bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluctuating Palmar Erythema in a Toddler during COVID-19 Pandemic: Do You Know the Offender?
Authors: Panda Prateek Kumar , Sharawat Indar Kumar 
Published: February 2021

AbstractPalmar erythema in children can be due to various reasons, such as chronic liver disease, rheumatological disorders, medications, irritant contact dermatitis and atopic dermatitis. Recently, there are few reports about contact dermatitis caused by frequent, daily use of hand sanitizers during this COVID-19 pandemic. A 3-year-old toddler brought with the concern of waxing-waning bilateral palmar erythema for the past 2 weeks. The parents revealed that the child liked the bright color of a recently bought hand sanitizer bottle so much he used to wash his hands every 20–30 min throughout the day. The atypical presentation of contact dermatitis might be because the child was using the sanitizer more frequently during the daytime. The dermatitis resolved with stopping excessive use of the hand sanitizer by the toddler. Clinicians should be aware of contact dermatitis during these pandemic times. Instead of investigating them extensively, careful history taking and merely advising them to judicially utilize the sanitizer can lead to complete reversal of symptoms.
Tuberous Sclerosis Complex: Early Screening and Infant Outcome in NICU
Authors: Su Yajie , Wei Qiufen , Wan Jing , Li Long 
Published: February 2021

Abstract

Objective
We describe the clinical and genetic features, drug use and neuropsychiatric disorders of infants diagnosed with tuberous sclerosis complex (TSC) within 3 months of age at a neonatal intensive care unit (NICU) to better understand the different outcomes from early screening.

Methods
In this retrospective study, we consisted of 42 infants with a definitive TSC diagnosis by genetic criteria (TSC1 = 8, TSC2 = 34). The different phenotypes and outcomes between patients with TSC1 and TSC2 mutations were analyzed.

Results
The most common initial presenting features of TSC were cortical tubers on magnetic resonance imaging (50%), hypomelanotic macules on skin (47.61%) and spasm (42.85%), when they were diagnosed. Following disease progression to time of follow-up 1 year later, we found that the rate of epilepsy increased from 42.85% to 75.61% and that of cardiac rhabdomyoma increased from 28.57% to 43.9%. The median age at first presentation was 7.84 ± 1.88 months. We also found that 54.83% of patients on medication were seizure free for over 1 year, and that 43.9% of patients have intellectual disability. In total, 42 variants of TSC were detected, including 12 novel variants. We found no evidence of an association between different clinical features and their outcomes among patients with different gene mutations.

Conclusion
Early diagnosis of TSC in NICU opens a window of opportunity for early, more effective treatment of epilepsy as well as reduces the risk of neurological conditions.
Lack of Causal Effects or Genetic Correlation between Restless Legs Syndrome and Parkinson’s Disease
Authors: Estiar Mehrdad A , Senkevich Konstantin , Yu Eric , Varghaei Parizad , Krohn Lynne , Bandres-Ciga Sara , Noyce Alastair J , Rouleau Guy A , Gan-Or Ziv 
Published: February 2021

AbstractBackgroundEpidemiological studies have reported association between Parkinson’s disease (PD) and restless legs syndrome (RLS).ObjectivesWe aimed to use genetic data to study whether these two disorders are causally linked or share genetic architecture.MethodsWe performed two-sample Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) using summary statistics from recent genome-wide meta-analyses of PD and RLS.ResultsWe found no evidence for a causal relationship between RLS (as the exposure) and PD (as the outcome, inverse variance-weighted; b=-0.003, se=0.031, p=0.916, F-statistic=217.5). Reverse MR also did not demonstrate any causal effect of PD on RLS (inverse variance-weighted; b=-0.012, se=0.023, p=0.592, F-statistic=191.7). LDSC analysis demonstrated lack of genetic correlation between RLS and PD (rg=-0.028, se=0.042, p=0.507).ConclusionsThere was no evidence for a causal relationship or genetic correlation between RLS and PD. The associations observed in epidemiological studies could be, in part, attributed to confounding or non-genetic determinants.
RNA-binding proteins regulate aldosterone homeostasis in human steroidogenic cells
Authors: Fu Rui , Wellman Kimberly , Baldwin Amber , Rege Juilee , Walters Kathryn , Hirsekorn Antje , Riemondy Kent , Rainey William , Mukherjee Neelanjan 
Published: February 2021

