bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classical galactosemia: neuropsychological and psychosocial functioning beyond intellectual abilities
Authors: Welsink-Karssies Mendy M. , Oostrom Kim J. , Hermans Merel E. , Hollak Carla E. M. , Janssen Mirian C. H. , Langendonk Janneke G. , Oussoren Esmee , Rubio Gozalbo M. Estela , de Vries Maaike , Geurtsen Gert J. , Bosch Annet M. 
Published: February 2020

Abstract
Background
Despite early diagnosis and treatment, Classical Galactosemia (CG) patients frequently develop long-term complications, such as cognitive impairment. Available literature primarily reports on general intellectual abilities and shows a substantially lower Full Scale Intelligence Quotient (FSIQ) in CG patients than in the general population. Both problems in social functioning as well as internalizing problems are often reported in CG patients. The combination of intelligence, cognitive functioning, behavior and social functioning has not been studied systematically in CG patients.

Methods
To determine if CG patients demonstrate a specific neuropsychological and psychosocial profile, we investigated intelligence, functioning on multiple cognitive domains, behavior and social functioning with a comprehensive neuropsychological test battery and questionnaires (self- and proxy-reported).

Results
The data of 48 patients, aged 4–47 years are reported. FSIQ ranged from 45 to 103 (mean 77 ± 14). A negative correlation between age and FSIQ was demonstrated (p = 0.037) which resulted directly from the inclusion of four young ‘milder’ patients detected by newborn screening (NBS) with an expected better clinical outcome. Compared to normative data, patients had significantly lower but highly variable scores on all cognitive domains, especially on tests requiring mental speed. In the context of the FSIQ, 43% of the cognitive test results exceeded IQ based expectations. Overall, the patients’ scores on social functioning were in the normal range but internalizing problems were frequently reported. In our cohort, an early initiation of dietary treatment due to NBS or family screening did not result in a more favorable neuropsychological outcome.

Conclusions
In this study, we demonstrated that as a cohort, CG patients have a below average intelligence and impaired cognitive functioning without a distinctive neuropsychological profile. The effect of age on neurocognitive functioning should be assessed in longitudinal studies. Social functioning was not impaired, but patients may be at risk for internalizing problems. Considering the large variability in cognitive, behavioral and social functioning and the finding that cognitive outcomes may exceed IQ based expectations, an individual evaluation and follow-up is warranted in all CG patients to ensure timely support if needed.
Eleven grand challenges in single-cell data science
Authors: Lähnemann David , Köster Johannes , Szczurek Ewa , McCarthy Davis J. , Hicks Stephanie C. , Robinson Mark D. , Vallejos Catalina A. , Campbell Kieran R. , Beerenwinkel Niko , Mahfouz Ahmed , Pinello Luca , Skums Pavel , Stamatakis Alexandros , Attolini Camille Stephan-Otto , Aparicio Samuel , Baaijens Jasmijn , Balvert Marleen , Barbanson Buys de , Cappuccio Antonio , Corleone Giacomo , Dutilh Bas E. , Florescu Maria , Guryev Victor , Holmer Rens , Jahn Katharina , Lobo Thamar Jessurun , Keizer Emma M. , Khatri Indu , Kielbasa Szymon M. , Korbel Jan O. , Kozlov Alexey M. , Kuo Tzu-Hao , Lelieveldt Boudewijn P.F. , Mandoiu Ion I. , Marioni John C. , Marschall Tobias , Mölder Felix , Niknejad Amir , Rączkowska Alicja , Reinders Marcel , Ridder Jeroen de , Saliba Antoine-Emmanuel , Somarakis Antonios , Stegle Oliver , Theis Fabian J. , Yang Huan , Zelikovsky Alex , McHardy Alice C. , Raphael Benjamin J. , Shah Sohrab P. , Schönhuth Alexander 
Published: February 2020

