bluuebunny/crossref_metadata_2025 huggingface dataset:
Expectations boost the reconstruction of auditory features from electrophysiological responses to noisy speech
Authors: Corcoran Andrew W , Perera Ricardo , Koroma Matthieu , Kouider Sid , Hohwy Jakob , Andrillon Thomas
Published: February 2022

Online speech processing imposes significant computational demands on the listening brain, the underlying mechanisms of which remain poorly understood. Here, we exploit the perceptual “pop-out” phenomenon (i.e. the dramatic improvement of speech intelligibility after receiving information about speech content) to investigate the neurophysiological effects of prior expectations on degraded speech comprehension. We recorded electroencephalography (EEG) and pupillometry from 21 adults while they rated the clarity of noise-vocoded and sine-wave synthesized sentences. Pop-out was reliably elicited following visual presentation of the corresponding written sentence, but not following incongruent or neutral text. Pop-out was associated with improved reconstruction of the acoustic stimulus envelope from low-frequency EEG activity, implying that improvements in perceptual clarity were mediated via top-down signals that enhanced the quality of cortical speech representations. Spectral analysis further revealed that pop-out was accompanied by a reduction in theta-band power, consistent with predictive coding accounts of acoustic filling-in and incremental sentence processing. Moreover, delta-band power, alpha-band power, and pupil diameter were all increased following the provision of any written sentence information, irrespective of content. Together, these findings reveal distinctive profiles of neurophysiological activity that differentiate the content-specific processes associated with degraded speech comprehension from the context-specific processes invoked under adverse listening conditions.
The Effect of Gestational Age at BNT162b2 mRNA Vaccination on Maternal and Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Levels
Authors: Rottenstreich Amihai , Zarbiv Gila , Oiknine-Djian Esther , Vorontsov Olesya , Zigron Roy , Kleinstern Geffen , Wolf Dana G , Porat Shay
Published: February 2022

Background

Coronavirus disease 2019 (COVID-19) during pregnancy and early infancy can result in severe disease. Evaluating the effect of gestational age at the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on maternal antibody levels and transplacental antibody transfer has important implications for maternal care and vaccination strategies.

Methods

Maternal and cord blood sera were collected from mother–newborn dyads (n = 402), following term delivery after antenatal 2-dose SARS-CoV-2 BNT162b2 mRNA vaccination. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)–specific IgG levels were evaluated in the samples collected.

Results

Median anti-S and anti–RBD-specific IgG levels in maternal sera at the time of delivery were lowest following first-trimester vaccination (n = 90; anti-S IgG: 76 AU/mL; anti–RBD-specific IgG: 478 AU/mL), intermediate in those vaccinated in the second trimester (n = 124; anti-S IgG: 126 AU/mL; anti–RBD-specific IgG: 1263 AU/mL), and highest after third-trimester vaccination (n = 188; anti-S IgG: 240 AU/mL; anti–RBD-specific IgG: 5855 AU/mL). Antibody levels in neonatal sera followed a similar pattern and were lowest following antenatal vaccination in the first trimester (anti-S IgG: 126 AU/mL; anti–RBD-specific IgG: 1140 AU/mL). In a subgroup of parturients vaccinated in the first trimester (n = 30), a third booster dose was associated with significantly higher maternal and neonatal antibody levels.

Conclusions

These results suggest a considerable antibody waning throughout pregnancy in those vaccinated at early gestation. The observed boosting effect of a third vaccine dose hints at its potential benefit in those who completed the 2-dose vaccine series at early pregnancy or before conception. The impact of antenatal immunization timing on SARS-CoV-2 transplacental antibody transfer may influence neonatal seroprotection.
Low-density lipoprotein cholesterol levels exceed the recommended European threshold for PCSK9i initiation: lessons from the HEYMANS study
Authors: Ray Kausik K , Dhalwani Nafeesa , Sibartie Mahendra , Bridges Ian , Ebenbichler Christoph , Perrone-Filardi Pasquale , Villa Guillermo , Vogt Anja , Bruckert Eric
Published: February 2022

Aims

To describe the characteristics of patients receiving evolocumab in clinical practice across 12 European countries and simulate the association between low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular (CV) risk reduction.

Methods and results

The characteristics of hyperlipidaemic patients at initiation of evolocumab and treatment patterns study—HEYMANS (n = 1952) is a prospective registry of patients ≥18 years old who initiated evolocumab from 1 August 2015 onwards. Mean (standard deviation) age was 60 (10.8), 85% had a prior CV event, 45% were diagnosed with familial hypercholesterolaemia (FH), and 60% had statin intolerance. At evolocumab initiation, 43% were receiving any statin, 16% were receiving ezetimibe without statin, and 41% received no background lipid-lowering therapy (LLT), with LDL-C levels reflecting local proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) reimbursement criteria. Median LDL-C decreased from 3.98 to 1.63 mmol/L within 3 months of evolocumab initiation and was maintained over 24 months. Overall, 58% achieved risk-based 2019 European Society of Cardiology/European Atherosclerosis Society LDL-C goals but that proportion was higher (68%) in patients receiving background LLT compared with those not receiving background LLT (44%). In patients with atherosclerotic cardiovascular disease without FH, the simulated relative CV risk reduction associated with evolocumab treatment was 34% (25–44%).

