bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 on pediatric emergencies and hospitalizations in Singapore
Authors: Chong Shu-Ling , Soo Jenifer Shui Lian , Allen John Carson , Ganapathy Sashikumar , Lee Khai Pin , Tyebally Arif , Yung Chee Fu , Thoon Koh Cheng , Ng Yong Hong , Oh Jean Yin , Teoh Oon Hoe , Mok Yee Hui , Chan Yoke Hwee 
Published: December 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) has impacted the provision of health services in all specialties. We aim to study the impact of COVID-19 on the utilization of pediatric hospital services including emergency department (ED) attendances, hospitalizations, diagnostic categories and resource utilization in Singapore.MethodsWe performed a retrospective review of ED attendances and hospital admissions among children < 18 years old from January 1st to August 8th 2020 in a major pediatric hospital in Singapore. Data were analyzed in the following time periods: Pre-lockdown (divided by the change in Disease Outbreak Response System Condition (DORSCON) level), during-lockdown and post-lockdown. We presented the data using proportions and percentage change in mean counts per day with the corresponding 95% confidence intervals (CIs).ResultsWe attended to 58,367 children with a mean age of 5.1 years (standard deviation, SD 4.6). The mean ED attendance decreased by 331 children/day during lockdown compared to baseline (p < 0.001), attributed largely to a drop in respiratory (% change − 87.9, 95% CI − 89.3 to − 86.3,p < 0.001) and gastrointestinal infections (% change − 72.4, 95%CI − 75.9 to − 68.4,p < 0.001). Trauma-related diagnoses decreased at a slower rate across the same periods (% change − 40.0, 95%CI − 44.3 to − 35.3,p < 0.001). We saw 226 children with child abuse, with a greater proportion of total attendance seen post-lockdown (79, 0.6%) compared to baseline (36, 0.2%) (p < 0.001). In terms of ED resource utilization, there was a decrease in the overall mean number of procedures performed per day during the lockdown compared to baseline, driven largely by a reduction in blood investigations (% change − 73.9, 95%CI − 75.9 to − 71.7,p < 0.001).ConclusionsWe highlighted a significant decrease in infection-related presentations likely attributed to the lockdown and showed that the relative proportion of trauma-related attendances increased. By describing the impact of COVID-19 on health services, we report important trends that may provide guidance when planning resources for future pandemics.
Contextual factors of self-regulation in children and adolescents with chronic diseases – a qualitative analysis
Authors: Höhn Cindy , Metzner Gloria , Waldeck Edith , Glattacker Manuela 
Published: December 2020

Abstract
Background
In recent decades, the prevalence of chronic diseases in children and adolescents has increased significantly. Contextual factors play a central role in the self-regulation of chronic diseases. They influence illness and treatment representations, disease management, and health outcomes. While previous studies have investigated the influence of contextual factors on children’s beliefs about their illness, little is known about subjective contextual factors of treatment representations of children and adolescents with chronic diseases, especially in the context of rehabilitation. Therefore, the aim of this qualitative analysis was to examine the contextual factors reported by chronically ill children and adolescents in relation to their treatment representations. Furthermore, we aimed to assign the identified themes to classifications of environmental and personal contextual factors in the context of the International Classification of Functioning, Disability and Health (ICF).

Methods
Between July and September 2018, semi-structured interviews were conducted with N = 13 children and adolescents in rehabilitation to explore their rehab-related treatment representations and associated contextual factors. The interviews started with an open narrative question about expectations and beliefs about rehabilitation, followed by further detailed questions. The interviews were recorded on audio tape, transcribed, and analysed using thematic content analysis.

Results
Participants raised six themes associated with their rehab-related treatment representations that were interpreted as contextual factors: the living situation before rehabilitation, the idea of rehabilitation, previous solution attempts, rehab pre-experiences, information that the children and adolescents received from the clinic or sought themselves, and the assumed attitudes of their parents concerning rehabilitation. All the themes could be assigned to the classification of environmental and personal factors in the context of the ICF for children and youth.

