bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian Stiffness Is Significantly Increased in Polycystic Ovary Syndrome and Related With Anti-Mullerian Hormone
Authors: Sumbul Hilmi Erdem , Avci Begum Seyda , Bankir Mehmet , Pekoz Burcak Cakir , Gulumsek Erdinc , Koc Ayse Selcan
Published: January 2022

Objectives

Parenchymal stiffness obtained by point shear-wave elastography (pSWE) in solid organs is used as a sign of damage in these organs. However, its clinical use and whether patients with polycystic ovary syndrome (PCOS) have increased ovarian tissue stiffness are still unclear. The aim of this study is to determine the parameters related to ovarian stiffness and whether there is an increase in ovarian stiffness in patients with PCOS compared with healthy controls.

Methods

Forty-five women who were followed up regularly with the diagnosis of PCOS and 30 healthy controls similar to age and sex were included in this study. In addition to the routine follow-up parameters for PCOS, serum homeostatic model assessment of insulin resistance and anti-Mullerian hormone (AMH) levels were examined in all patients, and pSWE examination was performed with pelvic ultrasound (US) and ElastPQ technique.

Results

Serum dehydroepiandrosterone sulfate, luteinizing hormone/follicle-stimulating hormone, testosterone, homeostatic model assessment of insulin resistance, and AMH were higher in PCOS compared with healthy controls (P < 0.001). Right, left, and mean ovary stiffness and volumes were significantly higher in PCOS group than healthy controls (P < 0.001). Correlation analysis was performed between mean ovary stiffness and dehydroepiandrosterone sulfate, luteinizing hormone/follicle-stimulating hormone, testosterone, homeostatic model assessment, and AMH and ovary volumes (P < 0.01 for each one). In linear regression analysis, only AMH was found to be related to mean ovary stiffness (P < 0.001 and β = 0.734).

Conclusions

Ovarian stiffness value obtained by ElastPQ technique and pSWE method increases in PCOS patients compared with healthy controls and is closely related to serum AMH levels. In patients with PCOS, in addition to the conventional US, ovarian stiffness measured by pSWE may be an auxiliary examination in the follow-up of the disease. However, it was concluded that the ovarian stiffness measurement obtained in our current study should be supported by studies involving more patients and the transvaginal US method.
Comparing transmission potential networks based on social network surveys, close contacts and environmental overlap in rural Madagascar
Authors: Kauffman Kayla , Werner Courtney S. , Titcomb Georgia , Pender Michelle , Rabezara Jean Yves , Herrera James P. , Shapiro Julie Teresa , Solis Alma , Soarimalala Voahangy , Tortosa Pablo , Kramer Randall , Moody James , Mucha Peter J. , Nunn Charles
Published: January 2022

Social and spatial network analysis is an important approach for investigating infectious disease transmission, especially for pathogens transmitted directly between individuals or via environmental reservoirs. Given the diversity of ways to construct networks, however, it remains unclear how well networks constructed from different data types effectively capture transmission potential. We used empirical networks from a population in rural Madagascar to compare social network survey and spatial data-based networks of the same individuals. Close contact and environmental pathogen transmission pathways were modelled with the spatial data. We found that naming social partners during the surveys predicted higher close-contact rates and the proportion of environmental overlap on the spatial data-based networks. The spatial networks captured many strong and weak connections that were missed using social network surveys alone. Across networks, we found weak correlations among centrality measures (a proxy for superspreading potential). We conclude that social network surveys provide important scaffolding for understanding disease transmission pathways but miss contact-specific heterogeneities revealed by spatial data. Our analyses also highlight that the superspreading potential of individuals may vary across transmission modes. We provide detailed methods to construct networks for close-contact transmission pathogens when not all individuals simultaneously wear GPS trackers.
Optimal strategies to protect a sub-population at risk due to an established epidemic
Authors: Bussell Elliott H. , Cunniffe Nik J.
Published: January 2022

Epidemics can particularly threaten certain sub-populations. For example, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the elderly are often preferentially protected. For diseases of plants and animals, certain sub-populations can drive mitigation because they are intrinsically more valuable for ecological, economic, socio-cultural or political reasons. Here, we use optimal control theory to identify strategies to optimally protect a ‘high-value’ sub-population when there is a limited budget and epidemiological uncertainty. We use protection of the Redwood National Park in California in the face of the large ongoing state-wide epidemic of sudden oak death (caused by
Phytophthora ramorum
) as a case study. We concentrate on whether control should be focused entirely within the National Park itself, or whether treatment of the growing epidemic in the surrounding ‘buffer region’ can instead be more profitable. We find that, depending on rates of infection and the size of the ongoing epidemic, focusing control on the high-value region is often optimal. However, priority should sometimes switch from the buffer region to the high-value region only as the local outbreak grows. We characterize how the timing of any switch depends on epidemiological and logistic parameters, and test robustness to systematic misspecification of these factors due to imperfect prior knowledge.
Connectivity conservation at the crossroads: protected areas versus payments for ecosystem services in conserving connectivity for Colombian carnivores
Authors: Zárrate Charry Diego A. , González-Maya José F. , Arias-Alzate Andrés , Jiménez-Alvarado J. Sebastián , Reyes Arias Jessica Dayanh , Armenteras Dolors , Betts Matthew G.
Published: January 2022

