bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of Morphological Changes in the Inferior Turbinate After Le Fort I Osteotomy
Authors: Tomomatsu Nobuyoshi , Takahara Namiaki , Nakakuki Koichi , Kurasawa Yasuhiro , Iwasaki Takuya , Yoda Tetsuya
Published: June 2022

Objective:

There are cases in which patients complain of nasal obstruction after Le Fort I osteotomy, but the relationship with postoperative morphological changes in the nasal cavity, including the septum and inferior turbinate, is not clear.

Study Design:

The authors evaluated the three-dimensional relationship of the morphological changes in the inferior turbinate before and after surgery in 84 patients who underwent Le Fort I osteotomy. Three classifications were made according to superior amount of maxillary movement at the base of nasal cavity.

Results:

The high elevation group (4.0 mm or more) had 31 sides, the moderate elevation group had 93 sides, and the low elevation group (less than 2.0 mm) had 44 sides. The volume of inferior turbinate was 76.9 ± 12.8% of that before surgery in the high elevation group. The high- and moderate-elevation groups had significantly higher changes than the low elevation group, and the rate of contact between inferior turbinate and nasal cavity floor was 67.7%.

Conclusions:

After Le Fort I osteotomy, the volume of inferior turbinate tissue decreased in proportion to the amount of elevation of the maxilla. Although the soft tissue volume may be reduced due to adaptation of respiratory function, the inferior nasal passage was not completely ventilated in the high elevation group. If the elevation exceeds 4.0 mm counterclockwise with maxillary movement, it is necessary to consider the concomitant inferior turbinate resection because it may lead to nasal obstruction.
Personal Guide Assisted Orthognathic Surgery: Application of a T-shaped Tooth Bone Combined Supporting Osteotomy Guide Plate and Positioning Guide Plate
Authors: Wang Hang , Guan Qun Li , Yang Yin Hui , Wang Yao Zhong
Published: June 2022

The precise movement of the maxilla is particularly important for orthognathic surgery, especially for patients with maxillary segmentation. In this preliminary study, the authors present a new tooth bone combined with a supporting osteotomy guide and positioning guide to guide the osteotomy and reduction of the maxilla. Through our preoperative simulation and postoperative image fusion, the authors found that the overlapping area is more than 90%. According to compare of the virtual plans and the postoperative results based on distances from the maxillary land- marks to the horizontal plane, sagittal plane, and coronal plane, the surgical error was about 2mm. Our T-shaped guide provides a reliable method for patients with maxillary segmental osteotomy, which may be a useful alternative to the intermediate.
Repetitive transcranial magnetic stimulation decreased effortful frontal activity for shifting in patients with major depressive disorder
Authors: Shirakawa Yuka , Yamazaki Ryuichi , Kita Yosuke , Kitamura Yuzuki , Okumura Yasuko , Inoue Yuki , Matsuda Yuki , Kodaka Fumitoshi , Shigeta Masahiro , Kito Shinsuke
Published: June 2022

Patients with major depressive disorder (MDD) exhibit several clinical symptoms including difficulties in flexible thinking. Flexible thinking mainly relies on a cognitive ability called shifting; however, the mechanisms underlying shifting in patients with MDD have not yet been clarified. Therefore, we conducted a preliminary intervention study to clarify the association between depression and shifting ability. We examined the hemodynamic responses in the frontal regions during the shifting task using functional near-infrared spectroscopy (fNIRS) in 21 patients with MDD who were treated using high-frequency repetitive transcranial magnetic stimulation (rTMS). Behavioral performance on the shifting task did not change between pre- and posttreatments, whereas patients who responded well to rTMS treatment showed a significant decrease in hemodynamic responses posttreatment. On the other hand, the poor responders did not show significant changes in the hemodynamic responses between pre- and posttreatments. These results suggest that the good responders were successfully remedied with rTMS treatment and did not need effortful activity in frontal regions for shifting, which made their brain activity more efficient.
Adjustment to an Ostomy
Authors: Kittscha Julia , Fairbrother Greg , Bliokas Vida , Wilson Val
Published: June 2022

This integrative literature review summarizes recent literature relating to patient adjustment to stoma. The search strategy included 5 databases (CINAHL Plus, PsychINFO, Web of Science, Scopus, and MEDLINE); 65 articles meeting criteria were retrieved. Eleven were removed as duplicates, and a further 29 were removed when read in full, yielding 25 elements. Three were randomized controlled trials; 2 were prospective descriptive studies; 15 were cross-sectional descriptive studies; and 5 were qualitative studies. The quality of studies was evaluated using the Mixed Methods Appraisal Tool (MMAT). The calculated mean quality score was 97%, and no studies were excluded on quality grounds. Limited evidence suggests that adjustment occurs over time and provides some insight concerning how rehabilitation leads to resumption of an altered normality. Some evidence suggests that long-term adjustment is associated with demographic and pre- and postoperative factors. A knowledge gap was identified regarding the role of support groups, which in other fields has been shown to positively benefit psychological well-being. This review revealed a paucity of interventional studies seeking to test ways to address adjustment-related problems. Longitudinal studies are recommended as ostomy care nurses work to facilitate adjustment in the person with a stoma over time.
A new gecko from the earliest Eocene of Dormaal, Belgium: a thermophilic element of the ‘greenhouse world’
Authors: Čerňanský Andrej , Daza Juan D. , Smith Richard , Bauer Aaron M. , Smith Thierry , Folie Annelise
Published: June 2022

