bluuebunny/crossref_metadata_2025 huggingface dataset:
The ‘branding’ of IAPT and private cognitive behaviour therapy services in England
Authors: Veale David , Bowles Chloe , Avramescu Mara
Published: December 2021

Over the past decade, provision of cognitive behaviour therapy has expanded massively in the UK, both within the private sector and through the Improving Access to Psychological Therapies (IAPT) programme. Our aim in this study was to explore and compare the brand names adopted by IAPT and private CBT services. We obtained the names of all the IAPT and private services in England and created a word cloud for each sector. There was no significant difference in the proportion of services that adopted a brand name (72% of IAPT services vs 67% of the private services). In those with a brand name, IAPT services were significantly more likely than private services to contain positive words, and to have a theme of togetherness and collaboration. However, private services were more likely to include a psychological therapy in their name and have a theme of efficacy compared with IAPT. The most common keywords in IAPT services were ‘talking’ and ‘thinking’. IAPT services use a variety of euphemisms such as ‘talking’ for a psychological therapy. There is no theme for ‘doing’ in the IAPT or private services, despite behavioural interventions being one of the most common therapeutic components. The brand names in IAPT are overwhelmingly positive and convey the hope of a good outcome. They do not include the experience of difficult emotions, such as sadness and fear during therapy. We found just one private service that evoked the history of CBT named after Vic Meyer. Perhaps we will have some Clark and Layard centres in the years to come!

Key learning aims

After reading this paper, the reader should:

(1)

Recognise the importance of a brand name in shaping service user expectations.

(2)

Understand the differences between how private CBT and IAPT services present themselves to the public.

(3)

Recognise the omission of words conveying an active ‘doing’ theme in IAPT and private CBT service names.
From Subduction to LLSVP: The Core‐Mantle Boundary Heterogeneities Across North Atlantic
Authors: Fan An , Sun Xinlei , Zhang Zhou , Zhang Peng , Zong Jianye
Published: December 2021

The distribution of Ultra‐low Velocity Zones (ULVZs) is generally associated with the Large Low Shear Velocity Zones (LLSVPs). However, subducted slabs may be important for the characteristics of the ULVZs as well. Here we use ScS precursor (SdS) and postcursor (ScscS) phases, as well as Scd phases recorded by USArray to investigate the lowermost mantle structure across the north Atlantic, which spans the African LLSVP and the subducted Farallon slab. Our results show a ULVZ located near the edge of the African LLSVP, with thicknesses ranging from 11–16 km and S wave velocity reductions of 12%–24%. At the same time, a thin high‐velocity layer (HVL) with thicknesses of 20–30 km, Vs increases of 3%–4%, is also detected outside the LLSVP in the northwest region. Further west there is a clear D" layer at 250 km above the core mantle boundary (CMB), overlaid by a low velocity layer with Vs reduction of 3%. This transition profile from D" to HVL to ULVZ provides an excellent opportunity for us to understand the heterogeneities near the CMB region. We propose that interactions between the subducted Farallon slab with ambient mantle and LLSVP material, together with thermal effects, may result in this transition between different seismic structures along the CMB.
Statistical Characteristics of the Low‐Latitude E‐Region Irregularities Observed by the HCOPAR in South China
Authors: Yan Chunxiao , Chen Gang , Wang Zhihua , Zhang Min , Zhang Shaodong , Li Yaxian , Huang Kaiming , Gong Wanlin , He Zhiqiu
Published: December 2021

Statistical characteristics of the E‐region irregularities observed by the HCOPAR in the low‐latitudes of China are presented and analyzed. The data come from the observations between September 2015 and August 2016. Benefit from the high data acquisition rate and the relatively high time and height resolutions, we have found many interesting and unreported details in the statistical characteristics of the E‐region irregularities. The lowest occurrence rate of the E‐region irregularities appears at around sunrise and another low rate appears at around noon. The daytime irregularities are generated in the region where the zonal winds turn around at the E‐region altitudes. There is clear boundary between the irregularities occurring in the morning and afternoon. The nighttime irregularities appear at higher altitudes with steeper background plasma density gradient. The higher tidal amplitude is suggested to increase the irregularity occurrence rate and the greater solar radiation is suggested to decrease it. The steep plasma density gradient in the night may be the main reason for the nighttime irregularities through gradient drift instability. The turning around of the zonal wind field is considered to generate the irregularities in the day through Kelvin‐Helmholtz instability.
A Meta‐Analysis of Fault Slip Rates Across the Central Apennines
Authors: Carafa M. M. C. , Di Naccio D. , Di Lorenzo C. , Kastelic V. , Bird P.
Published: December 2021