ABSTRACTAngiotensin II (AngII) binds to the type I angiotensin receptor in the adrenal cortex to initiate a cascade of events leading to the production of aldosterone, a master regulator of blood pressure. Despite extensive characterization of the transcriptional and enzymatic control of adrenocortical steroidogenesis, there are still major gaps in our knowledge related to precise regulation of AII-induced gene expression kinetics. Specifically, we do not know the regulatory contribution of RNA-binding proteins (RBPs) and RNA decay, which can control the timing of stimulus-induced gene expression. To investigate this question, we performed a high-resolution RNA-seq time course of the AngII stimulation response and 4-thiouridine pulse labeling in a steroidogenic human cell line (H295R). We identified twelve temporally distinct gene expression responses that contained mRNA encoding proteins known to be important for various steps of aldosterone production, such as cAMP signaling components and steroidogenic enzymes. AngII response kinetics for many of these mRNAs revealed a coordinated increase in both synthesis and decay. These findings were validated in primary human adrenocortical cells stimulated ex vivo with AngII. Using a candidate siRNA screen, we identified a subset of RNA-binding protein and RNA decay factors that activate or repress AngII-stimulated aldosterone production. Among the repressors of aldosterone were BTG2, which promotes deadenylation and global RNA decay. BTG2 was induced in response to AngII stimulation and promoted the repression of mRNAs encoding pro-steroidogenic factors indicating the existence of an incoherent feedforward loop controlling aldosterone homeostasis. Together, these data support a model in which coordinated increases in transcription and regulated RNA decay facilitates the major transcriptomic changes required to implement a pro-steroidogenic gene expression program that is temporally restricted to prevent aldosterone overproduction.
Whole-genome analysis of antimicrobial-resistantEscherichia coliin human gut microbiota reveals its origin and flexibility in transmittingmcr-1
Authors: Ding Yichen , Saw Woei-Yuh , Tan Linda Wei Lin , Moong Don Kyin Nwe , Nagarajan Niranjan , Teo Yik Ying , Seedorf Henning 
Published: February 2021

AbstractMultidrug resistant (MDR)Escherichia colistrains that carry extended-spectrum β-lactamases (ESBLs) or colistin resistance genemcr-1have been identified in the human gut at an increasing incidence worldwide. In this study, we sampled and characterized MDR Enterobacteriaceae from the gut microbiota of healthy Singaporeans and show that the prevalence of ESBL-producing andmcr-positive Enterobacteriaceae is 26.6% and 7.3%, respectively. Whole-genome sequencing of 37E. coliisolates identified 25 sequence types and assigned them into six different phylogroups, suggesting that the human intestinal MDRE. colistrains are highly diverse. In addition, we found thatE. coliisolates belonging to phylogroup D, B2 and F carry a higher number of virulence genes, whereas isolates of phylogroup A, B1 and E carry fewer virulence factor genes but are frequent carriers of florfenicol resistance genefloRand colistin resistance genemcr-1. Comparison of the sevenmcr-1-positiveE. coliisolates revealed thatmcr-1is carried by conjugative plasmids or embedded in composite transposons, which could potentially mobilizemcr-1to other pathogenic Enterobacteriaceae strains or MDR plasmids. Finally, we found that 12 out of the 37 MDRE. coliisolates in this study show high similarity to ESBL-producingE. coliisolates from raw meats from local markets, suggesting a potential transmission of MDRE. colifrom meat products to the human gut microbiota. Our findings show diverse antibiotic resistance and virulence profiles of intestinalE. coliand call for better countermeasures to block the transmission of MDRE. colivia the food chain.ImportanceThe human gut can harbor both antibiotic resistant and virulentE. coliwhich may subsequently cause infections. In this study, the antibiotic resistance and virulence traits of antibiotic-resistantE. coliisolates from human gut microbiota of healthy subjects were investigated. The isolatedE. colistrains carry a diverse range of antibiotic resistance mechanisms and virulence factor genes, are highly diverse to each other, and are likely to originate from raw meat products from the local markets. Of particular concern are sevenE. coliisolates which carry colistin resistance genemcr-1. This gene can be mobilized into other pathogens and MDR plasmids, thereby spreading resistance to the last-resort antibiotic colistin. Our findings also suggest that raw meat could serve as important source to transmit MDR bacteria into the human gut microbiota.
Strategies to assure optimal trade-offs among competing objectives for genetic improvement of soybean
Authors: Ramasubramanian Vishnu , Beavis William 
Published: February 2021