We here describe a new gekkotan lizard from the earliest Eocene (MP 7) of the Dormaal locality in Belgium, from the time of the warmest global climates of the past 66 million years (Myr). This new taxon, with an age of 56 Myr, together with indeterminate gekkotan material reported from Silveirinha (Portugal, MP 7) represent the oldest Cenozoic gekkotans known from Europe. Today gekkotan lizards are distributed worldwide in mainly warm temperate to tropical areas and the new gecko from Dormaal represents a thermophilic faunal element. Given the Palaeocene–Eocene thermal maximum at that time, the distribution of this group in such northern latitudes (above 50° North – the latitude of southern England) is not surprising. Although this new gekkotan is represented only by a frontal (further, dentaries and a mandibular fragment are described here as Gekkota indet. 1 and 2—at least two gekkotan species occurred in Dormaal), it provides a new record for squamate diversity from the earliest Eocene ‘greenhouse world’. Together with the Baltic amber gekkotanYantarogekko balticus, they document the northern distribution of gekkotans in Europe during the Eocene. The increase in temperature during the early Eocene led to a rise in sea level, and many areas of Eurasia were submerged. Thus, the importance of this period is magnified by understanding future global climate change.
Regolith flow on top-shaped asteroids
Authors: Banik Deepayan , Gaurav Kumar , Sharma Ishan
Published: June 2022

We develop a continuum framework of regolith flow on asteroids. We focus on top-shaped asteroids that may be taken as consisting of regolith lying on a solid core. Depth-averaging is employed to model the regolith flow, and effects due to the asteroid’s rotation and its complex gravity field are retained. Angular momentum conservation is invoked to couple regolith flow to the asteroid’s changing shape and spin. This framework is first used to explore the equilibrium of regolith as a function of its friction, and the asteroid’s shape and spin rate. Next, we study regolith flow on top-shaped spinning asteroids and find conditions for the regolith’s shedding or deposition. We also discuss how the regolith’s flow and the asteroid’s spin influence each other. Finally, as an application, we propose and investigate the following evolution history of Bennu: a fast spinning Bennu was slowed down by multiple, impact-induced global landslides to its present spin state. Regolith was shed if the spin was higher than a critical rate. Once the spin rate fell below this critical value, regolith flow from higher latitudes began depositing regolith at its equator, giving Bennu its distinctive shape.
Analysis of a model for surfactant transport around a foam meniscus
Authors: Grassia P.
Published: June 2022

A model developed by Bussonnière & Cantat [
1
] is considered for film-to-film surfactant transport around a meniscus within a foam, with the transport rate dependent upon film-to-film tension difference. The model is applied to the case of a five-film device, in which motors are used to compress two peripheral films on one side of a central film and to stretch another two peripheral films on the central film’s other side. Moreover, it is considered that large amounts of compression or stretch are imposed on peripheral films, and also that compression or stretch might be imposed at high velocities (relative to a characteristic velocity associated with physico-chemical properties of the foam films themselves). The actual strain that results on elements within each film might differ from the imposed strain, with the instantaneous film length coupled to the actual strain determining the amount of surfactant currently on each film (and hence also the amount of surfactant that has transferred either from or onto films). Quite distinct surfactant transport behaviour is predicted for the stretched film compared with the compressed one. In particular, when a film is stretched sufficiently at high enough velocity, surfactant flux onto it is predicted to become extremely ‘plastic’, increasing significantly.
Interfacial metric mechanics: stitching patterns of shape change in active sheets
Authors: Feng Fan , Duffy Daniel , Warner Mark , Biggins John S.
Published: June 2022

A flat sheet programmed with a planar pattern of spontaneous shape change will morph into a curved surface. Such metric mechanics is seen in growing biological sheets, and may be engineered in actuating soft matter sheets such as phase-changing liquid crystal elastomers (LCEs), swelling gels and inflating baromorphs. Here, we show how to combine multiple patterns in a sheet by stitching regions of different shape changes together piecewise along interfaces. This approach allows simple patterns to be used as building blocks, and enables the design of multi-material or active/passive sheets. We give a general condition for an interface to be geometrically compatible, and explore its consequences for LCE/LCE, gel/gel and active/passive interfaces. In contraction/elongation systems such as LCEs, we find an infinite set of compatible interfaces between any pair of patterns along which the metric is discontinuous, and a finite number across which the metric is continuous. As an example, we find all possible interfaces between pairs of LCE logarithmic spiral patterns. By contrast, in isotropic systems such as swelling gels, only a finite number of continuous interfaces are available, greatly limiting the potential of stitching. In both continuous and discontinuous cases, we find the stitched interfaces generically carry singular Gaussian curvature, leading to intrinsically curved folds in the actuated surface. We give a general expression for the distribution of this curvature, and a more specialized form for interfaces in LCE patterns. The interfaces thus also have rich geometric and mechanical properties in their own right.
The thermal niche and phylogenetic assembly of evergreen tree metacommunities in a mid-to-upper tropical montane zone
Authors: Das Arundhati Abin , Ratnam Jayashree
Published: June 2022

