bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost of Respiratory Syncytial Virus Infections in US Infants: Systematic Literature Review and Analysis
Authors: Bowser Diana M , Rowlands Katharine R , Hariharan Dhwani , Gervasio Raíssa M , Buckley Lauren , Halasa-Rappel Yara , Glaser Elizabeth L , Nelson Christopher B , Shepard Donald S
Published: April 2022

Background

Limited data are available on the economic costs of respiratory syncytial virus (RSV) infections among infants and young children in the United States.

Methods

We performed a systematic literature review of 10 key databases to identify studies published between 1 January 2014 and 2 August 2021 that reported RSV-related costs in US children aged 0–59 months. Costs were extracted and a systematic analysis was performed.

Results

Seventeen studies were included. Although an RSV hospitalization (RSVH) of an extremely premature infant costs 5.6 times that of a full-term infant ($10 214), full-term infants accounted for 82% of RSVHs and 70% of RSVH costs. Medicaid-insured infants were 91% more likely than commercially insured infants to be hospitalized for RSV treatment in their first year of life. Medicaid financed 61% of infant RSVHs. Paying 32% less per hospitalization than commercial insurance, Medicaid paid 51% of infant RSVH costs. Infants’ RSV treatment costs $709.6 million annually, representing $187 per overall birth and $227 per publicly funded birth.

Conclusions

Public sources pay for more than half of infants’ RSV medical costs, constituting the highest rate of RSVHs and the highest expenditure per birth. Full-term infants are the predominant source of infant RSVHs and costs.
Development and application of triangulation joint network based on an FEM program (RS2)
Authors: Xi Peiqi , Huo Yuming , Zhu Defu , Xing Cunen , Wang Zhonglun
Published: April 2022

It is widely known that the triangle is the finest geometric unit, and therefore applying the triangulation joint to the rock mass simulation can not only accurately describe the fracture morphology of rock engineering, but also inversely deduce the mechanical parameters of blocks and joints. Based on the rock and soil two-dimensional analysis program (RS2), this paper compiles a program with MATLAB and realizes the parameterized setting of triangulation joint network (TJN) in RS2 for the first time, using it for the uniaxial compression model and roadway model accordingly. In the simulation of a RS2-TJN uniaxial compression model, its element parameters and joint parameters are calibrated according to the uniaxial compression strength and the elastic modulus obtained from the uniaxial compression test in a laboratory. Then its simulation results are compared with those of the particle flow code (PFC), which shows that the stress–strain curve obtained from the RS2-TJN uniaxial compression model matches the laboratory test one more closely. In the RS2-TJN roadway model, the simulation results obtained by adjusting the joint density are in good agreement with the roadway deformation in situ so as to study the failure characteristics of roadway surrounding rocks. Since the research on adding the triangulation joint network (cracks) to RS2 has not been found, its development and the realization of the parameterized control in this paper enrich the joint base of RS2 and provide a reference for the variety of joint numerical model.
High-frequency wavefield extrapolation using the Fourier neural operator
Authors: Song Chao , Wang Yanghua
Published: April 2022

In seismic wave simulation, solving the wave equation in the frequency domain requires calculating the inverse of the impedance matrix. The total cost strictly depends on the number of frequency components that are considered, if using a finite-difference method. For the applications such as seismic imaging and inversion, high-frequency information is always required and thus the wave simulation is always a challenging task as it demands tremendous computational cost for obtaining dispersion-free high-frequency wavefields for large subsurface models. This paper demonstrates that a data-driven machine learning method, called the Fourier neural operator (FNO), is capable of predicting high-frequency wavefields, based on a limited number of low-frequency components. As the FNO method is for the first time applied to seismic wavefield extrapolation, the experiment reveals three attractive features with FNO: high efficiency, high accuracy and, importantly, the predicted high-frequency wavefields are dispersion free.
Are Refugees (Really) a Hard-to-Survey Group? Fieldwork Experience with Syrian Refugees in Germany
Authors: Aljadeeah Saleh
Published: April 2022

Despite the increasing need for representative data on refugee health, refugees are underrepresented in health research in Germany and other European countries. Researchers often describe refugees as a hard-to-survey (or hard-to-reach) population. Labelling refugee populations with this phrase reflects the perspective of mainly local European researchers on a population they do not belong to. Moreover, refugees may not describe themselves with this phrase. Drawing upon my fieldwork experience as a member of the Syrian community in Germany who has conducted research with Syrian refugees, this practice paper challenges a common narrative among researchers in Europe in regard to refugee populations. I strongly recommend that researchers who are interested in conducting research with refugee populations involve them in all research design and implementation stages. I further call upon researchers to refrain from using the label ‘hard-to-survey’ to describe refugee populations before ensuring that they have done enough to engage with and involve their target population in their research.
Dark Energy Survey Year 3 results: calibration of lens sample redshift distributions using clustering redshifts with BOSS/eBOSS
Authors: Cawthon R , Elvin-Poole J , Porredon A , Crocce M , Giannini G , Gatti M , Ross A J , Rykoff E S , Carnero Rosell A , DeRose J , Lee S , Rodriguez-Monroy M , Amon A , Bechtol K , De Vicente J , Gruen D , Morgan R , Sanchez E , Sanchez J , Sevilla-Noarbe I , Abbott T M C , Aguena M , Allam S , Annis J , Avila S , Bacon D , Bertin E , Brooks D , Burke D L , Carrasco Kind M , Carretero J , Castander F J , Choi A , Costanzi M , da Costa L N , Pereira M E S , Dawson K , Desai S , Diehl H T , Eckert K , Everett S , Ferrero I , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , Huterer D , James D J , Kim A G , Kneib J-P , Kuehn K , Kuropatkin N , Lahav O , Lima M , Lin H , Maia M A G , Melchior P , Menanteau F , Miquel R , Mohr J J , Muir J , Myles J , Palmese A , Pandey S , Paz-Chinchón F , Percival W J , Plazas A A , Roodman A , Rossi G , Scarpine V , Serrano S , Smith M , Soares-Santos M , Suchyta E , Swanson M E C , Tarle G , To C , Troxel M A , Wilkinson R D ,   (DES Collaboration)
Published: April 2022

