr , Rosa Marcello G. P. , Okano Hideyuki , Yamamori Tetsuo , Ishii Shin , Reisert Marco , Watakabe Akiya
Published: June 2022

We report on the implementation and features of the Brain/MINDS Marmoset Connectivity Atlas, BMCA, a new resource that provides access to anterograde neuronal tracer data in the prefrontal cortex of a marmoset brain. Neuronal tracers combined with fluorescence microscopy are a key technology for the systematic mapping of structural brain connectivity. We selected the prefrontal cortex for mapping due to its important role in higher brain functions. This work introduces the BMCA standard image preprocessing pipeline and tools for exploring and reviewing the data. We developed the BMCA-Explorer, which is an online image viewer designed for data exploration. Unlike other existing image explorers, it visualizes the data of different individuals in a common reference space at an unprecedented high resolution, facilitating comparative studies. To foster the integration with other marmoset brain image databases and cross-species comparisons, we added fiber tractography data from diffusion MRI, retrograde neural tracer data from the Marmoset Brain Connectivity Atlas project, and tools to map image data between marmoset and the human brain image space. This version of BMCA allows direct comparison between the results of 52 anterograde and 164 retrograde tracer injections in the cortex of the marmoset.
UVC Inactivation of Black Mold is Wavelength-Dependent, and its Growth in HVAC Systems is Preventable Using Periodic Dosing with commercially available UVC LEDs
Authors: Mariita Richard M. , Randive Rajul V. , Lottridge Michelle M. , Davis James H. , Bryson Benjamin W.
Published: June 2022

Mold growth in HVAC systems poses a threat to human health, increases facility management operating costs due to decreased air flow efficiency, and damages buildings, impacting buildings’ attractiveness in an ever more competitive property market concerned with both carbon footprint and ventilation quality. Although UVC treatment of HVAC systems has been shown to reduce growth, efficient design requires a specified amount of UVC dose coupled with a specific dosing strategy. UVC disinfection efficacy and wavelength sensitivity of spores from the most common and notorious black mold, Cladosporium halotolerans is not known. This study investigates the sensitivity of C. halotolerans and demonstrates that growth of black mold on HVAC coils can be effectively prevented with a periodic dosing scheme using commercially available UVC LEDs. Multiple UVC LED arrays with varying wavelength peaks in the range of 252-280 nm were used to demonstrate the spectral sensitivity of C. halotolerans by keeping the wavelength specific UVC dose equal in order to avoid bias. The data obtained for doses of 25, 75, 125, 175, and 225 mJ/cm2 was used. The data obtained was used to determine a dose response curve and susceptibility patterns. Disinfection performances for the arrays were determined using log reduction value (LRV) by comparing the controls against the irradiated treatments. To study mold growth prevention on HVAC coils, the 267 nm array which had the best disinfection efficacy was utilized. The coils were placed in a chamber with a temperature set at 24 °C and relative humidity (RH) at 96%. Unlike the controls, the test coil was irradiated with a dose of 28.8 mJ/cm2 every 12 hours. The coils were monitored, and observations were recorded using time-lapse videos. The highest disinfection level of black mold observed in the range of 250-280nm occurred at 267 nm, with 225 mJ/cm2 obtaining 4.03 LRV. Linear regression analysis at 95% for 252 nm (R2 =0.9637, p=0.0030), 261 nm (R2 =0.9711, p=0.0021), 267 nm (R2 =0.9723, p=0.0020), 270 nm (R2 =0.9819, p=0.0010), 273 nm (R2 =0.9878, p=0.0006), and 280 nm (R2 =0.9914, p=0.0003) displayed significant association between arrays’ peak wavelengths and disinfection performances against C. halotolerans. The study revealed that a higher dose of 225 mJ/cm2 is required to disinfect C. halotolerans by 99.99% (4.03 LRV). However, using a periodic dosing strategy utilizing 28.8 mJ/cm2 prevented any mold growth, while the fungal levels in the positive control increased. The study allows for the design and implementation of mold growth prevention strategies in HVAC systems to improve health and lower operating costs.
Evidence of hatch-time based growth compensation in the early life history of two salmonid fishes
Authors: Penney Heather D. , Keefe Donald G. , Perry Robert C. , Purchase Craig F.
Published: June 2022