Protected areas (PAs) constitute one of the main tools for global landscape conservation. Recently, payments for environmental services (PES) have attracted interest from national and regional governments and are becoming one of the leading conservation policy instruments in tropical countries. However, the degree to which areas designated for PES overlap with areas that are critical for maintaining species' landscape connectivity is rarely evaluated. We estimated habitat distributions and connectivity for 16 of the 22 mammalian carnivores occurring in the Caribbean region of Colombia, and identified the overlap between existing PAs and areas identified as being important for connectivity for these species. We also evaluated the potential impact of creation of new PAs versus new PES areas on conserving connectivity for carnivores. Our results show that PAs cover only a minor percentage of the total area that is important for maintaining connectivity (x=26.8%±20.2 s.d.). On the other hand, PES, if implemented extensively, could contribute substantially to mammalian carnivores’ connectivity (x=45.4%±12.8 s.d.). However, in a more realistic scenario with limited conservation investment in which fewer areas are set aside, a strategy based on implementing new PAs seems superior to PES. We argue that prioritizing designation of new PAs will be the most efficient means through which to maintain connectivity.
Design of a custom-made device for real-time optical measurement of differential mineral concentrations in three-dimensional scaffolds for bone tissue engineering
Authors: Lovecchio J. , Betti V. , Cortesi M. , Ravagli E. , Severi S. , Giordano E.
Published: January 2022

Monitoring bone tissue engineered (TEed) constructs during their maturation is important to ensure the quality of applied protocols. Several destructive, mainly histochemical, methods are conventionally used to this aim, requiring the sacrifice of the investigated samples. This implies (i) to plan several scaffold replicates, (ii) expensive and time consuming procedures and (iii) to infer the maturity level of a given tissue construct from a cognate replica. To solve these issues, non-destructive techniques such as light spectroscopy-based methods have been reported to be useful. Here, a miniaturized and inexpensive custom-made spectrometer device is proposed to enable the non-destructive analysis of hydrogel scaffolds. Testing involved samples with a differential amount of calcium salt. When compared to a reference standard device, this custom-made spectrometer demonstrates the ability to perform measurements without requiring elaborate sample preparation and/or a complex instrumentation. This preliminary study shows the feasibility of light spectroscopy-based methods as useful for the non-destructive analysis of TEed constructs. Based on these results, this custom-made spectrometer device appears as a useful option to perform real-time/in-line analysis. Finally, this device can be considered as a component that can be easily integrated on board of recently prototyped bioreactor systems, for the monitoring of TEed constructs during their conditioning.
How disease risk awareness modulates transmission: coupling infectious disease models with behavioural dynamics
Authors: Cascante-Vega Jaime , Torres-Florez Samuel , Cordovez Juan , Santos-Vega Mauricio
Published: January 2022

Epidemiological models often assume that individuals do not change their behaviour or that those aspects are implicitly incorporated in parameters in the models. Typically, these assumptions are included in the contact rate between infectious and susceptible individuals. However, adaptive behaviours are expected to emerge and play an important role in the transmission dynamics across populations. Here, we propose a theoretical framework to couple transmission dynamics with behavioural dynamics due to infection awareness. We modelled the dynamics of social behaviour using a game theory framework, which is then coupled with an epidemiological model that captures the disease dynamics by assuming that individuals are aware of the actual epidemiological state to reduce their contacts. Results from the mechanistic model show that as individuals increase their awareness, the steady-state value of the final fraction of infected individuals in a susceptible-infected-susceptible (SIS) model decreases. We also incorporate theoretical contact networks, having the awareness parameter dependent on global or local contacts. Results show that even when individuals increase their awareness of the disease, the spatial structure itself defines the steady state.
Tetracycline adsorption on magnetic sludge biochar: size effect of the Fe
3
O
4
nanoparticles
Authors: Luo Suxing , Qin Jun , Wu Yuanhui , Feng Feng
Published: January 2022

Activated sludge, which is difficult and expensive to treat and dispose of, is a key concern in wastewater treatment plants. In this study, magnetic sludge biochar containing activated sludge and different sizes (14.3, 40.2 and 90.5 nm) of Fe
3
O
4
nanoparticles was investigated as an effective adsorbent for tetracycline (TC) adsorption. Magnetic sludge-based biochar was prepared by a facile cross-linking method and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, X-ray photoelectron spectroscopy (XPS) and zeta potential analysis. The adsorption performances of TC on three kinds of adsorbents were investigated. Although 14.3 nm Fe
3
O
4
nanoparticles could be inclined to aggregate and partially filled with pores of biochar, it turned out that magnetic sludge biochar with 14.3 nm Fe
3
O
4
nanoparticles exhibited optimum performance for TC removal with adsorption capacity up to 184.5 mg g
−1
, due to the larger amounts of functional groups and the change of zeta potential. Furthermore, the adsorption kinetics of TC on three kinds of adsorbents were studied, which implied that the pseudo-second-order kinetic model exhibited the better fit for the entire sorption process.
Exposure to the COVID-19 pandemic environment and generosity
Authors: Brañas-Garza P. , Jorrat D. , Alfonso A. , Espín A. M. , Muñoz T. García , Kovářík J.
Published: January 2022

