bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Role of Cardiac Magnetic Resonance Imaging in Diagnosing Myocarditis
Authors: Caredda Gloria , Bassareo Pier P. , Cau Riccardo , Mannelli Lorenzo , Suri Jasjit S. , Saba Luca
Published: February 2022

Acute myocarditis is a disease affecting the myocardial tissue, which is caused by infections, rheumatic diseases, especially sarcoidosis, or certain therapies. Its diagnosis may be difficult, owing to its variable clinical presentation. In this setting, cardiac magnetic resonance plays a pivotal role in detecting myocardial inflammation through qualitative, semiquantitative, and quantitative parameters, in particular with the new quantitative techniques such as T1 and T2 mapping, combined or not with late gadolinium enhancement evaluation. This is in accordance with the revised Lake Louise criteria. In this review, the emerging role of the new cutting-edge cardiac magnetic resonance imaging techniques in diagnosing myocarditis is extensively presented.
Thoracic Imaging Manifestations of Treated Lymphomas
Authors: Gooch Cory R. , Jain Manoj K. , Petranovic Milena , Chow David Z. , Muse Victorine V. , Gagne Staci M. , Wu Carol C. , Stowell Justin T.
Published: February 2022

Lymphoma is the most common hematologic malignancy comprising a diverse group of neoplasms arising from multiple blood cell lineages. Any structure of the thorax may be involved at any stage of disease. Imaging has a central role in the initial staging, response assessment, and surveillance of lymphoma, and updated standardized assessment criteria are available to assist with imaging interpretation and reporting. Radiologists should be aware of the modern approaches to lymphoma treatment, the role of imaging in posttherapeutic surveillance, and manifestations of therapy-related complications.
Dexmedetomidine alleviates the hypoxic-ischemic brain damage via miR-20a-5p/methionine adenosyltransferase 2B axis in rat pups
Authors: He Huan , Sun Mei , Chen Yun , Zhou Yang , Qie Wenbin , Tu Weifeng
Published: February 2022

Objective

The neuroprotective effect of dexmedetomidine (DEX) has been demonstrated in hypoxic-ischemic brain damage (HIBD) animal models, the mechanism of which will be the foothold in this work.

Methods

After establishment of HIBD rat model, the rats were treated with DEX, miR-20a-5p agomir and adenoviral methionine adenosyltransferase 2B (MAT2B) overexpression vector, and then their brain tissues were harvested. The infarction volume and pathological changes of these brain tissues were measured using the triphenyl tetrazolium chloride (TTC), Nissl and hematoxylin–eosin (HE) stainings. The levels of miR-20a-5p, Bcl-2, Bax and MAT2B in these brain tissues were detected by Real-Time PCR (RT-PCR) and western blot. The binding sites of MAT2B and miR-20a-5p were predicted using the TargetScan and verified using the dual-luciferase reporter assay. The memory deficits and spatial learning of rat pups were assessed by Morris water maze test.

Results

MiR-20a-5p expression was upregulated, while MAT2B expression was downregulated in rats with HIBD. MAT2B was targeted by miR-20a-5p. DEX treatment improved the neurons and hippocampal tissue damage and decreased miR-20a-5p level in brain tissues of rats with HIBD. MiR-20a-5p overexpression overturned the protective effect of DEX on brain tissues and learning and memory abilities in rats with HIBD. Moreover, DEX promoted Bcl-2 level while inhibiting Bax level in HIBD rats’ brain tissues. Besides, overexpressed MAT2B reversed the effect of overexpressed miR-20a-5p on the levels of MAT2B, Bcl-2 and Bax, brain tissue damage, as well as the learning and memory abilities in rats with HIBD.

Conclusion

DEX alleviated HIBD via the miR-20a-5p/MAT2B axis in rats.
Staphylococcus taiwanensis sp. nov., isolated from human blood
Authors: Lin Yu-Tzu , Hung Wei-Chun , Wan Tsai-Wen , Li Hsin , Lee Tai-Fen , Hsueh Po-Ren , Teng Lee-Jene
Published: February 2022

A novel coagulase-negative

Staphylococcus

strain (NTUH-S172T) was isolated from human blood culture in Taiwan with preliminary identification of

Staphylococcus saprophyticus

. 16S rRNA gene analysis and multilocus sequence analysis (MLSA) showed that NTUH-S172T was most closely related to

Staphylococcus haemolyticus

. The average nucleotide identity and digital DNA–DNA hybridization values with the whole genome sequence were <95 % and<70 % when compared to the related species. Strain NTUH-S172T could be distinguished from

S. haemolyticus

by urease production and from

Staphylococcus borealis

by nitrate reduction. In addition, the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) spectrum of NTHU-S172T was significantly different from that of

S. haemolyticus

, which could be used in clinical identification. In conclusion, it is proposed that this isolate represents a novel species, named Staphylococcus taiwanensis sp. nov., with type strain NTUH-S172T (=BCRC 81315T=JCM 34726T).
Accuracy of tongue swab testing using Xpert MTB-RIF Ultra for tuberculosis diagnosis
Authors: Andama A , Whitman GR , Crowder R , Reza TF , Jaganath D , Mulondo J , Nalugwa TK , Semitala C. F , Worodria W , Cook C , Wood RC , Weigel KM , Olson AM , Lohmiller Shaw J , Denkinger C , Nahid P , Cangelosi G , Cattamanchi A
Published: February 2022