Frost and freezing temperatures have posed an obstacle to tropical woody evergreen plants over evolutionary time scales. Thus, along tropical elevation gradients, frost may influence woody plant community structure by filtering out lowland tropical clades and allowing extra-tropical lineages to establish at higher elevations. Here we assess the extent to which frost and freezing temperatures influence the taxonomic and phylogenetic structure of naturally patchy evergreen forests (locally known as
shola
) along a mid-upper montane elevation gradient in the Western Ghats, India. Specifically, we examine the role of large-scale macroclimate and factors affecting local microclimates, including
shola
patch size and distance from
shola
edge, in driving
shola
metacommunity structure. We find that the
shola
metacommunity shows phylogenetic overdispersion with elevation, with greater representation of extra-tropical lineages above 2000 m, and marked turnover in taxonomic composition of
shola
woody communities near the frost-affected forest edge above 2000 m, from those below 2000 m. Both minimum winter temperature and patch size were equally important in determining metacommunity structure, with plots inside very large
sholas
dominated by older tropical lineages, with many endemics. Phylogenetic overdispersion in the upper montane
shola
metacommunity thus resulted from tropical lineages persisting in the interiors of large closed frost-free
sholas,
where their regeneration niche has been preserved over time.
Social influence in adolescence as a double-edged sword
Authors: Molleman Lucas , Ciranka Simon , van den Bos Wouter
Published: June 2022

Social learning is fundamental to human development, helping individuals adapt to changing circumstances and cooperate in groups. During the formative years of adolescence, the social environment shapes people's socio-cognitive skills needed in adulthood. Although peer influence among adolescents is traditionally associated with risky and unruly conduct, with long-term negative effects on educational, economic and health outcomes, recent findings suggest that peers may also have a positive impact. Here, we present a series of experiments with 10–20-year-olds (
n
= 146) showing that positive and negative peer effects reflect a domain-general factor of social information use which declines during adolescence. Exposure to disobedient peers provoked rule breaking, and selfish peers reduced prosocial behaviour, particularly in early adolescence. However, compliant peers also promoted rule compliance and fair peers increased prosociality. A belief formation task further revealed that younger adolescents tend to assimilate social information, while older adolescents prioritize personal views. Our results highlight early adolescence as a key window for peer-based interventions to improve developmental trajectories.
Inbreeding depression and the probability of racing in the Thoroughbred horse
Authors: Hill Emmeline W. , Stoffel Martin A. , McGivney Beatrice A. , MacHugh David E. , Pemberton Josephine M.
Published: June 2022

Small effective population sizes and active inbreeding can lead to inbreeding depression due to deleterious recessive mutations exposed in the homozygous state. The Thoroughbred racehorse has low levels of population genetic diversity, but the effects of genomic inbreeding in the population are unknown. Here, we quantified inbreeding based on runs of homozygosity (ROH) using 297 K SNP genotypes from 6128 horses born in Europe and Australia, of which 13.2% were unraced. We show that a 10% increase in inbreeding (
F
ROH
) is associated with a 7% lower probability of ever racing. Moreover, a ROH-based genome-wide association study identified a haplotype on ECA14 which, in its homozygous state, is linked to a 32.1% lower predicted probability of ever racing, independent of
F
ROH
. The haplotype overlaps a candidate gene,
EFNA5
, that is highly expressed in cartilage tissue, which when damaged is one of the most common causes of catastrophic musculoskeletal injury in racehorses. Genomics-informed breeding aiming to reduce inbreeding depression and avoid damaging haplotype carrier matings will improve population health and racehorse welfare.
Sperm whales (Physeteroidea) from the Pisco Formation, Peru, and their trophic role as fat sources for late Miocene sharks
Authors: Benites-Palomino Aldo , Velez-Juarbe Jorge , Altamirano-Sierra Ali , Collareta Alberto , Carrillo-Briceño Jorge D. , Urbina Mario
Published: June 2022

Shark–cetacean trophic interactions, preserved as bite marks in the fossil record, mostly correspond to isolated or fragmentary findings that bear limited information about major trophic patterns or roles. Here, we provide evidence of focalized foraging by sharks in the form of tooth bite marks over physeteroids fossil bones from the late Miocene of Peru. These findings indicate that sharks were targeting the forehead of coeval physeteroids to actively feed on their lipid-rich nasal complexes. Miocene physeteroids displayed a broad diversity, including giant predatorial forms, small benthic foragers and suction feeders. Like their extant relatives, these animals exhibited enlarged fatty forehead organs responsible for their sound production capabilities, thus evolving taxon-specific cranial architecture. Bite marks are found on the cranial bones where these structures were attached, indicating that sharks actively targeted this region; but also, in areas that would only be accessible following the consumption of the surrounding soft tissues. The shape of the bite marks and their distribution suggests a series of consecutive scavenging events by individuals of different shark species. Similar bite patterns can be recognized on other Miocene physeteroids fossils from across the globe, suggesting that sharks actively exploited physeteroid carcasses as fat sources.
Decoding the dynamics of dental distributions: insights from shark demography and dispersal
Authors: Kim Sora L. , Yeakel Justin D. , Balk Meghan A. , Eberle Jaelyn J. , Zeichner Sarah , Fieman Dina , Kriwet Jürgen
Published: June 2022