Conclusion

Across Europe, LDL-C levels at evolocumab initiation were three times higher than recommended thresholds for PCSK9i initiation, reflecting disparities between implementation and guidelines. More patients attained risk-based LDL-C goals when receiving evolocumab in combination with LLT vs. those not receiving combination therapy. Population health could be improved and LDL-C goals better attained if LDL-C thresholds for PCSK9i reimbursement were lowered, enabling more patients to receive combination therapy when needed.
Augmentation of the posterior mitral leaflet in secondary mitral valve insufficiency, mid-term results
Authors: Lakew Fitsum , Sodah Ayman , Zacher Michael , Batz Gerhard , Perier Patrick , Urbanski Paul , Diegeler Anno
Published: February 2022

OBJECTIVES

We evaluate the mid-term results of mitral valve (MV) repair with patch augmentation of the posterior leaflet in secondary mitral regurgitation.

METHODS

Patients were included after diagnosis of a severe symptomatic secondary MV insufficiency with grade III and IV according to the Carpentier classification IIIb. Indication for a patch augmentation technique was a dilatation of the left ventricle leading to a displacement of the papillary muscles, causing restricted leaflet motion and a marked leaflet tenting height. Data were collected prospectively between December 2011 and March 2020.

RESULTS

In total, 174 patients (mean age: 65 ± 12 years) received an MV repair with patch augmentation of the posterior leaflet and a true-sized remodelling annuloplasty (mean size 30.8 mm). Causes of the MV incompetence were dilatative cardiomyopathy in 126 patients and ischaemic myocardial disease in 48 patients. Concomitant bypass surgery was performed in 28 patients, and the tricuspid valve was repaired in 68 patients. The mean follow-up was 40 ± 28.2 months. There was no 30-day mortality. In-hospital mortality was 1.2% (n = 2); late mortality was 10.9% (n = 19). At 8 years, overall survival was 62.48%, freedom from moderate or severe recurrent mitral regurgitation was 91.9% and freedom from reoperation due to MV insufficiency was 97.1%.

CONCLUSIONS

Augmentation of the posterior MV leaflet in addition to remodelling annuloplasty is a safe and reproducible mitral reconstruction technique that renders sustainable MV competence.
Age Profiles of Cognitive Decline and Dementia in Late Life in the Aging, Demographics, and Memory Study
Authors: Walsh Christine E , Yang Yang C , Oi Katsuya , Aiello Allison , Belsky Daniel , Harris Kathleen Mullan , Plassman Brenda L
Published: February 2022

Objectives

To better understand the temporal dynamics of progression from cognitive decline to onset of dementia in the dementia-free older population in the United States.

Methods

We used longitudinal data from a diverse national population-based sample of older adults (N = 531) in the Aging, Demographics, and Memory Study from the Health and Retirement Study with repeated measures of cognitive function and dementia diagnosis during 12 years of follow-up from 1996 to 2009. We employed joint latent class mixed models to estimate the association between cognitive change and competing risks of dementia and nondementia death and identify heterogeneity in the age profiles of such association adjusting for baseline characteristics.

Results

Our analyses found 3 latent classes with distinct age profiles of cognitive decline and associated risk of dementia and mortality: “Rapid Cognitive Decline” (19.6%), “Moderate Progression” (44.6%), and “Optimal Cognitive Aging” (35.8%). When simultaneously accounting for cognitive trajectories and time-to-dementia/death, we also found associations of baseline covariates with slope of cognitive decline (e.g., steeper decline among non-Hispanic Blacks and more educated) and risk of dementia (e.g., greater risk for females and apolipoprotein E-4 carriers, but no difference by education level) that differ substantially from those in separate longitudinal mixed models or survival models.

Discussion

The differential age patterns of cognitive decline predicting dementia incidences identified in this study suggest variation in the course of cognitive aging in older adults that may inform future etiological and intervention studies.
Prevalence of PCOS and related hyperandrogenic traits in premenopausal women with type 1 diabetes: a systematic review and meta-analysis
Authors: Bayona Ane , Martínez-Vaello Victoria , Zamora Javier , Nattero-Chávez Lía , Luque-Ramírez Manuel , Escobar-Morreale Héctor F
Published: February 2022

BACKGROUND

An increased prevalence of functional hyperandrogenism—including polycystic ovary syndrome (PCOS)—has been described in women with type 1 diabetes (T1D). However, heterogeneity between studies is frequent, and prevalence rates vary according to different criteria used for the diagnosis of PCOS and the population studied.

OBJECTIVE AND RATIONALE

We aimed to perform a systematic review and meta-analysis of the prevalence of PCOS and related hyperandrogenic traits in premenopausal women with T1D. This way, we intend to increase the precision of the estimates of prevalence of PCOS and related traits in women with T1D, and to explore sources of heterogeneity while providing prevalence estimates for clinically relevant subgroups such as the different phenotypes.

SEARCH METHODS

We conducted a systematic review of the literature using Medline-OVID and Embase databases (Open Science Framework registry for systematic review protocols, https://osf.io/6cv9p/). Studies published up to 29 March 2021 were considered. We selected cross-sectional or prospective studies that reported, in patients with T1D, prevalence data on PCOS according to current definitions and different phenotypes, and/or prevalence rates of other related traits (hirsutism, hyperandrogenaemia, oligo-amenorrhoea and/or polycystic ovarian morphology: PCOM). Exclusion criteria for the review were studies addressing types of diabetes other than T1D; and studies using diagnostic definitions of PCOS different than those mentioned above. Two independent researchers performed data extraction. To assess the risk of bias, we used a tool developed specifically to appraise population-based prevalence studies.