We present clustering redshift measurements for Dark Energy Survey (DES) lens sample galaxies used in weak gravitational lensing and galaxy clustering studies. To perform these measurements, we cross-correlate with spectroscopic galaxies from the Baryon Acoustic Oscillation Survey (BOSS) and its extension, eBOSS. We validate our methodology in simulations, including a new technique to calibrate systematic errors that result from the galaxy clustering bias, and we find that our method is generally unbiased in calibrating the mean redshift. We apply our method to the data, and estimate the redshift distribution for 11 different photometrically selected bins. We find general agreement between clustering redshift and photometric redshift estimates, with differences on the inferred mean redshift found to be below |Δz| = 0.01 in most of the bins. We also test a method to calibrate a width parameter for redshift distributions, which we found necessary to use for some of our samples. Our typical uncertainties on the mean redshift ranged from 0.003 to 0.008, while our uncertainties on the width ranged from 4 to 9 per cent. We discuss how these results calibrate the photometric redshift distributions used in companion papers for DES Year 3 results.
Fine-Tuning a Global History of Music Theory: Divergences, Zhu Zaiyu, and Music-Theoretical Instruments
Authors: Rehding Alexander
Published: April 2022

The issue of equal temperament offers an object lesson in the challenges of the new global history of music theory: Twelve-tone equal temperament was mathematically formulated at almost the same time in Ming-dynasty China and sixteenth-century Europe. While the old debate got stuck on questions of dates and cultural rivalries, recent work in comparative humanities, especially Kuriyama (2002), opens up new avenues. His concept of “divergence” is applied to the specific “music-theoretical instruments” in which Chinese and European theories of tuning manifested themselves in sound. Zhu Zaiyu’s pathbreaking 1584 theory is reexamined specifically from this angle: He credits the qin (zither) for holding knowledge that the 12 lü, the traditional Chinese pitch-pipes, could not convey. Zhu’s example—and the concept of “divergence”—offers ways forward for a new, materially oriented, global history of music theory.
Producing decent work indicators: contested numbers at the ILO
Authors: Berten John
Published: April 2022

The article investigates the production of decent work indicators within the ILO, to demonstrate that developing measurement infrastructures in global policymaking requires political work. The concept of decent work responds to the perceived marginalization of the ILO in social and labor policy and was supposed to provide a new unifying normative framework for the organization. The article shows that creating decent work indicators encountered challenges due to its highly politicized production process. Proponents of quantification (mostly workers’ representatives) and opponents (mostly employers’ representatives) disagreed about the function of indicators: should they be country-specific or allow for universal assessment of progress from above. In effect, although indicators of decent work have been integrated into the Sustainable Development Goals—mostly as part of goal no. 8, many are still incomplete. As a result, the indicators did not establish a “framework of assessment,” which would have been guided by universal standards of progress allowing the ILO to “govern at a distance,” and could not initiate a paradigmatic policy shift, impeding the infrastructuralization of measurement. Theoretically, the article advances our understanding of policy formulation and design on the transnational level by showing the political foundation of knowledge-based instruments. Empirically, it rests on a Grounded Theory-based analysis of key ILO documents, including Governing Body minutes, conference and expert meeting reports, and official publications, mainly from the period from 1998 to 2015.
Understanding Bank Payouts during the Crisis of 2007–2009
Authors: Cziraki Peter , Laux Christian , Lóránth Gyöngyi
Published: May 2022

We study U.S. banks’ payout policy in 2007–2008. We benchmark these payouts against payouts before the crisis, measure stock price reactions to announcements of dividend changes, and analyze changes in the relation between payout growth and future performance. Further, we examine cross-sectional variation in banks’ payout policy to gauge the possible motives underlying banks’ payout decisions in 2007–2008. We do not find that banks that have a higher willingness to take risk or that have higher incentives to undertake asset substitution use their payout policy to engage in more wealth transfer compared to other banks. (JEL G21, G24, G28, G32, G35).

