bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlled Administration of Dehydrochloromethyltestosterone in Humans: Urinary Excretion and Long-Term Detection of Metabolites for Anti-Doping Purpose
Authors: Loke Steffen , de la Torre Xavier , Iannone Michele , Piana Giuseppe La , Schlörer Nils , Botrè Francesco , Bureik Matthias , Parr Maria Kristina 
Published: August 2021

AbstractDehydrochloromethyltestosterone (DHCMT) is an anabolic-androgenic steroid that was developed by Jenapharm in the 1960s and was marketed as Oral Turinabol®. It is prohibited in sports at all times; nevertheless, there are several findings by anti-doping laboratories every year. New long-term metabolites have been proposed in 2011/12, which resulted in adverse analytical findings in retests of the Olympic games of 2008 and 2012. However, no controlled administration trial monitoring these long-term metabolites was reported until now. In this study, DHCMT (5 mg, p.o.) was administered to five healthy male volunteers and their urine samples were collected for a total of 60 days. The unconjugated and the glucuronidated fraction were analyzed separately by gas chromatography coupled to tandem mass spectrometry. The formation of the described long-term metabolites was verified, and their excretion monitored in detail.Due to interindividual differences there were several varieties in the excretion profiles among the volunteers. The metabolite M3, which has a fully reduced A-ring and modified D-ring structure, was identified by comparison with reference material as 4α-chloro-17β-hydroxymethyl-17α-methyl-18-nor-5α-androstan-13-en-3α-ol. It was found to be suitable as long-term marker for the intake of DHCMT in four of the volunteers. In one of the volunteers, it was detectable for 45 days after single oral dose administration. However, in two of the volunteers M5 (already published as long-term metabolite in the 1990s) showed longer detection windows. In one volunteer M3 was undetectable but another metabolite, M2, was found as the longest detectable metabolite.The last sample clearly identified as positive was collected between 9.9 and 44.9 days. Furthermore, the metabolite epiM4 (partially reduced A-ring and a modified D-ring structure which is epimerized in position 17 compared to M3) was identified in the urine of all volunteers with the help of chemically synthesized reference as 4-chloro-17α-hydroxymethyl-17β-methyl-18-nor-androsta-4,13-dien-3β-ol. It may serve as additional confirmatory metabolite.It is highly recommended to screen for all known metabolites in both fractions, glucuronidated and unconjugated, to improve identification of cheating athletes. This study also offers some deeper insights into the metabolism of DHCMT and of 17α-methyl steroids in general.
Dynamic Cognitive States Predict Individual Variability in Behavior and Modulate with EEG Functional Connectivity during Working Memory
Authors: Beauchene Christine , Hinault Thomas , Sarma Sridevi V. , Courtney Susan 
Published: August 2021

AbstractFluctuations in strategy, attention, or motivation can cause large variability in performance across task trials. Typically, this variability is treated as noise, and assumed to cancel out, leaving supposedly stable relationships among behavior, neural activity, and experimental task conditions. Those relationships, however, could change with a participant’s internal cognitive states, and variability in performance may carry important information regarding those states, which cannot be directly measured. Therefore, we used a mathematical, state-space modeling framework to estimate internal states from measured behavioral data, quantifying each participant’s sensitivity to factors such as past errors or distractions, to predict their reaction time fluctuations. We show how modeling these states greatly improves trial-by-trial prediction of behavior. Further, we identify EEG functional connectivity features that modulate with each state. These results illustrate the potential of this approach and how it could enable quantification of intra- and inter-individual differences and provide insight into their neural bases.Statement of RelevanceCognitive behavioral performance and its neural bases vary both across individuals and within individuals over time. Understanding this variability may be key to the success of clinical or educational interventions. Internal cognitive states reflecting differences in strategy, attention, and motivation may drive much of these inter- and intra-individual differences, but often cannot be reliably controlled or measured in cognitive neuroscience research. The mathematical modeling framework developed here uses measured data to estimate a participant’s dynamic, internal cognitive states, with each state derived from specific factors hypothesized to affect attention, motivation or strategy. The results highlight potential sources of behavioral variability and reveal EEG features that modulate with each state. Our method quantifies and characterizes individual behavioral differences and highlights their underlying neural mechanisms, which could be used for future targeted training or neuromodulation therapies to improve cognitive performance.
Rapid Prototyping of Cell Culture Microdevices Using Parylene-Coated 3D Prints
Authors: O’Grady Brian J. , Geuy Michael D. , Kim Hyosung , Balotin Kylie M. , Allchin Everett R. , Florian David C. , Bute Neelansh N. , Scott Taylor E. , Lowen Gregory B. , Fricker Colin M. , Guelcher Scott A. , Wikswo John P. , Bellan Leon M. , Lippmann Ethan S. 
Published: August 2021