OUTCOMES

We selected 19 studies (1042 women) reporting the prevalence of PCOS and/or other hyperandrogenic traits. Regarding bias, 12 studies were considered of low-risk, and the remaining seven studies were considered intermediate risk. The pooled prevalence of PCOS when considering all possible phenotypes (ESHRE- American Society for Reproductive Medicine criteria) in T1D was 26% (95% CI: 19–34%; 13 studies, 684 women). Pooled prevalence of classic PCOS (US National Institutes of Health criteria) was 16% (95% CI: 10–22%; 9 studies, 614 women). Pooled prevalence of hyperandrogenic PCOS (Androgen Excess and PCOS Society criteria) was 26% (95% CI: 16–41%; 5 studies, 329 women). Hirsutism (24%), hyperandrogenaemia (29%), oligomenorrhoea (24%) and PCOM (34%) were also prevalent. Heterogeneity was high in almost all these meta-analyses.

WIDER IMPLICATIONS

This systematic review and meta-analysis showed that PCOS and related hyperandrogenic traits are present in approximately one in every four women with T1D. Larger studies are needed to confirm this association, to address the effect of different variables on the occurrence of PCOS.
On a Conjecture of J. Shallit About Apéry-Like Numbers
Authors: Shen Zhao
Published: February 2022

Put $a(n)=\sum \limits _{k=0}^{n} {{n}\choose{k}} {{n+k}\choose{k}}$ and $b(n)=v_{3}(a(n))$ for all integers $n\geqslant 0$, where $v_{3}$ is the $3$-adic valuation. In this work, we confirm a formula about $b(n)$, conjectured by J. Shallit in 2000. As an application, we show that the sequence $(b(n))_{n\geqslant 0}$ is $3$-regular.
Genomic Epidemiology Suggests Community Origins of Healthcare-Associated USA300 Methicillin-Resistant Staphylococcus aureus
Authors: Thiede Stephanie N , Snitkin Evan S , Trick William , Payne Darjai , Aroutcheva Alla , Weinstein Robert A , Popovich Kyle J
Published: February 2022

Background

Hospital-onset (HO) methicillin-resistant Staphylococcus aureus (MRSA) infections have declined over the past decade due to infection control strategies; community-onset (CO) and healthcare-associated community-onset (HACO) MRSA, particularly USA300, has declined less. We examined the role of community strains to explain the difference.

Methods

We performed whole-genome sequencing (WGS) on MRSA clinical isolates from Cook County Health patients during 2011–2014. We defined infections as CO, HO, or HACO epidemiologically. We integrated genomic, community exposure, and statewide hospital discharge data to infer MRSA origin.

Results

Among 1020 individuals with available WGS, most were USA300 wound infections (580 CO, 143 HO, 297 HACO). USA300 HO, CO, and HACO infections were intermixed on the USA300 phylogeny, consistent with common strains circulating across community and healthcare settings. Community exposures (eg, substance abuse, incarceration, homelessness) were associated with HACO and HO infections, and genetically linked individuals from both groups had little overlap in healthcare facilities, supporting community origins. Most repeat infections—over months to years—occurred in individuals persistently carrying their own strains. These individuals were more likely to have genetic linkages, suggesting a role of persistent colonization in transmission.

Conclusions

Efforts to reduce presumed nosocomial USA300 spread may require understanding and controlling community sources and transmission networks, particularly for repeat infections.
Exhibition of antifungal resistance by sterol-auxotrophic strains ofCandida glabratawith intact virulence
Authors: Nagi Minoru , Tanabe Koichi , Tanaka Kazuko , Ueno Keigo , Nakayama Hironobu , Ishikawa Jun , Abe Masahiro , Yamagoe Satoshi , Umeyama Takashi , Nakamura Shigeki , Sugai Motoyuki , Hazen Kevin C. , Miyazaki Yoshitsugu
Published: February 2022

Background

Candida glabrata is an emerging fungal pathogen in immune-compromised hosts. Previously undetected C. glabrata isolates were successfully recovered from clinical specimens by adding sterols to the growth medium. The clinical isolates are unable to synthesize ergosterol but can take up exogenous sterols under aerobic conditions.

Objectives

This study characterizes the sterol-auxotrophic C. glabrata strains, examines the mutation(s) in sterol synthesis genes, characterizes the drug susceptibility and evaluates the virulence in a mouse infection model.

Methods

Drug susceptibility of the C. glabrata strains was evaluated in a sterol-supplemented medium. The coding sequences of the sterol synthesis genes were analysed in six sterol-auxotrophic strains of C. glabrata. The fungal burden of mice infected with C. glabrata strain was determined.

Results

The sterol-auxotrophic strains showed high-level resistance to both azoles and amphotericin B when sterols were supplied in the test medium. Additionally, the strains harbour missense mutations in either ERG1 or ERG7. Significant differences in fungal burden were not observed between the sterol-auxotrophic strain and the sterol-competent strain with the mice infection models.