AbstractThe recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands—or even millions—of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems. Here, we outline eleven challenges that will be central to bringing this emerging field of single-cell data science forward. For each challenge, we highlight motivating research questions, review prior work, and formulate open problems. This compendium is for established researchers, newcomers, and students alike, highlighting interesting and rewarding problems for the coming years.
Opportunities and challenges in long-read sequencing data analysis
Authors: Amarasinghe Shanika L. , Su Shian , Dong Xueyi , Zappia Luke , Ritchie Matthew E. , Gouil Quentin 
Published: February 2020

AbstractLong-read technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long-read data are thus required, but the fast pace of development of such tools can be overwhelming. To assist in the design and analysis of long-read sequencing projects, we review the current landscape of available tools and present an online interactive database, long-read-tools.org, to facilitate their browsing. We further focus on the principles of error correction, base modification detection, and long-read transcriptomics analysis and highlight the challenges that remain.
The mixed model for repeated measures for cluster randomized trials: a simulation study investigating bias and type I error with missing continuous data
Authors: Bell Melanie L. , Rabe Brooke A. 
Published: February 2020

Abstract
Background
Cluster randomized trials (CRTs) are a design used to test interventions where individual randomization is not appropriate. The mixed model for repeated measures (MMRM) is a popular choice for individually randomized trials with longitudinal continuous outcomes. This model’s appeal is due to avoidance of model misspecification and its unbiasedness for data missing completely at random or at random.

Methods
We extended the MMRM to cluster randomized trials by adding a random intercept for the cluster and undertook a simulation experiment to investigate statistical properties when data are missing at random. We simulated cluster randomized trial data where the outcome was continuous and measured at baseline and three post-intervention time points. We varied the number of clusters, the cluster size, the intra-cluster correlation, missingness and the data-generation models. We demonstrate the MMRM-CRT with an example of a cluster randomized trial on cardiovascular disease prevention among diabetics.

Results
When simulating a treatment effect at the final time point we found that estimates were unbiased when data were complete and when data were missing at random. Variance components were also largely unbiased. When simulating under the null, we found that type I error was largely nominal, although for a few specific cases it was as high as 0.081.

Conclusions
Although there have been assertions that this model is inappropriate when there are more than two repeated measures on subjects, we found evidence to the contrary. We conclude that the MMRM for CRTs is a good analytic choice for cluster randomized trials with a continuous outcome measured longitudinally.

Trial registration
ClinicalTrials.gov, ID: NCT02804698.
A sharp upper bound on the spectral radius of a nonnegative k-uniform tensor and its applications to (directed) hypergraphs
Authors: Lv Chuang , You Lihua , Zhang Xiao-Dong 
Published: February 2020

AbstractIn this paper, we obtain a sharp upper bound on the spectral radius of a nonnegative k-uniform tensor and characterize when this bound is achieved. Furthermore, this result deduces the main result in [X. Duan and B. Zhou, Sharp bounds on the spectral radius of a nonnegative matrix, Linear Algebra Appl. 439:2961–2970, 2013] for nonnegative matrices; improves the adjacency spectral radius and signless Laplacian spectral radius of a uniform hypergraph for some known results in [D.M. Chen, Z.B. Chen and X.D. Zhang, Spectral radius of uniform hypergraphs and degree sequences, Front. Math. China 6:1279–1288, 2017]; and presents some new sharp upper bounds for the adjacency spectral radius and signless Laplacian spectral radius of a uniform directed hypergraph. Moreover, a characterization of a strongly connected k-uniform directed hypergraph is obtained.
Gene manipulation to test links between genome, brain and behavior in developing songbirds: a test case
Authors: London Sarah E. 
Published: February 2020

ABSTRACTSongbird research has made many seminal contributions to the fields of ethology, endocrinology, physiology, ecology, evolution and neurobiology. Genome manipulation is thus a promising new methodological strategy to enhance the existing strengths of the songbird system to advance and expand fundamental knowledge of how genetic sequences and regulation of genomic function support complex natural learned behaviors. In zebra finches (Taeniopygia guttata) in particular, a rich set of questions about the complex process of developmental song learning in juvenile males has been defined. This Review uses one area of zebra finch song learning to demonstrate how genome editing can advance causal investigations into known genome–brain–behavior relationships. Given the number and diversity of songbird species, comparative work leveraging genome manipulation would expand the influence of these birds in additional fields of ecology and evolution for song learning and other behaviors.
Progress towards engineering gene drives for population control
Authors: Raban Robyn R. , Marshall John M. , Akbari Omar S. 
Published: February 2020