Tongue dorsum swabs have shown promise as alternatives to sputum for detecting Mycobacterium tuberculosis (MTB) in patients with pulmonary tuberculosis (TB). Some of the most encouraging results have come from studies that used manual quantitative PCR (qPCR) to analyze swabs. Studies using the automated Cepheid Xpert® MTB/RIF Ultra qPCR test (Xpert Ultra) have yielded less encouraging results with tongue swabs, possibly because Xpert Ultra is optimized for testing sputum, not tongue swab samples. Using two new sample processing methods that demonstrated good sensitivity in preliminary experiments, we assessed diagnostic accuracy and semi-quantitative signals of 183 tongue swab samples using Xpert Ultra in a clinical setting. Relative to a sputum Xpert Ultra reference standard, the sensitivity of tongue swab Xpert Ultra was 68.5% (95% CI 54.4-80.5) and specificity was 100.0% (95% CI 97.2-100.0). When compared to a microbiological reference standard (MRS) incorporating both sputum Xpert Ultra and sputum culture, sensitivity was 64.9 (95% CI 51.1-77.1) and specificity remained the same. Higher sensitivity was observed (77.8% CI 64.4-88.0) when “trace” Xpert results were included among positive swabs. Semi-quantitative Xpert Ultra results were generally lower with swabs than with sputum. None of the eight sputum Xpert Ultra “trace” or “very low” results were detected using tongue swabs. Tongue swabs should be considered when sputum cannot be collected for Xpert Ultra testing, or in certain mass-screening settings. Further optimization of tongue swab analysis is needed to achieve parity with sputum-based molecular testing for TB.
Noncontact and high-precision sensing system for piano keys identified fingerprints of virtuosity
Authors: Oku Takanori , Furuya Shinichi
Published: February 2022

Dexterous tool use is typically characterized by fast and precise motions performed by multiple fingers. One representative task is piano playing, which involves fast performance of a sequence of complex motions with high spatiotemporal precision. However, for several decades, a lack of contactless sensing technologies that are capable of precision measurement of piano key motions has been a bottleneck for unveiling how such an outstanding skill is cultivated. Here, we developed a novel sensing system that can record the vertical position of all piano keys with a time resolution of 1 ms and a spatial resolution of 0.01 mm in a noncontact manner. Using this system, we recoded the piano key motions while 49 pianists played a complex sequence of tones that required both individuated and coordinated finger movements to be performed as fast and accurately as possible. Penalized regression using various feature variables of the key motions identified distinct characteristics of the key-depressing and key-releasing motions in relation to the speed and accuracy of the performance. For the maximum rate of the keystrokes, individual differences across the pianists were associated with the peak key descending velocity, the key depression duration, and key-lift timing. For the timing error of the keystrokes, the interindividual differences were associated with the peak ascending velocity of the key and the interstrike variability of both the peak key descending velocity and the key depression duration. These results highlight the importance of dexterous control of the vertical motions of the keys for fast and accurate piano performance.
Effects of bilateral sequential theta-burst stimulation on 5-HT1A receptors on dorsolateral prefrontal cortex in treatment resistant depression
Authors: Murgaš Matej , Unterholzner Jakob , Stöhrmann Peter , Philippe Cécile , Godbersen Godber M. , Nics Lukas , Reed Murray B. , Vraka Chrysoula , Vanicek Thomas , Wadsak Wolfgang , Kranz Georg S. , Hahn Andreas , Mitterhauser Markus , Hacker Marcus , Kasper Siegfried , Lanzenberger Rupert , Baldinger-Melich Pia
Published: February 2022

Theta-burst stimulation (TBS) represents a brain stimulation technique effective for treatment-resistant depression (TRD) as underlined by meta-analyses. While the methodology undergoes constant refinement, bilateral stimulation of the dorsolateral prefrontal cortex (DLPFC) appears promising to restore left DLPFC hypoactivity and right hyperactivity found in depression. The post-synaptic inhibitory serotonin-1A (5-HT1A) receptor, also occurring in the DLPFC, might be involved in this mechanism of action. To test this hypothesis, we performed PET-imaging using the tracer [carbonyl-11C]WAY-100635 including arterial blood sampling before and after a three-week treatment with TBS in 11 TRD patients compared to sham stimulation (n=8 and n=3, respectively). Treatment groups were randomly assigned, and TBS protocol consisted in excitatory intermittent TBS to the left and inhibitory continuous TBS to the right DLPFC. A linear mixed model including group, hemisphere time and Hamilton Rating Scale for Depression (HAMD) score revealed a 3-way interaction effect of group time and HAMD on 5-HT1A receptor specific binding VS. While post-hoc comparisons showed no significant changes of 5-HT1A VS in either group, higher 5-HT1A VS after treatment correlated with greater difference in HAMD (r=-0.62), indicative of potential effects of TBS on the 5-HT1A receptor. Due to the small sample size, all results, however, must be regarded with caution.
Effectiveness of targeted antenatal family planning information provision on early postpartum family planning uptake in Kisumu county: Study protocol for a Simple Randomized Control Trial
Authors: Shisanya Morris Senghor , Ouma Collins , Mary Kipmerewo
Published: February 2022