Conclusions

The sterol-auxotrophic C. glabrata strain investigated in this study seemed to maintain intact virulence, probably due to the supply of exogenous sterols from host organ(s). This suggests that exogenous sterol uptake develops antifungal resistance during infection.
Enhancing cancer prevention and survivorship care with a videoconferencing model for continuing education: a mixed-methods study to identify barriers and incentives to participation
Authors: Milgrom Zheng Z , Severance Tyler S , Scanlon Caitlin M , Carson Anyé T , Janota Andrea D , Burns John L , Vik Terry A , Duwve Joan M , Dixon Brian E , Mendonca Eneida A
Published: February 2022

Objective

To enhance cancer prevention and survivorship care by local health care providers, a school of public health introduced an innovative telelearning continuing education program using the Extension for Community Healthcare Outcomes (ECHO) model. In ECHO’s hub and spoke structure, synchronous videoconferencing connects frontline health professionals at various locations (“spokes”) with experts at the facilitation center (“hub”). Sessions include experts’ didactic presentations and case discussions led by spoke site participants. The objective of this study was to gain a better understanding of the reasons individuals choose or decline to participate in the Cancer ECHO program and to identify incentives and barriers to doing so.

Materials and methods

Study participants were recruited from the hub team, spoke site participants, and providers who attended another ECHO program but not this one. Participants chose to take a survey or be interviewed. The Consolidated Framework for Implementation Research guided qualitative data coding and analysis.

Results

We conducted 22 semistructured interviews and collected 30 surveys. Incentives identified included the program’s high-quality design, supportive learning climate, and access to information. Barriers included a lack of external incentives to participate and limited time available. Participants wanted more adaptability in program timing to fit providers’ busy schedules.

Conclusion

Although the merits of the Cancer ECHO program were widely acknowledged, adaptations to facilitate participation and emphasize the program’s benefits may help overcome barriers to attending. As the number of telelearning programs grows, the results of this study point to ways to expand participation and spread health benefits more widely.
Performance optimization of annealing salp swarm algorithm: frameworks and applications for engineering design
Authors: Song Jiuman , Chen Chengcheng , Heidari Ali Asghar , Liu Jiawen , Yu Helong , Chen Huiling
Published: February 2022

Swarm salp algorithm is a swarm intelligence optimization algorithm enlightened by the movement and foraging behaviors of the salp population. The salp swarm algorithm (SSA) has a simple structure and fast processing speed and can gain significant results on objective functions with fewer local optima. However, it has poor exploration ability and is easy to suffer from the local optimal solutions, so it performs poorly on multimodal objective functions. Besides, its unfair balance of exploration and exploitation is another notable shortcoming. To ameliorate these shortcomings and enhance the algorithm’s performance on multimodal functions, this research proposes simulated annealing (SA) improved salp swarm algorithm (SASSA). SASSA embeds the SA strategy into the followers’ position updating method of SSA, performs a certain number of iterations of the SA strategy, and uses Lévy flight to realize the random walk in the SA strategy. SASSA and 23 original and improved competitive algorithms are compared on 30 IEEE CEC2017 benchmark functions. SASSA ranked first in the Friedman test. Compared with SSA, SASSA can obtain better solutions on 27 benchmark functions. The balance and diversity experiment and analysis of SSA and SASSA are carried out. SASSA’s practicability is verified by solving five engineering problems and the fertilizer effect function problem. Experimental and statistical results reveal that the proposed SASSA has strong competitiveness and outperforms all the competitors. SASSA has excellent exploration ability, suitable for solving composition functions with multiple peaks. Meanwhile, SASSA brings about a good balance of exploration and exploitation and dramatically improves the quality of the solutions.
A Framework for Equitable Partnerships to Promote Cancer Prevention and Control in Rural Settings
Authors: Ko Linda K , Scarinci Isabel C , Bouchard Elizabeth G , Drake Bettina F , Rodriguez Elisa M , Chen Moon S , Kepka Deanna , Kruse-Diehr Aaron J , Befort Christie , Shannon Jackilen , Farris Paige E , Trentham-Dietz Amy , Onega Tracy
Published: February 2022

Rural populations continue to experience persistent cancer disparities compared with urban populations particularly in cancers that can be prevented or detected early through screening and vaccination. Although the National Cancer Institute and the larger cancer research community have identified rural community partnerships as the foundation for reducing the disparities, we have identified limited application of community-based participatory research in cancer prevention and control research. Guided by the Community-Based Participatory Research Conceptual Model and our collective experience, we provide a framework for a community–cancer center partnership that focuses on promoting health equity. In this commentary, we articulate that the partnership process must foster capacity for communities and cancer centers, strive for rural representation in clinical trials and biobanking, build a pipeline for dissemination and implementation research, and create a bidirectional flow of knowledge between communities and academic institutions. Authentic partnerships with rural communities should be the ultimate goal of cancer centers, and the process described in this commentary can serve as an initial platform to build capacity and continue to strive toward that goal.
Accretion mode versus radio morphology in the LOFAR Deep Fields
Authors: Mingo B , Croston J H , Best P N , Duncan K J , Hardcastle M J , Kondapally R , Prandoni I , Sabater J , Shimwell T W , Williams W L , Baldi R D , Bonato M , Bondi M , Dabhade P , Gürkan G , Ineson J , Magliocchetti M , Miley G , Pierce J C S , Röttgering H J A
Published: February 2022