Conclusions
Although contextual factors have an important impact on self-regulation, little attention is paid to their investigation. Personal and environmental factors probably influence patients’ treatment representations in terms of expectations and concerns as well as emotions regarding the treatment. Considering contextual factors could lead to the more appropriate allocation of medical care and the better customisation of treatment.
Potentially adaptive SARS-CoV-2 mutations discovered with novel spatiotemporal and explainable AI models
Authors: Garvin Michael R. , T. Prates Erica , Pavicic Mirko , Jones Piet , Amos B. Kirtley , Geiger Armin , Shah Manesh B. , Streich Jared , Felipe Machado Gazolla Joao Gabriel , Kainer David , Cliff Ashley , Romero Jonathon , Keith Nathan , Brown James B. , Jacobson Daniel 
Published: December 2020

AbstractBackgroundA mechanistic understanding of the spread of SARS-CoV-2 and diligent tracking of ongoing mutagenesis are of key importance to plan robust strategies for confining its transmission. Large numbers of available sequences and their dates of transmission provide an unprecedented opportunity to analyze evolutionary adaptation in novel ways. Addition of high-resolution structural information can reveal the functional basis of these processes at the molecular level. Integrated systems biology-directed analyses of these data layers afford valuable insights to build a global understanding of the COVID-19 pandemic.ResultsHere we identify globally distributed haplotypes from 15,789 SARS-CoV-2 genomes and model their success based on their duration, dispersal, and frequency in the host population. Our models identify mutations that are likely compensatory adaptive changes that allowed for rapid expansion of the virus. Functional predictions from structural analyses indicate that, contrary to previous reports, the Asp614Gly mutation in the spike glycoprotein (S) likely reduced transmission and the subsequent Pro323Leu mutation in the RNA-dependent RNA polymerase led to the precipitous spread of the virus. Our model also suggests that two mutations in the nsp13 helicase allowed for the adaptation of the virus to the Pacific Northwest of the USA. Finally, our explainable artificial intelligence algorithm identified a mutational hotspot in the sequence of S that also displays a signature of positive selection and may have implications for tissue or cell-specific expression of the virus.ConclusionsThese results provide valuable insights for the development of drugs and surveillance strategies to combat the current and future pandemics.
Defining the Optimal Total Number of Chemotherapy Courses in Younger Patients With Acute Myeloid Leukemia: A Comparison of Three Versus Four Courses
Authors: Burnett Alan K. , Russell Nigel H. , Hills Robert K. , Knapper Stephen , Freeman Sylvie , Huntly Brian , Clark Richard E. , Thomas Ian F. , Kjeldsen Lars , McMullin Mary Frances , Drummond Mark , Kell Jonathan , Spearing Ruth 
Published: December 2020

PURPOSE The optimum number of treatment courses for younger patients with acute myeloid leukemia (AML) is uncertain. The United Kingdom National Cancer Research Institute AML17 trial randomly assigned patients who were not high risk to a total of three versus four courses. PATIENTS AND METHODS Patients received two induction courses based on daunorubicin and cytarabine (Ara-C), usually with gemtuzumab ozogamicin. Following remission, 1,017 patients were randomly assigned to a third course, MACE (amsacrine, Ara-C, and etoposide), plus a fourth course of MidAc (mitoxantrone and Ara-C) and following an amendment to one or two courses of high-dose Ara-C. Primary end points were cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS). Outcomes were correlated with patient characteristics, mutations, cytogenetics, induction treatments, and measurable residual disease (MRD) postinduction. RESULTS In logrank analyses, CIR and RFS at 5 years were improved in recipients of four courses (50% v 58%: hazard ratio [HR] 0.81 [0.69-0.97], P = .02 and 43% v 36%: HR 0.83 [0.71-0.98], P = .03, respectively). While OS was not significantly better (63% v 57%: HR 0.84 [0.69-1.03], P = .09), the noninferiority of three courses to four courses was not established. The impact on relapse was only significant when the fourth course was Ara-C. In exploratory analyses, although MRD impacted survival, a fourth course had no effect in either MRD-positive or MRD-negative patients. A fourth course was beneficial in patients who lacked a mutation of FLT3 or NPM1, had < 3 mutations in other genes, or had a presenting WBC of < 10 × 109 L−1. CONCLUSION Although a fourth course of high-dose Ara-C reduced CIR and improved RFS, it did not result in a significant OS benefit. Subsets including those with favorable cytogenetics, those lacking a mutation of FLT3 or NPM1, or those with < 3 other mutations may derive survival benefit.
Ciona embryonic tail bending is driven by asymmetrical notochord contractility and coordinated by epithelial proliferation
Authors: Lu Qiongxuan , Gao Yuan , Fu Yuanyuan , Peng Hongzhe , Shi Wenjie , Li Bo , Lv Zhiyi , Feng Xi-Qiao , Dong Bo 
Published: December 2020