Overlooking the contraceptive needs of postpartum women constitutes missed opportunities in health system. Inter-birth interval of at least three years can prevent poor maternal, perinatal and neonatal outcomes and afford women socioeconomic benefits of family planning (FP). The unmet need for FP in the postpartum period remains unacceptably high and far exceeds the FP unmet need of other women. The Kenya Demographic and Health Survey (KDHS) estimate the unmet need for postpartum FP to be 74%. Maternal and Child Health (MCH) continuum provides a great opportunity for postpartum FP (PPFP) interventions integration especially Antenatal targeted FP information giving and gauging fertility intentions. However, there is no protocol for structured, targeted Antenatal FP information giving and behavioural contracting to influence postpartum fertility intentions of mothers before delivery. Knowledge gap regarding fertility intentions and best antenatal strategies for postpartum FP still exists. The available evidence differs across settings and demography. Equally, there has been inadequate exploration of operationally-feasible ways to integrate FP counselling into existing ANC services with limited number of methodologically rigorous trials. This study will therefore examine the effectiveness of antenatal family planning information provision on early postpartum FP uptake using a randomized control trial in Kisumu. The researcher will; assess socio-cultural beliefs towards of PPFP and perceived individual control of PPFP choice, analyze knowledge and intention for PPFP, compare and examine the determinants of PPFP uptake between study groups. A group of 246 antenatal mothers will be randomly assigned to control, community and facility intervention groups as per eligibility criteria in the study facilities that will be cluster sampled. After at least 3 months of intervention and 3 months of postpartum follow-up, clinical superiority will be used to gauge which invention was effective and the model superiority. Questionnaire and Case Report Forms will be the main source of data. The participant will form the unit of analysis which will be by intention to treat. Bivariate analysis will be done as the selection criteria for inclusion of predictors of intention and uptake with a P≤ 0.05 in the final logistic regression model. P-values, ≤0.05, Odds Ratios and 95% confidence interval (CI) will be used to demonstrate significance and the strength of association between selected variables. Dissemination will be through conference presentations and peer reviewed journals. The trial has been registered with the Pan African Clinical Trials Registry PACTR202109586388973 on the 28th September 2021.
Alteration of plasma von Willebrand factor in the treatment of retinal vein occlusion with cystoid macular edema
Authors: Hirai Hiromasa , Yamashita Mariko , Matsumoto Masanori , Nishiyama Takeyuki , Wada Daishi , Okabe Naoko , Mizusawa Yutaro , Jimura Hironobu , Ueda Tetsuo , Ogata Nahoko
Published: February 2022

Retinal vein occlusion (RVO) is a major retinal disease accompanied by venous thrombosis. Although several studies have proposed an association between venous thrombosis and von Willebrand factor (VWF), the association between RVO and VWF remains unclear. We aimed to investigate the association between RVO and VWF and the alteration of VWF levels under the anti-vascular endothelial growth factor (VEGF) treatment. We enrolled 55 patients with RVO involved cystoid macular edema. They received intravitreal injection of anti-VEGF drugs, either ranibizumab or aflibercept. We examined the clinical data, measured plasma VWF: antigen (VWF: Ag) and plasma a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (ADAMTS13: AC) and analyzed them to identify variabilities during the treatment. At the baseline there was no significant difference between the RVO group and age-matched controls in both VWF: Ag and ADAMTS13: AC levels but ADAMTS13:AC was significantly lower in central RVO (CRVO) than in branch RVO (BRVO) (P = 0.015). In BRVO, the negative correlation was found between VWF: Ag and central choroidal thickness (CCT) (r = −0.51, P < 0.001). In BRVO after the anti-VEGF treatment, VWF: Ag decreased significantly from 134% at the baseline to 109% at 1 day after (P = 0.002) and to 107% at 1 month after (P = 0.030). In contrast, ADAMTS13: AC showed no significant difference during this period. In BRVO at 1 month after treatment, we found a negative correlation between VWF: Ag and CCT (r = −0.47, P = 0.001). Our findings suggest an association between VWF and CCT in patients with BRVO, thus the measurement of VWF may be useful for evaluating the disease activity and prognosis.
The Effect of Genome Graph Expressiveness on the Discrepancy Between Genome Graph Distance and String Set Distance
Authors: Qiu Yutong , Kingsford Carl
Published: February 2022

Motivation

Intra-sample heterogeneity describes the phenomenon where a genomic sample contains a diverse set of genomic sequences. In practice, the true string sets in a sample are often unknown due to limitations in sequencing technology. In order to compare heterogeneous samples, genome graphs can be used to represent such sets of strings. However, a genome graph is generally able to represent a string set universe that contains multiple sets of strings in addition to the true string set. This difference between genome graphs and string sets is not well characterized. As a result, a distance metric between genome graphs may not match the distance between true string sets.