AbstractFabrication of microfluidic devices by photolithography generally requires specialized training and access to a cleanroom. As an alternative, 3D printing enables cost-effective fabrication of microdevices with complex features that would be suitable for many biomedical applications. However, commonly used resins are cytotoxic and unsuitable for devices involving cells. Furthermore, 3D prints are generally refractory to elastomer polymerization such that they cannot be used as master molds for fabricating devices from polymers (e.g. polydimethylsiloxane, or PDMS). Different post-print treatment strategies, such as heat curing, ultraviolet light exposure, and coating with silanes, have been explored to overcome these obstacles, but none have proven universally effective. Here, we show that deposition of a thin layer of parylene, a polymer commonly used for medical device applications, renders 3D prints biocompatible and allows them to be used as master molds for elastomeric device fabrication. When placed in culture dishes containing human neurons, regardless of resin type, uncoated 3D prints leached toxic material to yield complete cell death within 48 hours, whereas cells exhibited uniform viability and healthy morphology out to 21 days if the prints were coated with parylene. Diverse PDMS devices of different shapes and sizes were easily casted from parylene-coated 3D printed molds without any visible defects. As a proof-of-concept, we rapid prototyped and tested different types of PDMS devices, including triple chamber perfusion chips, droplet generators, and microwells. Overall, we suggest that the simplicity and reproducibility of this technique will make it attractive for fabricating traditional microdevices and rapid prototyping new designs. In particular, by minimizing user intervention on the fabrication and post-print treatment steps, our strategy could help make microfluidics more accessible to the biomedical research community.
Rescue of behavioral and electrophysiological phenotypes in a Pitt-Hopkins syndrome mouse model by genetic restoration of Tcf4 expression
Authors: Kim Hyojin , Gao Eric B. , Draper Adam , Berens Noah C. , Vihma Hanna , Zhang Xinyuan , Higashi-Howard Alexandra , Ritola Kimberly D. , Simon Jeremy M. , Kennedy Andrew J. , Philpot Benjamin D. 
Published: August 2021

AbstractPitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by monoallelic mutation or deletion in the transcription factor 4 (TCF4) gene. Individuals with PTHS typically present in the first year of life with developmental delay and exhibit intellectual disability, lack of speech, and motor incoordination. There are no effective treatments available for PTHS, but the root cause of the disorder, TCF4 haploinsufficiency, suggests that it could be treated by normalizing TCF4 gene expression. Here we performed proof-of-concept viral gene therapy experiments using a conditional Tcf4 mouse model of PTHS and found that postnatally reinstating Tcf4 expression in neurons improved anxiety-like behavior, activity levels, innate behaviors, and memory. Postnatal reinstatement also partially corrected EEG abnormalities, which we characterized here for the first time, and the expression of key TCF4-regulated genes. Our results support a genetic normalization approach as a treatment strategy for PTHS, and possibly other TCF4-linked disorders.
QT-AMP: Quanti-Tray-based amplicon sequencing for simultaneous quantification and identification of enterococci for microbial source tracking
Authors: Urakawa Hidetoshi , Hancock Taylor L. , Kratz Michael A. , Armstrong Rick A. 
Published: August 2021

ABSTRACTEnterococcus is ubiquitous in human feces and has been adopted as a useful indicator of human fecal pollution in water. Although regular enterococci monitoring only examines their numbers, identification of human-specific Enterococcus species or genotypes could help in the discrimination of human fecal contamination from other environmental sources. We documented a new approach to characterize enterococci using an amplicon sequencing platform from Quanti Trays after following the counting of most probable numbers (MPN) of enterococci. We named this method as QT-AMP (Quanti-Tray-based amplicon sequencing). We tested surface water samples collected from three rivers in southwest Florida. We detected 11 Enterococcus species from 45 samples in 1.1 million sequence reads. The method detected three rare species and eight cosmopolitan species (Enterococcus faecalis, E.faecium, E. casseliflavus, E. hirae, E. mundtii, E. gallinarum, E. avium, and E. durans) which have been commonly documented in various enterococci isolation studies. It is likely that the approximate detection level of QT-AMP is four orders of magnitude higher than regular 16S rRNA gene amplicon sequencing. QT-AMP revealed that a majority of Enterolert positive signals are actually the mixture of both enterococci and other facultative aerobes and anaerobes. QT-AMP may have the potential to monitor not only enterococci but also other pathogenic bacteria commonly found in natural environments. This QT-AMP could be a powerful tool to streamline the quantification and identification of enterococci and allows us to do more accurate and efficient microbial source tracking in various water management projects and human health risk assessment.HighlightsA selected primer set (27f-519r) can differentiate over 50 Enterococcus species and is suitable for Illumina amplicon sequencing.The median of the relative contribution of enterococci reads among total sequencing reads was 82.7% and ranged between 0% and 100%.Enterolert signals are most likely the mixture of enterococci and other facultative aerobes and anaerobes.We identified eight cosmopolitan enterococci species and three rare species.The median of the relative contribution of non-enterococci reads among total sequencing reads was 17.3%, respectively, and ranged between 0% and 100%.
Event-Related Phase Synchronization Propagates Rapidly across Human Ventral Visual Cortex
Authors: Woolnough Oscar , Forseth Kiefer J. , Rollo Patrick S. , Roccaforte Zachary J. , Tandon Nitin 
Published: August 2021

