bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex and gender impacts on the behavioural presentation and recognition of autism
Authors: Lai Meng-Chuan , Szatmari Peter 
Published: December 2019

Purpose of review
With increasing awareness of potential differences of autism presentation in nonmale versus male individuals, this review summarizes the rapidly evolving literature on sex and gender impacts on autism across nosology, behavioural presentation, developmental change and contextual recognition biases.

Recent findings
Most studies have not differentiated sex versus gender impacts. Regarding behavioural presentation, measurement invariance across sex/gender was found in several standard measures. On this basis, diagnosed females overall showed lower restricted/repetitive behaviour/interests/activities (RRBI) than males, with small and variable effects depending on age, developmental level and kinds of RRBI. Differences insufficiently captured by standard measures may include autistic females displaying female-gender-typical narrow interests, higher social attention, linguistic abilities, motivation for friendship and more camouflaging than autistic males. Regarding developmental change, diagnosed young girls were more likely to have better cognitive development, less intense autistic symptoms and reduction of symptoms over time. Difficulties in adaptive functioning and social challenges, however, may emerge more for females in adolescence. Regarding diagnosis, general expectancy biases and gender-stereotypes may impede timely recognition of autism in females.

Summary
Appreciating the multilevel sex and gender impacts on presentation, development, and diagnosis is key to sex-equitable and gender-equitable care for autistic individuals. A holistic approach to understanding the person in the contexts of sex and gender is essential for timely and accurate diagnosis and support.
From partitions to Hodge numbers of Hilbert schemes of surfaces
Authors: Gillman Nate , Gonzalez Xavier , Ono Ken , Rolen Larry , Schoenbauer Matthew 
Published: December 2019

We celebrate the 100th anniversary of Srinivasa Ramanujan's election as a Fellow of the Royal Society, which was largely based on his work with G. H. Hardy on the asymptotic properties of the partition function. After recalling this revolutionary work, marking the birth of the ‘circle method’, we present a contemporary example of its legacy in topology. We deduce the equidistribution of Hodge numbers for Hilbert schemes of suitable smooth projective surfaces.
This article is part of a discussion meeting issue ‘Srinivasa Ramanujan: in celebration of the centenary of his election as FRS’.
The Ramanujan conjecture and its applications
Authors: Winnie Li Wen-Ching 
Published: December 2019

In this paper, we review the Ramanujan conjecture in classical and modern settings and explain its various applications in computer science, including the explicit constructions of the spectrally extremal combinatorial objects, called Ramanujan graphs and Ramanujan complexes, points uniformly distributed on spheres, and Golden-Gate Sets in quantum computing. The connection between Ramanujan graphs/complexes and their zeta functions satisfying the Riemann hypothesis is also discussed.This article is part of a discussion meeting issue ‘Srinivasa Ramanujan: in celebration of the centenary of his election as FRS’.
Enough evidence and other endings: a descriptive study of stable Cochrane systematic reviews in 2019
Authors: Bastian Hilda , Hemkens Lars G. 
Published: December 2019

AbstractBackgroundFrom 2006 to 2019, Cochrane reviews could be designated “stable” if they were not being updated but highly likely to be current. This provides an opportunity to observe practice in ending systematic reviewing and what is regarded as enough evidence.MethodsWe identified Cochrane reviews designated stable in 2013 and 2019 and reasons for this designation. For those with conclusions stated to be so firm that new evidence is unlikely to change them, we assessed conclusions, strength of evidence ratings, and recommendations for further research. We assessed the fate of the 2013 stable reviews. We also estimated usage of formal analytic methods to determine when there is enough evidence in protocols for Cochrane reviews.ResultsCochrane reviews were rarely designated stable. In 2019, there were 507 stable Cochrane reviews (6.6% of 7,645 non-withdrawn reviews). The most common reasons related to no, little, or infrequent research activity expected (331 of 505; 65.5%). Only 39 reviews were stable because of firm conclusions unlikely to be changed by new evidence (7.7%), but that declaration was mostly not supported by judgments made in the review about strength of evidence and implications for research. Among the 180 reviews stable in 2013, 16 reverted to normal status (8.9%), with 2 of those changing conclusions because of new studies. Few Cochrane protocols specified an analytic method for determining when there was enough evidence to stop updating the review (116 of 2,415; 4.8%).ConclusionCochrane reviews were more likely to end because important future primary research activity was believed to be unlikely, than because there was enough evidence. Judgments about the strength of evidence and need for research were often inconsistent with the declaration that conclusions were unlikely to change. The inconsistencies underscore the need for reliable analytic methods to support decision-making about the conclusiveness of evidence.
Development of bioactive electrospun scaffolds suitable to support skin fibroblasts and release Lucilia sericata maggot excretion/secretion
Authors: Giacaman Annesi G , Styliari Ioanna D. , Taresco Vincenzo , Pritchard David , Alexander Cameron , Rose Felicity R 
Published: December 2019