Shark teeth are one of the most abundant vertebrate fossils, and because tooth size generally correlates with body size, their accumulations document the size structure of populations. Understanding how ecological and environmental processes influence size structure, and how this extends to influence these dental distributions, may offer a window into the ecological and environmental dynamics of past and present shark populations. Here, we examine the dental distributions of sand tigers, including extant
Carcharias taurus
and extinct
Striatolamia macrota
, to reconstruct the size structure for a contemporary locality and four Eocene localities. We compare empirical distributions against expectations from a population simulation to gain insight into potential governing ecological processes. Specifically, we investigate the influence of dispersal flexibility to and from protected nurseries. We show that changing the flexibility of initial dispersal of juveniles from the nursery and annual migration of adults to the nursery explains a large amount of dental distribution variability. Our framework predicts dispersal strategies of an extant sand tiger population, and supports nurseries as important components of sand tiger life history in both extant and Eocene populations. These results suggest nursery protection may be vital for shark conservation with increasing anthropogenic impacts and climate change.
Reindeer eyes seasonally adapt to ozone-blue Arctic twilight by tuning a photonic tapetum lucidum
Authors: Fosbury Robert A. E. , Jeffery Glen
Published: June 2022

Reindeer are the only mammal known to seasonally adapt their eyes to the extremely blue colour of the extended twilight that occupies a large part of the winter 24 h cycle in their Arctic habitat. We describe the atmospheric phenomenon that results in this extreme spectral change in light environment. Reflectance spectroscopy is used to characterize the photonic nanostructure that generates the reflective region of the tapetum lucidum behind the retina. A model is proposed to explain the reversible reformatting of the reflector by seasonal changes in the volume of interstitial fluid within the two-dimensional photonic crystal of parallel collagen fibrils. This model is tested by allowing slow evaporation of the fluid from both summer and winter tapetum surfaces while monitoring changes in the reflectance spectrum. Coupled variations in the spacing and the degree of order of the fibril packing can transform the typical gold-turquoise colour of such a tapetal reflector to a deep blue that matches the peak spectral irradiance of twilight. The mechanism we describe might be applied by other animals with similar tapeta that experience prolonged changes in light environment.
Chronic inflammation suppresses del(5q)-like MDS HSCs via p53
Authors: Muto Tomoya , Walker Callum S. , Choi Kwangmin , Niederkorn Madeline , Ishikawa Chiharu , Varney Melinda , Hueneman Kathleen , Starczynowski Daniel T.
Published: June 2022

Inflammation is associated with the pathogenesis of Myelodysplastic syndromes (MDS). Emerging evidence suggests that MDS hematopoietic stem and progenitor cells (HSPCs) exhibit an altered response to systemic low-grade inflammation, which contributes to their competitive advantage over wild-type HSPCs and ensuing hematopoietic defects. Deletion of the long arm of chromosome 5 (del(5q)) is the most common chromosomal abnormality in patients with MDS. Although this subtype of MDS contains several haploinsufficient genes that directly impact innate immune signaling, the effects of an inflammatory milieu on del(5q) MDS HSPCs remains poorly defined. Utilizing a model of del(5q)-like MDS, wherein two 5q genes, miR-146a and TIFAB, are deleted, we found that chronic low-grade inflammation impaired the function of del(5q)-like MDS HSPCs and contributed to a more severe disease. The del(5q)-like MDS HSPCs exposed to chronic inflammation became less quiescent, but without changes in cell viability. In response to inflammation, mouse and human del(5q) MDS HSPCs activated a partial p53 response. The impaired function and reduced cellular quiescence of del(5q) MDS HSPCs exposed to inflammation could be restored by deletion of p53. Since TP53 mutations are highly enriched in del(5q) AML patients following an initial MDS diagnosis, increased p53 activation in del(5q) MDS HSPCs due to inflammation may create a selective pressure for genetic inactivation of p53. These findings uncover the contribution of systemic inflammation on dyshematopoiesis in del(5q) MDS and provide a potential explanation for acquired p53 mutations in myeloid malignancies with del(5q).
ADGRG6 promotes adipogenesis and is involved in sex-specific fat distribution
Authors: Nguyen Hai P. , Ushiki Aki , Sheng Rory , Biellak Cassidy , An Kelly , Choquet Hélène , Hoffman Thomas J. , Gray Ryan S. , Ahituv Nadav
Published: June 2022