Several methods such as paleoseismic trenching, mapping of offset geomorphic markers, and dating of scarp profiles have been used to determine slip rates of normal faults in the central Apennines. Combining measurements obtained with different methods remains challenging because non‐tectonic processes can introduce noise or spurious signals that are elusive to quantify, and these influence slip rate estimates. To this end, we meta‐analyzed throw measurements with associated ages collected in the central Apennines with several methods to quantify such erratic fluctuations and method‐related variances. We show that throw rates are overdispersed with respect to nominal uncertainties in throw and age; therefore, they are commonly affected by unmodeled noise processes. After comparing throw rate distributions sampling the same faults with different techniques, no clear spatio‐temporal patterns appear, but only quasi‐random noise. Assuming that field investigators sampled real tectonic features (i.e., fault scarps), we find that such erratic throw rates indicate total uncertainties are two to three times greater than the stated observation uncertainties. In this situation, a simple and robust null hypothesis is appropriate. We propose that most faults should be assumed to have uniform throw rate along their traces, except for possible tapering near unconnected ends. We also propose that models in which throw rates are time‐dependent (within the last 25 kyr) are not yet justified. Then, relying on the estimated total uncertainties, we determine the most probable long‐term fault throw rate for each active fault by combining different throw‐rate probability density functions.
Soil minerals affect taxon-specific bacterial growth
Authors: Finley Brianna K , Mau Rebecca L , Hayer Michaela , Stone Bram W , Morrissey Ember M , Koch Benjamin J , Rasmussen Craig , Dijkstra Paul , Schwartz Egbert , Hungate Bruce A
Published: December 2021

Secondary minerals (clays and metal oxides) are important components of the soil matrix. Clay minerals affect soil carbon persistence and cycling, and they also select for distinct microbial communities. Here we show that soil mineral assemblages—particularly short-range order minerals—affect both bacterial community composition and taxon-specific growth. Three soils with different parent material and presence of short-range order minerals were collected from ecosystems with similar vegetation and climate. These three soils were provided with 18O-labeled water and incubated with or without artificial root exudates or pine needle litter. Quantitative stable isotope probing was used to determine taxon-specific growth. We found that the growth of bacteria varied among soils of different mineral assemblages but found the trend of growth suppression in the presence of short-range order minerals. Relative growth of bacteria declined with increasing concentration of short-range order minerals between 25–36% of taxa present in all soils. Carbon addition in the form of plant litter or root exudates weakly affected relative growth of taxa (p = 0.09) compared to the soil type (p < 0.01). However, both exudate and litter carbon stimulated growth for at least 34% of families in the soils with the most and least short-range order minerals. In the intermediate short-range order soil, fresh carbon reduced growth for more bacterial families than were stimulated. These results highlight how bacterial-mineral-substrate interactions are critical to soil organic carbon processing, and how growth variation in bacterial taxa in these interactions may contribute to soil carbon persistence and loss.
Social buffering of human fear is shaped by gender, social concern, and the presence of real vs virtual agents
Authors: Qi Yanyan , Bruch Dorothée , Krop Philipp , Herrmann Martin J. , Latoschik Marc E. , Deckert Jürgen , Hein Grit
Published: December 2021

The presence of a partner can attenuate physiological fear responses, a phenomenon known as social buffering. However, not all individuals are equally sociable. Here we investigated whether social buffering of fear is shaped by sensitivity to social anxiety (social concern) and whether these effects are different in females and males. We collected skin conductance responses (SCRs) and affect ratings of female and male participants when they experienced aversive and neutral sounds alone (alone treatment) or in the presence of an unknown person of the same gender (social treatment). Individual differences in social concern were assessed based on a well-established questionnaire. Our results showed that social concern had a stronger effect on social buffering in females than in males. The lower females scored on social concern, the stronger the SCRs reduction in the social compared to the alone treatment. The effect of social concern on social buffering of fear in females disappeared if participants were paired with a virtual agent instead of a real person. Together, these results showed that social buffering of human fear is shaped by gender and social concern. In females, the presence of virtual agents can buffer fear, irrespective of individual differences in social concern. These findings specify factors that shape the social modulation of human fear, and thus might be relevant for the treatment of anxiety disorders.
The MYEOV-MYC association promotes oncogenic miR-17/93-5p expression in pancreatic ductal adenocarcinoma
Authors: Shen Hongzhang , Ye Fuqiang , Xu Dongchao , Fang Liangliang , Zhang Xiaofeng , Zhu Juanjuan
Published: December 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy worldwide. As metastasis and malignant progression are primarily responsible for the poor clinical outcomes of PDAC, identifying key genes involved in these processes and the underlying molecular mechanisms of PDAC is vital. In this study, by analyzing TCGA PDAC data and matched GTEx data, we found that MYEOV expression is associated with poor survival in PDAC patients and higher in carcinoma tissues than in healthy tissues. Elevated levels of MYEOV led to enhanced cell proliferation, invasion and migration in vitro and in vivo. Transcriptome analysis results revealed that MYEOV mediates global alterations in gene expression profiles in PDAC cells. MiRNA-seq analysis showed that MYEOV regulates the expression levels of miR-17-5p and miR-93-5p, and its depletion resulted in reduced cell proliferation, invasion and migration, as observed in MYEOV-knockdown PDAC cells. These effects are likely due to the ability of MYEOV to regulate enrichment of the transcription factor MYC at the gene promoter regions of the two miRNAs. Furthermore, we identified a complex containing MYEOV and MYC in the nucleus, providing additional evidence for the association of MYEOV with MYC. Taken together, our results suggest that MYEOV promotes oncogenic miR-17/93-5p expression by associating with MYC, contributing to PDAC progression.
Decreasing extents of Archean serpentinization contributed to the rise of an oxidized atmosphere
Authors: Leong James Andrew M. , Ely Tucker , Shock Everett L.
Published: December 2021