We report data from an online experiment which allows us to study how generosity changed over a 6-day period during the initial explosive growth of the COVID-19 pandemic in Andalusia, Spain, while the country was under a strict lockdown. Participants (n= 969) could donate a fraction of a €100 prize to an unknown charity. Our data are particularly rich in the age distribution and we complement them with daily public information about COVID-19-related deaths, infections and hospital admissions. We find correlational evidence that donations decreased in the period under study, particularly among older individuals. Our analysis of the mechanisms behind the detected decrease in generosity suggests that expectations about others' behaviour, perceived mortality risk and (alarming) information play a key—but independent—role for behavioural adaptation. These results indicate that social behaviour is quickly adjusted in response to the pandemic environment, possibly reflecting some form of selective prosociality.
Numerical biomechanics modelling of indirect mitral annuloplasty treatments for functional mitral regurgitation
Authors: Galili Lee , White Zeira Adi , Marom Gil
Published: January 2022

Mitral valve regurgitation (MR) is a common valvular heart disease where an improper closure leads to leakage from the left ventricle into the left atrium. There is a need for less-invasive treatments such as percutaneous repairs for a large inoperable patient population. The aim of this study is to compare several indirect mitral annuloplasty (IMA) percutaneous repair techniques by finite-element analyses. Two types of generic IMA devices were considered, based on coronary sinus vein shortening (IMA-CS) to reduce the annulus perimeter and based on shortening of the anterior–posterior diameter (IMA-AP). The disease, its treatments, and the heart function post-repair were modelled by modifying the living heart human model (Dassault Systèmes). A functional MR pathology that represents ischaemic MR was generated and the IMA treatments were simulated in it, followed by heart function simulations with the devices and leakage quantification from blood flow simulations. All treatments were able to reduce leakage, the IMA-AP device achieved better sealing, and there was a correlation between the IMA-CS device length and the reduction in leakage. The results of this study can help in bringing IMA-AP to market, expanding the use of IMA devices, and optimizing future designs of such devices.
Single cell transfection of human-induced pluripotent stem cells using a droplet-based microfluidic system
Authors: Pérez-Sosa Camilo , Sanluis-Verdes Anahí , Waisman Ariel , Lombardi Antonella , Rosero Gustavo , Greca Alejandro La , Bhansali Shekhar , Bourguignon Natalia , Luzzani Carlos , Pérez Maximiliano. S. , Miriuka Santiago , Lerner Betiana
Published: January 2022

Microfluidic tools have recently made possible many advances in biological and biomedical research. Research in fields such as physics, engineering, chemistry and biology have combined to produce innovation in microfluidics which has positively impacted diverse areas such as nucleotide sequencing, functional genomics, single-cell studies, single molecules assays and biomedical diagnostics. Among these areas, regenerative medicine and stem cells have benefited from microfluidics since these tools have had a profound impact on their applications. In this study, we present a high-performance droplet-based system for transfecting individual human-induced pluripotent stem cells. We will demonstrate that this system has great efficiency in single cells and captured droplets, like other microfluidic methods but with lower cost. Moreover, this microfluidic approach can be associated with the PiggyBac transposase-based system to increase its transfection efficiency. Our results provide a starting point for subsequent applications in more complex transfection systems, single-cell differentiation interactions, cell subpopulations and cell therapy, among other potential applications.
Long-read sequencing reveals atypical mitochondrial genome structure in a New Zealand marine isopod
Authors: Pearman William S. , Wells Sarah J. , Dale James , Silander Olin K. , Freed Nikki E.
Published: January 2022

Most animal mitochondrial genomes are small, circular and structurally conserved. However, recent work indicates that diverse taxa possess unusual mitochondrial genomes. In Isopoda
,
species in multiple lineages have atypical and rearranged mitochondrial genomes. However, more species of this speciose taxon need to be evaluated to understand the evolutionary origins of atypical mitochondrial genomes in this group. In this study, we report the presence of an atypical mitochondrial structure in the New Zealand endemic marine isopod,
Isocladus armatus.
Data from long- and short-read DNA sequencing suggest that
I. armatus
has two mitochondrial chromosomes. The first chromosome consists of two mitochondrial genomes that have been inverted and fused together in a circular form, and the second chromosome consists of a single mitochondrial genome in a linearized form. This atypical mitochondrial structure has been detected in other isopod lineages, and our data from an additional divergent isopod lineage (Sphaeromatidae) lends support to the hypothesis that atypical structure evolved early in the evolution of Isopoda
.
Additionally, we find that an asymmetrical site previously observed across many species within Isopoda is absent in
I. armatus
, but confirm the presence of two asymmetrical sites recently reported in two other isopod species.
Oxidase enzymes as sustainable oxidation catalysts
Authors: Wahart Alice J. C. , Staniland Jessica , Miller Gavin J. , Cosgrove Sebastian C.
Published: January 2022