AbstractLarval therapy has been reported to exert beneficial actions upon chronic wound healing by promoting granulation tissue formation, antimicrobial activity and degrading necrotic tissue. However, the use of live maggots is problematic for patient acceptance, and thus there is a need to develop materials which can adsorb and release therapeutic biomolecules from maggot secretions. Here we describe the fabrication of a novel bioactive scaffold that can be loaded with Lucilia sericata maggot excretion/secretion (L. sericata maggot E/S) for wound therapy, and which also provides structural stability for mammalian cell-growth and migration. We show that electrospun scaffolds can be prepared from polycaprolactone-poly (ethylene glycol)–block copolymer (PCL-b-PEG) blended with PCL, to form fibres with average diameters of ~4 μm. We further demonstrate that the fibres are able to be loaded with L. sericata maggot E/S, in order to influence fibroblast migration through protease activity. Finally, we show that after 21 days, the cumulative amount of released L. sericata maggot E/S was ~14 μg/mL from PCL-b-PEG/PCL scaffolds and that the protease activity of L. sericata maggot E/S was preserved when PCL-b-PEG/PCL scaffolds were used as the release platform.
Integrated biophysical characterization of fibrillar collagen-based hydrogels
Authors: Avendano Alex , Chang Jonathan C. , Cortes-Medina Marcos G. , Seibel Aaron J. , Admasu Bitania R. , Boutelle Cassandra M. , Bushman Andrew R. , Garg Ayush Arpit , DeShetler Cameron M. , Cole Sara L. , Song Jonathan W. 
Published: December 2019

ABSTRACTThis paper describes an experimental characterization scheme of the biophysical properties of reconstituted hydrogel matrices based on indentation testing, quantification of transport via microfluidics, and confocal reflectance microscopy analysis. While methods for characterizing hydrogels exist and are widely used, they often do not measure diffusive and convective transport concurrently, determine the relationship between microstructure and transport efficiency, and decouple matrix mechanics and transport properties. Our integrated approach enabled independent and quantitative measurements of the structural, mechanical, and transport properties of hydrogels in a single study. We used fibrillar type I collagen as the base matrix and investigated the effects of two different matrix modifications: 1) cross-linking with human recombinant tissue transglutaminase II (hrTGII) and 2) supplementation with the non-fibrillar matrix constituent hyaluronic acid (HA). hrTGII modified matrix structure and transport but not mechanical parameters. Furthermore, changes in matrix structure due to hrTGII were seen to be dependent on the concentration of collagen. In contrast, supplementation of HA at different collagen concentrations altered matrix microstructure and mechanical indentation behavior but not transport parameters. These experimental observations reveal the important relationship between ECM composition and biophysical properties. The integrated techniques are versatile, robust, and accessible; and as matrix-cell interactions are instrumental for many biological processes, the methods and findings described here should be broadly applicable for characterizing hydrogel materials used for 3-D tissue engineered culture models.
Functional angiogenesis requires microenvironmental cues balancing endothelial cell migration and proliferation
Authors: Wang William Y. , Lin Daphne , Jarman Evan H. , Polacheck William J. , Baker Brendon M. 
Published: December 2019