At present, molecular hydrogen (H2) produced through Fe(II) oxidation during serpentinization of ultramafic rocks represents a small fraction of the global sink for O2due to limited exposures of ultramafic rocks. In contrast, ultramafic rocks such as komatiites were much more common in the Early Earth and H2production via serpentinization was a likely factor in maintaining an O2-free atmosphere throughout most of the Archean. Using thermodynamic simulations, this work quantifies the global O2consumption attributed to serpentinization during the past 3.5 billion years. Results show that H2generation is strongly dependent on rock compositions where serpentinization of more magnesian lithologies generated substantially higher amounts of H2. Consumption of >2 Tmole O2yr−1via low-temperature serpentinization of Archean continents and seafloor is possible. This O2sink diminished greatly towards the end of the Archean as ultramafic rocks became less common and helped set the stage for the Great Oxidation Event.
Forty years of durability assessment of nuclear waste glass by standard methods
Authors: Thorpe Clare L. , Neeway James J. , Pearce Carolyn I. , Hand Russell J. , Fisher Adam J. , Walling Sam A. , Hyatt Neil C. , Kruger Albert A. , Schweiger Michael , Kosson David S. , Arendt Christina L. , Marcial Jose , Corkhill Claire L.
Published: December 2021

Standard methods to assess the durability of vitrified radioactive waste were first developed in the 1980’s and, over the last 40 years, have evolved to yield a range of responses depending on experimental conditions and glass composition. Mechanistic understanding of glass dissolution has progressed in parallel, enhancing our interpretation of the data acquired. With the implementation of subsurface disposal for vitrified radioactive waste drawing closer, it is timely to review the available standard methodologies and reflect upon their relative advantages, limitations, and how the data obtained can be interpreted to support the post-closure safety case for radioactive waste disposal.
Complex free-space magnetic field textures induced by three-dimensional magnetic nanostructures
Authors: Donnelly Claire , Hierro-Rodríguez Aurelio , Abert Claas , Witte Katharina , Skoric Luka , Sanz-Hernández Dédalo , Finizio Simone , Meng Fanfan , McVitie Stephen , Raabe Jörg , Suess Dieter , Cowburn Russell , Fernández-Pacheco Amalio
Published: December 2021

The design of complex, competing effects in magnetic systems—be it via the introduction of nonlinear interactions1–4, or the patterning of three-dimensional geometries5,6—is an emerging route to achieve new functionalities. In particular, through the design of three-dimensional geometries and curvature, intrastructure properties such as anisotropy and chirality, both geometry-induced and intrinsic, can be directly controlled, leading to a host of new physics and functionalities, such as three-dimensional chiral spin states7, ultrafast chiral domain wall dynamics8–10 and spin textures with new spin topologies7,11. Here, we advance beyond the control of intrastructure properties in three dimensions and tailor the magnetostatic coupling of neighbouring magnetic structures, an interstructure property that allows us to generate complex textures in the magnetic stray field. For this, we harness direct write nanofabrication techniques, creating intertwined nanomagnetic cobalt double helices, where curvature, torsion, chirality and magnetic coupling are jointly exploited. By reconstructing the three-dimensional vectorial magnetic state of the double helices with soft-X-ray magnetic laminography12,13, we identify the presence of a regular array of highly coupled locked domain wall pairs in neighbouring helices. Micromagnetic simulations reveal that the magnetization configuration leads to the formation of an array of complex textures in the magnetic induction, consisting of vortices in the magnetization and antivortices in free space, which together form an effective B field cross-tie wall14. The design and creation of complex three-dimensional magnetic field nanotextures opens new possibilities for smart materials15, unconventional computing2,16, particle trapping17,18 and magnetic imaging19.
Ostrich eggshell beads reveal 50,000-year-old social network in Africa
Authors: Miller Jennifer M. , Wang Yiming V.
Published: December 2021

Humans evolved in a patchwork of semi-connected populations across Africa1,2; understanding when and how these groups connected is critical to interpreting our present-day biological and cultural diversity. Genetic analyses reveal that eastern and southern African lineages diverged sometime in the Pleistocene epoch, approximately 350–70 thousand years ago (ka)3,4; however, little is known about the exact timing of these interactions, the cultural context of these exchanges or the mechanisms that drove their separation. Here we compare ostrich eggshell bead variations between eastern and southern Africa to explore population dynamics over the past 50,000 years. We found that ostrich eggshell bead technology probably originated in eastern Africa and spread southward approximately 50–33 ka via a regional network. This connection breaks down approximately 33 ka, with populations remaining isolated until herders entered southern Africa after 2 ka. The timing of this disconnection broadly corresponds with the southward shift of the Intertropical Convergence Zone, which caused periodic flooding of the Zambezi River catchment (an area that connects eastern and southern Africa). This suggests that climate exerted some influence in shaping human social contact. Our study implies a later regional divergence than predicted by genetic analyses, identifies an approximately 3,000-kilometre stylistic connection and offers important new insights into the social dimension of ancient interactions.
Normalization by valence and motivational intensity in the sensorimotor cortices (PMd, M1, and S1)
Authors: Yao Zhao , Hessburg John P. , Francis Joseph Thachil
Published: December 2021