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Dezocine induces apoptosis in human cervical carcinoma Hela cells via the endoplasmic reticulum stress pathway
Authors: Wang Hanlin , Chiang Chengyao , Xue Chenyang , Zhou Lu , Li Shuaihu , Zhou Yaqi , Zhang Zhucheng , Xie Meng , Xiao Tian , Hu Hongyi , Zhu Lizhi , Long Cheng , Zou Yongdong , Wang Ting , Zheng Duo
Published: April 2022

Dezocine, a dual agonist and antagonist of the μ-opioid receptor and κ-opioid receptor, is widely used as an analgesic in China. At present, there are few studies on anti-tumor effects of dezocine, most of which are used to treat cancer pain. However, it has recently been reported that dezocine can induce apoptosis of triple negative breast cancer cells. Dezocine may have some anti-tumor activity, but the effect and potential mechanism of dezocine in the treatment of other types of cancer remain to be fully studied. The purpose of the present study was to investigate the effect of dezocine on human Hela cervical carcinoma cells, and to elucidate the underlying molecular mechanisms. We performed CCK-8 assays, clone formation assays, xenograft, flow cytometry analysis, western blot and RNA-seq analysis to evaluate the effects of dezocine on Hela cells. In addition, the role of endoplasmic reticulum (ER) stress in dezocine-induced apoptosis was investigated using qPCR and western blot analysis. Dezocine inhibited Hela cell viability in dose-dependent and time-dependent manners, and notably did not achieve this effect by targeting the opioid receptors. Further mechanistic studies demonstrated that dezocine activated ER stress by upregulating the expression of GRP78, IRE1 and p-JNK, and that dezocine-induced apoptosis was attenuated when the ER stress pathway was blocked. Our results provide a foundation to support the redefinition of dezocine as a novel, adjuvant treatment for patients with cervical cancer, although further research will be required to support its application in clinical practice.
Which Factors Are Important to Women When Choosing a Breast Reconstruction Surgeon?
Authors: Sergesketter Amanda R. , Lam Shravika , Broadwater Gloria , Shammas Ronnie L. , Langdell Hannah C. , Plichta Jennifer K. , Clancy Sharon , Rezak Kristen , Phillips Brett T. , Hollenbeck Scott T.
Published: May 2022

Background:

Women undergoing breast reconstruction often research their health care provider options. The authors studied which factors may influence how a woman selects a plastic surgeon for breast reconstruction surgery.

Methods:

An online survey was distributed by means of Amazon Mechanical Turk (MTurk; Amazon Web Services, Inc., Seattle, Wash.) to 1025 adult women. Participants were asked to imagine a scenario in which they had breast cancer, needed to undergo mastectomy, and were choosing a reconstructive surgeon. They were then asked to rank factors influencing this decision on a 1 to 7 Likert scale. Two-sample t tests were used to compare Likert scores between dichotomized categories based on participant characteristics.

Results:

Women assigned the highest scores [mean (standard deviation)] to online reviews on Vitals or WebMD [6.1 (1.2)], years of experience [5.7 (1.4)], recommendations from another surgeon [5.7 (1.3)] or family/friend [4.9 (1.7)], and attending a top medical school [4.7 (1.7)]. Lowest ranked factors were online advertising and surgeon demographics, including having a sex concordant (female) surgeon. After amalgamation into attribute subsections, mean (standard deviation) rated relative importance of surgeon reputation [0.72 (0.13)] was higher than that of appearance [0.46 (0.19)] and demographics [0.31 (0.13)]. Patient demographics influenced relative importance of certain attributes; older, educated, and higher-income patients placed higher value on surgeon appearance (all p < 0.05).

Conclusions:

When selecting a breast reconstruction surgeon, women place the highest value on surgeons’ online, educational, and personal reputations. Though most show no strong preferences for surgeon demographics or physical attributes, specific features may be important for some patients. Cognizance of these preferences may enable providers to more effectively understand patient expectations.
Long-Term Clinical and Aesthetic Results of a Systematic Fat Transfer Protocol for Total Breast Reconstruction after Nipple-Sparing Mastectomy
Authors: Sorotos Michail , Paolini Guido , D’Orsi Gennaro , Firmani Guido , Santanelli di Pompeo Fabio
Published: May 2022

Background:

Autologous fat transfer can be safely offered for total breast reconstruction after nipple-sparing mastectomy. The aim of this study was to extend a fat transfer protocol to smokers and compare the long-term results among them and irradiated and nonirradiated patients.

Methods:

One hundred seventeen breasts after nipple-sparing mastectomy were prospectively enrolled and stratified in group A (25 irradiated), group B (21 smokers), or group C (71 controls). A standardized fat transfer protocol was used. Data collected were patient demographics, surgery information, and aesthetic analysis. Continuous and categorical variables were analyzed with the Kruskal-Wallis test, and the Cohen Kappa test was used to test interrater variability for the aesthetic analysis.

Results:

Groups were homogeneous for demographics (p > 0.05) but significantly different in number of fat transfer sessions (p < 0.001), mean volume of the first two treatments (p = 0.003), and mean total volume of injected fat (p = 0.002). Volume, shape, position of the breast mound, inframammary fold, and scar location subscales obtained high score evaluations without a significant difference among groups (p > 0.05), whereas skin texture subscale showed a lower score evaluation in group A (p = 0.003). Although a significant difference for total subscales was worse in group A (p = 0.004), the global score had a high rate evaluation in all groups (p = 0.145). Interrater reliability showed substantial agreement among all categories.