Oxidation is one of the most important processes used by the chemical industry. However, many of the methods that are used pose significant sustainability and environmental issues. Biocatalytic oxidation offers an alternative to these methods, with a now significant enzymatic oxidation toolbox on offer to chemists. Oxidases are one of these options, and as they only depend on molecular oxygen as a terminal oxidant offer perfect atom economy alongside the selectivity benefits afforded by enzymes. This review will focus on examples of oxidase biocatalysts that have been used for the sustainable production of important molecules and highlight some important processes that have been significantly improved through the use of oxidases. It will also consider emerging classes of oxidases, and how they might fit in a future biorefinery approach for the sustainable production of important chemicals.
Elasticity and damping ratio measurement of droplets on super-hydrophobic surfaces
Authors: Sun Yukai , Zheng Yelong , Song Le , Sun Peiyuan , Zhao Meirong , Zhou Yixiong , Tee Clarence Augustine TH
Published: January 2022

The measurement of the droplets’ elasticity is vitally important in microfluidic and ink-jet printing. It refers to the ability of the droplet to restore its original shape and strong robustness. This study investigated a novel method to measure elasticity. The plate coated with super-hydrophobic layers pressed on a droplet and the elastic force was recorded by an electronic balance. Meanwhile, a mathematical model was constructed to calculate the changes of the droplet area under the force. The measurement showed that external work mainly converts into surface energy and the damping ratio increases from 0.068 to 0.261 with the increase of mass fraction from 0 to 80 wt%. It also indicates that the novel method can accurately and efficiently measure the elasticity of droplets.
Quantitative mapping of thickness variations along a ray path using geometrical full waveform inversion and guided wave mode conversion
Authors: Zuo Peng , Huthwaite Peter
Published: January 2022

Quantitative guided wave thickness mapping in plate-like structures and pipelines is of significant importance for the petrochemical industry to accurately estimate the minimum remaining wall thickness in the presence of corrosion, as guided waves can inspect a large area without needing direct access. Although a number of inverse algorithms have been studied and implemented in guided wave reconstruction, a primary assumption is widely used: the three-dimensional guided wave inversion of thickness is simplified as a two-dimensional acoustic wave inversion of velocity, with the dispersive nature of the waves linking thickness to velocity. This assumption considerably simplifies the inversion procedure; however, it makes it impossible to account for mode conversion. In reality, mode conversion is quite common in guided wave scattering with asymmetric wall loss, and compared with non-converted guided wave modes, converted modes may provide greater access to valuable information about the thickness variation, which, if exploited, could lead to improved performance. Geometrical full waveform inversion (GFWI) is an ideal tool for this, since it can account for mode conversion. In this paper, quantitative thickness reconstruction based on GFWI is developed in a plate cross-section and applied to study the performance of thickness reconstruction using mode conversion.
The generalized Wiener–Hopf equations for the elastic wave motion in angular regions
Authors: Daniele Vito G. , Lombardi Guido
Published: January 2022

In this work, we introduce a general method to deduce spectral functional equations in elasticity and thus, the generalized Wiener–Hopf equations (GWHEs), for the wave motion in angular regions filled by arbitrary linear homogeneous media and illuminated by sources localized at infinity. The work extends the methodology used in electromagnetic applications and proposes for the first time a complete theory to get the GWHEs in elasticity. In particular, we introduce a vector differential equation of first-order characterized by a matrix that depends on the medium filling the angular region. The functional equations are easily obtained by a projection of the reciprocal vectors of this matrix on the elastic field present on the faces of the angular region. The application of the boundary conditions to the functional equations yields GWHEs for practical problems. This paper extends and applies the general theory to the challenging canonical problem of elastic scattering in angular regions.
Development and function explain the modular evolution of phalanges in gecko lizards
Authors: Rothier Priscila S. , Simon Monique N. , Marroig Gabriel , Herrel Anthony , Kohlsdorf Tiana
Published: January 2022

Selective regimes favouring the evolution of functional specialization probably affect covariation among phenotypic traits. Phalanges of most tetrapods develop from a conserved module that constrains their relative proportions. In geckos, however, biomechanical specializations associated with adhesive toepads involve morphological variation in the autopodium and might reorganize such modular structures. We tested two hypotheses to explain the modular architecture of hand bones in geckos, one based on developmental interactions and another incorporating functional associations related to locomotion, and compared the empirical support for each hypothetical module between padded and padless lineages. We found strong evidence for developmental modules in most species, which probably reflects embryological constraints during phalangeal formation. Although padded geckos exhibit a functional specialization involving the hyperextension of the distal phalanges that is absent in padless species, the padless species are the ones that show a distal functional module with high integration. Some ancestrally padless geckos apparently deviate from developmental predictions and present a relatively weak developmental module of phalanges and a strongly integrated distal module, which may reflect selective regimes involving incipient frictional adhesion in digit morphology. Modularity of digit elements seems dynamic along the evolutionary history of geckos, being associated with the presence/absence of adhesive toepads.
Habitat mediates coevolved but not novel species interactions
Authors: Twining Joshua P. , Sutherland Chris , Reid Neil , Tosh David G.
Published: January 2022