Results

We extend a genome graph distance metric, Graph Traversal Edit Distance (GTED) proposed by Ebrahimpour Boroojeny et al., to FGTED to model the distance between heterogeneous string sets and show that GTED and FGTED always underestimate the Earth Mover’s Edit Distance (EMED) between string sets. We introduce the notion of string set universe diameter of a genome graph. Using the diameter, we are able to upper-bound the deviation of FGTED from EMED and to improve FGTED so that it reduces the average error in empirically estimating the similarity between true string sets. On simulated TCR sequences and Hepatitis B virus genomes, we show that the diameter-corrected FGTED reduces the average deviation of the estimated distance from the true string set distances by more than 250%.

Availability

Data and source code for reproducing the experiments are available at:https://github.com/Kingsford-Group/gtedemedtest/

Contact

carlk@cs.cmu.edu
Tensor decomposition- and principal component analysis-based unsupervised feature extraction to select more reasonable differentially expressed genes: Optimization of standard deviation versus state-of-art methods
Authors: Taguchi Y-h. , Turki Turki
Published: February 2022

Background

Tensor decomposition- and principal component analysis-based unsupervised feature extraction were proposed almost 5 and 10 years ago, respectively; although these methods have been successfully applied to a wide range of genome analyses, including drug repositioning, biomarker identification, and disease-causing genes’ identification, some fundamental problems have been identified: the number of genes identified was too small to assume that there were no false negatives, and the histogram of P-values derived was not fully coincident with the null hypothesis that principal component and singular value vectors follow the Gaussian distribution.

Results

Optimizing the standard deviation such that the histogram of P-values is as much as possible coincident with the null hypothesis results in an increase in the number and biological reliability of the selected genes.

Conclusions

Tensor decomposition- and principal component analysis-based unsupervised feature extraction are perhaps better than state-of-art methods in regard to predicting differentially expressed genes because they achieve the desired property that the less expressed differentially expressed genes should be less likely selected or even associated with the same amount of logarithmic fold change, although they assume neither negative binomial distribution nor dispersion relation, which is usually assumed in state-of-art methods.
Occurrence and significance of Omicron BA.1 infection followed by BA.2 reinfection
Authors: Stegger Marc , Edslev Sofie Marie , Sieber Raphael Niklaus , Cäcilia Ingham Anna , Ng Kim Lee , Tang Man-Hung Eric , Alexandersen Soren , Fonager Jannik , Legarth Rebecca , Utko Magdalena , Wilkowski Bartlomiej , Gunalan Vithiagaran , Bennedbæk Marc , Byberg-Grauholm Jonas , Møller Camilla Holten , Christiansen Lasse Engbo , Svarrer Christina Wiid , Ellegaard Kirsten , Baig Sharmin , Johannesen Thor Bech , Espenhain Laura , Skov Robert , Cohen Arieh Sierra , Larsen Nicolai Balle , Sørensen Karina Meden , White Emily Dibba , Lillebaek Troels , Ullum Henrik , Krause Tyra Grove , Fomsgaard Anders , Ethelberg Steen , Rasmussen Morten
Published: February 2022

The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection.

To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death.

In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.
Voxel-wise Intermodal Coupling Analysis of Two or More Modalities using Local Covariance Decomposition
Authors: Hu Fengling , Weinstein Sarah M. , Baller Erica B. , Valcarcel Alessandra M. , Adebimpe Azeez , Raznahan Armin , Roalf David R. , Robert-Fitzgerald Timothy E. , Gonzenbach Virgilio , Gur Ruben C. , Gur Raquel E. , Vandekar Simon , Detre John A. , Linn Kristin A. , Alexander-Bloch Aaron , Satterthwaite Theodore D. , Shinohara Russell T.
Published: February 2022

When individual subjects are imaged with multiple modalities, biological information is present not only within each modality, but also between modalities – that is, in how modalities covary at the voxel level. Previous studies have shown that local covariance structures between modalities, or intermodal coupling (IMCo), can be summarized for two modalities, and that two-modality IMCo reveals otherwise undiscovered patterns in neurodevelopment and certain diseases. However, previous IMCo methods are based on the slopes of local weighted linear regression lines, which are inherently asymmetric and limited to the two-modality setting. Here, we present a generalization of IMCo estimation which uses local covariance decompositions to define a symmetric, voxel-wise coupling coefficient that is valid for two or more modalities. We use this method to study coupling between cerebral blood flow, amplitude of low frequency fluctuations, and local connectivity in 803 subjects ages 8 through 22. We demonstrate that coupling is spatially heterogeneous, varies with respect to age and sex in neurodevelopment, and reveals patterns that are not present in individual modalities. As availability of multi-modal data continues to increase, principal-component-based IMCo (pIMCo) offers a powerful approach for summarizing relationships between multiple aspects of brain structure and function. An R package for estimating pIMCo is available at: https://github.com/hufengling/pIMCo.
Assessing evidence accumulation and rule learning in humans with an online game
Authors: Do Quan , Kane Gary A. , McGuire Joseph T. , Scott Benjamin B.
Published: February 2022