Conclusion:

Although further investigation is required, the authors confirm the efficacy of their fat transfer protocol for both irradiated and nonirradiated nipple-sparing mastectomy patients and propose its indication to smokers with comparable clinical and aesthetic results.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Understanding Diagnostic Delays for Kaposi Sarcoma in Kenya: A Qualitative Study
Authors: McMahon Devon E. , Chemtai Linda , Grant Merridy , Singh Rhea , Semeere Aggrey , Byakwaga Helen , Laker-Oketta Miriam , Maurer Toby , Busakhala Naftali , Martin Jeffrey , Bassett Ingrid V. , Butler Lisa , Freeman Esther E.
Published: May 2022

Background:

Although HIV-associated Kaposi sarcoma (KS) is frequently diagnosed at an advanced stage in sub-Saharan Africa, reasons for diagnostic delays have not been well described.

Methods:

We enrolled patients >18 years with newly diagnosed KS between 2016 and 2019 into the parent study, based in western Kenya. We then purposively selected 30 participants with diversity of disease severity and geographic locations to participate in semistructured interviews. We used 2 behavioral models in developing the codebook for this analysis: situated Information, Motivation, and Behavior framework and Andersen model of total patient delay. We then analyzed the interviews using framework analysis.

Results:

The most common patient factors that delayed diagnosis were lack of KS awareness, seeking traditional treatments, lack of personal efficacy, lack of social support, and fear of cancer, skin biopsy, amputation, and HIV diagnosis. Health system factors that delayed diagnosis included previous negative health care interactions, incorrect diagnoses, lack of physical examination, delayed referral, and lack of tissue biopsy availability. Financial constraints were prominent barriers for patients to access and receive care. Facilitators for diagnosis included being part of an HIV care network, living near health facilities, trust in the health care system, desire to treat painful or disfiguring lesions, and social support.

Conclusions:

Lack of KS awareness among patients and providers, stigma surrounding diagnoses, and health system referral delays were barriers in reaching KS diagnosis. Improved public health campaigns, increased availability of biopsy and pathology facilities, and health provider training about KS are needed to improve early diagnosis of KS.
Machine learning-based detection of label-free cancer stem-like cell fate
Authors: Chambost Alexis J. , Berabez Nabila , Cochet-Escartin Olivier , Ducray François , Gabut Mathieu , Isaac Caroline , Martel Sylvie , Idbaih Ahmed , Rousseau David , Meyronet David , Monnier Sylvain
Published: May 2022

Most imaging methods rely on labelling biological samples in order to provide specific and easily detectable features. However, label-free imaging is a non-invasive and non-toxic alternative that requires accurate image analysis algorithm based on cell morphology. Such analysis has to deal with a high image variability while fewer features are extractable, so far, fast analysis of label-free brightfield microscopy (LFBM) images remains a challenging task. With the development of microfabricated devices during the last decades, high throughput image generation makes it possible to use machine learning-based algorithms in order to analyse LFBM images. Fast algorithms are also crucially needed to analyze high throughput experiments. In this paper, we provide a data-driven study in order to assess the complexity of LFBM time-lapses monitoring isolated cancer stem-like cells (CSCs) fate in non-adherent conditions. We combined for the first time individual cell fate and cell state temporality analysis in a unique algorithm. Several image analysis algorithms of increasing processing capacities were tested: a classical computer vision algorithm (CCVA), a shallow learning-based algorithm (SLBA) and a deep learning-based algorithm (DLBA). We show that our optimized DLBA has by far the best accuracy compared to CCVA and SLBA, is at least as accurate as other state-of-the-art DLBAs while being faster. With this study, we demonstrate that optimizing our DLBA accordingly to the image analysis problem can overall provide better results than pretrained models. Such a fast and accurate DLBA is therefore compatible with the generation of high throughput data and opens the route for on-the-fly analysis of CSC fate from LFBM time-lapses.
Evolution of the quorum sensing systems in Pseudomonas aeruginosa can involve both loss of regulon function and network modulation
Authors: Jayakumar Priyanikha , Figueiredo Alexandre R. T. , Kümmerli Rolf
Published: May 2022

Pseudomonas aeruginosa populations evolving in cystic fibrosis (CF) lungs, animal infection models, natural environments or in vitro undergo extensive genetic adaption and diversification. A common mutational target is the quorum sensing (QS) regulon, a three-unit regulatory system that controls the expression of a suite of virulence factors and secreted public goods. Three scenarios have been advocated to explain selection for QS mutants, which include (I) disuse of the regulon, (II) cheating on public goods, or (III) modulation of the network. Here, we test these scenarios by examining a set of 61 QS mutants from an experimental evolution study. We observed non-synonymous mutations in all three QS systems – Las, Rhl and PQS. Most Las mutants carried large deletions, resulting in loss of QS function, and the inability to produce QS-regulated traits (scenario I or II). Conversely, phenotypic and gene expression analyses of Rhl mutants support network modulation (scenario III), as these mutants overexpressed the Las and Rhl regulators and showed an altered QS-regulated trait production portfolio. PQS mutants also showed patterns of network modulation (scenario III), spurring strain diversification and phenotypic trade-offs, where the upregulation of certain QS traits is associated with the downregulation of others. Overall, our results indicate that mutations in different QS systems lead to diverging effects on the social portfolio of bacterial populations. These mutations might not only affect the plasticity and diversity of evolved populations but could also impact bacterial fitness and virulence in infections.