AbstractVisual inputs to early visual cortex integrate with semantic, linguistic and memory inputs in higher visual cortex, in a manner that is rapid and accurate, and enables complex computations such as face recognition and word reading. This implies the existence of fundamental organizational principles that enable such efficiency. To elaborate on this, we performed intracranial recordings in 82 individuals while they performed tasks of varying visual and cognitive complexity. We discovered that visual inputs induce highly organized posterior-to-anterior propagating patterns of phase modulation across the ventral occipitotemporal cortex. At individual electrodes there was a stereotyped temporal pattern of phase progression following both stimulus onset and offset, consistent across trials and tasks. The phase of low frequency activity in anterior regions was predicted by the prior phase in posterior cortical regions. This spatiotemporal propagation of phase likely serves as a feed-forward organizational influence enabling the integration of information across the ventral visual stream. This phase modulation manifests as the early components of the event related potential; one of the most commonly used measures in human electrophysiology. These findings illuminate fundamental organizational principles of the higher order visual system that enable the rapid recognition and characterization of a variety of inputs.
Predictive framework of macrophage activation
Authors: Sanin David E. , Ge Yan , Marinkovic Emilija , Kabat Agnieszka M. , Castoldi Angela , Caputa George , Grzes Katarzyna M. , Curtis Jonathan D. , Willenborg Sebastian , Dichtl Stefanie , Reinhardt Susanne , Dahl Andreas , Pearce Erika L. , Eming Sabine A. , Gerbaulet Alexander , Roers Axel , Murray Peter J. , Pearce Edward J. 
Published: August 2021

AbstractMacrophages populate every organ during homeostasis and disease, displaying features of tissue imprinting and heterogeneous activation. The disjointed picture of macrophage biology that emerged from these observations are a barrier for integration across models or within vitromacrophage activation paradigms. We set out to contextualize macrophage heterogeneity across mouse tissues and inflammatory conditions, specifically aiming to define a common framework of macrophage activation. We built a predictive model with which we mapped the activation of macrophages across 12 tissues and 25 biological conditions, finding a striking commonality and finite number of transcriptional profiles, which we modelled as defined stages along four conserved activation paths. We verified this model with adoptive cell transfer experiments and identified transient RELMɑ expression as a feature of macrophage tissue engraftment. We propose that this integrative approach of macrophage classification allows the establishment of a common predictive framework of macrophage activation in inflammation and homeostasis.One Sentence SummaryWe propose an integrative approach of macrophage classification that allows the establishment of a common framework of macrophage activation in inflammation and homeostasis.
Broadening the toolkit for quantitatively evaluating noncanonical amino acid incorporation in yeast
Authors: Stieglitz J.T. , Potts K.A. , Van Deventer J.A. 
Published: August 2021

AbstractGenetic code expansion is a powerful approach for advancing critical fields such as biological therapeutic discovery. However, the machinery for genetically encoding noncanonical amino acids (ncAAs) is only available in limited plasmid formats, constraining potential applications. In extreme cases, the introduction of two separate plasmids, one containing an orthogonal translation system (OTS) to facilitate ncAA incorporation and a second for expressing a ncAA-containing protein of interest, is not possible due to lack of convenient selection markers. One strategy to circumvent this challenge is to express the OTS and protein of interest from a single vector. For what we believe is the first time in yeast, we describe here several sets of single plasmid systems (SPSs) for performing genetic code manipulation and compare the ncAA incorporation capabilities of these plasmids against the capabilities of previously described dual plasmid systems (DPSs). For both dual fluorescent protein reporters and yeast display reporters tested with multiple OTSs and ncAAs, measured ncAA incorporation efficiencies with SPSs were determined to be equal to or improved relative to efficiencies determined with DPSs. Click chemistry on yeast cells displaying ncAA-containing proteins was also shown to be feasible in both formats, although differences in reactivity between formats suggest the need for caution when using such approaches. Additionally, we investigated whether these reporters would support separation of yeast strains known to exhibit distinct ncAA incorporation efficiencies. Model sorts conducted with mixtures of two strains transformed with the same SPS or DPS led to enrichment of a strain known to support higher efficiency ncAA incorporation, suggesting that these reporters will be suitable for conducting screens for strains exhibiting enhanced ncAA incorporation efficiencies. Overall, our results confirm that SPSs are well-behaved in yeast and provide a convenient alternative to DPSs. In particular, SPSs are expected to be invaluable for conducting high-throughput investigations of the effects of genetic or genomic changes on ncAA incorporation efficiency and, more fundamentally, the eukaryotic translation apparatus.Abstract Figure
A role of cryptochrome for magnetic field-dependent improvement of sleep quality, lifespan and motor function in Drosophila
Authors: Kawasaki Haruhisa , Okano Hideyuki , Ishiwatari Hiromi , Kishi Tetsuo , Ishida Norio 
Published: August 2021