ABSTRACT
Vector-borne diseases, such as dengue, Zika and malaria, are a major cause of morbidity and mortality worldwide. These diseases have proven difficult to control and currently available management tools are insufficient to eliminate them in many regions. Gene drives have the potential to revolutionize vector-borne disease control. This suite of technologies has advanced rapidly in recent years as a result of the availability of new, more efficient gene editing technologies. Gene drives can favorably bias the inheritance of a linked disease-refractory gene, which could possibly be exploited (i) to generate a vector population incapable of transmitting disease or (ii) to disrupt an essential gene for viability or fertility, which could eventually eliminate a population. Importantly, gene drives vary in characteristics such as their transmission efficiency, confinability and reversibility, and their potential to develop resistance to the drive mechanism. Here, we discuss recent advancements in the gene drive field, and contrast the benefits and limitations of a variety of technologies, as well as approaches to overcome these limitations. We also discuss the current state of each gene drive technology and the technical considerations that need to be addressed on the pathway to field implementation. While there are still many obstacles to overcome, recent progress has brought us closer than ever before to genetic-based vector modification as a tool to support vector-borne disease elimination efforts worldwide.
The coding loci of evolution and domestication: current knowledge and implications for bio-inspired genome editing
Authors: Courtier-Orgogozo Virginie , Martin Arnaud 
Published: February 2020

ABSTRACT
One promising application of CRISPR/Cas9 is to create targeted mutations to introduce traits of interest into domesticated organisms. However, a major current limitation for crop and livestock improvement is to identify the precise genes and genetic changes that must be engineered to obtain traits of interest. Here, we discuss the advantages of bio-inspired genome editing, i.e. the engineered introduction of natural mutations that have already been associated with traits of interest in other lineages (breeds, populations or species). To obtain a landscape view of potential targets for genome editing, we used Gephebase (www.gephebase.org), a manually curated database compiling published data about the genes responsible for evolutionary and domesticated changes across eukaryotes, and examined the &gt;1200 mutations that have been identified in the coding regions of more than 700 genes in animals, plants and yeasts. We observe that our genetic knowledge is relatively important for certain traits, such as xenobiotic resistance, and poor for others. We also note that protein-null alleles, often owing to nonsense and frameshift mutations, represent a large fraction of the known loci of domestication (42% of identified coding mutations), compared with intraspecific (27%) and interspecific evolution (11%). Although this trend may be subject to detection, publication and curation biases, it is consistent with the idea that breeders have selected large-effect mutations underlying adaptive traits in specific settings, but that these mutations and associated phenotypes would not survive the vagaries of changing external and internal environments. Our compilation of the loci of evolution and domestication uncovers interesting options for bio-inspired and transgene-free genome editing.
Molecular evolution of gland cell types and chemical interactions in animals
Authors: Brückner Adrian , Parker Joseph 
Published: February 2020

