bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cistrome and transcriptome analysis identifies unique androgen receptor (AR) and AR-V7 splice variant chromatin binding and transcriptional activities
Authors: Basil Paul , Robertson Matthew J. , Bingman William E. , Dash Amit K. , Krause William C. , Shafi Ayesha A. , Piyarathna Badrajee , Coarfa Cristian , Weigel Nancy L. 
Published: March 2022

AbstractThe constitutively active androgen receptor (AR) splice variant, AR-V7, plays an important role in resistance to androgen deprivation therapy in castration resistant prostate cancer (CRPC). Studies seeking to determine whether AR-V7 is a partial mimic of the AR, or also has unique activities, and whether the AR-V7 cistrome contains unique binding sites have yielded conflicting results. One limitation in many studies has been the low level of AR variant compared to AR. Here, LNCaP and VCaP cell lines in which AR-V7 expression can be induced to match the level of AR, were used to compare the activities of AR and AR-V7. The two AR isoforms shared many targets, but overall had distinct transcriptomes. Optimal induction of novel targets sometimes required more receptor isoform than classical targets such as PSA. The isoforms displayed remarkably different cistromes with numerous differential binding sites. Some of the unique AR-V7 sites were located proximal to the transcription start sites (TSS). A de novo binding motif similar to a half ARE was identified in many AR-V7 preferential sites and, in contrast to conventional half ARE sites that bind AR-V7, FOXA1 was not enriched at these sites. This supports the concept that the AR isoforms have unique actions with the potential to serve as biomarkers or novel therapeutic targets.
Influence of beech and spruce on potentially toxic elements-related health risk of edible mushrooms growing on unpolluted forest soils
Authors: Pecina Václav , Valtera Martin , Drápela Karel , Novotný Radek , Vahalík Petr , Komendová Renata , Brtnický Martin , Juřička David 
Published: March 2022

AbstractAtmospheric deposition-related potentially toxic elements (PTEs) can contaminate mountain forest ecosystems. The influence of tree species is being increasingly recognised as an important factor in the deposition loads in forest soils. However, relevant modelling studies about the forest pollution with PTEs, concerning the tree species composition, are lacking. The aim of this study was to evaluate the effect of European beech (Fagus sylvatica L.) and Norway spruce (Picea abies (L.) H. Karst.) on soil and mushroom pollution and the associated health risks to define their significance for pollution modelling. Therefore, topsoil samples and samples of eight edible mushroom species were taken from 51 mature beech- and spruce-dominated stands. The results showed that forest composition had an indirect influence on the PTEs contents in the topsoil; it significantly differentiated the relationship between PTEs and soil C as the beech stands showed significantly increasing PTEs content with increasing C content. Despite the absence of soil pollution, above-limit levels of Cd and Zn were found in mushrooms. The total content of PTEs in mushrooms posed a potential health risk to consumers in 82% of the samples. The most Cd-contaminated and potentially the riskiest species for consumption was Xerocomellus pruinatus (Fr. and Hök) Šutara. The results suggest that the source of PTEs for mushrooms is not only the soil but probably also the current wet deposition. The influence of the forest type on the accumulation of PTEs in mushrooms was confirmed mainly due to the strongly divergent behaviour of Zn in beech- vs. spruce-dominated stands. The results point to the need to evaluate mushroom contamination even in the contamination-unburdened forest areas. For future modelling of PTEs pollution in forests, it is necessary to differentiate the tree species composition.
The superiority of manual over automated methods in identifying bronchial trees on identical CT images
Authors: Takata So , Miyake Kotaro , Kumanogoh Atsushi 
Published: March 2022