Radio-loud active galaxies have two accretion modes [radiatively inefficient (RI) and radiatively efficient (RE)], with distinct optical and infrared signatures, and two jet dynamical behaviours, which in arcsec- to arcmin-resolution radio surveys manifest primarily as centre- or edge-brightened structures [Fanaroff–Riley (FR) class I and II]. The nature of the relationship between accretion mode and radio morphology (FR class) has been the subject of long debate. We present a comprehensive investigation of this relationship for a sample of 286 well-resolved radio galaxies in the LOFAR Two-metre Sky Survey Deep Fields (LoTSS-Deep) first data release, for which robust morphological and accretion mode classifications have been made. We find that two-thirds of luminous FRII radio galaxies are RI, and identify no significant differences in the visual appearance or source dynamic range (peak/mean surface brightness) of the RI and RE FRIIs, demonstrating that both RI and RE systems can produce FRII structures. We also find a significant population of low-luminosity FRIIs (predominantly RI), supporting our earlier conclusion that FRII radio structures can be produced at all radio luminosities. We demonstrate that in the luminosity range where both morphologies are present, the probability of producing FRI or FRII radio morphology is directly linked to stellar mass, while across all morphologies and luminosities, RE accretion occurs in systems with high specific star formation rate, presumably because this traces fuel availability. In summary, the relationship between accretion mode and radio morphology is very indirect, with host-galaxy environment controlling these two key parameters in different ways.
A multiwavelength-motivated X-ray model for the Circinus Galaxy
Authors: Andonie Carolina , Ricci Claudio , Paltani Stéphane , Arévalo Patricia , Treister Ezequiel , Bauer Franz , Stalevski Marko
Published: February 2022

Reprocessed X-ray emission in active galactic nuclei can provide fundamental information about the circumnuclear environments of supermassive black holes. Recent mid-infrared studies have shown evidence of an extended dusty structure perpendicular to the torus plane. In this work, we build a self-consistent X-ray model for the Circinus Galaxy including the different physical components observed at different wavelengths and needed to reproduce both the morphological and spectral properties of this object in the mid-infrared. The model consists of four components: the accretion disc, the broad-line region (BLR), a flared disc in the equatorial plane, and a hollow cone in the polar direction. Our final model reproduces well the 3–70 keV Chandra and NuSTAR spectra of Circinus, including the complex Fe Kα zone and the spectral curvature, although several additional Gaussian lines, associated with either ionized iron or broadened Fe Kα/Kβ lines, are needed. We find that the flared disc is Compton-thick ($N_{\rm H,d}= \rm 1.01^{+0.03}_{-0.24}\times 10^{25}\, cm^{-2}$) and geometrically thick ($\mathrm{ CF}=0.55^{+0.01}_{-0.05}$), and that the hollow cone has a Compton-thin column density ($N_{\rm H,c}= \rm 2.18^{+0.47}_{-0.43}\times 10^{23}\, cm^{-2}$), which is consistent with the values inferred by mid-infrared studies. Including also the BLR, the effective line-of-sight column density is $N_{\rm H}= \rm 1.47^{+0.03}_{-0.24}\times 10^{25}\, cm^{-2}$. This approach to X-ray modelling, i.e. including all the different reprocessing structures, will be very important to fully exploit data from future X-ray missions.
Shot noise and scatter in the star formation efficiency as a source of 21-cm fluctuations
Authors: Reis Itamar , Barkana Rennan , Fialkov Anastasia
Published: February 2022

The 21-cm signal from cosmic dawn and the epoch of reionization probes the characteristics of the high redshift galaxy population. Many of the astrophysical properties of galaxies at high redshifts are currently unconstrained due to the lack of observations. This creates a vast space of possible astrophysical scenarios where the 21-cm signal needs to be modeled in order to plan for, and eventually fit, future observations. This is done with fast numerical methods which make simplifying approximations for the underlying physical processes. In this work, we quantify the effect of Poisson fluctuations and scatter in the star formation efficiency; while Poisson fluctuations are included in some works and not in others, scatter in the star formation efficiency is usually neglected, and all galaxies of a given mass are assumed to have the same properties. We show that both features can have a significant effect on the 21-cm power spectrum, most importantly in scenarios where the signal is dominated by massive galaxies. Scatter in the star formation efficiency does not simply enhance the effect of Poisson fluctuations; for example, we show that the power spectrum shape at cosmic dawn has a feature corresponding to the width of the galaxy brightness distribution. We also discuss some of the consequences for 21-cm imaging, and the signature of reduced correlation between the density and radiation fields.
TransposonUltimate: software for transposon classification, annotation and detection
Authors: Riehl Kevin , Riccio Cristian , Miska Eric A , Hemberg Martin
Published: February 2022