Ongoing recovery of native predators has the potential to alter species interactions, with community and ecosystem wide implications. We estimated the co-occurrence of three species of conservation and management interest from a multi-species citizen science camera trap survey. We demonstrate fundamental differences in novel and coevolved predator–prey interactions that are mediated by habitat. Specifically, we demonstrate that anthropogenic habitat modification had no influence on the expansion of the recovering native pine marten in Ireland, nor does it affect the predator's suppressive influence on an invasive prey species, the grey squirrel. By contrast, the direction of the interaction between the pine marten and a native prey species, the red squirrel, is dependent on habitat. Pine martens had a positive influence on red squirrel occurrence at a landscape scale, especially in native broadleaf woodlands. However, in areas dominated by non-native conifer plantations, the pine marten reduced red squirrel occurrence. These findings suggest that following the recovery of a native predator, the benefits of competitive release are spatially structured and habitat-specific. The potential for past and future landscape modification to alter established interactions between predators and prey has global implications in the context of the ongoing recovery of predator populations in human-modified landscapes.
An evaluation of risk factors for Staphylococcus aureus colonization in a pre-surgical population
Authors: Edwin Erayil Serin , Palzer Elise , Kline Susan
Published: January 2022

Staphylococcus aureus

(SA) colonization has significant implications in healthcare-associated infections. Here we describe a prospective study conducted in pre-surgical outpatients, done with the aim of identifying demographic and clinical risk factors for SA colonization. We found younger age to be a potential predictor of SA colonization.
A UHM – ULM interface contributes to U2AF2 and SF3B1 association for pre-mRNA splicing
Authors: Galardi Justin , Bela Victoria N. , Jeffery Nazish , He Xueyang , Glasser Eliezra , Loerch Sarah , Jenkins Jermaine L. , Pulvino Mary J. , Boutz Paul L. , Kielkopf Clara L.
Published: January 2022

In the early stages of spliceosome assembly, the 3’ splice site is recognized by sequential complexes of U2AF2 with SF1 followed by the SF3B1 subunit of the U2 small nuclear ribonucleoprotein particle. The U2AF2 – SF1 interface comprises a U2AF homology motif (UHM) of U2AF2 and a well-characterized U2AF ligand motif (ULM)/coiled coil region of SF1. However, the structure of the U2AF2 – SF3B1 interface and its importance for pre-mRNA splicing is unknown. To address this knowledge gap, we determined the crystal structure of the U2AF2 UHM bound to a SF3B1 ULM site at 1.8 Å resolution. The trajectory of the SF3B1 ULM across the U2AF2 UHM surface differed from prior UHM/ULM structures. This distinctive structure is expected to modulate the orientations of the fulllength proteins. Using isothermal titration calorimetry, we established similar binding affinities of a minimal U2AF2 UHM – SF3B1 ULM complex and a nearly full-length U2AF2 protein binding the N-terminal SF3B1 region, with or without an auxiliary SF3B6 subunit. We showed that key residues at the U2AF2 UHM – SF3B1 ULM interface are required for high affinity association and co-immunoprecipitation of the splicing factors. Moreover, disrupting the U2AF2 – SF3B1 interface altered splicing of representative human transcripts. Further analysis of these transcripts and genome-wide data sets indicated that the subset of splice sites co-regulated by U2AF2 and SF3B1 are largely distinct from those co-regulated by U2AF2 and SF1. Altogether, these findings support distinct structural and functional roles for the sequential SF1 and SF3B1 complexes with U2AF2 during the pre-mRNA splicing process.
Nosocomial RSV-related in-hospital mortality in children <5 years: a global case series
Authors: Löwensteyn Yvette N. , Willemsen Joukje E. , Mazur Natalie I. , Scheltema Nienke M. , van Haastregt Nynke C. J. , Buuren Amber ten , van Roessel Ichelle , Scheepmaker Dunja , Nair Harish , van de Ven Peter M. , Bont Louis J. ,   RSV GOLD study group
Published: January 2022

Background

According to the World Health Organization the global burden of nosocomial infections is poorly characterized as surveillance systems for nosocomial infection are lacking. Nosocomial infections occur at higher rates in low- and lower-middle-income countries (LMICs) than in high-income countries (HICs). Current global RSV burden estimates are largely based on community-acquired disease. We aimed to characterize children with nosocomial RSV-related mortality and to understand the potential impact of RSV immunization strategies.

Methods

RSV GOLD is a global registry of children younger than 5 years who died with laboratory-confirmed RSV infection. We compared clinical and demographic characteristics of children with nosocomial and community-acquired RSV in-hospital mortality.