Importance

Pseudomonas aeruginosa uses quorum sensing (QS), a three-unit multi-layered network, to coordinate expression of traits for growth and virulence in the context of infections. Despite its importance for bacterial fitness, the QS regulon appears to be a common mutational target during long-term adaptation of P. aeruginosa in the host, natural environments and experimental evolutions. This raises the questions why such an important regulatory system is under selection and how mutations change the portfolio of QS-regulated traits. Here, we examine a set of 61 naturally evolved mutants to address these questions. We found that mutations involving the master regulator, LasR, resulted in an almost complete breakdown of QS, while mutations in RhlR and PqsR resulted in modulations of the QS regulon, where both the QS regulon structure and the QS-regulated trait portfolio changed. Our work reveals that natural selection drives diversification in QS activity patterns in evolving populations.
Perfusion Quantification in the Human Brain Using DSC MRI – Simulations and Validations at 3T
Authors: Schulman J. , Sayin E.S. , Manalac A. , Poublanc J. , Sobczyk O. , Duffin J. , Fisher J.A. , Mikulis D.J. , Uludağ K.
Published: May 2022

Gadolinium (Gd) and deoxyhemoglobin (dOHb) are paramagnetic contrast agents capable of inducing changes in T2*-weighted MRI signal, utilized in dynamic susceptibility contrast (DSC) MRI. With multiple contrast agents and analysis choices, there are a variety of questions as to its capability to accurately quantify perfusion values. To address these questions, we developed a novel signal model for DSC MRI that incorporates signal contributions from intravascular and extravascular water proton spins at 3T for arterial, venous, and cerebral tissue voxels. This framework allowed us to model the MRI signal in response to changes in Gd and dOHb concentrations, and the effects that various experimental and tissue parameters have on perfusion quantification. We compared the predictions of the numerical simulations with those obtained from experimental data at 3T on six healthy human subjects using Gd and dOHb boluses as contrast agents. Using standard DSC analysis, we identified perfusion quantification dependencies in the experimental results that were in close agreement with the simulations. We found that a reduced baseline oxygen saturation (base-SaO2), greater susceptibility of applied contrast agent (Gd vs dOHb), and larger magnitude of the hypoxic drop (ΔSaO2) reduces overestimation of the cerebral blood volume (rCBV) and flow (rCBF). Furthermore, shortening the bolus duration increases the accuracy and reduces the calculated values of mean transit time (MTT). This study demonstrates that changes in Gd and dOHb can be described by the same unifying theoretical framework, as validated by the experimental results. Based on our work, we suggest practices in DSC MRI that increase accuracy and reduce inter- and intra-subject variability. In uncovering a wide array of quantification dependencies, we argue that caution must be exercised when comparing perfusion values obtained from a standard DSC MRI analysis when employing different experimental paradigms.
Cortex-wide fast activation of VIP-expressing inhibitory neurons by reward and punishment
Authors: Szadai Zoltán , Pi Hyun-Jae , Chevy Quentin , Ócsai Katalin , Albeanu Florin , Chiovini Balázs , Szalay Gergely , Katona Gergely , Kepecs Adam , Rózsa Balázs
Published: April 2022

Reward and punishment powerfully inform ongoing behaviors and drive learning throughout the brain, including neocortex. Yet it remains elusive how these global signals are represented and impact local cortical computations. Previously we found that in auditory cortex, VIP-expressing interneurons are recruited by reinforcement feedback. Here, we used 3D random-access two-photon microscopy and fiber photometry to monitor VIP neural activity in dozens of cortical areas while mice learned an auditory decision task. We show that reward and punishment evoke a rapid, cortex-wide activation of most VIP interneurons. This global recruitment mode of VIP interneurons showed variations in temporal dynamics in individual neurons and across areas. Neither their weak sensory tuning in visual cortex, nor their arousal state modulation was predictive of reinforcer responses of VIP interneurons. We suggest that VIP-expressing cortical inhibitory neurons transduce global reinforcement signals to provide disinhibitory control over local circuit computations and their plasticity.
Increasing transposase abundance with ocean depth correlates with a particle-associated lifestyle
Authors: Zhong Juntao , del Rosario Hernández Thais , Kyrysyuk Oleksandr , Tully Benjamin J. , Anderson Rika E.
Published: May 2022

Transposases are mobile genetic elements (MGEs) that move within and between genomes, promoting genomic plasticity in microorganisms. In marine microbial communities, the abundance of transposases increases with depth, but the reasons behind this trend remain unclear. Our analysis of metagenomes from theTaraOceans and Malaspina Expeditions suggests that a particle-associated lifestyle is the main covariate for the high occurrence of transposases in the deep ocean. We observed a strong and depth-independent correlation between transposase abundance and the presence of biofilm-associated genes, as well as the prevalence of secretory enzymes. This suggests that mobile genetic elements readily propagate among microbial communities within crowded biofilms. Furthermore, we show that particle association positively correlates with larger genome size, which is in turn is associated with higher transposase abundance. Cassette sequences associated with transposons are enriched with genes related to defense mechanisms, which are more highly expressed in the deep sea. Thus, while transposons spread at the expense of their microbial hosts, they also introduce novel genes and potentially benefit the hosts in helping to compete for limited resources. Overall, our results suggest a new understanding of deep ocean particles as highways for gene sharing among defensively oriented microbial genomes.