AbstractThe purpose of this study was to compare a manual bronchoscopic navigation technique, the direct oblique method (DOM), with conventional virtual bronchoscopic navigation software in terms of bronchial identification ability involving reconstruction of a whole bronchial tree from identical CT images. A whole bronchial tree was drawn using manual bronchial recognition with the DOM. The tree was compared with that reconstructed by SYNAPSE VINCENT bronchoscopic navigation-dedicated software. The number of bronchial generations at each terminal tip was then compared between the two approaches. Physicians spent 20 h tracing all bronchi on CT scan images and obtained a bronchial tree. The hand-made bronchial tree had five times the number of tips as that reconstructed by automatic bronchial recognition (1482 vs. 279 tips, respectively). The number of bronchial generations prior to each terminal tip was larger with the DOM than with VINCENT (median, 10; interquartile range (IQR), 9–11 vs. median, 5; IQR, 5–7, respectively; p-value < 0.001). Using the CT image data in this case, manual bronchial recognition with the DOM identified more bronchi than automatic bronchial recognition. This result implies that manual bronchial recognition is a valid basis for detailed bronchoscopic navigation analysis.
Genetic and phenotypic diversity of fecal Candida albicans strains in irritable bowel syndrome
Authors: van Thiel Isabelle A. M. , Stavrou Aimilia A. , de Jong Auke , Theelen Bart , Davids Mark , Hakvoort Theodorus B. M. , Admiraal-van den Berg Iris , Weert Isabelle C. M. , de Kruijs Martine A. M. Hesselink-van , Vu Duong , Moissl-Eichinger Christine , Heinsbroek Sigrid E. M. , Jonkers Daisy M. A. E. , Hagen Ferry , Boekhout Teun , de Jonge Wouter J. , van den Wijngaard René M. 
Published: March 2022

AbstractIrritable bowel syndrome (IBS) is a common disorder characterized by chronic abdominal pain and changes in bowel movements. Visceral hypersensitivity is thought to be responsible for pain complaints in a subset of patients. In an IBS-like animal model, visceral hypersensitivity was triggered by intestinal fungi, and lower mycobiota α-diversity in IBS patients was accompanied by a shift toward increased presence of Candida albicans and Saccharomyces cerevisiae. Yet, this shift was observed in hypersensitive as well as normosensitive patients and diversity did not differ between IBS subgroups. The latter suggests that, when a patient changes from hyper- to normosensitivity, the relevance of intestinal fungi is not necessarily reflected in compositional mycobiota changes. We now confirmed this notion by performing ITS1 sequencing on an existing longitudinal set of fecal samples. Since ITS1 methodology does not recognize variations within species, we next focused on heterogeneity within cultured healthy volunteer and IBS-derived C. albicans strains. We observed inter- and intra-individual genomic variation and partial clustering of strains from hypersensitive patients. Phenotyping showed differences related to growth, yeast-to-hyphae morphogenesis and gene expression, specifically of the gene encoding fungal toxin candidalysin. Our investigations emphasize the need for strain-specific cause-and-effect studies within the realm of IBS research.
Neuromorphic chip integrated with a large-scale integration circuit and amorphous-metal-oxide semiconductor thin-film synapse devices
Authors: Kimura Mutsumi , Shibayama Yuki , Nakashima Yasuhiko 
Published: March 2022

AbstractArtificial intelligences are promising in future societies, and neural networks are typical technologies with the advantages such as self-organization, self-learning, parallel distributed computing, and fault tolerance, but their size and power consumption are large. Neuromorphic systems are biomimetic systems from the hardware level, with the same advantages as living brains, especially compact size, low power, and robust operation, but some well-known ones are non-optimized systems, so the above benefits are only partially gained, for example, machine learning is processed elsewhere to download fixed parameters. To solve these problems, we are researching neuromorphic systems from various viewpoints. In this study, a neuromorphic chip integrated with a large-scale integration circuit (LSI) and amorphous-metal-oxide semiconductor (AOS) thin-film synapse devices has been developed. The neuron elements are digital circuit, which are made in an LSI, and the synapse devices are analog devices, which are made of the AOS thin film and directly integrated on the LSI. This is the world's first hybrid chip where neuron elements and synapse devices of different functional semiconductors are integrated, and local autonomous learning is utilized, which becomes possible because the AOS thin film can be deposited without heat treatment and there is no damage to the underneath layer, and has all advantages of neuromorphic systems.
Transcriptome-wide association study reveals increased neuronal FLT3 expression is associated with Tourette’s syndrome
Authors: Liao Calwing , Vuokila Veikko , Catoire Hélène , Akçimen Fulya , Ross Jay P. , Bourassa Cynthia V. , Dion Patrick A. , Meijer Inge A. , Rouleau Guy A. 
Published: March 2022