ABSTRACTAcross the Metazoa, the emergence of new ecological interactions has been enabled by the repeated evolution of exocrine glands. Specialized glands have arisen recurrently and with great frequency, even in single genera or species, transforming how animals interact with their environment through trophic resource exploitation, pheromonal communication, chemical defense and parental care. The widespread convergent evolution of animal glands implies that exocrine secretory cells are a hotspot of metazoan cell type innovation. Each evolutionary origin of a novel gland involves a process of ‘gland cell type assembly’: the stitching together of unique biosynthesis pathways; coordinated changes in secretory systems to enable efficient chemical release; and transcriptional deployment of these machineries into cells constituting the gland. This molecular evolutionary process influences what types of compound a given species is capable of secreting, and, consequently, the kinds of ecological interactions that species can display. Here, we discuss what is known about the evolutionary assembly of gland cell types and propose a framework for how it may happen. We posit the existence of ‘terminal selector’ transcription factors that program gland function via regulatory recruitment of biosynthetic enzymes and secretory proteins. We suggest ancestral enzymes are initially co-opted into the novel gland, fostering pleiotropic conflict that drives enzyme duplication. This process has yielded the observed pattern of modular, gland-specific biosynthesis pathways optimized for manufacturing specific secretions. We anticipate that single-cell technologies and gene editing methods applicable in diverse species will transform the study of animal chemical interactions, revealing how gland cell types are assembled and functionally configured at a molecular level.
<p><strong>Two new species of <em>Odontotrypes</em> (Coleoptera: Geotrupidae) from Ningxia and Sichuan, China</strong></p>
Authors: KRÁL DAVID , LU YUANYUAN , BAI MING 
Published: February 2020

The following two new species from China are described: Odontotrypes (Odontotrypes) anthracinus Král & Lu, sp. nov. (Sichuan) and Odontotrypes (Odontotrypes) liupan Král & Lu, sp. nov. (Ningxia). New species are compared with similar and probably related species. Relevant diagnostic characters of the new species including external male genitalia are illustrated. Key words: Taxonomy, new species, Coleoptera, Scarabaeoidea, Geotrupidae, Geotrupinae, Geotrupini, Odontotrypes, Palaearctic region
Advanced Imaging Techniques for the Detection of Breast Cancer
Authors: Jochelson Maxine 
Published: February 2020

Overview: Mammography is the only breast imaging examination that has been shown to reduce breast cancer mortality. Population-based sensitivity is 75% to 80%, but sensitivity in high-risk women with dense breasts is only in the range of 50%. Breast ultrasound and contrast-enhanced breast magnetic resonance imaging (MRI) have become additional standard modalities used in the diagnosis of breast cancer. In high-risk women, ultrasound is known to detect approximately four additional cancers per 1,000 women. MRI is exquisitely sensitive for the detection of breast cancer. In high-risk women, it finds an additional four to five cancers per 100 women. However, both ultrasound and MRI are also known to lead to a large number of additional benign biopsies and short-term follow-up examinations. Many new breast imaging tools have improved and are being developed to improve on our current ability to diagnose early-stage breast cancer. These can be divided into two groups. The first group is those that are advances in current techniques, which include digital breast tomosynthesis and contrast-enhanced mammography and ultrasound with elastography or microbubbles. The other group includes new breast imaging platforms such as breast computed tomography (CT) scanning and radionuclide breast imaging. These are exciting advances. However, in this era of cost and radiation containment, it is imperative to look at all of them objectively to see which will provide clinically relevant additional information.
Research and Standard of Care: Lung Cancer in Romania
Authors: Ciuleanu Tudor E. 
Published: February 2020

Overview: In Romania, lung cancer is the most frequent cancer in men and fourth most frequent in women, and its incidence and mortality continue to rise. Recently, firm antitobacco policies were implemented, in agreement with the MPOWER strategies recommended by the World Health Organization (WHO). As of January 2012, the recognized “official” standard of care in lung cancer is still represented by the 2009 edition of the European Society for Medical Oncology (ESMO) guidelines. Cancer treatment is free, as the National Program of Oncology covers the budget for all cytotoxic agents and targeted therapy. However, reimbursement for several expensive drugs such as pemetrexed, erlotinib, and bevacizumab is individually approved by a centralized commission. All new drugs registered in Europe by the European Medicines Agency are concomitantly registered in Romania. However, no new drugs (such as gefitinib) or new indications (such as first-line tyrosine-kinase inhibitors or maintenance treatment) have been accepted for reimbursement since 2008. Clinical research is rapidly growing, and Romanian centers demonstrate a high recruitment rate in pivotal trials, despite initial delays because of a slow approval of the studies by authorities.
Parody and Garden Path
Authors: Hou Guojin , Feng Mei 
Published: February 2020