Initial body size can indicate quality within-species, with large size increasing the likelihood of survival. However, some populations or individuals may have body size disadvantages due to spatial/temporal differences in temperature, photoperiod, or food availability. Across-populations animals often have locally adapted physiology to compensate for poor environmental influences on development and growth, while within-populations behavioural adjustments that increase food intake after periods of deprivation provide opportunities to catch up (growth compensation). We posit a theoretical extension of growth compensation to include within-population differences related to short growing seasons due to delayed hatch time. We tested the hypothesis that individual fish that hatch later grow faster than those that hatch earlier. The relative magnitude of such a response was compared to growth variation among populations and between related species. We sampled young of the year Arctic charr and brook trout from five rivers in northern Labrador. Daily increments from otoliths were used to back-calculate size to a common age and calculate growth rates. Supporting the hypothesis, older fish were not larger at capture than younger fish, because animals that hatched later grew faster which may indicate age-based growth compensation.
A class IV adenylate cyclase CyaB is required for capsule polysaccharide production and biofilm formation inVibrio parahaemolyticus
Authors: Regmi A. , Tague J.G. , Boas Lichty K. , Boyd E.F.
Published: June 2022

CRP (cyclic AMP receptor protein), encoded bycrp, is a global regulator that is activated by cAMP (cyclic AMP), a second messenger synthesized by a class I adenylate cyclase (AC-I) encoded bycyaAinEscherichia coli. cAMP-CRP is required for growth on non-preferred carbon sources and is a global regulator. We constructed in-frame non- polar deletions of thecrpandcyaAhomologs inVibrio parahaemolyticusand found that the Δcrpmutant did not grow in minimal media supplemented with non-preferred carbon sources, but the ΔcyaAmutant grew similar to wild type. Bioinformatics analysis of theV. parahaemolyticusgenome identified a 181 amino acid protein annotated as a class IV adenylate cyclase (AC-IV) named CyaB, a member of the CYTH protein superfamily. AC-IV phylogeny showed CyaB was present in Gamma- and Alpha- Proteobacteria as well as Planctomycete and Archaea. Only the bacterial CyaB proteins contained an N-terminal motif HFxxxExExK indicative of adenylyl cyclase activity. BothV. parahaemolyticus cyaAandcyaBgenes functionally complemented anE. coliΔcyaAmutant. The Δcrpand ΔcyaB/ΔcyaAmutants showed defects in growth on non- preferred carbon sources, and in swimming and swarming motility, indicating cAMP- CRP is an activator. The ΔcyaAand ΔcyaBsingle mutants had no defects in these phenotypes indicating AC-IV complements AC-I. Capsule polysaccharide and biofilm production assays showed significant defects in Δcrp, ΔcyaB/ΔcyaA,and the ΔcyaBmutant, whereas ΔcyaAbehaved similar to wild type. This is consistent with a role of cAMP-CRP as an activator of these phenotypes and establishes a cellular role for AC-IV in capsule and biofilm formation, which to date has been unestablished.