Importance

Genes can move within and between microbial genomes via mobile genetic elements, which include transposases and transposons. In the oceans, there is a puzzling increase in transposase abundance in microbial genomes as depth increases. To gain insight into this trend, we conducted an extensive analysis of marine microbial metagenomes and metatranscriptomes. We found a significant correlation between transposase abundance and a particle-associated lifestyle among marine microbes. We also observed a link between transposase abundance and genes related to defense mechanisms. These results suggest that as microbes become densely packed into crowded particles, mobile genes are more likely to spread and carry genetic material that provides a competitive advantage in crowded habitats. This may enable deep sea microbes to effectively compete in such environments.
Volitional generation of reproducible energy-efficient temporal patterns
Authors: Ning Yuxiao , Wan Guihua , Liu Tengjun , Zhang Shaomin
Published: May 2022

One of the extraordinary characteristics of the biological brain is its low energy expense to implement a variety of biological functions and intelligence compared to the modern artificial intelligence (AI). Spike-based energy-efficient temporal codes have long been suggested as the contributor for the brain to run with a low energy expense. Despite this code having been largely reported in the sensory cortex, whether this code can be implemented in other brain areas to serve broader functions and how the brain learns to generate it have remained unaddressed. In this study, we designed a novel brain-machine interface (BMI) paradigm, by learning which two macaques could volitionally generate reproducible energy-efficient temporal patterns in the primary motor cortex (M1). Moreover, most neurons that were not directly assigned for controlling the BMI did not boost their excitability, demonstrating an overall energy-efficiency manner in performing the task. Over the course of learning, we found that the firing rates and temporal precision of selected neurons co-evolved to generate the energy-efficient temporal patterns, suggesting a cohesive rather than dissociable processing underlie the refinement of energy-efficient temporal patterns.
Intraoperative calculus or hemorrhage in transurethral seminal vesiculoscopy as a risk factor for recurrent hemospermia
Authors: Mei Cheng-En , Hu Ju-Chuan , Li Jian-Ri , Chiu Kun-Yuan , Wang Shian-Shiang , Chen Chuan-Shu
Published: May 2022

We summarized our experience regarding Transurethral Seminal Vesiculoscopy (TUSV) and analyzed both recurrence status and risk factors for recurrence. From January 2010 to December 2020, 48 patients with intractable hemospermia received successful TUSV at Taichung Invalids General Hospital. For the intraoperative findings, the five-year Disease-free Survival rates (DFS) were 74.1% in the no calculus group compared to 37.1% in the calculus group with a significant difference (log-rank p = 0.015), 75.0% in the no hemorrhage or no blood clot group compared to 43.2% in the hemorrhage or blood clot group with significant difference (log-rank p = 0.032). Univariate analysis showed intraoperative calculus (p = 0.040; HR: 2.94, 95% CI: 1.05–8.21) to be significantly associated with recurrence (p < 0.05). Patients with intractable hemospermia who were diagnosed with stones or blood clots found during TUSV experienced a higher rate of hemospermia recurrence.
Multi-scale phase separation by explosive percolation with single chromatin loop resolution
Authors: Sengupta Kaustav , Denkiewicz Michał , Chiliński Mateusz , Szczepińska Teresa , Mollah Ayatullah Faruk , Korsak Sevastianos , D’Souza Raissa , Ruan Yijun , Plewczynski Dariusz
Published: May 2022

The 2m-long human DNA is tightly intertwined into the cell nucleus of the size of 10μm. The DNA packing is explained by folding of chromatin fiber. This folding leads to the formation of such hierarchical structures as: chromosomal territories, compartments; densely packed genomic regions known as Chromatin Contact Domains (CCDs), and loops. We propose models of dynamical genome folding into hierarchical components in human lymphoblastoid, stem cell, and fibroblast cell lines. Our models are based on explosive percolation theory. The chromosomes are modeled as graphs where CTCF chromatin loops are represented as edges. The folding trajectory is simulated by gradually introducing loops to the graph following various edge addition strategies that are based on topological network properties, chromatin loop frequencies, compartmentalization, or epigenomic features. Finally, we propose the genome folding model - a biophysical pseudo-time process guided by a single scalar order parameter. The parameter is calculated by Linear Discriminant Analysis. We simulate the loop formation by using Loop Extrusion Model (LEM) while adding them to the system. The chromatin phase separation, where fiber folds into topological domains and compartments, is observed when the critical number of contacts is reached. We also observe that 80% of the loops are needed for chromatin fiber to condense in 3D space, and this is constant through various cell lines. Overall, our in-silico model integrates the high-throughput 3D genome interaction experimental data with the novel theoretical concept of phase separation, which allows us to model event-based time dynamics of chromatin loop formation and folding trajectories.
Sweet taste receptor cells may participate in mucosal immune surveillance
Authors: Qin Yumei , Zheng Xin , Tian Shiyi , Margolskee Robert F. , Sukumaran Sunil K.
Published: May 2022