Most genomes harbor a large number of transposons, and they play an important role in evolution and gene regulation. They are also of interest to clinicians as they are involved in several diseases, including cancer and neurodegeneration. Although several methods for transposon identification are available, they are often highly specialised towards specific tasks or classes of transposons, and they lack common standards such as a unified taxonomy scheme and output file format. We present TransposonUltimate, a powerful bundle of three modules for transposon classification, annotation, and detection of transposition events. TransposonUltimate comes as a Conda package under the GPL-3.0 licence, is well documented and it is easy to install through https://github.com/DerKevinRiehl/TransposonUltimate. We benchmark the classification module on the large TransposonDB covering 891,051 sequences to demonstrate that it outperforms the currently best existing solutions. The annotation and detection modules combine sixteen existing softwares, and we illustrate its use by annotating Caenorhabditis elegans, Rhizophagus irregularis and Oryza sativa subs. japonica genomes. Finally, we use the detection module to discover 29 554 transposition events in the genomes of 20 wild type strains of C. elegans. Databases, assemblies, annotations and further findings can be downloaded from (https://doi.org/10.5281/zenodo.5518085).
Bridging: Accelerating Regulatory Acceptance of Reduced-Risk Tobacco and Nicotine Products
Authors: Gaca Marianna , Williamson Justine , Digard Helena , Adams Louise , Hawkridge Lauren , Proctor Christopher
Published: February 2022

Introduction

The number and variety of alternative tobacco and nicotine products that can potentially provide reduced-risk choices for cigarette smokers who switch completely to such products instead of continued smoking have grown substantially in the past decade. Innovation and choice are likely to improve the prospects of smokers making the switch, but this provides challenges to regulators and manufacturers to ensure that changes to regulations and products promote and do not hinder contributions to tobacco harm reduction.

Aims and Methods

This paper looks at where bridging data sets for tobacco heating products, closed system vaping products, and oral nicotine products might enable innovation while protecting the interests of consumers.

Results

We review product data from chemical studies and a toxicological study showing how bridging can be applied and consider what product development changes might allow bridging from existing datasets or trigger the need for new ones.

Conclusions

Bridging across specific product ranges can increase the speed of innovation, foster competition, and limit the burden of assessment for regulators while maintaining product safety and quality.

Implications

Bridging partial data sets is an established practice within other industries, that aims to improve efficiency with regulatory approvals, accepts natural product variation, and supports product innovation. We review product data from chemical studies and a toxicological study showing how bridging can be applied and consider what product development changes might allow bridging from existing datasets or trigger the need for new ones. This in turn can increase the speed of innovation, foster competition, and limit the burden of assessment for regulators while maintaining product safety and quality.
The Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Otitis Media–Related Antibiotic Use Among Young Children in Tennessee, USA
Authors: Griffith Hannah , Wiese Andrew D , Mitchel Edward F , Grijalva Carlos G
Published: February 2022

Otitis media (OM) is a leading cause of pediatric antibiotic use. Introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) led to reductions in OM among US children, though its impact on OM-related antibiotic use remains unclear. Among 499 683 Tennessee children <2 years of age, the OM-related antibiotic fill rate was stable after PCV13 introduction.
A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients With Hematological Malignancies
Authors: Chaftari Anne-Marie , Hachem Ray , Malek Alexandre E , Mulanovich Victor E , Szvalb Ariel D , Jiang Ying , Yuan Ying , Ali Shahnoor , Deeba Rita , Chaftari Patrick , Raad Issam
Published: February 2022

Background

With increased use of antibiotics in high-risk patients, the investigation of new antibiotics to cover potentially resistant pathogens is warranted. In this prospective randomized trial, we compared ceftolozane/tazobactam (C/T), a new cephalosporin/β-lactamase inhibitor, to the standard of care (SOC) for the empiric treatment of neutropenia and fever in patients with hematological malignancies.

Methods

We enrolled 100 patients to receive intravenous (IV) C/T or SOC antibiotics (cefepime, piperacillin/tazobactam, or meropenem) in combination with gram-positive antibacterial agents. We evaluated responses at the end of IV therapy (EOIV), test of cure (TOC; days 21–28), and late follow-up (LFU; days 35–42).

Results

We analyzed 47 C/T patients and 50 SOC patients. C/T patients had a higher rate of favorable clinical response at EOIV (87% vs 72%). A 1-sided noninferiority analysis indicated that C/T was at least not inferior to the SOC for favorable clinical response at EOIV (P = .002), TOC (P = .004), and LFU (P = .002). Superiority tests showed that C/T led to significantly lower rates of clinical failure at TOC (6% vs 30%; P = .003) and LFU (9% vs 30%; P = .008). C/T and SOC patients with documented infections had similar rates of favorable microbiological response. Serious adverse events leading to drug discontinuation (2% vs 0%; P = .48) and overall mortality (6% vs 4%; P = .67) were similar in both groups.

Conclusions

The empiric use of C/T in high-risk patients with hematological malignancies and febrile neutropenia is safe and associated with better clinical outcomes than SOC antimicrobial agents.

Clinical Trials Registration

NCT03485950.
Translational Landscape of a C4 Plant, Sorghum bicolor, Under Normal and Sulfur-Deficient Conditions
Authors: Sotta Naoyuki , Chiba Yukako , Aoyama Haruka , Takamatsu Seidai , Suzuki Takamasa , Miwa Kyoko , Yamashita Yui , Naito Satoshi , Fujiwara Toru
Published: February 2022