ABSTRACTAngiogenesis is a complex morphogenetic process that involves intimate interactions between multicellular endothelial structures and their extracellular milieu.In vitromodels of angiogenesis can aid in reducing the complexity of thein vivomicroenvironment and provide mechanistic insight into how soluble and physical extracellular matrix cues regulate this process. To investigate how microenvironmental cues regulate angiogenesis and the function of resulting microvasculature, we multiplexed an established angiogenesis-on-a-chip platform that affords higher throughput investigation of 3D endothelial cell sprouting emanating from a parent vessel through defined biochemical gradients and extracellular matrix. We found that two fundamental endothelial cell functions, migration and proliferation, dictate endothelial cell invasion as single cells vs. multicellular sprouts. Microenvironmental cues that elicit excessive migration speed incommensurate with proliferation resulted in microvasculature with poor barrier function and an inability to transport fluid across the microvascular bed. Restoring the balance between migration speed and proliferation rate rescued multicellular sprout invasion, providing a new framework for the design of pro-angiogenic biomaterials that guide functional microvasculature formation for regenerative therapies.
Vibrio choleraeType VI Secretion System Auxiliary Cluster 3 is a Pandemic-associated Mobile Genetic Element
Authors: Santoriello Francis J. , Michel Lina , Unterweger Daniel , Pukatzki Stefan 
Published: December 2019

AbstractAll sequencedVibrio choleraeisolates encode a contact-dependent type VI secretion system (T6SS) in three loci that terminate in a toxic effector and cognate immunity protein (E/I) pair, allowing for competitor killing and clonal expansion in aquatic environments and the host gut. Recent studies have demonstrated variability in the toxic effectors produced by differentV. choleraestrains and the propensity for effector genes to undergo horizontal gene transfer. Here we demonstrate that a fourth cluster, auxiliary cluster 3 (Aux3), encoding the E/I pairtseH/tsiH, is located directly downstream from two putative recombinases and is flanked by repeat elements resemblingattsites. Genomic analysis of 749V. choleraeisolates, including both pandemic and environmental strains, revealed that Aux3 exists in two states: a ∼40 kb prophage-like element in nine environmental isolates and a ∼6 kb element in pandemic isolates. These findings indicate that Aux3 in pandemicV. choleraeis evolutionarily related to an environmental prophage-like element. In both states, Aux3 excises from the chromosome via site-specific recombination to form a circular product, likely priming the module for horizontal transfer. Finally, we show that Aux3 can integrate into the Aux3-naïve chromosome in an integrase-dependent, site-specific manner. This highlights the potential of Aux3 to undergo horizontal transfer by a phage-like mechanism, which based on pandemic coincidence may confer currently unknown fitness advantages to the recipientV. choleraecell.Significance StatementV. choleraeis a human pathogen that causes pandemics affecting 2.8 million people annually (1). The O1 El Tor lineage is responsible for the current pandemic. A subset of non-O1 strains cause cholera-like disease by producing the major virulence factors cholera toxin and toxin co-regulated pilus but fail to cause pandemics. The full set ofV. choleraepandemic factors is unknown. Here we describe the type VI secretion system (T6SS) Aux3 element as a largely pandemic-specific factor that is evolutionarily related to an environmental prophage-like element circulating in non-pathogenic strains. These findings shed light onV. choleraeT6SS evolution and indicate the Aux3 element as a pandemic-enriched mobile genetic element.
Synthetic Cellular Immunity based on CAR repertoire for Human Immunotherapy
Authors: Fu Wenyan , Wang Chuqi , Ma Zetong , Li Tian , Lin Fangxing , Mao Ruixue , Lei Changhai , Zhao Jian , Hu Shi 
Published: December 2019