ABSTRACT
Ventral bending of the embryonic tail within the chorion is an evolutionarily conserved morphogenetic event in both invertebrates and vertebrates. However, the complexity of the anatomical structure of vertebrate embryos makes it difficult to experimentally identify the mechanisms underlying embryonic folding. This study investigated the mechanisms underlying embryonic tail bending in chordates. To further understand the mechanical role of each tissue, we also developed a physical model with experimentally measured parameters to simulate embryonic tail bending. Actomyosin asymmetrically accumulated at the ventral side of the notochord, and cell proliferation of the dorsal tail epidermis was faster than that in the ventral counterpart during embryonic tail bending. Genetic disruption of actomyosin activity and inhibition of cell proliferation dorsally caused abnormal tail bending, indicating that both asymmetrical actomyosin contractility in the notochord and the discrepancy of epidermis cell proliferation are required for tail bending. In addition, asymmetrical notochord contractility was sufficient to drive embryonic tail bending, whereas differential epidermis proliferation was a passive response to mechanical forces. These findings showed that asymmetrical notochord contractility coordinates with differential epidermis proliferation mechanisms to drive embryonic tail bending.
This article has an associated ‘The people behind the papers’ interview.
Coordinated assembly and release of adhesions builds apical junctional belts during de novo polarisation of an epithelial tube
Authors: Symonds Andrew C. , Buckley Clare E. , Williams Charlotte A. , Clarke Jonathan D. W. 
Published: December 2020

ABSTRACT
Using the zebrafish neural tube as a model, we uncover the in vivo mechanisms allowing the generation of two opposing apical epithelial surfaces within the centre of an initially unpolarised, solid organ. We show that Mpp5a and Rab11a play a dual role in coordinating the generation of ipsilateral junctional belts whilst simultaneously releasing contralateral adhesions across the centre of the tissue. We show that Mpp5a- and Rab11a-mediated resolution of cell-cell adhesions are both necessary for midline lumen opening and contribute to later maintenance of epithelial organisation. We propose that these roles for both Mpp5a and Rab11a operate through the transmembrane protein Crumbs. In light of a recent conflicting publication, we also clarify that the junction-remodelling role of Mpp5a is not specific to dividing cells.
CD301 mediates fusion in IL-4-driven multinucleated giant cell formation
Authors: Brooks Patricia J. , Wang Yongqiang , Magalhaes Marco A. , Glogauer Michael , McCulloch Christopher A. 
Published: December 2020

ABSTRACT
Multinucleated giant cells (MGCs) are prominent in foreign body granulomas, infectious and inflammatory processes, and auto-immune, neoplastic and genetic disorders, but the molecular determinants that specify the formation and function of these cells are not defined. Here, using tandem mass tag-mass spectrometry, we identified a differentially upregulated protein, C-type lectin domain family 10 member (herein denoted CD301, also known as CLEC10A), that was strongly upregulated in mouse RAW264.7 macrophages and primary murine macrophages undergoing interleukin (IL-4)-induced MGC formation. CD301+ MGCs were identified in biopsy specimens of human inflammatory lesions. Function-inhibiting CD301 antibodies or CRISPR/Cas9 deletion of the two mouse CD301 genes (Mgl1 and Mgl2) inhibited IL-4-induced binding of N-acetylgalactosamine-coated beads by 4-fold and reduced MGC formation by 2.3-fold (P&lt;0.05). IL-4-driven fusion and MGC formation were restored by re-expression of CD301 in the knockout cells. We conclude that in monocytes, IL-4 increases CD301 expression, which mediates intercellular adhesion and fusion processes that are required for the formation of MGCs.
This article has an associated First Person interview with the first author of the paper.
Notch in mechanotransduction – from molecular mechanosensitivity to tissue mechanostasis
Authors: Stassen Oscar M. J. A. , Ristori Tommaso , Sahlgren Cecilia M. 
Published: December 2020

ABSTRACT
Tissue development and homeostasis are controlled by mechanical cues. Perturbation of the mechanical equilibrium triggers restoration of mechanostasis through changes in cell behavior, while defects in these restorative mechanisms lead to mechanopathologies, for example, osteoporosis, myopathies, fibrosis or cardiovascular disease. Therefore, sensing mechanical cues and integrating them with the biomolecular cell fate machinery is essential for the maintenance of health. The Notch signaling pathway regulates cell and tissue fate in nearly all tissues. Notch activation is directly and indirectly mechanosensitive, and regulation of Notch signaling, and consequently cell fate, is integral to the cellular response to mechanical cues. Fully understanding the dynamic relationship between molecular signaling, tissue mechanics and tissue remodeling is challenging. To address this challenge, engineered microtissues and computational models play an increasingly large role. In this Review, we propose that Notch takes on the role of a ‘mechanostat’, maintaining the mechanical equilibrium of tissues. We discuss the reciprocal role of Notch in the regulation of tissue mechanics, with an emphasis on cardiovascular tissues, and the potential of computational and engineering approaches to unravel the complex dynamic relationship between mechanics and signaling in the maintenance of cell and tissue mechanostasis.
Developmental and reproductive physiology of small mammals at high altitude: challenges and evolutionary innovations
Authors: Robertson Cayleih E. , Wilsterman Kathryn 
Published: December 2020