Evidence accumulation, how the brain integrates sensory information over time, is an essential component of perception and decision making. In humans, evidence accumulation is commonly modeled as a diffusion process in which noise accumulates linearly with the incoming evidence. However, recent studies in rodents have shown that during perceptual decision making, noise scales non-linearly with the strength of accumulated evidence. The question of whether nonlinear noise scaling also holds for humans has been clouded by differences in the methodologies typically used to collect and analyze human and rodent data. For example, whereas humans are typically given explicit instructions in these tasks, rodents are trained using feedback. Therefore, to evaluate how perceptual noise scales with accumulated evidence, we developed an online evidence accumulation game and nonverbal training pipeline for humans inspired by pulse-based evidence accumulation tasks for rodents. Using this game, we collected and analyzed behavioral data from hundreds of participants trained either with an explicit description of the relevant decision rule or merely with experiential feedback. Across all participants, performance was well described by an accumulation process, in which stimuli were integrated equally across time. Participants trained using feedback alone learned the game rules rapidly and used similar strategies to those who received explicit instructions. Decisions in both groups were influenced in similar ways by biases and perceptual noise, suggesting that explicit instructions did not reduce bias or noise in pulse-based accumulation tasks. Finally, by leveraging data across all participants, we show that perceptual noise during evidence accumulation was best described by a non-linear model of noise scaling, consistent with previous animal studies, but inconsistent with diffusion models widely used in human studies. These results challenge the conventional description of humans’ accumulation process and suggest that online games inspired by evidence accumulation tasks provide a valuable large-scale behavioral assessment platform to examine perceptual decision making and learning in humans. In addition, the feedback-based training pipeline developed for this game may be useful for evaluating perceptual decision making in human populations with difficulty following verbal instructions.

Highlights

Development and validation of an online video game to measure perceptual decision making.

Humans trained using a feedback-based pipeline exhibit similar strategies and performance compared with those receiving instructions.

Perceptual noise increases superlinearly with sensory evidence.
Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection
Authors: Guarnieri Joseph W. , Dybas Joseph M. , Fazelinia Hossein , Kim Man S. , Frere Justin , Zhang Yuanchao , Albrecht Yentli Soto , Murdock Deborah G. , Angelin Alessia , Singh Larry N. , Weiss Scott L. , Best Sonja M. , Lott Marie T. , Cope Henry , Zaksas Viktorija , Saravia-Butler Amanda , Meydan Cem , Foox Jonathan , Mozsary Christopher , Kidane Yared H. , Priebe Waldemar , Emmett Mark R. , Meller Robert , Singh Urminder , Bram Yaron , tenOever Benjamin R. , Heise Mark T. , Moorman Nathaniel J. , Madden Emily A. , Taft-Benz Sharon A. , Anderson Elizabeth J. , Sanders Wes A. , Dickmander Rebekah J. , Baxter Victoria K. , Baylin Stephen B. , Wurtele Eve Syrkin , Moraes-Vieira Pedro M. , Taylor Deanne , Mason Christopher E. , Schisler Jonathan C. , Schwartz Robert E. , Beheshti Afshin , Wallace Douglas C.
Published: February 2022

Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been reported in COVID-19 patients, but the timing and organs affected vary among reports. Here, we reveal the dynamics of COVID-19 through transcription profiles in nasopharyngeal and autopsy samples from patients and infected rodent models. While mitochondrial bioenergetics is repressed in the viral nasopharyngeal portal of entry, it is up regulated in autopsy lung tissues from deceased patients. In most disease stages and organs, discrete OXPHOS functions are blocked by the virus, and this is countered by the host broadly up regulating unblocked OXPHOS functions. No such rebound is seen in autopsy heart, results in severe repression of genes across all OXPHOS modules. Hence, targeted enhancement of mitochondrial gene expression may mitigate the pathogenesis of COVID-19.

One-Sentence Summary

Covid-19 is associated with targeted inhibition of mitochondrial gene transcription.
Omicron booster in ancestral strain vaccinated mice augments protective immunities against both the Delta and Omicron variants
Authors: Jia Liqiu , Zhou Yang , Li Shaoshuai , Zhang Yifan , Yan Dongmei , Wang Wanhai , Zhang Wenhong , Wan Yanmin , Qiu Chao
Published: February 2022

A booster vaccination is called for constraining the evolving epidemic of SARS-CoV-2. However, the necessity of a new COVID-19 vaccine is currently unclear. To compare the effect of an Omicron-matched S DNA vaccine and an ancestral S DNA vaccine in boosting cross-reactive immunities, we firstly immunized mice with two-dose of a DNA vaccine encoding the spike protein of the ancestral Wuhan strain. Then the mice were boosted with DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8+ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron-matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-reactive immunities.
Single-cell Gene Regulation Network Inference by Large-scale Data Integration
Authors: Dong Xin , Tang Ke , Xu Yunfan , Wei Hailin , Han Tong , Wang Chenfei
Published: February 2022