Fat distribution differences between males and females are a major risk factor for metabolic disease, but their genetic etiology remains largely unknown. Here, we establish ADGRG6 as a major factor in adipogenesis and gender fat distribution. Deletion of ADGRG6 in human adipocytes impairs adipogenesis due to reduced cAMP signaling. Conditionally knocking out Adgrg6 in mouse adipocytes or deleting an intronic enhancer associated with gender fat distribution generates males with female-like fat deposition, which are protected against high-fat-diet-induced obesity and have improved insulin response. To showcase its therapeutic potential, we demonstrate that CRISPRi targeting of the Adgrg6 promoter or enhancer prevents high-fat-diet-induced obesity. Combined, our results associate ADGRG6 as a gender fat distribution gene and highlight its potential as a therapeutic target for metabolic disease.
Extracellular vesicles carrying HIV-1 Nef induce trained immunity in myeloid cells
Authors: Dubrovsky Larisa , Brichacek Beda , Prashant N.M. , Pushkarsky Tatiana , Mukhamedova Nigora , Dragoljevic Dragana , Fitzgerald Michael , Horvath Anelia , Murphy Andrew J. , Sviridov Dmitri , Bukrinsky Michael I
Published: June 2022

Persistent inflammation is a hallmark of HIV infection and is not reversed after suppression of viral replication by anti-retroviral therapy (ART). One explanation for chronic inflammation in ART-treated HIV-infected individuals is hyperreactivity of the myeloid cells due to a phenomenon called ‘trained immunity’. Here, we demonstrate that human monocyte derived macrophages originating from monocytes initially treated with extracellular vesicles containing HIV-1 protein Nef (exNef), but differentiating in the absence of exNef, released increased levels of pro-inflammatory cytokines after lipopolysaccharide stimulation. This effect was associated with epigenetic changes related to inflammation and cholesterol metabolism pathways, upregulation of the lipid rafts, and was blocked by methyl-β-cyclodextrin, statin, and inhibitor of activity of lipid raft-associated receptor IGF1R. Bone marrow-derived macrophages from exNef-injected mice had higher abundance of lipid rafts and produced elevated levels of TNFα. These phenomena are consistent with trained immunity and may contribute to persistent inflammation and co-morbidities in HIV-infected individuals.
The value of volunteer surveillance for the early detection of biological invaders
Authors: van den Bosch Frank , McRoberts Neil , Bourhish Yoann , Parnell Stephen , Hassall Kirsty L.
Published: June 2022

Early detection of invaders requires finding small numbers of individuals across large landscapes. It has been argued that the only feasible way to achieve the sampling effort needed for early detection of an invader is to involve volunteer groups (citizen scientists, passive surveyors, etc.). A key concern is that volunteers may have a considerable false-positive and false-negative rate. The question then becomes whether verification of a report from a volunteer is worth the effort. This question is the topic of this paper.

We show that the maximum plausible incidence when the expert samples on its own, , and the maximum plausible incidence when the expert only verifies cases reported by the volunteer surveyor to be infected, , are related as

Where θfp and θfn are the false positive and false negative rate of the volunteer surveyor, respectively. We also show that the optimal monitoring programme consists of verifying only the cases reported by the volunteer surveyor if

Where TN is the cost of a sample taken by the expert and TX is the cost of an expert verifying a case reported by a volunteer surveyor.
Correlated responses to experimental evolution of increased post-infection survival in Drosophila melanogaster: Life-history trade-offs and reaction to novel stressors
Authors: Singh Aparajita , Basu Aabeer , Hegde Tejashwini , Shit Biswajit , Bansal Nitin , Chauhan Ankita , Prasad Nagaraj Guru
Published: June 2022

Evolution of increased immune defence is often limited by costs: correlated changes in other traits (viz. life-history traits) that otherwise reduce the fitness of the host organisms. Experimental evolution studies are useful for understanding the evolution of immune function, and correlated changes in other traits. We experimentally evolved replicate Drosophila melanogaster populations to better survive infection challenge with an entomopathogenic bacteria, Enterococcus faecalis. Within 35 generations of forward selection, selected populations showed marked increase in post-infection survival compared to ancestrally paired controls. We next measured various life-history traits of these populations. Our results show that the selected populations do not differ from control populations for larval development time and body weight at eclosion. No difference is also observed in case of fecundity and longevity (following the acute phase of infection), either when the flies are subjected to infection or when the flies were uninfected; although infected flies from all populations die much earlier compared to uninfected flies. Selected flies and control flies are also equally good at surviving abiotic stressors (starvation and desiccation), although infected flies from all populations are more susceptible to stress than uninfected flies. Therefore, we conclude that (a) D. melanogaster populations can rapidly evolve to be more immune to infection with E. faecalis; (b) evolution of increased defence against E. faecalis entails no life-history cost for the hosts; and (c) evolving defence against a biotic threat (pathogen) does not make flies more resistant to abiotic stressors.
Tailoring electrode surface charge to achieve discrimination and quantification of chemically similar small molecules with electrochemical aptamers
Authors: Kesler Vladimir , Fu Kaiyu , Chen Yihang , Park Chan Ho , Eisenstein Michael , Murmann Boris , Soh H. Tom
Published: June 2022