Results

We included 231 nosocomial and 931 community-acquired RSV-related in-hospital deaths from 65 countries. Median age at death was similar for both groups (5.4 vs 6 months). As expected, a higher proportion of children with nosocomial infection had comorbidities (87% vs 57%; p<0.001) or was born preterm (46% vs 24%; p<0.001) than children with community-acquired infection. The proportion of nosocomial deaths among all RSV deaths was lower in LMICs than in upper-middle-income countries (UMICs) and HICs (12% vs 18% and 26%, respectively).

Conclusions

This is the first global case series of children dying with nosocomial RSV infection. Future infant-targeted immunization strategies can prevent the majority of nosocomial RSV-related deaths. Although nosocomial RSV deaths are expected to occur at highest rates in LMICs, the number of reported nosocomial RSV deaths was low in these countries. Hospital-based surveillance is needed to capture the full burden of nosocomial RSV mortality in LMICs.

Key points

The proportion of reported nosocomial RSV-related deaths is substantially lower in lower-middle-income countries than in upper-middle-income countries and high-income countries (12% vs 18% and 26%, respectively).

The majority of nosocomial RSV-related deaths can be prevented by infant-targeted immunization strategies as more than half were younger than 6 months of age.
Local interactions between steady-state visually evoked potentials at nearby flickering frequencies
Authors: Liza Kumari , Ray Supratim
Published: January 2022

Steady-state visually evoked potentials (SSVEP) are widely used to index top-down cognitive processing in human electroencephalogram (EEG) studies. Typically, two stimuli flickering at different temporal frequencies (TFs) are presented, each producing a distinct response in the EEG at its flicker frequency. However, how SSVEP responses in EEG are modulated in the presence of a competing flickering stimulus just due to sensory interactions is not well understood. We have previously shown in local field potentials (LFP) recorded from awake monkeys that when two overlapping full screen gratings are counter-phased at different TFs, there is an asymmetric SSVEP response suppression, with greater suppression from lower TFs, which further depends on the relative orientations of the gratings (stronger suppression and asymmetry for parallel compared to orthogonal gratings). Here, we first confirmed these effects in both male and female human EEG recordings. Then, we mapped the response suppression of one stimulus (target) by a competing stimulus (mask) over a much wider range than the previous study. Surprisingly, we found that the suppression was not stronger at low frequencies in general, but systematically varied depending on the target TF, indicating local interactions between the two competing stimuli. These results were confirmed in both human EEG and monkey LFP and electrocorticogram (ECoG) data. Our results show that sensory interactions between multiple SSVEPs are more complex than shown previously and are influenced by both local and global factors, underscoring the need to cautiously interpret the results of studies involving SSVEP paradigms.
Establishment of a hypoxia ischemia reperfusion brain damage model in neonatal rats
Authors: Fu Xiaoqin , Zhang Tianlei , Lin Wei , Jiao Mengdie , Zhang Zhiwei , Geng Jiayi , Wei Qing , Qi Ailin , Kexin Lin , Zheng Yi hui , Fang Mingchu , Li Peijun , Lin Zhenlang
Published: January 2022

Objective

Rice-Vannucci model has been widely used as HIE (Hypoxic ischemic encephalopathy) animal model in the past forty years, but it does not mimic reperfusion injury that occurs during HIE. The aim of the present study was to establish a new neonatal rat model by simulating hypoxia ischemia reperfusion brain damage (HIRBD) through “common carotid artery (CCA) muscle bridge”.

Methods

Sixty 7-day-old male Sprague-Dawley rats were randomly assigned to group A (HIRBD groups, n=36), group B (Rice-Vannucci group, n=12), and group C (sham-operated group, n=12). Rats in group A were assigned to 3 subgroups (A1-A3, 12 animals/subgroup). Dynamic changes in cerebral blood flow (CBF) were evaluated by the laser speckle imaging system. The status of the CCA was observed under a stereomicroscope. Changes in body weight, gross morphology as well as pathological sections of brain tissue were examined to evaluate the feasibility of the model.

Results

The results indicated that CCA muscle bridge successfully blocked the CBF. CBF was restored after removal of the CCA muscle bridge in HIRBD groups. The CCA was in good condition after removing the muscle bridge, and blood supply was not affected. Changes in body weight, gross morphology and pathological sections of brain tissue indicated that ischemia reperfusion induced by the CCA muscle bridge method caused varying degrees of brain damage.

Conclusion

CCA muscle bridge method is effective for establishing a reliable, stable, and reproducible neonatal rat model for study of HIRBD.
Humanized CYP2C19 transgenic mouse as an animal model of cerebellar ataxia
Authors: Milosavljević Filip , Brusini Irene , Atanasov Andrea , Manojlović Marina , Novalen Maria , Vučić Marija , Dušić Zorana Oreščanin , Brkljačić Jelena , Miksys Sharon , Miljević Čedo , Nikolić Aleksandra , Blagojević Duško , Wang Chunliang , Damberg Peter , Pešić Vesna , Tyndale Rachel F , Ingelman-Sundberg Magnus , Jukić Marin M
Published: January 2022

Background

Animal models are essential for understanding etiology and pathophysiology of movement disorders. Previously, we have found that mice transgenic for the human CYP2C19 gene, expressed in the liver and developing brain, exhibit altered neurodevelopment associated with impairments of their motor function and emotionality.