AbstractThe immune surveillance hypothesis is regarded as the intellectual underpinning of cancer immunology. We find that engineered T cell library displaying CAR constructs, where the antibody repertoires took the place of the antigen-recognition region, has the capacity to recognize nonself-antigens and showed antigen dependent clonal expanding and persistence. This process coupled with long-lasting anti-tumour effect in a broad spectrum of epithelial tumours. Moreover, CAR-T library showed robust immunologic memory and maintenance of diversity to recognize mutated or evolved tumours in both immunodeficiency and immunoresponsive murine tumor models. Large CAR library was further developed in logic-gated NK-92 cells to develop an off-the shelf therapeutic library. Thus, the biological behaviour of synthetic cell library is highly accordance with the immune surveillance function, which proved the way to rebuilt functional MHC unrestricted cellular immunity in vitro using synthetic method.
Multiplexed single-cell transcriptomic analysis of normal and impaired lung development in the mouse
Authors: Hurskainen K. M. , Mižíková I. , Cook D. P. , Cyr-Depauw C. , Lesage F. , Andersson N. , Helle E. , Renesme L. , Jankov R.P. , Heikinheimo M. , Vanderhyden B. C. , Thébaud B 
Published: December 2019

ABSTRACTDuring late lung development alveolar and microvascular development is finalized to enable sufficient gas exchange. Impaired late lung development manifests as bronchopulmonary dysplasia (BPD) in preterm infants. Single-cell RNA sequencing (scRNA-seq) allows for assessment of complex cellular dynamics during biological processes, such as development. Here, we use MULTI-seq to generate scRNA-seq profiles of over 66,000 cells from 36 mice during normal or impaired lung development secondary to hyperoxia. We observed dynamic populations of cells, including several rare cell types and putative progenitors. Hyperoxia exposure, which mimics the BPD phenotype, alters the composition of all cellular compartments, particularly alveolar epithelium, capillary endothelium and macrophage populations. We identified several BPD-associated signatures, including Pdgfra in fibroblasts, Activin A in capillary endothelial cells, and Csf1-Csf1r and Ccl2-Ccr2 signaling in macrophages and neutrophils. Our data provides a novel single-cell view of cellular changes associated with late lung development in health and in disease.
Age-related macular degeneration-like phenotypic features develop at the early ages of Cxcr5/Nrf2 double knockout mice: An accelerated AMD model
Authors: Huang Hu , Lennikov Anton 
Published: December 2019

AbstractAge-related macular degeneration (AMD) is a leading cause of blindness for older adults. The aim of this study is to develop an accelerated mouse model of AMD and characterize its phenotypic features. Cxcr5 knockout (KO) mice and Nrf2 KO mice were bred to create Cxcr5/Nrf2 double knockout (DKO) mice. AMD-like features in Cxcr5/Nrf2 DKO mice were compared with those in CXCR5 KO mice and C57BL6 wild-type (WT) controls. The assessment included fundus and optical coherence tomography (OCT) imaging, periodic acid-Schiff (PAS) and immunofluorescence staining of retinal pigment epithelium (RPE)–choroid flat mounts and sections. Stained samples were imaged with fluorescent microscopy, and Western blots were used to monitor protein expression changes. The staining of cleaved caspase-3, peanut agglutinin (PNA) lectin, and MAP2 was performed to assess the presence of retinal degeneration and cell apoptosis. Quantification with statistical analysis was performed with Graphpad software. The 2- 4-, and 6-month-old DKO mice exhibited increased hypopigmented spots on fundus and sub-RPE abnormalities on OCT as compared to the Cxcr5 KO mice, and C57BL6 WT controls. Aberrant RPE/sub-RPE depositions and increased Bruch’s membrane (BM) thickness were demonstrated by PAS-stained sections. The DKO mice had strong autofluorescence (A2E) and increased RPE/sub-RPE depositions of IgG and AMD-associated proteins (β amyloid, Apolipoprotein E, complement 5b-9, and αB-crystallin). The protein expression of AMD-associated proteins and Transmembrane Protein 119 (TMEM119) microglia marker were upregulated at the RPE/BM/choroid complex of DKO mice. The adult DKO mice underwent accelerated retinal degeneration and cell apoptosis compared to the KO and the WT mice. Together, the data suggest that the Cxcr5/Nrf2 DKO mice develop significant AMD-like characteristics at an early age and may serve as an accelerated AMD model.Sumary StatementA new animal model is developed to mimic early AMD characteristics in adult mice
A multifunctional R package for identification of tumor-specific neoantigens
Authors: Hasegawa Takanori , Hayashi Shuto , Shimizu Eigo , Mizuno Shinichi , Niida Atsushi , Yamaguchi Rui , Miyano Satoru , Nakagawa Hidewaki , Imoto Seiya 
Published: December 2019