Our brain’s ability to represent vast amounts of information, such as continuous ranges of reward spanning orders of magnitude, with limited dynamic range neurons, may be possible due to normalization. Recently our group and others have shown that the sensorimotor cortices are sensitive to reward value. Here we ask if psychological affect causes normalization of the sensorimotor cortices by modulating valence and motivational intensity. We had two non-human primates (NHP) subjects (one male bonnet macaque and one female rhesus macaque) make visually cued grip-force movements while simultaneously cueing the level of possible reward if successful, or timeout punishment, if unsuccessful. We recorded simultaneously from 96 electrodes in each the following: caudal somatosensory, rostral motor, and dorsal premotor cortices (cS1, rM1, PMd). We utilized several normalization models for valence and motivational intensity in all three regions. We found three types of divisive normalized relationships between neural activity and the representation of valence and motivation, linear, sigmodal, and hyperbolic. The hyperbolic relationships resemble receptive fields in psychological affect space, where a unit is susceptible to a small range of the valence/motivational space. We found that these cortical regions have both strong valence and motivational intensity representations.
The activation fragment of PAR2 is elevated in serum from patients with rheumatoid arthritis and reduced in response to anti-IL6R treatment
Authors: Kalogera Stefania , He Yi , Bay-Jensen Anne-Christine , Gantzel Thorbjørn , Sun Shu , Manon-Jensen Tina , Karsdal Morten Asser , Thudium Christian S.
Published: December 2021

Osteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and pain. PAR2 is activated via cleavage of its N-terminus by serine proteases. In this study a competitive ELISA assay was developed targeting the 36-amino acid peptide that is cleaved and released after PAR2 activation (PRO-PAR2). Technical assay parameters including antibody specificity, intra- and inter-assay variation (CV%), linearity, accuracy, analyte stability and interference were evaluated. PRO-PAR2 release was confirmed after in vitro cleavage of PAR2 recombinant protein and treatment of human synovial explants with matriptase. Serum levels of 22 healthy individuals, 23 OA patients and 15 RA patients as well as a subset of RA patients treated with tocilizumab were evaluated. The PRO-PAR2 antibody was specific for the neo-epitope and intra-inter assay CV% were 6.4% and 5.8% respectively. In vitro cleavage and matriptase treated explants showed increased PRO-PAR2 levels compared to controls. In serum, PRO-PAR2 levels were increased in RA patients and decreased in RA patients treated with tocilizumab. In conclusion, PRO-PAR2 may be a potential biomarker for monitoring RA disease and pharmacodynamics of treatment.
Serotonin transporter (SERT) polymorphisms, personality and problem-solving in urban great tits
Authors: Grunst Andrea S. , Grunst Melissa L. , Staes Nicky , Thys Bert , Pinxten Rianne , Eens Marcel
Published: December 2021

Understanding underlying genetic variation can elucidate how diversity in behavioral phenotypes evolves and is maintained. Genes in the serotonergic signaling pathway, including the serotonin transporter gene (SERT), are candidates for affecting animal personality, cognition and fitness. In a model species, the great tit (Parus major), we reevaluated previous findings suggesting relationships between SERT polymorphisms, neophobia, exploratory behavior and fitness parameters, and performed a first test of the relationship between single nucleotide polymorphisms (SNPs) in SERT and problem-solving in birds. We found some evidence for associations between SERT SNPs and neophobia, exploratory behavior and laying date. Furthermore, several SNPs were associated with behavioral patterns and success rates during obstacle removal problem-solving tests performed at nest boxes. In females, minor allele homozygotes (AA) for nonsynonymous SNP226 in exon 1 made fewer incorrect attempts and were more likely to problem-solve. In both sexes, there was some evidence that minor allele homozygotes (CC) for SNP84 in exon 9 were more likely to problem-solve. Only one SNP-behavior relationship was statistically significant after correcting for multiple comparisons, but several were associated with substantial effect sizes. Our study provides a foundation for future research on the genetic basis of behavioral and cognitive variation in wild animal populations.
Inflammatory activation of surface molecule shedding by upregulation of the pseudoprotease iRhom2 in colon epithelial cells
Authors: Giese Anja Adelina , Babendreyer Aaron , Krappen Peter , Gross Annika , Strnad Pavel , Düsterhöft Stefan , Ludwig Andreas
Published: December 2021

The metalloproteinase ADAM17 contributes to inflammatory and proliferative responses by shedding of cell-surface molecules. By this ADAM17 is implicated in inflammation, regeneration, and permeability regulation of epithelial cells in the colon. ADAM17 maturation and surface expression requires the adapter proteins iRhom1 or iRhom2. Here we report that expression of iRhom2 but not iRhom1 is upregulated in intestinal tissue of mice with acute colitis. Our analysis of public databases indicates elevated iRhom2 expression in mucosal tissue and epithelial cells from patients with inflammatory bowel disease (IBD). Consistently, expression of iRhom2 but not iRhom1 is upregulated in colon or intestinal epithelial cell lines after co-stimulation with tumor necrosis factor (TNF) and interferon gamma (IFNgamma). This upregulation can be reduced by inhibition of Janus kinases or transcription factors NF-kappaB or AP-1. Upregulation of iRhom2 can be mimicked by iRhom2 overexpression and is associated with enhanced maturation and surface expression of ADAM17 which then results in increased cleavage of transforming growth factor (TGF) alpha and junctional adhesion molecule (JAM)-A. Finally, the induction of these responses is suppressed by inhibition of iRhom2 transcription. Thus, inflammatory induction of iRhom2 may contribute to upregulated ADAM17-dependent mediator and adhesion molecule release in IBD. The development of iRhom2-dependent inhibitors may allow selective targeting of inflammatory ADAM17 activities.
Contributions of NaV1.8 and NaV1.9 to excitability in human induced pluripotent stem-cell derived somatosensory neurons
Authors: Alsaloum Matthew , Labau Julie I. R. , Liu Shujun , Estacion Mark , Zhao Peng , Dib-Hajj Fadia , Waxman Stephen G.
Published: December 2021