Objectives

To characterize motoric phenotype of the CYP2C19 transgenic mice and validate its usefulness as an animal model of ataxia.

Methods

The rotarod and beam-walking tests were utilized to quantify the functional alterations induced by motoric phenotype. Dopaminergic system was assessed by tyrosine hydroxylase immunohistochemistry and by chromatographic quantification of the whole-brain dopamine levels. Beam-walking test was also repeated after the treatment with the dopamine receptor antagonists, ecopipam and raclopride. The volumes of 20 brain regions in the CYP2C19 transgenic mice and controls were quantified by 9.4T gadolinium-enhanced postmortem structural neuroimaging.

Results

CYP2C19 transgenic mice were found to exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips using the beam-walking test (p<0.0001, n=89); the phenotype was more pronounced in younger animals. Hyperdopaminergism was observed in the CYP2C19 mice; however, the motoric impairment was not ameliorated by dopamine receptor antagonists and there was also no midbrain dopamine neuron loss in CYP2C19 mice. However, in these mice, cerebellar volume was drastically decreased (11.8% [95%CI: −14.7, −9.0], q<0.0001, n=59), whereas a moderate decrease in hippocampal volume was observed (−4.2% [95%CI: −6.4%, −1.9%], q=0.015, n=59).

Conclusions

Humanized CYP2C19 transgenic mice exhibit altered motoric function and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development.
A striatal plasticity that supports the long-term preservation of motor function in Parkinsonian mice
Authors: Brague Joe C. , Seal Rebecca P.
Published: January 2022

Motor deficits of Parkinson’s disease (PD) such as rigidity, bradykinesia and akinesia result from a progressive loss of nigrostriatal dopamine neurons. No therapies exist that slow their degeneration and the most effective treatments for the motor symptoms: L-dopa -the precursor to dopamine, and deep brain stimulation can produce dyskinesias and are highly invasive, respectively. Hence, alternative strategies targeted to slow the progression or delay the onset of motor symptoms are still highly sought. Here we report the identification of a long-term striatal plasticity mechanism that delays for several months, the onset of motor deficits in a mouse PD model. Specifically, we show that a one-week transient daily elevation of midbrain dopamine neuron activity during depletion preserves the connectivity of direct but not indirect pathway projection neurons. The findings are consistent with the balance theory of striatal output pathways and suggest a novel approach for treating the motor symptoms of PD.
Efficient coding of natural scenes improves neural system identification
Authors: Qiu Yongrong , Klindt David A. , Szatko Klaudia P. , Gonschorek Dominic , Hoefling Larissa , Schubert Timm , Busse Laura , Bethge Matthias , Euler Thomas
Published: January 2022

Neural system identification aims at learning the response function of neurons to arbitrary stimuli using experimentally recorded data, but typically does not leverage normative principles such as efficient coding of natural environments. Visual systems, however, have evolved to efficiently process input from the natural environment. Here, we present a normative network regularization for system identification models by incorporating, as a regularizer, the efficient coding hypothesis, which states that neural response properties of sensory representations are strongly shaped by the need to preserve most of the stimulus information with limited resources. Using this approach, we explored if a system identification model can be improved by sharing its convolutional filters with those of an autoencoder which aims to efficiently encode natural stimuli. To this end, we built a hybrid model to predict the responses of retinal neurons to noise stimuli. This approach did not only yield a higher performance than the “stand-alone” system identification model, it also produced more biologically-plausible filters. We found these results to be consistent for retinal responses to different stimuli and across model architectures. Moreover, our normatively regularized model performed particularly well in predicting responses of direction-of-motion sensitive retinal neurons. In summary, our results support the hypothesis that efficiently encoding environmental inputs can improve system identification models of early visual processing.
Alignment of spatial genomics and histology data using deep Gaussian processes
Authors: Jones Andrew , Townes F. William , Li Didong , Engelhardt Barbara E.
Published: January 2022

Spatially-resolved genomic technologies have allowed us to study the physical organization of cells and tissues, and promise an understanding of the local interactions between cells. However, it remains difficult to precisely align spatial observations across slices, samples, scales, individuals, and technologies. Here, we propose a probabilistic model that aligns a set of spatially-resolved genomics and histology slices onto a known or unknown common coordinate system into which the samples are aligned both spatially and in terms of the phenotypic readouts (e.g., gene or protein expression levels, cell density, open chromatin regions). Our method consists of a two-layer Gaussian process: the first layer maps the observed samples’ spatial locations into a common coordinate system, and the second layer maps from the common coordinate system to the observed readouts. Our approach also allows for slices to be mapped to a known template coordinate space if one exists. We show that our registration approach enables complex downstream spatially-aware analyses of spatial genomics data at multiple resolutions that are impossible or inaccurate with unaligned data, including an analysis of variance, differential expression across the z-axis, and association tests across multiple data modalities.
Escherichia coli YigI is a conserved ɣ-proteobacterial acyl-CoA thioesterase permitting metabolism of unusual fatty acid substrates
Authors: Schmidt Michael , Proctor Theresa , Diao Rucheng , Freddolino Peter L.
Published: January 2022