The oral microbiome is second only to its intestinal counterpart in diversity and abundance, but its effects on taste cells remains largely unexplored. Using single cell RNASeq, we found that mouse taste receptor cells (STRCs) have a gene expression signature reminiscent of Microfold (M) cells, a central player in immune surveillance in the mucosa associated lymphoid tissue (MALT) such as those in the Peyer’s patch and tonsils. Administration of Tumor Necrosis Factor Ligand Superfamily Member 11 (TNFSF11, also known as RANKL), a growth factor required for differentiation of M cells dramatically increased M cell proliferation and marker gene expression in the taste papillae and in cultured taste organoids from wild type (WT) mice. Taste papillae and organoids from knockout mice lacking Spib (SpibKO), a RANKL-regulated transcription factor required for M cell development and regeneration on the other hand, failed to respond to RANKL. Taste papillae from SpibKO mice also showed reduced expression of NF-κB signaling pathway components and proinflammatory cytokines and attracted fewer immune cells. However, lipopolysaccharide-induced expression of cytokines was strongly upregulated in SpibKO mice compared to their WT counterparts. Like M cells, STRCs from WT but not SpibKO mice readily took up fluorescently labeled microbeads, a proxy for microbial transcytosis. The proportion of STRCs and other taste cell subtypes are unaltered in SpibKO mice; however, they displayed increased attraction to sweet and umami taste stimuli. We propose that STRCs are involved in immune surveillance at the taste papillae and tune their taste responses to microbial signaling and infection.
Face Familiarity Revealed by Fixational Eye Movements and Fixation-Related Potentials in Free Viewing
Authors: Kadosh Oren , Bonneh Yoram
Published: May 2022

Event-related potentials (ERPs) and the oculomotor inhibition (OMI) in response to transient visual stimuli are known to be sensitive to different stimulus properties, including attention and expectation. In natural vision, transient stimulation of the visual cortex is generated primarily by saccades. Recent studies suggest that the core EEG components in free viewing, induced by saccades (fixation-related potentials, RPs), are similar to the ERP components with flashed stimuli. We have recently found that the OMI in response to flashed stimuli is sensitive to face familiarity. Here, we investigated whether fixation-related-potentials (FRPs) and microsaccade inhibition (OMI) in free viewing are sensitive to face familiarity. Observers (N=15) freely watched a slideshow of seven unfamiliar and one familiar world leader’s facial images presented randomly for 4-seconds periods, with multiple images per identity. We measured the occipital fixation-related N1 relative to the P1 magnitude as well as the associated fixation-triggered OMI. We found that the average N1 was significantly smaller and the OMI was shorter for the familiar face, compared with any of the 7 unfamiliar faces. Moreover, the P1 was suppressed across saccades for the familiar but not for the unfamiliar faces. Overall, the results indicate that the occipital FRP and the OMI in free viewing are sensitive to face familiarity; this could perhaps be used as a novel physiological measure for studying hidden suppressed memories.
Microglial ferroptotic stress causes non-cell autonomous neuronal death
Authors: Liddell Jeffrey R. , Hilton James B.W. , Kysenius Kai , Nikseresht Sara , McInnes Lachlan E. , Hare Dominic J. , Paul Bence , Trist Benjamin G. , Double Kay L. , Mercer Stephen W. , Ayton Scott , Roberts Blaine R. , Beckman Joseph S. , McLean Catriona A. , White Anthony R. , Donnelly Paul S. , Bush Ashley I. , Crouch Peter J.
Published: May 2022

Background

Ferroptosis is a form of regulated cell death characterised by lipid peroxidation as the terminal endpoint and a requirement for iron. Although it protects against cancer and infection, ferroptosis is also implicated in causing neuronal death in degenerative diseases of the central nervous system (CNS). The precise role for ferroptosis in causing neuronal death is yet to be fully resolved.

Methods

To elucidate the role of ferroptosis in neuronal death we utilised co-culture and conditioned medium transfer experiments involving microglia, astrocytes and neurones. We ratified clinical significance of our cell culture findings via assessment of human CNS tissue from cases of the fatal, paralysing neurodegenerative condition of amyotrophic lateral sclerosis (ALS). Finally, we utilised the SOD1G37R mouse model of ALS and a novel CNS-permeant ferroptosis inhibitor to verify pharmacological significance in vivo.

Results

We found that sublethal ferroptotic stress selectively affecting microglia triggers an inflammatory cascade that results in non-cell autonomous neuronal death. Central to this cascade is the conversion of astrocytes to a neurotoxic state. We show that spinal cord tissue from cases of ALS exhibits a signature of ferroptosis that encompasses atomic, molecular and biochemical features. Moreover, a molecular correlation between ferroptosis and neurotoxic astrocytes evident in ALS-affected spinal cord is recapitulated in the SOD1G37R mouse model where treatment with the novel, CNS-permeant ferroptosis inhibitor, CuII(atsm), ameliorated these markers and was neuroprotective.