The inhibition of voltage-gated sodium (NaV) channels in somatosensory neurons presents a promising novel modality for the treatment of pain. However, the precise contribution of these channels to neuronal excitability, the cellular correlate of pain, is unknown; previous studies using genetic knockout models or pharmacologic block of NaV channels have identified general roles for distinct sodium channel isoforms, but have never quantified their exact contributions to these processes. To address this deficit, we have utilized dynamic clamp electrophysiology to precisely tune in varying levels of NaV1.8 and NaV1.9 currents into induced pluripotent stem cell-derived sensory neurons (iPSC-SNs), allowing us to quantify how graded changes in these currents affect different parameters of neuronal excitability and electrogenesis. We quantify and report direct relationships between NaV1.8 current density and action potential half-width, overshoot, and repetitive firing. We additionally quantify the effect varying NaV1.9 current densities have on neuronal membrane potential and rheobase. Furthermore, we examined the simultaneous interplay between NaV1.8 and NaV1.9 on neuronal excitability. Finally, we show that minor biophysical changes in the gating of NaV1.8 can render human iPSC-SNs hyperexcitable, in a first-of-its-kind investigation of a gain-of-function NaV1.8 mutation in a human neuronal background.
Exploring the potential of moringa leaf extract as bio stimulant for improving yield and quality of black cumin oil
Authors: Mehmood Abid , Naveed Khalid , Ayub Qasim , Alamri Saud , Siddiqui Manzer H. , Wu Chao , Wang Depeng , Saud Shah , Banout Jan , Danish Subhan , Datta Rahul , Hammad Hafiz Mohkum , Nasim Wajid , Mubeen Muhammad , Shah Farooq , Fahad Shah
Published: December 2021

The history of plants to be utilized as medicines is thousands of years old. Black cumin is one of the most widely examined plant possessing naturally occurring compounds with antimicrobial potential. Foliar application of growth stimulators is a successful strategy to enhance yield and quality in many crops. A field study was planned to apply growth stimulator like moringa leaf extract on black cumin crop grown under field conditions using RCB design with three replications. All other agronomic inputs and practices were uniform. The treatments were moringa leaf extract concentrations (10%, 20%), growth stages (40 days after sowing, 80 DAS, 120 DAS, 40 + 80 DAS, 40 + 120 DAS, 80 + 120 DAS, 40 + 80 + 120 days after sowing) and two controls unsprayed check (i.e. no moringa leaf extract, no water) and sprayed check (no moringa leaf extract + water). Application of 20% moringa leaf extract at stage-7 (40 + 80 + 120 days after sowing) had significantly increased plant height, branches plant−1, essential oil content, fixed oil content, peroxidase value and iodine value of black cumin oil over unsprayed control. Application of moringa leaf extract showed maximum results and improves growth and yield of black cumin when applied at 40 + 80 + 120 days after sowing. As this study was only conducted using moringa leaf extract, it is advisable to conduct an experiment with various bio stimulants along with fertilizer combinations and growth regulators to check their synergistic effects for more reliable and acceptable recommendations in future.
Three topological features of regulatory networks control life-essential and specialized subsystems
Authors: Wolf Ivan Rodrigo , Simões Rafael Plana , Valente Guilherme Targino
Published: December 2021

Gene regulatory networks (GRNs) play key roles in development, phenotype plasticity, and evolution. Although graph theory has been used to explore GRNs, associations amongst topological features, transcription factors (TFs), and systems essentiality are poorly understood. Here we sought the relationship amongst the main GRN topological features that influence the control of essential and specific subsystems. We found that the Knn, page rank, and degree are the most relevant GRN features: the ones are conserved along the evolution and are also relevant in pluripotent cells. Interestingly, life-essential subsystems are governed mainly by TFs with intermediary Knn and high page rank or degree, whereas specialized subsystems are mainly regulated by TFs with low Knn. Hence, we suggest that the high probability of TFs be toured by a random signal, and the high probability of the signal propagation to target genes ensures the life-essential subsystems’ robustness. Gene/genome duplication is the main evolutionary process to rise Knn as the most relevant feature. Herein, we shed light on unexplored topological GRN features to assess how they are related to subsystems and how the duplications shaped the regulatory systems along the evolution. The classification model generated can be found here: https://github.com/ivanrwolf/NoC/.
Seasonal shedding patterns of diverse henipavirus-related paramyxoviruses in Egyptian rousette bats
Authors: Mortlock Marinda , Geldenhuys Marike , Dietrich Muriel , Epstein Jonathan H. , Weyer Jacqueline , Pawęska Janusz T. , Markotter Wanda
Published: December 2021

Bat-borne viruses in the Henipavirus genus have been associated with zoonotic diseases of high morbidity and mortality in Asia and Australia. In Africa, the Egyptian rousette bat species (Rousettus aegyptiacus) is an important viral host in which Henipavirus-related viral sequences have previously been identified. We expanded these findings by assessing the viral dynamics in a southern African bat population. A longitudinal study of henipavirus diversity and excretion dynamics identified 18 putative viral species circulating in a local population, three with differing seasonal dynamics, and the winter and spring periods posing a higher risk of virus spillover and transmission. The annual peaks in virus excretion are most likely driven by subadults and may be linked to the waning of maternal immunity and recolonization of the roost in early spring. These results provide insightful information into the bat-host relationship that can be extrapolated to other populations across Africa and be communicated to at-risk communities as a part of evidence-based public health education and prevention measures against pathogen spillover threats.
Usefulness of arterial spin labeling perfusion as an initial evaluation of status epilepticus
Authors: Kim Tae-Joon , Choi Jin Wook , Han Miran , Kim Byung Gon , Park Sun Ah , Huh Kyoon , Choi Jun Young
Published: December 2021