AbstractPlant breeding is a decision making discipline based on understanding project objectives. Genetic improvement projects can have two competing objectives: maximize rate of genetic improvement and minimize loss of useful genetic variance. For commercial plant breeders competition in the marketplace forces greater emphasis on maximizing immediate genetic improvements. In contrast public plant breeders have an opportunity, perhaps an obligation, to place greater emphasis on minimizing loss of useful genetic variance while realizing genetic improvements. Considerable research indicates that short term genetic gains from Genomic Selection (GS) are much greater than Phenotypic Selection (PS), while PS provides better long term genetic gains because PS retains useful genetic diversity during the early cycles of selection. With limited resources must a soybean breeder choose between the two extreme responses provided by GS or PS? Or is it possible to develop novel breeding strategies that will provide a desirable compromise between the competing objectives? To address these questions, we decomposed breeding strategies into decisions about selection methods, mating designs and whether the breeding population should be organized as family islands. For breeding populations organized into islands decisions about possible migration rules among family islands were included. From among 60 possible strategies, genetic improvement is maximized for the first five to ten cycles using GS, a hub network mating design in breeding populations organized as fully connected family islands and migration rules allowing exchange of two lines among islands every other cycle of selection. If the objectives are to maximize both short-term and long-term gains, then the best compromise strategy is similar except a genomic mating design, instead of a hub networked mating design, is used. This strategy also resulted in realizing the greatest proportion of genetic potential of the founder populations. Weighted genomic selection applied to both non-isolated and island populations also resulted in realization of the greatest proportion of genetic potential of the founders, but required more cycles than the best compromise strategy.
Cultivation-based quantification and identification of bacteria at two hygienic key sides of domestic washing machines
Authors: Jacksch Susanne , Zohra Huzefa , Weide Mirko , Schnell Sylvia , Egert Markus 
Published: February 2021

AbstractDetergent drawer and door seal represent important sites for microbial life in domestic washing machines. Interestingly, quantitative data on microbial contamination of these sites is scarce. Here, 10 domestic washing machines were swap-sampled for subsequent bacterial cultivation at four different sampling sites, each: detergent drawer, detergent drawer chamber as well as top and bottom part of the rubber door seal. The average bacterial load over all washing machines and sites was 2.1 ± 1.0 × 104CFU cm−2(average ± standard error of the mean (SEM)). The top part of the door seal showed the lowest contamination (11.1 ± 9.2 × 101CFU cm−2), probably due to less humidity.Out of 212 isolates, 178 (84%) were identified on genus level and 118 (56%) on species level using MALDI biotyping, resulting in 29 genera and 40 identified species across all machines. The predominant bacterial genera wereStaphylococcusandMicrococcus, which were found at all sites. 21 out of 40 species were classified as opportunistic pathogens, emphasizing the need for regular cleaning of the investigated sites.
Stable behavioral state-specific large scale activity patterns in the developing cortex of neonates
Authors: Mojtahedi Nima , Kovalchuk Yury , Böttcher Alexander , Garaschuk Olga 
Published: February 2021

AbstractEndogenous neuronal activity is a hallmark of the developing brain. In rodents, a handful of such activities were described in different cortical areas but the unifying macroscopic perspective is still lacking. Here we combined large-scalein vivoCa2+imaging of the dorsal cortex in non-anesthetized neonatal mice with advanced mathematical analyses to reveal unique behavioral state-specific maps of endogenous activity. These maps were remarkably stable over time within and across experiments and used patches of correlated activity with little hemispheric symmetry as well as stationary and propagating waves as building blocks. Importantly, the maps recorded during motion and rest were almost inverse, with sensory-motor areas active during motion and posterior-lateral areas active at rest. The retrosplenial cortex engaged in both resting- and motion-related activities, building functional long-range connections with respective cortical areas. The data obtained bind different region-specific activity patterns described so far into a single consistent picture and set the stage for future inactivation studies, probing the exact function of this complex activity pattern for cortical wiring in neonates.
Quantitative Analysis of Plasmodesmata Permeability using Cultured Tobacco BY-2 Cells Entrapped in Microfluidic Chips
Authors: Shimizu Kazunori , Kikkawa Masahiro , Tabata Ryo , Kurihara Daisuke , Kurotani Ken-ichi , Honda Hiroyuki , Notaguchi Michitaka 
Published: February 2021