Electrochemical biosensors based on structure-switching aptamers offer many advantages because they can operate directly in complex samples and offer the potential to integrate with miniaturized electronics. Unfortunately, these biosensors often suffer from cross-reactivity problems when measuring a target in samples containing other chemically similar molecules, such as precursors or metabolites. While some progress has been made in selecting highly specific aptamers, the discovery of these reagents remains slow and costly. In this work, we demonstrate a novel strategy to distinguish molecules with miniscule difference in chemical composition (such as a single hydroxyl group) – with cross reactive aptamer probes - by tuning the charge state of the surface on which the aptamer probes are immobilized. As an exemplar, we show that our strategy can distinguish between DOX and many structurally similar analytes, including its primary metabolite doxorubicinol (DOXol). We then demonstrate the ability to accurately quantify mixtures of these two molecules based on their differential response to sensors with different surface-charge properties. We believe this methodology is general and can be extended to a broad range of applications.
Explanation of Hand, Foot, and Mouth Disease Cases in Japan Using Google Trends Before and During the COVID-19: Infodemiology Study
Authors: Niu Qian , Liu Junyu , Zhao Zixi , Onishi Miyu , Kawaguchi Asuka , Bandara Anuradhi , Harada Keiko , Aoyama Tomoki , Nagai-Tanima Momoko
Published: June 2022

Background

COVID-19 pandemic affected common disease infections, while the impact on hand, foot, and mouth disease (HFMD) is unclear. Google Trends data is beneficial in approximately real-time statistics and easily accessed, expecting to be used for infection explanation from information-seeking behavior perspectives. We aimed to explain HFMD cases before and during COVID-19 using Google Trends data.

Methods

HFMD cases were obtained from the National Institute of Infectious Disease, and Google search data from 2009 to 2021 was downloaded using Google Trends in Japan. Pearson correlation coefficients were calculated between HFMD cases and the search topic “HFMD” from 2009 to 2021. Japanese tweets containing “HFMD” were retrieved to select search terms for further analysis. Search terms were retained with counts larger than 1000 and belonging to ranges of infection sources, susceptible sites, susceptible populations, symptoms, treatment, preventive measures, and identified diseases. Cross-correlation analyses were conducted to detect lag changes between HFMD cases and HFMD search terms before and during COVID-19. Multiple linear regressions with backward elimination processing were used to identify the most significant terms for HFMD explanation.

Results

HFMD cases and Google search volume peaked around July in most years without 2020 and 2021. The search topic “HFMD” presented strong correlations with HFMD cases except in 2020 when COVID-19 outbroke. In addition, differences in lags for 73 (72.3%) search terms were negative, might indicating increasing public awareness of HFMD infections during the COVID-19 pandemic. Results of multiple linear regression demonstrated that significant search terms contained the same meanings but expanded informative search content during COVID-19.

Conclusions

Significant terms for HFMD cases explanation before and during COVID-19 were different. The awareness of HFMD infection in Japan may improve during the COVID-19 pandemic. Continuous monitoring is important to promote public health and prevent resurgence. Public interest reflected in information-seeking behavior can be helpful for public health surveillance.
Differential migration mechanics and immune responses of glioblastoma subtypes
Authors: Shamsan Ghaidan A. , Liu Chao J. , Braman Brooke C. , Rathe Susan K. , Sarver Aaron L. , Ghaderi Nima , McMahon Mariah M. , Klank Rebecca L. , Tschida Barbara R. , McFarren S. Joey , Rosato Pamela C. , Masopust David , Sarkaria Jann N. , Clark H. Brent , Rosenfeld Steven S. , Largaespada David A. , Odde David J.
Published: June 2022

Glioblastoma remains a deadly cancer driven by invasion of tumor cells into the brain. Transcriptomic analyses have revealed distinct molecular subtypes, but mechanistic differences that explain clinical differences are not clear. Here, we show that, as predicted by the motor-clutch model for cell migration, mesenchymal glioma cells are more spread, generate larger traction forces, and migrate faster in brain tissue compared to proneural cells. Despite their fast migration and comparable proliferation rate in vitro, mice with mesenchymal tumors live longer than mice with proneural tumors, which was correlated with an immune response in the mesenchymal mice that included T cell-mediated killing of cancer cells, similar to human tumors. Thus, mesenchymal tumors have aggressive migration, but are relatively immunologically ‘hot’ which suppresses net proliferation. These two features counteract each other and may explain the lack of a strong survival difference between subtypes clinically, while also opening up new opportunities for subtype-specific therapies.
Speech intelligibility changes the temporal evolution of neural speech tracking
Authors: Chen Ya-Ping , Schmidt Fabian , Keitel Anne , Rösch Sebastian , Hauswald Anne , Weisz Nathan
Published: June 2022