This study aimed to evaluate the sensitivity and prognostic value of arterial spin labeling (ASL) in a large group of status epilepticus (SE) patients and compare them with those of other magnetic resonance (MR) sequences, including dynamic susceptibility contrast (DSC) perfusion imaging. We retrospectively collected data of patients with SE in a tertiary center between September 2016 and March 2020. MR images were visually assessed, and the sensitivity for the detection of SE and prognostication was compared among multi-delay ASL, DSC, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). We included 51 SE patients and 46 patients with self-limiting seizures for comparison. Relevant changes in ASL were observed in 90.2% (46/51) of SE patients, a percentage higher than those for DSC, FLAIR, and DWI. ASL was the most sensitive method for initial differentiation between SE and self-limiting seizures. The sensitivity of ASL for detecting refractory SE (89.5%) or estimating poor outcomes (100%) was higher than those of other MR protocols or electroencephalography and comparable to those of clinical prognostic scores, although the specificity of ASL was very low as 9.4% and 15.6%, respectively. ASL showed a better ability to detect SE and predict the prognosis than other MR sequences, therefore it can be valuable for the initial evaluation of patients with SE.
A mild aqueous synthesis of ligand-free copper nanoparticles for low temperature sintering nanopastes with nickel salt assistance
Authors: Imamura Hiroshi , Kamikoriyama Yoichi , Muramatsu Atsushi , Kanie Kiyoshi
Published: December 2021

An organic ligand-free aqueous-phase synthesis of copper (Cu) nanoparticles (NPs) under an air atmosphere was successfully achieved by reducing copper(II) oxide particles with a leaf-like shape in the presence of Ni salts at room temperature. The resulting Cu NPs with a mean particle diameter of ca. 150 nm exhibited low-temperature sintering properties due to their polycrystalline internal structure and ligand-free surface. These Cu NPs were applied to obtain Cu NP-based nanopastes with low-temperature sintering properties, and the resistivities of the obtained Cu electrodes after annealing at 150 °C and 200 °C for 30 min were 64 μΩ∙cm and 27 μΩ∙cm, respectively. The bonding strength between oxygen-free Cu plates prepared using the Cu NP-based nanopastes reached 32 MPa after pressure-less sintering at 260 °C for 30 min under a nitrogen atmosphere. The developed manufacturing processes using the developed Cu nanopastes could provide sustainable and low-CO2-emission approaches to obtain Cu electrodes on flexible films and high-strength bonding between metal plates as die-attach materials for power devices under energy- and resource-saving conditions.
RETRACTED ARTICLE: The randomized clinical trial results of the anxiety treatment in patients with somatoform dysfunction and neurotic disorders
Authors: Parfenov Vladimir Anatolevich , Kamchatnov Pavel Rudolfovich , Khasanova Dina Rustemovna , Bogdanov Enver Ibragimovich , Lokshtanova Tatiana Markovna , Amelin Aleksandr Vitalevich , Maslova Natalya Nikolaevna , Pizova Nataliia Vyacheslavovna , Belskaya Galina Nikolaevna , Barantsevich Evgeny Robertovich , Duchshanova Gulsum Abdurahmanovna , Kamenova Saltanat Ualihanovna , Kolokolov Oleg Vladimirovich , Glazunov Alexey Borisovich
Published: December 2021

The existing treatments for somatoform dysfunction (SfD), reaction to severe stress (RSS), and adjustment disorders (AjD) are insufficiently effective and safe. Anxiolytic drug Tenoten proved effective in clinical trials (CT). The aim of this multicenter double-blind placebo-controlled randomized CT was to investigate the safety and efficacy of Tenoten in the treatment of anxiety in adults with SfD, RSS, AjD and other neurotic disorders (oNDs). 390 adult patients with SfD, RSS and AjD or oNDs with the Hospital Anxiety and Depression scale-anxiety (HADS-A) score ≥ 11 were randomized into 4 groups (n = 127 in Tenoten group 1 (4 tablets/day); n = 131 in Tenoten group 3 (8 tablets/day), n = 132 in combined Placebo group 2 + 4). The changes from baseline in the mean Hamilton Anxiety Rating Scale (HAM-A) score in groups 1 and 3 after 12 weeks were the primary outcome. The decrease of the HAM-A score from 18.81 ± 5.81 to 7.26 ± 4.63 (in group 1) and from 18.38 ± 4.3 to 6.40 ± 4.02 (in group 3) was observed post-treatment (pgroup 1/placebo = 0.0055, pgroup 3/placebo < 0.0001). Overall, 46 adverse events (28 in the Tenoten groups and 18 in the Placebo) were reported without any difference between the study groups. Tenoten performed significantly more effective than placebo in the anxiety treatment of adults with SfD, RSS, AjD and oNDs (clinicaltrials.gov NCT03036293).
The effect of toll-like receptor ligands on energy metabolism and myokine expression and secretion in cultured human skeletal muscle cells
Authors: Tingstad Ragna H. , Norheim Frode , Haugen Fred , Feng Yuan Z. , Tunsjø Hege S. , Thoresen G. Hege , Rustan Arild C. , Charnock Colin , Aas Vigdis
Published: December 2021

