bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonsurgical Correction of Congenital Ear Deformities: The Relationship Between Age of Presentation and Regression
Authors: Hazkour Nissim , Palacios Jose , Gray Rachel , Pessino Kenneth , Rivera Robin , Bastidas Nicholas 
Published: September 2022

Purpose:
After 3 weeks of age, studies show ear molding to be unsuccessful due to increased regression rates. Studies have not differentiated success rates based on regression severity; partial regressions may be deemed successful and satisfactory by parents. We examined successful ear molding at different ages of presentation by measuring regression severity and parental satisfaction.

Methods:
Patients who presented to [blinded for review] for ear molding from January 2017 to October 2018 were eligible for inclusion. Molds were applied on the initial visit and monitored biweekly. Treatment length was based on age, deformity type, and severity. One month after treatment completion, parents completed a satisfaction survey where they assessed regression on a 3-point severity scale.

Results:
A total of 165 patients were included in this study. Sixty-seven were younger than 3 weeks of age and had an overall correction rate of 95%. The complete correction rate was 80% and only 5% saw complete regression. In the remaining 98, the overall correction rate was 94%, with a 63% complete correction rate. Only 6% saw complete regression. There was no statistical significance in parental satisfaction, perceived improvement, or likelihood to recommend ear molding between age groups.

Conclusions:
Regression rates are higher in children older than 3 weeks although not statistically significant. Most regressions were partial and ear molding still significantly corrected most deformities. We suggest that ear molding be offered past 3 weeks of age, with maximum age being dependent on deformity type, as it still leads to high parental satisfaction.
Long-Term Outcomes after Adolescent Bariatric Surgery
Authors: de la Cruz-Muñoz Nestor , Xie Luyu , Quiroz Hallie J , Kutlu Onur C , Atem Folefac , Lipshultz Steven E , Mathew M Sunil , Messiah Sarah E 
Published: September 2022

BACKGROUND:
Metabolic and bariatric surgery (MBS) is a safe and effective treatment option for adolescents with severe obesity, but no long-term studies are available with more than10 years of follow-up data to document sustained improved outcomes.

METHODS:
A total of 96 patients who completed MBS at 21 years of age or younger in a tertiary academic center 2002 to 2010 were contacted for a telehealth visit. Body weight, comorbidity status, social/physical function status, and long-term complications were evaluated 10 to 18 years after surgery.

RESULTS:
Mean participant (83% female, 75% Hispanic) age at MBS was 18.8 (±1.6) years (median age 19 years, range 15–21 years), and median pre-MBS BMI was 44.7 kg/m2 (SD 6.5). At follow-up (mean 14.2 [±2.2] years) post-MBS (90.6% Roux-en-Y gastric bypass [RYGB] or 8.3% laparoscopic adjustable gastric banding [LAGB]) mean total body weight decreased by 31.3% (interquartile range [IQR] 20.0% to 38.9%); 32.0% (IQR, 21.3% to 40.1%) among RYGB participants and 22.5% (IQR, 0.64% to 28.3%) among LAGB participants. Patients with pre-MBS hyperlipidemia (14.6%), asthma (10.4%), and diabetes/hyperglycemia (5.2%) reported 100% remission at follow-up (p < 0.05 for all). Pre–post decrease in hypertension (13.5% vs 1%, p = 0.001), sleep apnea (16.7% vs 1.0%, p < 0.001), gastroesophageal reflux disease (13.5% vs 3.1%, p = 0.016), anxiety (7.3% vs 2.1%, p = 0.169), and depression (27.1% vs 4.2%, p < 0.001) were also found.

CONCLUSIONS:
Significant sustained reductions in weight and comorbidities, and low rates of long-term complications, a decade or more after completing MBS as an adolescent were found. These findings have important implications for adolescents who may be considering MBS for weight reduction and overall health improvements that extend into adulthood.
Bi-stable lateral buckled beam: quasi-static snap-through behaviour analysis
Authors: Jiang Weihong , Dai Fuhong 
Published: September 2022