AbstractThis is a study of Chinese rhetorical constructions, parody and garden path (GP), from the perspective of lexico-constructional pragmatics (LCP). LCP adopts a holographic view of lexicon and construction so that they can be analyzed alike. We take parody and GP examples from Chinese advertisements for analysis. The LCP analysis highlights the pragmaticity and rhetoricality of each case: for a particular effect. When difficulty arises, pragmatic means may be used to “pragma-coerce” the right, clever, or erroneous use of a rhetorical construction for delivery of a retrievable intended effect, an Aha-effect. We conduct a mini-questionnaire with two cases, the former dealing with parody and the latter with GP. The study indicates the humor competence of ordinary Chinese participants (around the level of BA) as far as parody and GP are concerned and the participants’ potential for cognition of the pragma-rhetorical values of parody and GP or their potential for generation of such utterances. It is suggested that rhetorical constructions outwit the less rhetorical or grammatical constructionsiffthey are available and accessible, and that LCP can offer us a feasible interpretation of such tropes as parody and GP.
Spectral property of the planar self-affine measures with three-element digit sets
Authors: Chen Ming-Liang , Liu Jing-Cheng , Su Juan 
Published: February 2020

Abstract
Let the self-affine measure

μ

M
,
D

{\mu_{M,D}}

be generated by an expanding real matrix

M
=

diag
⁡

(

ρ
1

-
1

,

ρ
2

-
1

)

{M=\operatorname{diag}(\rho_{1}^{-1},\rho_{2}^{-1})}

and an integer digit set

D
=

{

(
0
,
0
)

t

,

(

α
1

,

α
2

)

t

,

(

β
1

,

β
2

)

t

}

{D=\{(0,0)^{t},(\alpha_{1},\alpha_{2})^{t},(\beta_{1},\beta_{2})^{t}\}}

with

α
1

⁢

β
2

-

α
2

⁢

β
1

≠
0

{\alpha_{1}\beta_{2}-\alpha_{2}\beta_{1}\neq 0}

. In this paper, the sufficient and necessary conditions for

L
2

⁢

(

μ

M
,
D

)

{L^{2}(\mu_{M,D})}

to contain an infinite orthogonal set of exponential functions are given.
A combined experimental and first-principle study on the effect of plasma surface Ta–W co-alloying on the oxidation behavior of γ-TiAl at 900 °C
Authors: Wei Dongbo , Li Fengkun , Li Shuqin , Wang Shiyuan , Ding Feng , Liang Hongxuan , Yan Yuqin , Zhang Pingze 
Published: February 2020

Abstract
Cross-talk of Signaling Pathways in the Pathogenesis of Allergic Asthma and Cataract
Authors: Zhao Yang , Liu Sumei , Li Xiangsheng , Xu Zhenzhen , Hao Lifang , Cui Zhe , Bi Kewei , Zhang Yanfen , Liu Zhongcheng 
Published: February 2020

:
Allergic asthma is a chronic inflammatory disease, which involves many cellular and
cellular components. Cataract is a condition that affects the transparency of the lens, which the
opacity of the lens caused by any innate or acquired factor degrades its transparency or changes in
color. Both of them belong to diseases induced by immune disorders or inflammation. We want to
confirm the signaling pathways involved in the regulation of asthma and cataract simultaneously,
and provide reference for the later related experiments. So we conducted a scoping review of many
databases and searched for studies (Academic research published in Wiley, Springer and Bentham
from 2000 to 2019) about the possible relationship between asthma and cataract. It was found that
during the onset of asthma and cataract, Rho/Rock signaling pathway, Notch signaling pathway,
Wnt/β-catenin signaling pathway, PI3K/AKT signaling pathway, JAK/STAT signaling pathway,
MAPK signaling pathway, TGF-β1/Smad signaling pathway and NF-κB signaling pathway are all
active, so they may have a certain correlation in pathogenesis. Asthma may be associated with
cataract through the eight signaling pathways, causing inflammation or immune imbalance based
on allergy that can lead to cataract. According to these studies, we speculated that the three most
likely signaling pathways are PI3K/AKT, MAPK and NF-κB signaling pathway.