AbstractPlasmodesmata are unique channel structures in plants that link the fluid cytoplasm between adjacent cells. Plants have evolved these microchannels to allow trafficking of nutritious substances as well as signaling molecules for intercellular communication. However, tracking the behavior of plasmodesmata in real time is difficult because they are located inside tissues. Hence, we developed a microfluidic device that traps cultured cells and fixes their positions to allow testing of plasmodesmata permeability. The device has 112 tandemly aligned trap zones in the flow channel. Cells of the tobacco line BY-2 were cultured for 7 days and filtered using a sieve and a cell strainer before use to isolate short cell clusters consisting of only a few cells. The isolated cells were introduced into the flow channel, resulting in entrapment of cell clusters at 25 out of 112 trap zones (22.3%). Plasmodesmata permeability was tested from 1 to 4 days after trapping the cells. During this period, the cell numbers increased through cell division. Fluorescence recovery after photobleaching experiments using a transgenic marker line expressing nuclear-localized H2B-GFP demonstrated that cell-to-cell movement of H2B-GFP protein occurred within 200 min of photobleaching. The transport of H2B-GFP protein was not observed when sodium chloride, a compound known to cause plasmodesmata closure, was present in the microfluid channel. Thus, this microfluidic device and one-dimensional plant cell samples allowed us to observe plasmodesmata behavior in real time under controllable conditions.
Optimizing EEG source reconstruction with concurrent fMRI-derived spatial priors
Authors: Abreu Rodolfo , F. Soares Júlia , Batista Sónia , Cláudia Lima Ana , Sousa Lívia , Castelo-Branco Miguel , Duarte João Valente 
Published: February 2021

AbstractReconstructing EEG sources involves a complex pipeline, with the inverse problem being the most challenging. Multiple inversion algorithms are being continuously developed, aiming to tackle the non-uniqueness of this problem, which has been shown to be partially circumvented by also including fMRI-derived spatial priors in the inverse models. However, only task activation maps and resting-state networks (RSNs) have been explored so far, overlooking the recent, but already accepted, notion that brain networks exhibit dynamic functional connectivity (dFC) fluctuations. Moreover, there is no consensus regarding the inversion algorithm of choice, nor a systematic comparison between different sets of spatial priors. Using simultaneous EEG-fMRI data, here we compared four different inversion algorithms (MN, LORETA, EBB and MSP) under a Bayesian framework, each with three different sets of priors consisting of: 1) those specific to the algorithm (S1); 2) S1plus fMRI task activation maps and RSNs (S2); and 3) S2plus network modules of task-related dFC states estimated from the dFC fluctuations (S3). The quality of the reconstructed EEG sources was quantified in terms of model-based metrics, namely the free-energy and variance explained of the inversion models, and the overlap/proportion of brain regions known to be involved in the visual perception tasks that the participants were submitted to, and RSN templates, with/within EEG source components. Model-based metrics suggested that model parsimony is preferred, with the combination MSP+S1exhibiting the best performance. However, optimal overlap/proportion values were found using EBB+S2or MSP+S3, respectively, indicating that fMRI spatial priors, including dFC state modules, are crucial for the EEG source components to reflect neuronal activity of interest. Our results pave the way towards a more informative selection of the optimal EEG source reconstruction approach, which may be crucial in future studies.
Rules for the self-assembly of ESCRT-III on endosomes
Authors: Sprenger Simon , Migliano Simona M. , Oleschko Florian , Kobald Marvin , Hess Michael , Teis David 
Published: February 2021

We, the authors, have withdrawn this manuscript. During our work on the revision of this manuscript for eLife, it became clear that several key results of the manuscript were not reproducible by my lab. The rules for ESCRT-III assembly and the model that we have proposed in this manuscript are no longer supported by the data. Currently we are performing additional experiments to test some of our conclusions further. Therefore, we do not wish this work to be cited.We sincerely apologize to the scientific community for any inconvenience resulting from this manuscript.If you have any questions, please contact the corresponding author.
Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma
Authors: Ray Arja , Callaway Mackenzie K. , Rodríguez-Merced Nelson J. , Crampton Alexandra L. , Carlson Marjorie , Emme Kenneth B. , Ensminger Ethan A. , Kinne Alexander A. , Schrope Jonathan H. , Rasmussen Haley R. , Jiang Hong , Denardo David G. , Wood David K. , Provenzano Paolo P. 
Published: February 2021

AbstractPancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here in both murine and human PDA we demonstrate that extracellular matrix architecture regulates cell extrusion and subsequent invasion from intact ductal structures through Tumor-Associated Collagen Signatures (TACS), resulting in early dissemination from histologically pre-malignant lesions and continual invasion from well-differentiated disease. Furthermore, we show that pancreatitis results in invasion-conducive architectures, thus priming the stroma prior to malignant disease. Analysis in novel microfluidics-derived microtissues andin vivodemonstrates decreased extrusion and invasion following focal adhesion kinase (FAK) inhibition, consistent with decreased metastasis. Thus, data suggest that targeting FAK or strategies to re-engineer and normalize tumor microenvironments, may have a role not only in also in very early disease but also for limiting continued dissemination from unresectable disease. Likewise, it may be beneficial to employ stroma targeting strategies to resolve precursor diseases such as pancreatitis in order to remove stromal architectures that increase risk for early dissemination.Impact StatementCollagen architectures in the tumor stroma facilitate dissemination of carcinoma cells from the earliest histologically “pre-malignant” lesions and continue to promote disease spread from well-differentiated PDA.
Structural connectome fingerprinting and age prediction in pediatric development: assessing voxel- and surface-based white matter connectivity
Authors: Al-Sharif Noor B , St-Onge Etienne , Vogel Jacob W , Descoteaux Maxime , Evans Alan C 
Published: February 2021

AbstractMapping structural white matter connectivity is a challenge, with many barriers to accurate representation. Here, we assessed the replicability and reliability of two connectome-generating methods, voxel- or surface-based, using test-retest analyses, fingerprinting and age prediction. The two connectomic methods are initiated by the same state-of-the-art dMRI processing pipeline before diverging at the tractography and connectome-generating steps using either voxels or surfaces. While both methods performed very well across all analyses, voxel-based connectomes performed marginally better than surface-based connectomes. Notably, structural connectomes derived from either method demonstrate reliably accurate representations of both individuals and their chronological age, comparable to similar analyses employing multi-modal features. The difference in methodological performance could be attributed to a number of method-specific features but ultimately show that cutting-edge tractography with robust dMRI processing produces reliable white matter connectivity measures.
Paradoxical Roles of Peritumoral Myofibroblasts in Intrahepatic Cholangiocarcinoma Growth and Metastasis
Authors: Tian Cheng , Li Liyuan , Li Yizhen , Fan Li , Brown Anthony , Morrison Michelle , Norris Eric J. , Yang Jun J. , Glazer Evan S. , Zhu Liqin 
Published: February 2021

ABSTRACTIntrahepatic cholangiocarcinoma (iCCA) is an aggressive type of primary liver cancer characterized by its highly desmoplastic stroma. Compared to the ample knowledge on cancer-associated fibroblast residing within iCCA tumor mass, little is known about the fibrotic response from the tumor-surrounding liver and its role in iCCA development. In this study, we find a significant accumulation of peritumoral myofibroblasts (pMFs) in both patient iCCA and tumors from an iCCA orthotopic allograft mouse model. Using tumor and liver spheroid coculture we show that iCCA-liver interaction induces rapid pMF accumulation at the interface. We find pMFs placed around iCCA spheroids exert a strong suppressive effect on tumor cells growth, in contrast to the pro-proliferative effect of MFs mixed within tumor spheroids. However, prolonged iCCA-pMF interaction elicits tumor cell dissemination in vitro. We find an upregulation of Vcam1 in tumor cells in the early phase of iCCA-pMF interaction both in vitro and in vivo which is downregulated when tumor cells disseminate. Blocking Vcam1 activity in iCCA allograft mouse models slows primary tumor growth but lead to increased tumor metastasis. Our data suggest that pMFs are beyond simple pro- or anti-tumorigenic in iCCA, with the ability to suppress tumor growth but elicit tumor cell dissemination.