Listening to speech with poor signal quality is challenging. Neural speech tracking of degraded speech has been used to advance the understanding of how brain processes and speech intelligibility are interrelated, however the temporal dynamics of neural speech tracking are not clear. In the present MEG study, we thereby exploited temporal response functions (TRFs) and generated signal-degraded speech to depict the temporal evolution of speech intelligibility modulation on neural speech tracking. In addition, we inter-related facets of neural speech tracking (e.g., speech envelope reconstruction, speech-brain coherence, and components of broadband coherence spectra) to endorse our findings in TRFs. Our TRF analysis yielded marked temporally differential effects of vocoding: reduction of intelligibility went along with large increases of early peak responses (∼50-110 ms, M50TRF), but strongly reduced responses around 175-230 ms (M200TRF). For the late responses 315-380 ms (M350TRF), the maximum response occurred for degraded speech that was still comprehensible then declined with reduced intelligibility. Furthermore, we related the TRF components to our other neural “tracking“ measures and found that M50TRF and M200TRF play a differential role in the shifting center frequency of the broadband coherence spectra. Overall, our study highlights the importance of time-resolved computation and parametrization of coherence spectra on neural speech tracking and provides a better understanding of degraded speech processing.

Highlights

We use MEG to show that speech intelligibility differentially impacts the temporal evolution of neural speech tracking.

TRF responses around 200 ms show the strongest relationship with behaviour.

Relating TRF effects to parameterized coherence spectra using FOOOF suggests that M50TRF and M200TRF reflect shifts in which speech features are tracked over time.
On the similarities of representations in artificial and brain neural networks for speech recognition
Authors: Wingfield Cai , Zhang Chao , Devereux Barry , Fonteneau Elisabeth , Thwaites Andrew , Liu Xunying , Woodland Phil , Marslen-Wilson William , Su Li
Published: June 2022

How the human brain supports speech comprehension is an important question in neuroscience. Studying the neurocomputational mechanisms underlying human language is not only critical to understand and develop treatments for many human conditions that impair language and communication but also to inform artificial systems that aim to automatically process and identify natural speech. In recent years, intelligent machines powered by deep learning have achieved near human level of performance in speech recognition. The fields of artificial intelligence and cognitive neuroscience have finally reached a similar phenotypical level despite of their huge differences in implementation, and so deep learning models can—in principle—serve as candidates for mechanistic models of the human auditory system. Utilizing high-performance automatic speech recognition systems, and advanced noninvasive human neuroimaging technology such as magnetoencephalography and multivariate pattern-information analysis, the current study aimed to relate machine-learned representations of speech to recorded human brain representations of the same speech. In one direction, we found a quasi-hierarchical functional organisation in human auditory cortex qualitatively matched with the hidden layers of deep neural networks trained in an automatic speech recognizer. In the reverse direction, we modified the hidden layer organization of the artificial neural network based on neural activation patterns in human brains. The result was a substantial improvement in word recognition accuracy and learned speech representations. We have demonstrated that artificial and brain neural networks can be mutually informative in the domain of speech recognition.

Author summary

The human capacity to recognize individual words from the sound of speech is a cornerstone of our ability to communicate with one another, yet the processes and representations underlying it remain largely unknown. Software systems for automatic speech-to-text provide a plausible model for how speech recognition can be performed. In this study, we used an automatic speech recogniser model to probe recordings from the brains of participants who listened to speech. We found that the parts of the dynamic, evolving representations inside the machine system were a good fit for representations found in the brain recordings, both showing similar hierarchical organisations. Then, we observed where the machine’s representations diverged from the brain’s, and made experimental adjustments to the automatic recognizer’s design so that its representations might better fit the brain’s. In so doing, we substantially improved the recognizer’s ability to accurately identify words.
Newcastle disease burden in Nepal and efficacy of Tablet I-2 vaccine in commercial and backyard poultry production
Authors: Napit Rajindra , Poudel Ajit , Pradhan Saman M. , Manandhar Prajwol , Ghaju Sajani , Sharma Ajay N. , Joshi Jyotsna , Tha Suprim , Dhital Kavya , Rajbhandari Udaya , Basnet Amit , Rajbhandari Rajesh M. , Schwind Jessica S. , Karmacharya Dibesh B.
Published: June 2022

Poultry (Gallus domesticus) farming plays an important role as an income generating enterprise in a developing country like Nepal, contributing more than 4% to the national GDP. It is also one of the major sources of protein for growing population. Newcastle Disease (ND) is a major poultry disease affecting both commercial and backyard poultry production worldwide. There were more than 90 reported cases of ND outbreaks in Nepal in 2018, with over 74,986 birds being affected. ND might be responsible for over 7% of total poultry mortality in the country. Recent outbreak of ND in 2021 affected many farms throughout Nepal, and caused massive poultry production loss. ND is caused by a single stranded RNA virus which presents very similar clinical symptoms as Influenza A (commonly known as Bird flu), adding much complexity to clinical disease identification and intervention.