Skeletal muscle plays an important role in glycaemic control and metabolic homeostasis, making it a tissue of interest with respect to type 2 diabetes mellitus. The aim of the present study was to determine if ligands of Toll-like receptors (TLRs) could have an impact on energy metabolism and myokine expression and secretion in cultured human skeletal muscle cells. The myotubes expressed mRNA for TLRs 1–6. TLR3, TLR4, TLR5 and TLR6 ligands (TLRLs) increased glucose metabolism. Furthermore, TLR4L and TLR5L increased oleic acid metabolism. The metabolic effects of TLRLs were not evident until after at least 24 h pre-incubation of the cells and here the metabolic effects were more evident for the metabolism of glucose than oleic acid, with a shift towards effects on oleic acid metabolism after chronic exposure (168 h). However, the stimulatory effect of TLRLs on myokine expression and secretion was detected after only 6 h, where TLR3-6L stimulated secretion of interleukin-6 (IL-6). TLR5L also increased secretion of interleukin-8 (IL-8), while TLR6L also increased secretion of granulocyte–macrophage colony stimulating factor (GM-CSF). Pre-incubation of the myotubes with IL-6 for 24 h increased oleic acid oxidation but had no effect on glucose metabolism. Thus IL-6 did not mimic all the metabolic effects of the TLRLs, implying metabolic effects beyond the actions of this myokine.
Effectiveness assessment of using riverine water eDNA to simultaneously monitor the riverine and riparian biodiversity information
Authors: Yang Haile , Du Hao , Qi Hongfang , Yu Luxian , Hou Xindong , Zhang Hui , Li Junyi , Wu Jinming , Wang Chengyou , Zhou Qiong , Wei Qiwei
Published: December 2021

Both aquatic and terrestrial biodiversity information can be detected in riverine water environmental DNA (eDNA). However, the effectiveness of using riverine water eDNA to simultaneously monitor the riverine and terrestrial biodiversity information remains unidentified. Here, we proposed that the monitoring effectiveness could be approximated by the transportation effectiveness of land-to-river and upstream-to-downstream biodiversity information flows and described by three new indicators. Subsequently, we conducted a case study in a watershed on the Qinghai–Tibet Plateau. The results demonstrated that there was higher monitoring effectiveness on summer or autumn rainy days than in other seasons and weather conditions. The monitoring of the bacterial biodiversity information was more efficient than the monitoring of the eukaryotic biodiversity information. On summer rainy days, 43–76% of species information in riparian sites could be detected in adjacent riverine water eDNA samples, 92–99% of species information in riverine sites could be detected in a 1-km downstream eDNA sample, and half of dead bioinformation (the bioinformation labeling the biological material that lacked life activity and fertility) could be monitored 4–6 km downstream for eukaryotes and 13–19 km downstream for bacteria. The current study provided reference method and data for future monitoring projects design and for future monitoring results evaluation.
Interaction effect of serum serotonin level and age on the 12-week pharmacotherapeutic response in patients with depressive disorders
Authors: Choi Wonsuk , Kim Ju-Wan , Kang Hee-Ju , Kim Hee Kyung , Kang Ho-Cheol , Lee Ju-Yeon , Kim Sung-Wan , Stewart Robert , Kim Jae-Min
Published: December 2021

Despite the recognized antidepressant role of serotonin (5-hydroxytryptamine [5-HT]) signaling pathways in the central nervous system, the association between baseline peripheral 5-HT level and the antidepressant treatment response in clinical studies remains debatable. We investigated the interaction effects of baseline serum 5-HT level and age on the 12-week remission in outpatients with depressive disorders who received stepwise antidepressant treatment. Baseline serum serotonin levels were measured and the age of 1094 patients recorded. The patients received initial antidepressant monotherapy; then, patients with an insufficient response or who experienced uncomfortable side effects received alternative treatments every 3 weeks (3, 6, and 9 weeks). Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score of ≤ 7, was evaluated. Individual and interaction effects of serum 5-HT level (as a binary [low vs. high, based on the median value of 72.6 ng/mL] or continuous variable) and age (as a binary [< 60 vs. ≥ 60 years] or continuous variable) on the 12-week remission rate were analyzed using logistic regression models after adjusting for relevant covariates. High 5-HT (≥ 72.6 ng/mL) and age ≥ 60 years were associated with the highest 12-week remission rates and a significant multiplicative interaction effect. The interaction effect of the two variables on the 12-week remission rate was significant even when analyzed as a continuous variable. Our study suggests that the association between baseline serum 5-HT level and 12-week antidepressant treatment outcomes differs according to patient age.
Contribution of vascular risk factors to the relationship between ADHD symptoms and cognition in adults and seniors
Authors: Callahan Brandy L. , Plamondon André , Gill Sascha , Ismail Zahinoor
Published: December 2021