Recent accumulation of genomic and transcriptomic information has facilitated genetic studies. Increasing evidence has demonstrated that translation is an important regulatory step, and the transcriptome does not necessarily reflect the profile of functional protein production. Deep sequencing of ribosome-protected mRNA fragments (ribosome profiling or Ribo-seq) has enabled genome-wide analysis of translation. Sorghum is a C4 cereal important not only as food but also as forage and a bioenergy resource. Its resistance to harsh environments has made it an agriculturally important research subject. Yet genome-wide translational profiles in sorghum are still missing. In this study, we took advantage of Ribo-seq and identified actively translated reading frames throughout the genome. We detected translation of 4,843 main open reading frames (ORFs) annotated in the sorghum reference genome version 3.1 and revealed a number of unannotated translational events. A comparison of the transcriptome and translatome between sorghums grown under normal and sulfur-deficient conditions revealed that gene expression is modulated independently at transcript and translation levels. Our study revealed the translational landscape of sorghum’s response to sulfur and provides datasets that could serve as a fundamental resource to extend genetic research on sorghum, including studies on translational regulation.
Genetic analysis for type 1 diabetes genes in juvenile dermatomyositis unveils genetic disease overlap
Authors: Qu Hui-Qi , Qu Jingchun , Vaccaro Courtney , Chang Xiao , Mentch Frank , Li Jin , Mafra Fernanda , Nguyen Kenny , Gonzalez Michael , March Michael , Pellegrino Renata , Glessner Joseph , Sleiman Patrick , Kao Charlly , Hakonarson Hakon
Published: February 2022

Objectives

JDM is a serious autoimmune and complex genetic disease. Another autoimmune genetic disease, type 1 diabetes (T1D), has been observed for significantly increased prevalence in families with JDM, while increased JDM risk has also been observed in T1D cases. This study aimed to study whether these two autoimmune diseases, JDM and T1D, share common genetic susceptibility.

Methods

From 169 JDM families, 121 unrelated cases with European ancestry (EA) were identified by genome-wide genotyping, principal component analysis and identical-by-descent (IBD) analysis. T1D genetic risk score (GRS) were calculated in these cases and were compared with 361 EA T1D cases and 1943 non-diabetes EA controls. A total of 113 cases of the 121 unrelated European cases were sequenced by whole exome sequencing.

Results

We observed increased T1D GRS in JDM cases (P = 9.42E-05). Using whole exome sequencing, we uncovered the T1D genes, phospholipase B1, cystic fibrosis transmembrane conductance regulator, tyrosine hydroxylase, CD6 molecule, perforin 1 and dynein axonemal heavy chain 2, potentially associated with JDM by the burden test of rare functional coding variants.

Conclusion

Novel mechanisms of JDM related to these T1D genes are suggested by this study, which may imply novel therapeutic targets for JDM and warrant further study.
Premedication for Nonemergent Neonatal Intubation
Authors: O'Connor Terri Lynn
Published: February 2022

This systematic review evaluates research regarding the use of premedication for nonemergent neonatal intubation. Unmedicated intubation is associated with adverse outcomes such as physiologic instability and decompensation, repeat and prolonged intubation attempts, and trauma. Included studies compared medicated intervention groups against an unmedicated control. Medications vary greatly across studies and include anesthetics, opioids, benzodiazepines, barbiturates, vagolytics, and neuromuscular blockades (muscle relaxants). A comprehensive search of randomized control trials, retrospective cohort studies, and prospective observational studies was completed from the electronic databases of CINAHL EBSCOhost, Ovid MEDLINE, PubMed, EMBASE, Google Scholar, Cochrane Collaboration, and ClinicalTrials.gov and footnotes were used to complete the search. Twelve studies are included in this review dating back to 1984 and are from 5 countries. Outcome measures include changes in heart rate, oxygen saturation, and blood pressure; number and duration of attempts to intubate; and trauma to the oral cavity and upper airway. Twelve studies are included in this review and include 5410 patients. No studies were excluded based on level of evidence or quality appraisal. Findings in this review support the recommendation that opioids and vagolytic agents should be used for premedication for nonemergent neonatal intubation and adjuvant sedation and muscle relaxants should be considered.
Time-modulated excitation for enhanced single-molecule localization microscopy
Authors: Jouchet Pierre , Poüs Christian , Fort Emmanuel , Lévêque-Fort Sandrine
Published: February 2022

Structured illumination in single-molecule localization microscopy provides new information on the position of molecules and thus improves the localization precision compared to standard localization methods. Here, we used a time-shifted sinusoidal excitation pattern to modulate the fluorescence signal of the molecules whose position information is carried by the phase and recovered by synchronous demodulation. We designed two flexible fast demodulation systems located upstream of the camera, allowing us to overcome the limiting camera acquisition frequency and thus to maximize the collection of photons in the demodulation process. The temporally modulated fluorescence signal was then sampled synchronously on the same image, repeatedly during acquisition. This microscopy, called ModLoc, allows us to experimentally improve the localization precision by a factor of 2.4 in one direction, compared to classical Gaussian fitting methods. A temporal study and an experimental demonstration both show that the short lifetimes of the molecules in blinking regimes impose a modulation frequency in the kilohertz range, which is beyond the reach of current cameras. A demodulation system operating at these frequencies would thus be necessary to take full advantage of this new localization approach.