AbstractIt is known that some mutated peptides, such as those resulting from missense mutations and frameshift insertions, can bind to the major histocompatibility complex and be presented to antitumor T-cells on the surface of a tumor cell. These peptides are termed neoantigen and it is important to understand this process for cancer immunotherapy. Here, we introduce an R package that can predict a list of potential neoantigens from a variety of mutations, which include not only somatic point mutations but insertions, deletions, and structural variants. Beyond the existing applications, this package is capable of attaching and reflecting several additional information, e.g., wild-type binding capability, allele specific RNA expression levels, single nucleotide polymorphism information, and combinations of mutations to filter out infeasible peptides as neoantigen.AvailabilityThe R package is available at http://github/hase62/Neoantimon.
AdaTiSS: A Novel Data-Adaptive Robust Method for Quantifying Tissue Specificity Scores
Authors: Wang Meng , Jiang Lihua , Snyder Michael P. 
Published: December 2019

AbstractMotivationAccurately detecting tissue specificity (TS) in genes helps researchers understand tissue functions at the molecular level, and further identify disease mechanisms and discover tissue-specific therapeutic targets. The Genotype-Tissue Expression (GTEx) project (Consortium, 2015), and the Human Protein Atlas (HPA) project (Uhlén, et al., 2015) are two publicly available data resources, providing large-scale gene expressions across multiple tissue types. Multiple tissue comparisons, technical background noise and unknown variation factors make it challenging to accurately identify tissue specific gene expressions. Several methods worked on measuring the overall TS in gene expressions and classifying genes into tissue-enrichment categories. There still lacks a robust method to provide quantitative TS scores for each tissue.MethodsWe recognized that the key to quantify tissue specific gene expressions is to properly define a concept of expression population. We considered that inside the population, the sample expressions from various tissues are more or less balanced, and the outlier expressions outside the population may indicate tissue specificity. We then formulated the question to robustly estimate the population distribution. In a linear regression problem, we developed a novel data-adaptive robust estimation based on density-power-weight under unknown outlier distribution and non-vanishing outlier proportion (Wang, et al., 2019). In the question of quantifying TS, we focused on the Gaussian-population mixture model. We took into account gene heterogeneities and applied the robust data-adaptive procedure to estimate the population. With the robustly estimated population parameters, we constructed the AdaTiSS algorithm to obtain data-adaptive quantitative TS scores.ResultsOur TS scores from the AdaTiSS algorithm achieve the goal that the TS scores are comparable across tissues and also across genes, which standardize gene expressions in terms of TS. Compared to the categorical TS method such as the HPA criterion, our method provides more information on the population fitting, and shows advantages in quantitatively analyzing tissue specific functions, making the biology functional analysis more precise. We also discuss some limitations and possible future work.Contactmpsnyder@stanford.edu
Interactive video-player to improve social smile in individuals with autism spectrum disorder
Authors: Khullar Vikas , Bala Manju , Singh Harjit Pal 
Published: December 2019

Purpose
The purpose of this paper is to propose and develop a live interaction-based video player system named LIV4Smile for the improvement of the social smile in individuals with autism spectrum disorder (ASD).

Design/methodology/approach
The proposed LIV4Smile intervention was a video player that operated by detecting smile using a convolutional neural network (CNN)-based algorithm. To maintain a live interaction, a CNN-based smile detector was configured and used in this system. The statistical test was also conducted to validate the performance of the system.

Findings
The significant improvement was observed in smile responses of individuals with ASD with the utilization of the proposed LIV4Smile system in a real-time environment.

Research limitations/implications
A small sample size and clinical utilizing for validation and initial training of ASD individuals for LIV4Smile could be considered under implications.

Originality/value
The main aim of this study was to address the inclusive practices for children with autism. The proposed CNN algorithm-based LIV4Smile intervention resulted in high accuracy in facial smile detection.