A cantilever beam with lateral buckled deformation performs bi-stable characteristic. The snapping mechanism between its two stable configurations can be triggered when applying displacement or angle on the free end. In this paper, an analytical model based on the modal superposition method is established to investigate the snap-through behaviour. A spring with stiffness
k
introduced in the analytical model ensures the quasi-static loading, bringing about the accurate snapping response. In addition, the initial lateral buckling of the cantilever beams and the snap-through behaviour of the lateral buckled beams are simulated using the FE method. The theoretical and numerical results are then validated on specially designed and built apparatus. Geometric parameters analysis indicates that the theoretical model is more accurate in predicating the snapping responses of bi-stable lateral buckled beams with slender features. Understanding the mechanics of snap-through behaviour is important for designing novel lateral buckled beams with target shapes and functions.
Jovian enables direct inference of germline haplotypes from short reads via sequence-to-sequence modeling
Authors: O’Fallon Brendan , Bolia Ashini , Durtschi Jacob , Yang Luobin , Frederickson Eric , Noble Katherine , Coleman Joshua , Best Hunter 
Published: September 2022

AbstractDetection of germline variants in next-generation sequencing data is an essential component of modern genomics analysis. Variant detection tools typically rely on statistical algorithms such as de Bruijn graphs, Hidden Markov Models and regression models, often coupled with heuristic techniques and thresholds to identify variants. Here we describe a new approach that replaces these handcrafted statistical methods with a single, end-to-end deep learning model that directly infers germline haplotypes from short read pileups. Our model, called Jovian, frames variant detection as a sequence-tosequence modeling task, akin to language translation, and employs a transformer-based architecture to translate alignment columns into two predicted haplotype sequences. After training with 17 whole genome sequences from Genome-in-a-Bottle cell lines, we demonstrate that this method learns to realign complex and ambiguous read mappings to produce accurate haplotype predictions, predicts variant genotypes and phase accurately, and leverages the local read context to inform predictions about a given position. We also demonstrate that a 2-dimensional positional encoding significantly improved precision of the detected variants. Compared to other callers, sensitivity and precision is higher than GATK HaplotypeCaller, but lower than DeepVariant and Strelka2.
Optimization and redevelopment of single-cell data analysis workflow based on deep generative models
Authors: Liu Yunhe , Fu Qiqing , Dong Chenyu , Xia Xiaoqiong , Liu Gang , Liu Lei 
Published: September 2022

AbstractThe present single-cell RNA sequencing(scRNA-seq) analysis pipelines require a combination of appropriate normalization, dimension reduction, clustering, and specific-gene analysis algorithms, but the rationale for the choice of these algorithms is relatively subjective because of the lack of ground truth assessment conclusions. As the number of captured single-cells increases, the number of different types of noise cells also increases, which can strongly affect the analysis efficiency. For scRNA-seq, a technology that generates data through multi-process operations, the deep generative model should be a good choice for this type of data analysis, allowing simultaneous estimation of multiple unobservable parameters assumed in the data generation process. Hence, in our study, we sequenced a pool of pre-labeled single cells to obtain a batch of scRNA-seq data with main and fine labels, which was then used to evaluate the clustering and specific-gene analysis methods. Afterward, we applied two deep generative models to infer the probabilities of pseudo and impurity cells. And by stepwise removing the inferred noise cells, the clustering performance and the consistency of different specific-gene analysis methods are both greatly improved. After that, we applied Deep-LDA (a latent Dirichlet allocation-based deep generative model) to scRNA-seq data analysis. And this model takes the count matrix as input, and makes the classification and specific gene optimization process mutually dependent, which has more practical sense and simplifies the analysis workflow. At last, we successfully implemented the model with transferred knowledge to make single-cell annotation and verified its superior performance.
Action prediction error: a value-free dopaminergic teaching signal that drives stable learning
Authors: Greenstreet Francesca , Vergara Hernando Martinez , Johansson Yvonne , Pati Sthitapranjya , Schwarz Laura , Lenzi Stephen C , Wisdom Matthew , Gubanova Alina , Marbach Fred , Rollik Lars , Kaur Jasvin , Moskovitz Theodore , Cohen Joseph , Thompson Emmett , Margrie Troy W , Clopath Claudia , Stephenson-Jones Marcus 
Published: September 2022