This article is part of the Theo Murphy meeting issue 'Super-resolution structured illumination microscopy (part 2)'.
Answering some questions about structured illumination microscopy
Authors: Manton James D.
Published: February 2022

Structured illumination microscopy (SIM) provides images of fluorescent objects at an enhanced resolution greater than that of conventional epifluorescence wide-field microscopy. Initially demonstrated in 1999 to enhance the lateral resolution twofold, it has since been extended to enhance axial resolution twofold (2008), applied to live-cell imaging (2009) and combined with myriad other techniques, including interferometric detection (2008), confocal microscopy (2010) and light sheet illumination (2012). Despite these impressive developments, SIM remains, perhaps, the most poorly understood ‘super-resolution’ method. In this article, we provide answers to the 13 questions regarding SIM proposed by Prakash
et al.
along with answers to a further three questions. After providing a general overview of the technique and its developments, we explain why SIM as normally used is still diffraction-limited. We then highlight the necessity for a non-polynomial, and not just nonlinear, response to the illuminating light in order to make SIM a true, diffraction-unlimited, super-resolution technique. In addition, we present a derivation of a real-space SIM reconstruction approach that can be used to process conventional SIM and image scanning microscopy (ISM) data and extended to process data with quasi-arbitrary illumination patterns. Finally, we provide a simple bibliometric analysis of SIM development over the past two decades and provide a short outlook on potential future work.

This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 2)’.
Polarized illumination coded structured illumination microscopy (picoSIM): experimental results
Authors: Appelt Daniel , Ehler Elisabeth , Shukla Mukherjee Sapna , Heintzmann Rainer , Wicker Kai
Published: February 2022

The need for acquiring at least three images to reconstruct an optical section of a sample limits the acquisition rate in structured illumination microscopy (SIM) for optical sectioning. In polarized illumination coded structured illumination microscopy (picoSIM) the three individual light patterns are encoded in a single polarized illumination light distribution, enabling the acquisition of the complete SIM data in a single exposure. Here, we describe our experimental set-up and show experimental results acquired with sequential and single-shot picoSIM.

This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 2)’.
Fundicoccus fermenti sp. nov., an indigo-reducing facultative anaerobic alkaliphile isolated from indigo fermentation liquor used for dyeing
Authors: Tu Zhihao , Lopes Helena de Fátima Silva , Yumoto Isao
Published: February 2022

Two facultative anaerobic and facultative alkaliphilic indigo-reducing strains, designated F-1T and F-2, were isolated from indigo fermentation liquor produced from couched woad fermentation-based Indian indigo fermentation fluid. The 16S rRNA gene phylogeny showed that

Fundicoccus ignavus

WS4937T (99.5%) was the closest neighbour of F-1T. The isolated bacterial cells were Gram-stain-positive and facultative anaerobic coccoids. Strain F-1T grew at between 5 and 37 °C with optimum growth between 28‒32 °C. The isolate grew in a pH range of 7.0‒10.5, with optimum growth between pH 9.0‒10.5. The DNA G+C content was 37.6 mol% (HPLC). The whole-cell fatty acid profile mainly consisted (>10 %) of C16 : 0, C16 : 1 ω9c, C18 : 0 and C18 : 1 ω9c. The digital DNA–DNA hybridization value between strain F-1T and

F. ignavus

WS4937T was 52.9 %. Based on their physiological and biochemical characteristics, and phylogenetic and genomic data, the isolates can be discriminated from

F. ignavus

WS4937T. The name Fundicoccus fermenti sp. nov. is proposed. The type strain of this species is F-1T (JCM 34140T=NCIMB 15255T).
Macrococcus armenti sp. nov., a novel bacterium isolated from the skin and nasal cavities of healthy pigs and calves
Authors: Keller Jennifer Eleonora , Schwendener Sybille , Overesch Gudrun , Perreten Vincent
Published: February 2022

Gram-positive coccoid bacteria were isolated from the nasal cavities of pigs and calves as well as from axillar and inguinal skin regions of pigs. Phylogenetic analysis of seven strains based on complete genome, 16S rRNA, hsp60, dnaJ, rpoB and sodA gene sequences and MALDI-TOF MS profiles revealed that they belonged to the genus

Macrococcus

with the closest relatedness to

Macrococcus canis

,

Macrococcus caseolyticus

subsp.

caseolyticus

and

Macrococcus caseolyticus

subsp.

hominis

. DNA relatedness of the type strain JEK37T with the type strains of

M. canis

,

M. caseolyticus

subsp.

caseolyticus

and

M. caseolyticus

subsp.

hominis

was 23.4, 23.1 and 23.0 % by digital DNA–DNA hybridization and 80.39, 80.45 and 80.87 % by average nucleotide identity (ANI) calculations, confirming that they do not belong to the same species. The DNA G+C content of JEK37T was 35.65 mol%. The novel strains can be differentiated from

M. canis

KM 45013T by the ability to fermentate d-ribose and by the absence of DNAase production and haemolysis, from

M. caseolyticus

subsp.

caseolyticus

CCUG 15606T by the ability to fermentate sucrose and from both species by the inability to grow in 9 and 12% NaCl. They differ from M. caseolyiticus subsp. hominis by the presence of α-glucosidase. The most common fatty acids of JEK37T were C14 : 0, C18 : 1 ω9c and C18 : 0. Known polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, aminolipid, aminoglycolipid, aminophospholipid, glycolipid and phospholipid. Cell-wall peptidoglycan of JEK37T was of type A3α l-Lys–Gly2–L-Ser–Gly (similar to A11.3) and the respiratory quinolone was menaquinone 6. Based on their genotypic and chemotaxonomic characteristics, these strains represent a novel species of the genus

Macrococcus

, for which we propose the name Macrococcus armenti sp. nov. The type strain is JEK37T (=DSM 112712T=CCOS 1982T).