AbstractTourette’s Syndrome (TS) is a neurodevelopmental disorder that is characterized by motor and phonic tics. A recent TS genome-wide association study (GWAS) identified a genome-wide significant locus. However, determining the biological mechanism of GWAS signals remains difficult. To characterize effects of expression quantitative trait loci (eQTLs) in TS and understand biological underpinnings of the disease. Here, we conduct a TS transcriptome-wide association study (TWAS) consisting of 4819 cases and 9488 controls. We demonstrate that increased expression ofFLT3in the dorsolateral prefrontal cortex (DLPFC) is associated with TS. We further show that there is global dysregulation ofFLT3across several brain regions and probabilistic causal fine-mapping of the TWAS signal prioritizesFLT3with a posterior inclusion probability of 0.849. After, we proxy the expression with 100 lymphoblastoid cell lines, and demonstrate that TS cells has a 1.72 increased fold change compared to controls. A phenome-wide association study also points towardFLT3having links with immune-related pathways such as monocyte count. We further identify several splicing events inMPHOSPH9,CSGALNACT2andFIP1L1associated with TS, which are also implicated in immune function. This analysis of expression and splicing begins to explore the biology of TS GWAS signals.
Resistance to chemical carcinogenesis induction via a dampened inflammatory response in naked mole-rats
Authors: Oka Kaori , Fujioka Shusuke , Kawamura Yoshimi , Komohara Yoshihiro , Chujo Takeshi , Sekiguchi Koki , Yamamura Yuki , Oiwa Yuki , Omamiuda-Ishikawa Natsuko , Komaki Shohei , Sutoh Yoichi , Sakurai Satoko , Tomizawa Kazuhito , Bono Hidemasa , Shimizu Atsushi , Araki Kimi , Yamamoto Takuya , Yamada Yasuhiro , Oshiumi Hiroyuki , Miura Kyoko 
Published: March 2022

AbstractNaked mole-rats (NMRs) have a very low spontaneous carcinogenesis rate, which has prompted studies on the responsible mechanisms to provide clues for human cancer prevention. However, it remains unknown whether and how NMR tissues respond to experimental carcinogenesis induction. Here, we show that NMRs exhibit extraordinary resistance against potent chemical carcinogenesis induction through a dampened inflammatory response. Although carcinogenic insults damaged skin cells of both NMRs and mice, NMR skin showed markedly lower immune cell infiltration. NMRs harbour loss-of-function mutations in RIPK3 and MLKL genes, which are essential for necroptosis, a type of necrotic cell death that activates strong inflammation. In mice, disruption of Ripk3 reduced immune cell infiltration and delayed carcinogenesis. Therefore, necroptosis deficiency may serve as a cancer resistance mechanism via attenuating the inflammatory response in NMRs. Our study sheds light on the importance of a dampened inflammatory response as a non-cell-autonomous cancer resistance mechanism in NMRs.
Gentamicin at sub-inhibitory concentrations selects for antibiotic resistance in the environment
Authors: Sanchez-Cid Concepcion , Guironnet Alexandre , Keuschnig Christoph , Wiest Laure , Vulliet Emmanuelle , Vogel Timothy M 
Published: March 2022

Abstract
Antibiotics released into the environment at low (sub-inhibitory) concentrations could select for antibiotic resistance that might disseminate to the human microbiome. In this case, low-level anthropogenic sources of antibiotics would have a significant impact on human health risk. In order to provide data necessary for the evaluation of this risk, we implemented river water microcosms at both sub-inhibitory and inhibitory concentrations of gentamicin as determined previously based on bacterial growth in enriched media. Using metagenomic sequencing and qPCR/RT-qPCR, we assessed the effects of gentamicin on water bacterial communities and their resistome. A change in the composition of total and active communities, as well as a gentamicin resistance gene selection identified via mobile genetic elements, was observed during a two-day exposure. We demonstrated the effects of sub-inhibitory concentrations of gentamicin on bacterial communities and their associated resistome in microcosms (simulating in situ conditions). In addition, we established relationships between antibiotic dose and the magnitude of the community response in the environment. The scope of resistance selection under sub-inhibitory concentrations of antibiotics and the mechanisms underlying this process might provide the basis for understanding resistance dispersion and associated risks in relatively low impacted ecosystems.
Phage-encoded ribosomal protein S21 expression is linked to late-stage phage replication
Authors: Chen Lin-Xing , Jaffe Alexander L , Borges Adair L , Penev Petar I , Nelson Tara Colenbrander , Warren Lesley A , Banfield Jillian F 
Published: March 2022