AbstractUnderstanding the molecular genetic basis of animal magnet reception has been one of the big challenges in biology. Recently it was discovered that the magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry).Here, using the fruit fly as a magnet receptive model organism, we show that exposure to a specific AC magnetic field during night time affected the health of the fly. AC magnetic field exposure showed lifespan extension under starvation, sleep improvement and prevention of decreased motor function. In contrast, all the health improvement effect was not observed in cryptochrome mutant flies (cryb). We showed that AC magnetic field exposure prevented motor dysfunction in Gaucher’s disease model Drosophila. The data suggests that magnetic field-dependent improvement of sleep quality, lifespan and motor function is mediated through a cry-dependent pathway in animals.
Comparative analysis of post-vaccination anti-spike IgG antibodies in old Nursing Home Residents and in middle-aged Healthcare workers
Authors: Jeulin H. , Craus D. , Labat C. , Benetos A. 
Published: August 2021

AbstractThe current consensus is that 2 doses of mRNA vaccines against SARS-CoV-2 are needed for people without COVID-19 history, while for those who had suffered COVID-19, a single dose may be enough to achieve high levels of immunization. This consensus has been based on results obtained in middle-aged populations, whereas only few data exist for the oldest and most frail adults such as nursing home residents (NH-Res) that is, the population most vulnerable to develop severe forms of COVID-19.In this study, we studied the anti-SARS-CoV-2 IgG(S) level of NH-Res and healthcare workers (HCWs) with or without a history of COVID-19 infection taking into account the time since immunization (COVID-19 and/or vaccination). 654 subjects were analyzed: 397 NH-Res (median age 88, IQR 82-93 years, 75% women) and 257 Health Care Workers (HCWs, median 46, IQR 38-54 years, 81% women). NH-Res and HCWs were classified in one of the following 3 groups: No-COVID history and 2 vaccine shots (COV-NO/2VACC); Yes-COVID history and 1 (COV-YES/1VACC) or 2 (COV-YES/2VACC) vaccine injections.The time-related decrease in IgG (S) in subjects without COVID-19 history, SARS-COV-2 serology would be negative in HCWs approximately 220 days and in residents 180 days after vaccination. This time-related decrease was much slower in those with history of COVID. NH-Res belonging into the COV-NO/2VACC and the COV-YES/1VACC groups showed lower IgG (S) levels than the same groups of HCWs (for both groups, p<0.0001), whereas in the group COV-YES/2VACC, IgG (S) levels were similar in NH-Res and HCWs (p=0.88). These results remained unchanged after adjustment for age and duration since immunization. Thus, in NH-Res, 2 vaccine shots were associated with a more pronounced immune response, whereas in HCWs, 1 or 2 vaccine shots in patients with COVID-19 history did make any difference. These results indicate significant differences in mRNA vaccination between NH-Res and middle-aged controls, and could contribute to the specification of vaccine policy in this very old, frail population.
Azithromycin in patients with Covid-19; a systematic review and metanalysis
Authors: Ayerbe Luis , Forgone Ivo , Risco-Risco Carlos , Pérez-Piñar Maria , Ayis Salma 
Published: August 2021

AbstractBackgroundAzithromycin (AZM) has been widely used in the management of Covid-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and metanalysis summarizes the available evidence to date on the beneficial and adverse effect of AZM in patients with Covid-19.MethodsThe PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated, and not treated, with AZM, indexed until the 5th of July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials, and MedRXivs. We used Random-effects models to estimate pooled effect size from aggregate data.ResultsThe initial search produced 4950 results. Finally, 16 studies, five RCTs and 11 with an observational design, with a total of 22984 patients, were included. The metanalysis showed no difference in mortality for those treated, or not, with AZM, OR: 0.95 (0.79-1.13). There was also no significant difference for those treated, and not, with AZM in need for hospital admission or time to admission from ambulatory settings, clinical severity, need for intensive care, or adverse effects.ConclusionsThese results presented in this review do not support the use of AZM in the management of Covid-19. They also show that any harm caused to the patient who received it is unlikely. Future research on treatment for patients with Covid-19 may need to focus on other drugs.