We conducted a nationwide ND and Influenza A prevalence study, collecting samples from commercial and backyard poultry farms from across the major poultry production hubs of Nepal, and conducted both serological and molecular assessments-giving us disease exposure history and identification of floating strains of ND Virus (NDV). Of 600 commercial chickens tested from various farms, both NDV (n=381, 64%) and IA (n=125, 21%) antibodies were detected in the majority of the samples. In backyard chicken (n=108, 39 farms), sero-prevalence was also relatively high for both NDV (n=38, 35%) and IA (n=17, 16%). Out of the 40 commercial farms, majority had detectable NDV (n=31, 78%) and IA (n=15, 38%) virus present. In backyard farms (n=36), we also detected NDV (n=6, 16%) and IA (n=1, 3%) virus. We Genotyped (strain) detected NDV, and found Genotype II to be present in most of the commercial farms (which might be coming from live vaccine usage) and Genotype I in some backyard poultry samples. The identified Genotype I strain is reported for the first time, and hence could be an endemic NDV strain found in Nepal. Our 2021 ND outbreak investigation identified Genotype VII c as the causative strain.

Additionally, we have developed a thermostable I-2 NDV vaccine (Ranigoldunga™) in tablet formulation and tested on various (mixed) breeds of chicken (G. domesticus). This vaccine seems to be highly effective against NDV, including a virulent 2021 outbreak strain (Genotype VII c). The I-2 Tablet ND vaccine showed more than 85% efficacy when administered either ocularly or in water, and has a stability of 30 days in room temperature.
Success probability of high-affinity DNA aptamer generation by genetic alphabet expansion
Authors: Kimoto Michiko , Tan Hui Pen , Sing Tan Yaw , Mohd Mislan Nur Afiqah Binte , Hirao Ichiro
Published: June 2022

Nucleic acid aptamers as antibody alternatives bind specifically to target molecules. These aptamers are generated by isolating candidates from libraries with random sequence fragments, through an evolutionary engineering system. We recently reported a high-affinity DNA aptamer generation method that introduces unnatural bases (UBs) as a fifth letter into the library, by genetic alphabet expansion. By incorporating hydrophobic UBs, the affinities of DNA aptamers to target proteins are increased over 100-fold, as compared to those of conventional aptamers with only the natural four letters. However, there is still plenty of room for improvement of the methods for routinely generating high-affinity UB-containing DNA (UB-DNA) aptamers. The success probabilities of the high-affinity aptamer generation depend on the existence of the aptamer candidate sequences in the initial library. We estimated the success probabilities by analysing several UB-DNA aptamers that we generated, as examples. In addition, we investigated the possible improvement of conventional aptamer affinities by introducing one UB at specific positions. Our data revealed that UB-DNA aptamers adopt specific tertiary structures, in which many bases including UBs interact with target proteins for high affinity, suggesting the importance of the UB-DNA library design.
Hypoxia causes pancreatic β-cell dysfunction by activating a transcriptional repressor BHLHE40
Authors: Tsuyama Tomonori , Sato Yoshifumi , Yoshizawa Tatsuya , Matsuoka Takaaki , Yamagata Kazuya
Published: June 2022

Hypoxia can occur in pancreatic β-cells in type 2 diabetes. Although hypoxia exerts deleterious effects on β-cell function, the associated mechanisms are largely unknown. Here, we show that the transcriptional repressor basic helix-loop-helix family member e40 (BHLHE40) is highly induced in hypoxic mouse and human β-cells and suppresses insulin secretion. Conversely, BHLHE40 deficiency in hypoxic MIN6 cells or in the β-cells ofob/obmice reversed the insulin secretion. Mechanistically, BHLHE40 represses expression ofMafa, which encodes the transcription factor musculoaponeurotic fibrosarcoma oncogene family A (MAFA), by attenuating binding of pancreas/duodenum homeobox protein 1 (PDX1) to its enhancer region. Impaired insulin secretion in hypoxic β-cells was recovered by MAFA expression. Collectively, this work identifies BHLHE40 as a key hypoxia-induced transcriptional repressor in β-cells and its implication in the β-cell dysfunction in type 2 diabetes.
A mixed methods exploratory study of family experiences of anticipatory injectable medicines at home: It's a really good idea but it's just implementing it.
Authors: Faull christina , Pilsworth Alison , Mcevoy Kerri , Hughes Helen , Bleazard Lucy , Patterson Anne
Published: June 2022

Objectives To explore the experiences of bereaved family of anticipatory (JIC) injectable medications for symptom management and to identify ways to improve practice. Methods A single site, mixed methods study in two phases. A postal questionnaire sent to 100 family carers (FCs) achieved a 38% response rate of whom 79% volunteered for an interview and 14 were sampled to reflect use of medication, concerns and relationship with the deceased. The descriptively analysed quantitative data and thematically analysed qualitative data were triangulated Results The vast majority (89%) perceived benefits to JIC medications but 18% of these described mixed feelings and issues, related to the context of dying and the responsibility for powerful medications. Communication was a key theme and some FCs described emotional impacts, misinterpretation of the intent of the medications and many desired more information to equip and empower them. There were diverse experiences of obtaining medications and guidance on storage and disposal resulting in distressing experiences. Whilst most described good experiences of care and effectiveness of treatment 50% experienced delay in attendance of staff to administer medication. The majority of those interviewed would have been prepared to administer injections and the key driver for this was their experience of delays in resolving symptoms. Conclusions FCs were generally positive about JIC medicines and care received but they had also been a source of distress and anxiety and people wanted more information and empowerment. Professional support had often been difficult to access at the point at which it had been needed.