AbstractAnimals’ choice behavior is characterized by two main tendencies: taking actions that led to rewards and repeating past actions. Theory suggests these strategies may be reinforced by different types of dopaminergic teaching signals: reward prediction error (RPE) to reinforce value-based associations and movement-based action prediction errors to reinforce value-free repetitive associations. Here we use an auditory-discrimination task in mice to show that movement-related dopamine activity in the tail of the striatum encodes the hypothesized action prediction error signal. Causal manipulations reveal that this prediction error serves as a value-free teaching signal that supports learning by reinforcing repeated associations. Computational modeling and experiments demonstrate that action prediction errors alone cannot support reward-guided learning but when paired with the RPE circuitry they serve to consolidate stable sound-action associations in a value-free manner. Together we show that there are two types of dopaminergic prediction errors that work in tandem to support learning.
Predicting host associations of the invasive spotted lanternfly on trees across the USA
Authors: Huron Nicholas A. , Helmus Matthew R. 
Published: September 2022

AbstractGlobal impacts of invasive insect pests cost billions of dollars annually, but the impact of any individual pest species depends on the strength of associations with economically important plant hosts. Estimating host associations for a pest requires surveillance field surveys that observe pest association on plant species within an invaded area. However, field surveys often miss rare hosts and cannot observe associations with plants found outside the invaded range. Associations for these plants instead are estimated with experimental assays such as controlled feeding trials, which are time consuming and for which few candidate hosts can be tested logistically. For emerging generalist pests, these methods are unable to rapidly produce estimates for the hundreds of potential suitable hosts that the pest will encounter as it spreads within newly invaded regions. In such cases, association data from these existing methods can be statistically leveraged to impute unknown associations. Here we use phylogenetic imputation to estimate potential host associations in an emergent generalist forest pest in the U.S., the spotted lanternfly (Lycorma delicatula; SLF). Phylogenetic imputation works when closely related plants have similar association strengths, termed phylogenetic signal in host association, which is common in phytophagous insects. We first aggregated known SLF host associations from published studies. Existing research has estimated association strengths for 144 species across both the invaded and native range of SLF. These known associations exhibited phylogenetic signal. We then developed two protocols that combined known host association data and fit phylogenetic imputation models based on hidden state prediction algorithms to estimate association strength for 569 candidate tree species found across the continental U.S. Of candidate species considered, 255 are predicted to have strong associations with SLF in the U.S. and can be found in several clades including Juglandaceae, Rutaceae, Salicaceae, and Sapindaceae. Uninvaded regions with the highest numbers of these strongly associated species include midwestern and west coast states such as Illinois and California. Survey efforts for SLF should be focused on these regions and predicted species, which should also be prioritized in experimental assays. Phylogenetic imputation scales up existing host association data, and the protocols we present here can be readily adapted to inform surveillance and management efforts for other invasive generalist plant pests.
Evaluation of endogenous and therapeutic 25-hydroxycholesterols in murine models of pulmonary SARS-CoV-2 infection
Authors: Fessler Michael B. , Madenspacher Jennifer , Baker Paul J. , Hilligan Kerry L. , Castro Ehydel , Meacham Julie , Chen Shih-Heng , Johnson Reed F. , Martin Negin P. , Tucker C.J. , Mahapatra Debabrata , Cesta Mark , Mayer-Barber Katrin D. 
Published: September 2022

AbstractOxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and tissue injury and be converted by CYP7B1 to 7α,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, usingin vitrostudies and two different murine models of SARS-CoV-2 infection, we investigate the effects of these two oxysterols on SARS-CoV-2 pneumonia. We show that while 25HC and enantiomeric-25HC are antiviralin vitroagainst human endemic coronavirus-229E, they did not inhibit SARS-CoV-2; nor did supplemental 25HC reduce pulmonary SARS-CoV-2 titers in the K18-human ACE2 mouse modelin vivo. 25HC treatment also did not alter immune cell influx into the airway, airspace cytokines, lung pathology, weight loss, symptoms, or survival but was associated with increased airspace albumin, an indicator of microvascular injury, and increased plasma pro-inflammatory cytokines. Conversely, mice treated with the EBI2/GPR183 inhibitor NIBR189 displayed a modest increase in lung viral load only at late time points, but no change in weight loss. Consistent with these findings, althoughCh25hwas upregulated in the lungs of SARS-CoV-2-infected WT mice, lung viral titers and weight loss inCh25h−/–andGpr183−/–mice infected with the beta variant were similar to control animals. Taken together, endogenous 25-hydroxycholesterols do not significantly regulate early SARS-CoV-2 replication or pathogenesis and supplemental 25HC may have pro-injury rather than therapeutic effects in SARS-CoV-2 pneumonia.
A gene expression analysis and immune infiltration between lesioned and preserved subchondral bone in osteoarthritis
Authors: Zhang Gang , Yin Chengliang , Wu Rilige , Wang Ren , Qin Yong , Lyu Songcen 
Published: September 2022