Single-cell ATAC-seq (scATAC-seq) has proven to be a state-of-art approach to investigating gene regulation at the single-cell level. However, existing methods cannot precisely uncover cell-type-specific binding of transcription regulators (TRs) and construct gene regulation networks (GRNs) in single-cell. ChIP-seq has been widely used to profile TR binding sites in the past decades. Here, we developed SCRIP, an integrative method to infer single-cell TR activity and targets based on the integration of scATAC-seq and a large-scale TR ChIP-seq reference. Our method showed improved performance in evaluating TR binding activity compared to the existing motif-based methods and reached a higher consistency with matched TR expressions. Besides, our method enables identifying TR target genes as well as building GRNs at the single-cell resolution based on a regulatory potential model. We demonstrate SCRIP’s utility in accurate cell-type clustering, lineage tracing, and inferring cell-type-specific GRNs in multiple biological systems. SCRIP is freely available at https://github.com/wanglabtongji/SCRIP.
Multi-pulse transcranial magnetic stimulation of human motor cortex produces short-latency corticomotor facilitation via two distinct mechanisms
Authors: Kesselheim Janine , Takemi Mitsuaki , Christiansen Lasse , Karabanov Anke Ninija , Siebner Hartwig Roman
Published: February 2022

Background

Single-pulse transcranial magnetic stimulation of the precentral hand representation (M1HAND) can elicit indirect waves in the corticospinal tract at a periodicity of ~660 Hz, called indirect or I-waves. These synchronized descending volleys are produced by transsynaptic excitation of fastconducting monosynaptic corticospinal axons in M1-HAND. Paired-pulse TMS can induce short-interval intracortical facilitation (SICF) of motor evoked potentials (MEPs) at inter-pulse intervals that match I-wave periodicity.

Objective

To examine whether short-latency corticospinal facilitation engages additional mechanisms independently of I-wave periodicity.

Methods

In 19 volunteers, one to four biphasic TMS pulses were applied to left M1-HAND with interpulse interval was adjusted to the first peak or first trough of the individual SICF curve. TMS was applied at different intensities to probe the intensity-response relationship.

Results

Pairs, triplets, or quadruplets at individual peak-latency facilitated MEP amplitudes across a wide range of TMS intensities compared to single pulses. Multi-pulse TMSHAND at individual troughlatency also produced a consistent facilitation of MEP amplitude. Short-latency facilitation at trough-latency was less pronounced than short-latency facilitation at peak-latency, but the relative difference in facilitation decreased with increasing stimulus intensity. Increasing the number of pulses from two to four pulses had only a modest effect on MEP facilitation.

Conclusion

Two mechanisms underly short-latency corticomotor facilitation caused by biphasic multi-pulse TMS. An intracortical mechanism is related to I-wave periodicity and engages fast-conducting direct projections to spinal motoneurons. A second corticospinal mechanism does not rely on I-wave rhythmicity and may be mediated by slower conducting indirect pyramidal tract projections from M1-HAND to spinal interneurons. The latter mechanism deserves more attention in TMS studies of the corticomotor system.
Effects of Experimental Design, Genetic Architecture and Threshold on Power and False Positive Rate of Genome-Wide Association Studies
Authors: Loh Zhi , Clark Sam , van der Werf Julius H. J.
Published: February 2022

Genome-Wide Association Studies are an important tool for identifying genetic markers associated with a trait, but it has been plagued by the multiple testing problem, which necessitates a multiple testing correction method. While many multiple testing methods have been suggested, e.g. Bonferroni and Benjamini-Hochberg’s False Discovery Rate, the quality of the adjusted threshold based on these methods is not as well investigated. The aim of this study was to evaluate the balance between power and false positive rate of a Genome-Wide Association Studies experiment with Bonferroni and Benjamini-Hochberg’s False Discovery Rate multiple testing correction methods and to test the effects of various experimental design and genetic architecture parameters on this balance. Our results suggest that when the markers are independent the threshold from Benjamini-Hochberg’s False Discovery Rate provides a better balance between power and false positive rate in an experiment. However, with correlations between markers the threshold of Benjamini-Hochberg’s False Discovery Rate becomes too lenient with an excessive number of false positives. Experimental design parameters such as sample size and number of markers used, as well as genetic architecture of a trait affect the balance between power and false positive rate. This experiment provided guidance in selecting an appropriate experimental design and multiple testing correction method when conducting an experiment.
Quantifying the effect of isolation and negative certification on COVID-19 transmission
Authors: Takeshita Jun-ichi , Murakami Michio , Kamo Masashi , Naito Wataru , Yasutaka Tetsuo , Imoto Seiya
Published: February 2022

Abstract

Isolation of close contact people and negative test certification are used to manage the spread of new coronavirus infections worldwide. These effectively prevent the spread of infection in advance, but they can lead to a decline in socio-economic activity. Thus, the present study quantified the extent to which isolation and negative test certification respectively reduce the risk of infection. To this end, a discrete-time SEIR model was used as the infectious disease model, and equations for calculating the conditional probability of non-infection status given negative test results on two different days were derived. Then the respective non-infection probabilities with two negative PCR test results, and with one negative PCR test result and one antigen test result, were quantified. By substituting initial parameters of the SEIR model into these probabilities, the present study revealed the following: (1) isolating close contact individuals can reduce by 80% the risk of infection during the first five days, but five more days are needed to reduce the risk 10% more, and seven more days to reduce the risk 20% more; and (2) if an individual with a negative PCR test result has a negative antigen test result the next day, then his or her infection probability is between 0.6% and 0.7%. Our results show that five-day isolation has a proportionally greater effect on risk reduction, compared to longer isolation; and thus, if an isolation period of longer than five days is contemplated, both the risk reduction and the negative effects from such increased isolation should be considered. Regarding negative test certification, our results provide those in managerial positions, who must decide whether to accept the risk and hold mass-gathering events, with quantitative information that may be useful in their decision-making.
An approach to quantify parameter uncertainty in early assessment of novel health technologies
Authors: Iskandar Rowan , Federici Carlo , Berns Cassandra , Blankart Carl Rudolf
Published: February 2022