Abstract
The ribosomal protein S21 (bS21) gene has been detected in diverse viruses with a large range of genome sizes, yet its in situ expression and potential significance have not been investigated. Here, we report five closely related clades of bacteriophages (phages) represented by 47 genomes (8 curated to completion and up to 331 kbp in length) that encode a bS21 gene. The bS21 gene is on the reverse strand within a conserved region that encodes the large terminase, major capsid protein, prohead protease, portal vertex proteins, and some hypothetical proteins. Based on CRISPR spacer targeting, the predominance of bacterial taxonomic affiliations of phage genes with those from Bacteroidetes, and the high sequence similarity of the phage bS21 genes and those from Bacteroidetes classes of Flavobacteriia, Cytophagia and Saprospiria, these phages are predicted to infect diverse Bacteroidetes species that inhabit a range of depths in freshwater lakes. Thus, bS21 phages have the potential to impact microbial community composition and carbon turnover in lake ecosystems. The transcriptionally active bS21-encoding phages were likely in the late stage of replication when collected, as core structural genes and bS21 were highly expressed. Thus, our analyses suggest that the phage bS21, which is involved in translation initiation, substitutes into the Bacteroidetes ribosomes and selects preferentially for phage transcripts during the late-stage replication when large-scale phage protein production is required for assembly of phage particles.
Viral diversity is linked to bacterial community composition in alpine stream biofilms
Authors: Bekliz Meriem , Pramateftaki Paraskevi , Battin Tom Jan , Peter Hannes 
Published: March 2022

Abstract
Biofilms play pivotal roles in fluvial ecosystems, yet virtually nothing is known about viruses in these communities. Leveraging an optimized sample-to-sequence pipeline, we studied the spatiotemporal turnover of dsDNA viruses associated with stream biofilms and found an astounding diversity to be structured by seasons and along the longitudinal gradient in the stream. While some vOTUs were region- or season-specific, we also identified a large group of permanent biofilm phages, taxonomically dominated by Myoviridae. Comparison of the observed viral distribution with predictions based on neutral community assembly indicated that chance and dispersal may be important for structuring stream biofilm viral communities. Deviation from neutral model predictions suggests that certain phages distribute efficiently across distant locations within the stream network. This dispersal capacity appears to be linked to EPS depolymerases that enable phages to efficiently overcome the biofilm barrier. Other phages, particularly vOTUs classified as Siphoviridae, appear locally overrepresented and to rely on a lysogenic life cycle, potentially to exploit the spatial distribution of bacterial populations in stream biofilms. Overall, biofilm viral and bacterial community turnover were significantly coupled. Yet, viral communities were linked to the presence of the most abundant bacterial community members. With this work, we provide a foundational ecological perspective on factors that structure viral diversity in stream biofilms and identify potentially important viral traits related to the biofilm mode of life.
Facing a Clinical Challenge: Limited Empirical Support for Toddler Speech Sound Production Intervention Approaches
Authors: DeVeney Shari L. , Peterkin Kristina 
Published: March 2022

Purpose:Speech sound production intervention in early childhood is relatively rare despite empirical and theoretical support for providing this type of targeted therapy for toddlers. Challenges perpetuate the present clinical condition including those related to treatment decision making (e.g., intervention approach).Method:Although there are numerous speech sound production treatment approaches appropriate for the pediatric population, a much smaller proportion are proposed to be appropriate for children under the age of 3 years. Of these, five approaches (i.e., core vocabulary, cycles, naturalist recast, stimulability, and psycholinguistic intervention) were selected for review because they can be used to treat functional speech sound disorders produced by toddlers and none required additional clinician training for implementation.Results:We found the empirical evidence supporting the use of these approaches with children under the age of 3 years scant to nonexistent.Conclusions:Due to the lack of empirical evidence, early intervention speech-language pathologists must primarily rely on internal factors (e.g., clinician experience and client/caregiver perspectives) to support evidence-based intervention decisions in the absence of external empirical support. Clinical action steps such as careful documentation of approaches used/discontinued and associated individual client outcomes are necessary for evidence-based decision making until more robust empirical evidence is established.
Control scheme for wind–solar photovoltaic and battery‐based microgrid considering dynamic loads and distorted grid
Authors: Singh Yashi , Singh Bhim , Mishra Sukuma 
Published: March 2022