AbstractBackgroundOsteoarthritis (OA) is a degenerative disease which need more research. The purpose of this study was to performed gene expression analysis and immune infiltration between lesioned and preserved subchondral bone, and validation with datasets and experiment of multiple tissues.MethodsThe different expressed genes(DEGs) of GSE51588 datasets between lesioned and preserved tibial plateaus of OA patients were conducted. Moreover, functional annotation and protein–protein interaction (PPI) network were applied for exploring the potential therapeutic targets in OA subchondral bones between lesioned and preserved sides. In addition, multiple tissues were used to screen out co-expressed genes and the expression levels of identified candidate DEGs was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OA. Finally, immune infiltration analysis was conducted.ResultsA total of 1010 DEGs were identified, including upregulated 423 genes, 587 downregulated genes. Upregulated genes showed that BP terms were enriched in “skeletal system development”, “sister chromatid cohesion”,”ossification” etc. Pathways were enriched in “Wnt signaling pathway,” “Proteoglycans in cancer,” Downregulated genes showed that BP terms were enriched in “inflammatory response,” “xenobiotic metabolic process”, “positive regulation of inflammatory response”. Pathways were enriched in “Neuroactive ligand–receptor interaction”, “AMPK signaling pathway” etc. JUN, TNF, IL1B,were the hub genes in the PPI network. Col1A1 and LRRC15 were screened out by multiple datasets and validated by experiments. Immune infiltration showed adipocytes and endothelial cells infiltrated less in lesioned samples.ConclusionOur research might provide valuable information for exploring the pathogenesis mechanism of OA and identifying the potential therapy targets for OA diagnosis.
Integrons, plasmids, and resistance genes in equine faecal bacteria
Authors: Mitchell Scott W. , Moran Robert A. , Elbourne Liam D. H. , Chapman Belinda , Bull Michelle , Muscatello Gary , Coleman Nicholas V. 
Published: September 2022

ABSTRACTAntimicrobial resistance in bacteria is a threat to both human and animal health. We aimed to understand the impact of domestication and antimicrobial treatment on the types and numbers of resistant bacteria, antibiotic resistance genes (ARGs), and class 1 integrons (C1I) in the equine gut microbiome. Antibiotic-resistant faecal bacteria were isolated from wild horses, healthy farm horses, and horses undergoing veterinary treatment, and isolates (9,083 colonies) were screened by PCR for C1I; these were found at frequencies of 9.8% (vet horses), 0.31% (farm horses), and 0.05% (wild horses). A collection of 71 unique C1I+ isolates (17 Actinobacteria and 54 Proteobacteria) was subjected to resistance profiling and genome sequencing. Farm horses yielded mostly C1I+ Actinobacteria (Rhodococcus, Micrococcus, Microbacterium, Arthrobacter, Glutamibacter, Kocuria), while vet horses primarily gave C1I+ Proteobacteria (Escherichia, Klebsiella, Enterobacter, Pantoea, Acinetobacter, Leclercia, Ochrobactrum); the vet isolates had more extensive resistance and stronger PC promoters in the C1Is. All integrons in Actinobacteria were flanked by copies of IS6100, except in Micrococcus, where a novel IS5 family element (ISMcte1) was implicated in mobilization. In the Proteobacteria, C1I’s were predominantly associated with IS26, and also IS1, Tn21, Tn1721, Tn512, and a putative formaldehyde-resistance transposon (Tn7489). Several large C1I-containing plasmid contigs were retrieved; two of these (plasmid types Y and F) also had extensive sets of metal resistance genes, including a novel copper-resistance transposon (Tn7519). Both veterinary treatment and domestication increase the frequency of C1I’s in equine gut microflora, and each of these anthropogenic factors selects for a distinct group of integron-containing bacteria.IMPORTANCEThere is increasing acknowledgement that a ‘One Health’ approach is required to tackle the growing problem of antimicrobial resistance. This requires that the issue is examined from not only the perspective of human medicine, but also includes consideration of the roles of antimicrobials in veterinary medicine and agriculture, and recognises the importance of other ecological compartments in the dissemination of ARGs and mobile genetic elements such as C1I. We have shown that domestication and veterinary treatment increase the frequency of occurrence of C1I’s in the equine gut microflora, and that in healthy farm horses, the C1I are unexpectedly found in Actinobacteria, while in horses receiving antimicrobial veterinary treatments, a taxonomic shift occurs, and the more typical integron-containing Proteobacteria are found. We identified several new mobile genetic elements (plasmids, IS and transposons) on genomic contigs from the integron-containing equine bacteria.
Paecilomycone inhibits quorum sensing in Gram-negative bacteria
Authors: Beenker Wouter A. G. , Hoeksma Jelmer , Bannier-Hélaouët Marie , Clevers Hans , Hertog Jeroen den 
Published: September 2022