Health economic modeling of novel technology at the early stages of a product lifecycle has been used to identify technologies that are likely to be cost-effective. Such early assessments are challenging due to the potentially limited amount of data. Modelers typically conduct uncertainty analyses to evaluate their effect on decision-relevant outcomes. Current approaches, however, are limited in their scope of application and imposes an unverifiable assumption, i.e., uncertainty can be precisely represented by a probability distribution. In the absence of reliable data, an approach that uses the fewest number of assumptions is desirable. This study introduces a generalized approach for quantifying parameter uncertainty, i.e., probability bound analysis (PBA), that does not require a precise specification of a probability distribution in the context of early-stage health economic modeling. We introduce the concept of a probability box (p-box) as a measure of uncertainty without necessitating a precise probability distribution. We provide formulas for a p-box given data on summary statistics of a parameter. We describe an approach to propagate p-boxes into a model and provide step-by-step guidance on how to implement PBA. We conduct a case and examine the differences between the status-quo and PBA approaches and their potential implications on decision-making.
Identifying the midline thalamus in humans in vivo
Authors: Reeders Puck C. , Rivera N. M. Vanessa , Vertes Robert P. , Mattfeld Aaron T. , Allen Timothy A.
Published: February 2022

The midline thalamus is essential to flexible cognition, memory, and stress regulation and its dysfunction is associated with several neurological and mental health disorders including Alzheimer’s disease, schizophrenia, and depression. Despite the pervasive role of the midline thalamus in cognition and disease, almost nothing is known about it in humans due to the lack of a rigorous methodology for finding this brain region using noninvasive imaging technologies. Here, we introduce a new method for identifying the midline thalamus in vivo using probabilistic tractography and k-means clustering with diffusion weighted imaging data. This method clusters thalamic voxels based on data-driven cortical and subcortical connectivity profiles, and then segments midline thalamic nuclei based on connectivity profiles established in rodent and macaque tracer studies. Results from two different diffusion weighted imaging sets, including adult data (22-35yrs) from the Human Connectome Project (n=127) and adolescent data (9-14yrs) collected at Florida International University (n=34) showed that this approach reliably classifies midline thalamic clusters. As expected, these clusters were most evident along the dorsal/ventral extent of the third ventricle and primarily connected to the agranular medial prefrontal cortex (e.g., anterior cingulate cortex), nucleus accumbens, and medial temporal lobe regions. The midline thalamic clusters were then bisected based on a human brain atlas (Ding et al., 2016) into a dorsal midline thalamic cluster (paraventricular and paratenial nuclei) and a ventral midline thalamic cluster (rhomboid and reuniens nuclei). This anatomical connectivity-based identification procedure for the midline thalamus offers new opportunities to study this region in vivo in healthy populations and in those with psychiatric and neurological disorders.

Significance Statement

The midline thalamus is essential for flexible cognition, decision making, and stress regulation. Abnormal development, dysfunction, and neurodegeneration of the midline thalamus is thought to be a critical pathology in several psychiatric and neurological disorders. Yet, little is known about the role of the human midline thalamus. Here we solve the problem of localization in vivo by using probabilistic tractography and data driven clustering (k-means), a method capable of capitalizing on known connectivity in non-human animal tracer studies. Localizing the midline thalamus based on its connectivity patterns provides a useful tool for future functional and structural human MRI studies to investigate clinical implications of the midline thalamus in diseases such as Alzheimer’s and schizophrenia.
Public volume electron microscopy data: An essential resource to study the brain microvasculature
Authors: Bonney Stephanie K. , Coelho-Santos Vanessa , Huang Sheng-Fu , Takeno Marc , Kornfeld Joergen , Keller Annika , Shih Andy Y.
Published: February 2022

Electron microscopy is the primary approach to study ultrastructural features of the cerebrovasculature. However, 2D snapshots of a vascular bed capture only a small fraction of its complexity. Recent efforts to synaptically map neuronal circuitry using volume electron microscopy have also sampled the brain microvasculature in 3D. Here, we perform a meta-analysis of 6 data sets spanning different species and brain regions, including 2 data sets from the MICrONS consortium that have made efforts to segment vasculature in addition to all parenchymal cell types in mouse visual cortex. Exploration of these data have revealed rich information for detailed investigation of the cerebrovasculature. Neurovascular unit cell types (including, but not limited to, endothelial cells, mural cells, perivascular fibroblasts, microglia, and astrocytes) could be discerned across broad microvascular zones. Image contrast was sufficient to identify subcellular details, including endothelial junctions, caveolae, peg-and-socket interactions, mitochondria, Golgi cisternae, microvilli and other cellular protrusions of potential significance to vascular signaling. Additionally, noncellular structures including the basement membrane and perivascular spaces were visible and could be traced between arterio-venous zones along the vascular wall. These explorations revealed structural features that may be important for vascular functions, such as blood-brain barrier integrity, blood flow control, brain clearance, and bioenergetics. They also identified limitations where accuracy and consistency of segmentation could be further honed by future efforts. The purpose of this article is to introduce these valuable community resources within the framework of cerebrovascular research by providing an assessment of their vascular contents, identifying features of significance for further study, and discussing next step ideas for refining vascular segmentation and analysis.
Profiling skeletal muscle-derived secretome with differentiation and acute contractile activity
Authors: Bydak Benjamin , Pierdoná Taiana M. , Seif Samira , Sidhom Karim , Obi Patience O. , Labouta Hagar I. , Gordon Joseph W. , Saleem Ayesha
Published: February 2022