Thioesterases play a critical role in metabolism, membrane biosynthesis, and overall homeostasis for all domains of life. In this present study, we characterize a putative thioesterase from Escherichia coli MG1655 and define its role as a cytosolic enzyme. Building on structure-guided functional predictions, we show that YigI is a medium- to -long chain acyl-CoA thioesterase that is involved in the degradation of conjugated linoleic acid (CLA) in vivo, showing overlapping specificity with two previously defined E. coli thioesterases TesB and FadM. We then bioinformatically identify the regulatory relationships that induce YigI expression, which include: an acidic environment, high oxygen availability, and exposure to aminoglycosides. Our findings define a role for YigI and shed light on why the E. coli genome harbors numerous thioesterases with closely related functions.

Importance

Previous research has shown that long chain acyl-CoA thioesterases are needed for E. coli to grow in the presence of carbon sources such as conjugated linoleic acid, but that E. coli must possess at least one such enzyme that had not previously been characterized. Building off of structure-guided function predictions, we showed that the poorly annotated protein YigI is indeed the previously unidentified third acyl CoA thioesterase. We found that the three potentially overlapping acyl-CoA thioesterases appear to be induced by non-overlapping conditions, and use that information as a starting point for identifying the precise functions catalyzed by each such thioesterase, which is an important prerequisite for their industrial application and for more accurate metabolic modeling of E. coli.
Sensitization of Chrysosplenetin against Artemisinin Resistant Plasmodium berghei K173 via Blocking Host ABC Transporters Potentially Mediated by NF-κB p52 or PXR/CAR Signaling Pathway
Authors: Zhao Xuesong , Ni Shanhong , Zhang Yuanyuan , Wu Xiuli , Yao Ying , Chen Jing
Published: January 2022

This study investigated if artemisinin-chrysosplenetin combination (ART-CHR) improved ART antimalarial efficacy against resistant Plasmodium berghei K173 via depressing host ABC transporter and potential molecular mechanism. Parasitaemia% and inhibition% were calculated and gene/protein expressions of ABC transporters or PXR/CAR/NF-κB p52 were detected by Western-blot and RT-qPCR. In vitro transcription of PXR/CAR was studied by dual-luciferase reporter assay. Our data indicated that ART-CHR improved ART efficacy against resistant parasites. P-gp inhibitor verapamil and CHR showed a stronger effect in killing resistant parasites while vehicle and Bcrp inhibitor novobiocin did not. ART activated intestinal ABCB1/ABCG2 and CHR inhibited them. ART decreased Bcrp protein whereas CHR increased it. ART ascended ABCC1/ABCC4/ABCC5 mRNA but ART-CHR descended them. CHR as well as rifampin (RIF) or 5-fluorouracil (5-FU) increased transcription levels of PXR/CAR while showed a versatile regulation on in vivo hepatic and enternal PXR/CAR in Mdr1a+/+ (WT) or Mdr1a-/- (KO) mice infected with sensitive or resistant parasites. Oppositely, hepatic and enteric N-κB p52 mRNA was conformably decreased in WT but increased in KO-resistant mice. NF-κB pathway should potentially involved in the mechanism of CHR on inhibiting ABC transporters and ART resistance while PXR/CAR play a more complicated role in this mechanism.
Diminished capacities to make treatment decision for COVID-19 vaccination in schizophrenia
Authors: Raffard Stephane , Bayard Sophie , Eisenblaetter Margot , Tattard Philippe , Attal Jerome , Laraki Yasmine , Capdevielle Delphine
Published: January 2022

Abstract

Recent evidence suggests that schizophrenia patients are at high risk for severe COVID-19 and should be prioritized for vaccination. However, impaired decision-making capacities could negatively affect the uptake of COVID-19 vaccination in this population. Competence to consent to COVID-19 vaccination was assessed in 80 outpatients with schizophrenia. Using the MacArthur Competence Assessment Tool for Treatment, 56.3% of the sample were classified as having diminished mental capacity. Poor performance was associated with lower vaccination rates, poorer cognition and higher level of psychotic symptoms. Developing interventions for enhancing informed consent for vaccination is urgent within this population.
Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection
Authors: Packer RJ , Shrine N , Hall R , Melbourne CA , Thompson R , Williams AT , Paynton ML , Guyatt AL , Lee PH , John C , Campbell A , Hayward C , de Vries M , Vonk JM , Davitte J , Hessel E , Michalovich D , Betts JC , Sayers I , Yeo A , Hall IP , Tobin MD , Wain LV
Published: January 2022

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (P<5×10−8) were investigated in additional independent studies, were fine-mapped, and putative causal genes identified by gene expression analysis. GWAS of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease amongst the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWAS).

Findings

From a GWAS of 9,714 cases and 48,471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the Human Leukocyte Antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and the FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2,203 cases and 17,627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino-acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations.

Interpretation

Novel signals at the FUT2 and mucin loci highlight mucin fucosylation as a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.