AbstractPseudomonas aeruginosa is an opportunistic pathogen that causes major healthcare concerns due to its virulence and high intrinsic resistance to antimicrobial agents. Therefore, new treatments are highly needed. An interesting approach is to target quorum sensing (QS). QS regulates the production of a wide variety of virulence factors and biofilm formation in P. aeruginosa. This study describes the identification of paecilomycone as inhibitor of QS in both C. violaceum and P. aeruginosa. Paecilomycone strongly inhibited the production of virulence factors, including various phenazines, and biofilm formation. In search of the working mechanism, we found that paecilomycone inhibited the production of 4-hydroxy-2-heptylquinoline (HHQ) and 3,4- dihydroxy-2-heptylquinoline (PQS), but not 2’-aminoacetophenone (2-AA). We suggest that paecilomycone affects QS in P. aeruginosa by targeting the PqsBC complex and alternative targets, or alters processes that influence the enzymatic activity of the PqsBC complex. The toxicity of paecilomycone towards eukaryotic cells and organisms was low, making it an interesting lead for further clinical research.ImportanceAntibiotics are becoming less effective against bacterial infections due to the evolution of resistance among bacteria. Pseudomonas aeruginosa is a Gram-negative pathogen that causes major healthcare concerns and is difficult to treat due to its high intrinsic resistance to antimicrobial agents. Therefore, new targets are needed and an interesting approach is to target quorum sensing (QS). QS is the communication system in bacteria that regulates multiple pathways including the production of virulence factors and biofilm formation, which leads to high toxicity in the host and low sensitivity to antibiotics, respectively. We found a compound, named paecilomycone, which inhibited biofilm formation and the production of various virulence factors in P. aeruginosa. The toxicity of paecilomycone towards eukaryotic cells and organisms was low, making it an interesting lead for further clinical research.
Teneurin-2 at the Synapse Construction Site is a Signpost for Cargo Unloading from Motor Proteins
Authors: Ichinose Sotaro , Susuki Yoshihiro , Kaneko Ryosuke , Iwasaki Hirohide 
Published: September 2022

AbstractIn mature neurons, excitatory synapses are formed on the dendritic spine, whereas inhibitory synapses are formed on the dendritic shaft. Thus, it is primarily the accumulation of synaptic proteins that characterizes inhibitory synapses as distinct from non-synaptic regions. Protein accumulation is achieved by a combination of microtubule (MT)-based transport by kinesins and lateral diffusion across the plasma membrane; however, how and when proteins are released from kinesins remains unclear. Using primary cultured hippocampal neurons, we found that Teneurin-2 (TEN2) promotes synaptic protein accumulation by recruiting MTs via the representative MT plus end-tracking protein, EB1. MTs recruitment was enhanced when the extracellular domain of TEN2 successfully chose partners, and the lateral diffusion of TEN2 was inhibited. Conversely, if TEN2 partner choice is not achieved, MTs are not recruited, and thus synaptogenesis is not followed. Our study revealed that cargo release from kinesins through TEN2-MTs interactions supports the continuity from partner choice to synaptogenesis, which is a critical step in synaptic maturation.