IMPORTANCE

Here, we characterized the roles of CRP and CyaA inV. parahaemolyticus,showing cAMP-CRP was an activator of metabolism, motility, capsule and biofilm formation. These results are in contrast to cAMP-CRP inV. cholerae,which represses capsule and biofilm formation. Previously, only an AC-I CyaA had been identified inVibriospecies. Our data showed that an AC-IV CyaB homolog is present inV. parahaemolyticusand was required for optimal growth. The data demonstrated that CyaB was essential for capsule production and biofilm formation uncovering a physiological role of AC-IV in bacteria. The data showed that thecyaBgene was widespread amongVibrionaceaespecies and several other Gamma-Proteobacteria, but in general, its phylogenetic distribution was limited. Our phylogenetic analysis also demonstrated that in some species thecyaBgene was acquired by horizontal gene transfer.
Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study
Authors: Cysique Lucette A. , Jakabek David , Bracken Sophia G. , Allen-Davidian Yasmin , Heng Benjamin , Chow Sharron , Dehhaghi Mona , Pires Ananda Staats , Darley David R. , Byrne Anthony , Phetsouphanh Chansavath , Kelleher Anthony , Dore Gregory J. , Matthews Gail V. , Guillemin Gilles J , Brew Bruce J.
Published: June 2022

Cognitive impairment and function post-acute mild to moderate COVID-19 are poorly understood. We report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung function, physical and mental health were assessed at 2-month post diagnosis. Blood cytokines, neuro-biomarkers, and kynurenine pathway (KP) metabolites were measured at 2-, 4-, 8- and 12- months. Mild to moderate cognitive impairment (demographically corrected) was present in 16%, 23%, and 26%, at 2-, 4- and 12-months post diagnosis, respectively. Overall cognitive performance mildly, but significantly (p<.001) declined. Cognitive impairment was more common in those with anosmia (p=.05), but only at 2 months. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly (p<.001) associated with cognitive decline. The KP as a unique biomarker offers a potential therapeutic target for COVID-19-related cognitive impairment.
Structural brain correlates of childhood trauma with replication across two large, independent community-based samples
Authors: Madden Rebecca A. , Atkinson Kimberley , Shen Xueyi , Green Claire , Hillary Robert F. , Hawkins Emma , Sandu Anca-Larisa , Waiter Gordon , McNeil Christopher , Harris Mathew , Campbell Archie , Porteous David , Macfarlane Jennifer A. , Murray Alison , Steele Douglas , Romaniuk Liana , Lawrie Stephen M. , McIntosh Andrew M. , Whalley Heather C.
Published: June 2022

Introduction

Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes, such as raised risk of lifetime depression, could be via associations with brain structure. This study aimed to elucidate the associations between childhood trauma scores and brain structure across two large, independent community cohorts.

Methods

The two samples comprised (i) a subsample of individuals from Generation Scotland with imaging and in-depth phenotyping, including the CTQ-28 (n=1,024); and (ii) individuals from UK Biobank with imaging and a modified summary CTQ measure (n=27,202). This comprised n=28,226 for mega-analysis. Scans were processed using FreeSurfer image processing software, providing cortical and subcortical as well as global brain metrics. Regression models were used to determine associations between these metrics and childhood trauma measures. Associations between childhood trauma measures and psychiatric phenotypes were also explored.

Results

Childhood trauma measures associated with lifetime risk of depression diagnosis with similar ORs across cohorts (OR 1.06, 1.23 GS and UKB respectively), which also related to earlier onset and more recurrent course within both samples. There was also evidence for associations between childhood trauma measures and a range of brain structures. Replicated findings included reduced global brain volumes, reduced cortical surface area but not thickness, with highest effects at mega-analysis seen in the frontal (β=-0.0385, SE=0.0048, p(FDR)=5.43×10−15) and parietal lobes (β=-0.0387, SE=0.005, p(FDR)=1.56×10−14). At a regional level, one subcortical regional volume in particular – the ventral diencephalon (VDc) – displayed significant associations with childhood trauma measures across the two cohorts and at mega-analysis (β=-0.0232, SE=0.0039, p(FDR)=2.91×10−8). There was also evidence for associations with reduced hippocampus, thalamus, and nucleus accumbens volumes, however these were not as consistent across cohorts.

Discussion

There was strong evidence for associations between childhood trauma and reduced global and regional brain volumes across cohorts. In particular, the presence of an association between childhood trauma and the volume of the VDc (which includes the hypothalamic area), with replication, provides further evidence of the importance of neuroendocrine stress response pathways in links between early life stress and clinical outcomes.