Extracellular vesicles (EVs) released from all cells, are essential to cellular communication, and contain biomolecular cargo that can affect recipient cell function. Studies on the effects of contractile activity (exercise) on EVs usually rely on plasma/serum-based assessments, which contain EVs from many different cells. To specifically characterize skeletal muscle-derived vesicles and the effect of acute contractile activity, we used an in vitro model where C2C12 mouse myoblasts were differentiated to form myotubes. EVs were isolated from conditioned media from muscle cells, pre-differentiation (myoblasts) and post-differentiation (myotubes), as well as from acutely stimulated myotubes (1hr @ 14V, C-Pace EM, IonOptix) using total exosome isolation reagent (TEI, ThermoFisher, referred to as extracellular particles [EPs]) and differential ultracentrifugation (dUC; EVs). Myotube-EPs (~98 nm) were 41% smaller than myoblast-EPs (~167 nm, p<0.001, N=8-10). Two-way ANOVA showed a significant main effect for size distribution of myotube vs. myoblast-EPs (p<0.01, N=10-13). Myoblast-EPs displayed a bimodal size distribution profile with peaks at <200 nm and 400-600 nm, compared to myotube-EPs that were largely 50-300 nm in size. Total protein yield from myotube-EPs was nearly 15-fold higher than myoblast-EPs, (p<0.001 N=6-9). Similar biophysical characteristics were observed when EVs were isolated using dUC: myotube-EVs (~195 nm) remained 41% smaller in average size than myoblast-EVs (~330 nm, p=0.07, N=4-6) and had comparable size distribution profiles as EPs isolated via TEI. Myotube-EVs also had 4.7-fold higher protein yield vs. myoblast EVs (p<0.05, N=4-6). Myotube-EPs had significantly decreased expression of exosomal marker proteins TSG101, CD63, ALIX and CD81 compared to myoblast-EPs (p<0.05, N=7-12). Conversely, microvesicle marker ARF6, and lipoprotein marker APO-A1was only found in the myotube-EPs (p<0.05, N=4-12). There was no effect of acute stimulation on myotube-EP biophysical characteristics (N=7), nor on expression of TSG101, ARF6 or CD81 (N=5-6). Myoblasts treated with control or acute stimulation-derived EPs (13 μg/well) for 48hrs and 72hrs showed no changes in mitochondrial mass (MitoTracker Red), cell viability or cell count (N=3-4). Myoblasts treated with EP-depleted media (72hrs) had ~90% lower cell counts (p<0.01, N=3). Our data show that EVs differ in size, distribution, protein yield and expression of subtype markers pre- vs. post-skeletal muscle differentiation. There was no effect of acute stimulation on biophysical profile or protein markers in EPs. Acute stimulation-derived EPs did not alter mitochondrial mass nor cell count/viability. Further investigation into the effects of chronic contractile activity on the biophysical characteristics and cargo of skeletal muscle-specific EVs are warranted.
A mesoscale connectome-based model of conscious access in the macaque monkey
Authors: Klatzmann Ulysse , Froudist-Walsh Sean , Bliss Daniel P. , Theodoni Panagiota , Mejías Jorge , Niu Meiqi , Rapan Lucija , Margulies Daniel S. , Palomero-Gallagher Nicola , Sergent Claire , Dehaene Stanislas , Wang Xiao-Jing
Published: February 2022

A growing body of evidence suggests that conscious perception of a sensory stimulus coincides with all-or-none activity across multiple cortical areas, a phenomenon called ‘ignition’. In contrast, the same stimulus, when undetected, induces only transient activity. In this work, we report a large-scale model of the macaque cortex based on recently quantified structural mesoscopic connectome data. We use this model to simulate a detection task, and demonstrate how a dynamical bifurcation mechanism produces ignition-like events in the model network. The model predicts that feedforward excitatory transmission is primarily mediated by the fast AMPA receptors to ensure rapid signal propagation from sensory to associative areas. In contrast, a greater proportion of the inter-areal feedback projections and local recurrent excitation depend on the slow NMDA receptors, to ensure ignition of distributed frontoparietal activity. Our model predicts, counterintuitively, that fast-responding sensory areas contain a higher ratio of NMDA to AMPA receptors compared to association cortical areas that show slow, sustained activity. We validate this prediction using cortex-widein-vitroreceptor autoradiography data. Finally, we show how this model can account for various behavioral and physiological effects linked to consciousness. Together, these findings clarify the neurophysiological mechanisms of conscious access in the primate cortex and support the concept that gradients of receptor densities along the cortical hierarchy contribute to distributed cognitive functions.