Conclusions

By showing that microglia responding to sublethal ferroptotic stress culminates in non-cell autonomous neuronal death, our results implicate microglial ferroptotic stress as a rectifiable cause of neuronal death in neurodegenerative disease. As ferroptosis is currently primarily regarded as an intrinsic cell death phenomenon, these results introduce an entirely new pathophysiological role for ferroptosis in disease.
C-Jun N-terminal Kinase Promotes Stress Granule Assembly and Neurodegeneration in C9orf72-mediated ALS and FTD
Authors: Sahana TG , Chase Katherine Johnson , Liu Feilin , Lloyd Thomas E. , Rossoll Wilfried , Zhang Ke
Published: May 2022

Stress granules (SGs), RNA/protein condensates assembled in cells under stress, are believed to play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, how SG assembly is regulated and related to pathomechanism is incompletely understood. Here, we show that ER stress activates JNK via IRE1 in fly and cellular models of C9orf72-mediated ALS/FTD (c9ALS/FTD), the most common genetic form of ALS/FTD. Furthermore, activated JNK promotes SG assembly induced by poly(GR) and poly(PR), two toxic proteins implicated in c9ALS/FTD, by promoting the transcription of G3BP1, a key SG protein. Consistent with these findings, JNK or IRE1 inhibition reduced SG formation, G3BP1 mRNA and protein levels, and neurotoxicity in cells overexpressing poly(GR) and poly(PR) or neurons derived from c9ALS/FTD patient induced pluripotent stem cells (iPSCs). Our findings connect ER stress, JNK, and SG assembly in a unified pathway contributing to c9ALS/FTD neurodegeneration.
TAMPA: interpretable analysis and visualization of metagenomics-based taxon abundance profiles
Authors: Sarwal Varuni , Brito Jaqueline , Mangul Serghei , Koslicki David
Published: May 2022

Metagenomic taxonomic profiling aims to predict the identity and relative abundance of taxa in a given whole genome sequencing metagenomic sample. A recent surge in computational methods that aim to accurately estimate taxonomic profiles, called taxonomic profilers, have motivated community driven efforts to create standardized benchmarking datasets and platforms, standardized taxonomic profile formats, as well as a benchmarking platform to assess tool performance. While this standardization is essential, there is currently a lack of tools to visualize the standardized output of the many existing taxonomic profilers, and benchmarking studies rely on a single value metrics to compare performance of tools and compare to benchmarking datasets. Here we report the development of TAMPA (Taxonomic metagenome profiling evaluation), a robust and easy-to-use method that allows scientists to easily interpret and interact with taxonomic profiles produced by the many different taxonomic profiler methods beyond the standard metrics used by the scientific community. We demonstrate the unique ability of TAMPA to provide important biological insights into the taxonomic differences between samples otherwise missed by commonly utilized metrics. Additionally, we show that TAMPA can help visualize the output of taxonomic profilers, enabling biologists to effectively choose the most appropriate profiling method to use on their metagenomics data. TAMPA is available on GitHub, Bioconda and Galaxy Toolshed at https://github.com/dkoslicki/TAMPA, and is released under the MIT license.
Immediate myeloid depot for SARS-CoV-2 in the human lung
Authors: Magnen Mélia , You Ran , Rao Arjun A. , Davis Ryan T. , Rodriguez Lauren , Simoneau Camille R. , Hysenaj Lisiena , Hu Kenneth H. ,   The UCSF COMET Consortium, Love Christina , Woodruff Prescott G. , Erle David J. , Hendrickson Carolyn M. , Calfee Carolyn S. , Matthay Michael A. , Roose Jeroen P. , Sil Anita , Ott Melanie , Langelier Charles R. , Krummel Matthew F. , Looney Mark R.
Published: May 2022

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, considerable focus has been placed on a model of viral entry into host epithelial populations, with a separate focus upon the responding immune system dysfunction that exacerbates or causes disease. We developed a precision-cut lung slice model to investigate very early host-viral pathogenesis and found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations in the human lung. Infection of alveolar macrophages was partially dependent upon their expression of ACE2, and the infections were productive for amplifying virus, both findings which were in contrast with their neutralization of another pandemic virus, Influenza A virus (IAV). Compared to IAV, SARS-CoV-2 was extremely poor at inducing interferon-stimulated genes in infected myeloid cells, providing a window of opportunity for modest titers to amplify within these cells. Endotracheal aspirate samples from humans with the acute respiratory distress syndrome (ARDS) from COVID-19 confirmed the lung slice findings, revealing a persistent myeloid depot. In the early phase of SARS-CoV-2 infection, myeloid cells may provide a safe harbor for the virus with minimal immune stimulatory cues being generated, resulting in effective viral colonization and quenching of the immune system.
GB_SynP: a modular dCas9-regulated synthetic promoter collection for fine-tuned recombinant gene expression in plants
Authors: Moreno-Giménez Elena , Selma Sara , Calvache Camilo , Orzáez Diego
Published: May 2022

Programable transcriptional factors based on the CRISPR architecture are becoming commonly used in plants for endogenous gene regulation. In plants, a potent CRISPR tool for gene induction is the so-called dCasEV2.1 activation system, which has shown remarkable genome-wide specificity combined with a strong activation capacity. To explore the ability of dCasEV2.1 to act as a transactivator for orthogonal synthetic promoters, a collection of DNA parts was created (GB_SynP) for combinatorial synthetic promoter building. The collection includes (i) minimal promoter parts with the TATA box and 5’UTR regions, (ii) proximal parts containing single or multiple copies of the target sequence for the gRNA, thus functioning as regulatory cis boxes, and (iii) sequence-randomized distal parts that ensure the adequate length of the resulting promoter. A total of 35 promoters were assembled using the GB_SynP collection, showing in all cases minimal background and predictable activation levels depending on the proximal parts used. GB_SynP was also employed in a combinatorial expression analysis of an auto-luminescence pathway in Nicotiana benthamiana, showing the value of this tool in extracting important biological information such as the determination of the limiting steps in an enzymatic pathway.