Symptoms of attention-deficit/hyperactivity disorder (ADHD) in childhood have been found to be predictive of compromised cognitive function, and possibly even dementia, in later adulthood. This study aimed to test vascular risk as a hypothesized moderator or mediator of this association, because individuals with elevated ADHD symptoms frequently have comorbid vascular disease or risk factors which are recognized to contribute to later-life cognitive decline. Data from 1,092 adults aged 18–85 were drawn from the Enhanced Nathan Kline Institute Rockland Sample. Childhood ADHD symptoms (assessed using the Adult ADHD Clinical Diagnostic Scale) were assessed as predictors of cognitive functioning in adulthood (assessed using subtests from the University of Pennsylvania Computerized Neurocognitive Battery, the Delis-Kaplan Executive Functioning System, and the Wechsler Memory Scale). Vascular risk factors (including diabetes, tobacco use, obesity, hypertension, and hypercholesterolemia) were tested as both a moderator and mediator of this relationship. Childhood ADHD symptoms and vascular risk factors were both independently associated with later-life cognition, but vascular risk was not a significant moderator or mediator of relationships between ADHD symptoms and cognition in statistical models. Results from this large community sample suggest that the relationship between ADHD symptoms and cognition is not accounted for by vascular risk. This question should also be investigated in clinical samples.
Predicting surgical outcomes for chronic exertional compartment syndrome using a machine learning framework with embedded trust by interrogation strategies
Authors: Houston Andrew , Cosma Georgina , Turner Phillipa , Bennett Alexander
Published: December 2021

Chronic exertional compartment syndrome (CECS) is a condition occurring most frequently in the lower limbs and often requires corrective surgery to alleviate symptoms. Amongst military personnel, the success rates of this surgery can be as low as 20%, presenting a challenge in determining whether surgery is worthwhile. In this study, the data of 132 fasciotomies for CECS was analysed and using combinatorial feature selection methods, coupled with input from clinicians, identified a set of key clinical features contributing to the occupational outcomes of surgery. Features were utilised to develop a machine learning model for predicting return-to-work outcomes 12-months post-surgery. An AUC of 0.85 ± 0.08 was achieved using a linear-SVM, trained using 6 features (height, mean arterial pressure, pre-surgical score on the exercise-induced leg pain questionnaire, time from initial presentation to surgery, and whether a patient had received a prior surgery for CECS). To facilitate trust and transparency, interrogation strategies were used to identify reasons why certain patients were misclassified, using instance hardness measures. Model interrogation revealed that patient difficulty was associated with an overlap in the clinical characteristics of surgical outcomes, which was best handled by XGBoost and SVM-based models. The methodology was compiled into a machine learning framework, termed AITIA, which can be applied to other clinical problems. AITIA extends the typical machine learning pipeline, integrating the proposed interrogation strategy, allowing to user to reason and decide whether to trust the developed model based on the sensibility of its decision-making.
Comprehensive multiomic characterization of human papillomavirus-driven recurrent respiratory papillomatosis reveals distinct molecular subtypes
Authors: Sievers Cem , Robbins Yvette , Bai Ke , Yang Xinping , Clavijo Paul E. , Friedman Jay , Sinkoe Andrew , Norberg Scott M. , Hinrichs Christian , Van Waes Carter , Allen Clint T.
Published: December 2021

Recurrent respiratory papillomatosis (RRP) is a debilitating neoplastic disorder of the upper aerodigestive tract caused by chronic infection with low-risk human papillomavirus types 6 or 11. Patients with severe RRP can require hundreds of lifetime surgeries to control their disease and pulmonary papillomatosis can be fatal. Here we report the comprehensive genomic and transcriptomic characterization of respiratory papillomas. We discovered and characterized distinct subtypes with transcriptional resemblance to either a basal or differentiated cell state that associate with disease aggressiveness and differ in key molecular, immune and APOBEC mutagenesis profiles. Through integrated comparison with high-risk HPV-associated head and neck squamous cell carcinoma, our analysis revealed divergent molecular and immune papilloma subtypes that form independent of underlying genomic alterations. Cumulatively our results support the development of dysregulated cellular proliferation and suppressed anti-viral immunity through distinct programs of squamous cell differentiation and associated expression of low-risk HPV genes. These analyses provide insight into the pathogenesis of respiratory papillomas and provide a foundation for the development of therapeutic strategies.
Transcriptomic and macroscopic architectures of intersubject functional variability in human brain white-matter
Authors: Li Jiao , Wu Guo-Rong , Li Bing , Fan Feiyang , Zhao Xiaopeng , Meng Yao , Zhong Peng , Yang Siqi , Biswal Bharat B. , Chen Huafu , Liao Wei
Published: December 2021

Intersubject variability is a fundamental characteristic of brain organizations, and not just “noise”. Although intrinsic functional connectivity (FC) is unique to each individual and varies across brain gray-matter, the underlying mechanisms of intersubject functional variability in white-matter (WM) remain unknown. This study identified WMFC variabilities and determined the genetic basis and macroscale imaging in 45 healthy subjects. The functional localization pattern of intersubject variability across WM is heterogeneous, with most variability observed in the heteromodal cortex. The variabilities of heteromodal regions in expression profiles of genes are related to neuronal cells, involved in synapse-related and glutamic pathways, and associated with psychiatric disorders. In contrast, genes overexpressed in unimodal regions are mostly expressed in glial cells and were related to neurological diseases. Macroscopic variability recapitulates the functional and structural specializations and behavioral phenotypes. Together, our results provide clues to intersubject variabilities of the WMFC with convergent transcriptomic and cellular signatures, which relate to macroscale brain specialization.