AbstractA concern regarding the deterioration in power quality (PQ) has escalated with the high level of integration of renewable energy sources to the utility, primarily in the scenario of a weak distribution grid. This paper presents a modified complex variable filter (MCVF)‐based control to enhance the power quality performance of wind–solar photovoltaic (PV) and battery‐based microgrid under the weak grid and dynamic load conditions. An MCVF attenuates the harmonics and DC bias infected voltage and current and extracts the fundamental components from distorted current and voltage. The control scheme for the voltage source converter (VSC) is presented to meet the active power demand of load/grid and attenuates harmonics to control the power quality issues at the point of common coupling. To achieve the round, the clock operation of the microgrid, a battery is interfaced to support the local loads under off‐grid mode. Therefore, the presented VSC controller supplies the continuous power to the local loads and maintains the total harmonic distortion value of grid current within the PQ Standard IEEE‐519‐2014. The simulated and test results are presented to validate the VSC controller in different operating conditions.
An LC-MS/MS Methodological Framework for Steroid Hormone
Measurement from Human Serum
Authors: Gasbarrino Karina , Daly Edward , Daskalopoulou Stella S. 
Published: March 2022

AbstractEstrogens and androgens are important regulators of sexual development and
physiological processes in men and women, acting on numerous organs throughout
the body. Moreover, they can contribute to a variety of pathologies, including
osteoporosis, cancer, and cardiovascular and neurologic diseases. Analysis of
estrogens and androgens in biological samples has been commonly performed using
immunoassays for many years. However, these assays are suboptimal, as there is
cross-reactivity with similar analytes, and they have moderate specificity and
sensitivity. Thus, there is a clinical need to develop highly sensitive and
specific methods for the accurate measurement of estrogen and androgen
concentrations. Herein, we describe the development of three liquid
chromatography coupled tandem mass spectrometry-based methods that incorporate
the use of a Triple Quadrupole Mass Spectrometer for quantitative measurement of
endogenous concentrations of various steroid hormones in human serum samples:
(1) the simultaneous measurement of testosterone, androstenedione, and cortisol,
(2) dehydroepiandrosterone (DHEA), and (3) 17β-estradiol
(E2). The use of derivatizing reagents, Girard’s reagent P
and dansyl chloride, allowed for significant gains in sensitivity in the
analysis of DHEA and E2, respectively, relative to the underivatized analyte.
These procedures proved efficient and adequately sensitive for steroid hormone
analysis in extracted patient sera samples from older men and postmenopausal
women, providing reliable data down to low nanogram/ml and
sub-nanogram/ml levels. Moreover, utilizing the combination of highly
specific mass transitions associated with these analytes and their respective
internal deuterated standards provided a high degree of specificity to the
identity of these hormones.
Quality Requirements for Medicinal Cannabis and Respective Products in the European Union – Status Quo
Authors: Veit Markus 
Published: March 2022

AbstractMedicinal cannabis and respective products have been available in EU member states as single-patient prescriptions without regular marketing authorizations for a couple of years. The
Netherlands was the first member state to realize this; in the meantime other member states have followed. Today, aside from the Netherlands, Germany is the most important market for such
products. The regulatory framework for the approval of medicinal cannabis and its distribution to patients in the EU member states is, however, not harmonized at all, and there are distinct
national regulations. Regarding the quality of such products, the general requirements for herbal medicinal products as defined in the European Pharmacopoeia, national pharmacopoeias, and
the EMA guidance documents in place beside GMP requirements in the EU are applicable. However, for a couple of aspects, every EU member state follows its own interpretation of these
requirements. To facilitate free distribution of such products between EU member states in future and to harmonize requirements for quality and GMP, an EU-wide approach is needed. As a first
step, this should be realized by implementing monographs for cannabis medicinal products in the European Pharmacopoeia.