ABSTRACTHigh-altitude environments, characterized by low oxygen levels and low ambient temperatures, have been repeatedly colonized by small altricial mammals. These species inhabit mountainous regions year-round, enduring chronic cold and hypoxia. The adaptations that allow small mammals to thrive at altitude have been well studied in non-reproducing adults; however, our knowledge of adaptations specific to earlier life stages and reproductive females is extremely limited. In lowland natives, chronic hypoxia during gestation affects maternal physiology and placental function, ultimately limiting fetal growth. During post-natal development, hypoxia and cold further limit growth both directly by acting on neonatal physiology and indirectly via impacts on maternal milk production and care. Although lowland natives can survive brief sojourns to even extreme high altitude as adults, reproductive success in these environments is very low, and lowland young rarely survive to sexual maturity in chronic cold and hypoxia. Here, we review the limits to maternal and offspring physiology – both pre-natal and post-natal – that highland-adapted species have overcome, with a focus on recent studies on high-altitude populations of the North American deer mouse (Peromyscus maniculatus). We conclude that a combination of maternal and developmental adaptations were likely to have been critical steps in the evolutionary history of high-altitude native mammals.
Dependence of radiomic features on pixel size affects the diagnostic performance of radiomic signature for the invasiveness of pulmonary ground-glass nodule
Authors: Tao Guangyu , Yin Lekang , Shi Dejun , Ye Jianding , Lu Zhenghai , Zhou Zhen , Yu Yizhou , Ye Xiaodan , Yu Hong 
Published: December 2020

Objective:
To investigate the effect of reducing pixel size on the consistency of radiomic features and the diagnostic performance of the downstream radiomic signatures for the invasiveness for pulmonary ground-glass nodules (GGNs) on CTs.

Methods:
We retrospectively collected the clinical data of 182 patients with GGNs on high resolution CT (HRCT). The CT images of different pixel sizes (0.8mm, 0.4mm, 0.18 mm) were obtained by reconstructing the single HRCT scan using three combinations of field of view and matrix size. For each pixel size setting, radiomic features were extracted for all GGNs and radiomic signatures for the invasiveness of GGNs were built through two modeling pipelines for comparison.

Results:
The study finally extracted 788 radiomic features. 87% radiomic features demonstrated inter pixel size variation. By either modeling pipeline, the radiomic signature under small pixel size performed significantly better than those under middle or large pixel sizes in predicting the invasiveness of GGNs (p’s value &lt;0.05 by Delong test). With the independent modeling pipeline, the three pixel size bounded radiomic signatures shared almost no common features.

Conclusions:
Reducing pixel size could cause inconsistency in most radiomic features and improve the diagnostic performance of the downstream radiomic signatures. Particularly, super HRCTs with small pixel size resulted in more accurate radiomic signatures for the invasiveness of GGNs.

Advances in knowledge:
The dependence of radiomic features on pixel size will affect the performance of the downstream radiomic signatures. The future radiomic studies should consider this effect of pixel size.
Breast cancer abutting the pectoralis major muscle on breast MRI: what are the clinical implications?
Authors: Myers Kelly S , Stern Erica , Ambinder Emily B , Oluyemi Eniola T 
Published: December 2020

Objectives:
Defining the posterior extent of breast cancer prior to surgery has clinical implications. However, there are limited data available to guide the interpretation of breast cancers seen on MRI that abut the pectoralis muscle but lack associated muscle enhancement.

Methods:
In this retrospective study of breast MRIs performed between May 2008 and July 2019, 43 female patients demonstrated breast cancers abutting the pectoralis muscle without enhancement of the muscle itself. Imaging features of the cancers as well as pathologic and clinical outcomes were recorded. Statistical analyses of associations between imaging findings and clinical outcomes were performed using Fisher’s exact test, logistic regression, a Mann–Whitney U test and/or Student’s t-test.

Results:
The pectoralis major muscle was pathologically invaded by carcinoma in 4/43 (9.3%). There was no significant association between pectoralis muscle invasion and any MR imaging feature of the breast cancer. Tumors causing deformation of the muscle contour by MRI, tumors larger in size, tumors with a larger extent abutting the muscle and tumors in which the imaging feature abutting the muscle was a mass or non-mass enhancement (rather than a spicule) were more commonly seen in patients with muscle invasion, although these did not reach statistical significance (p &gt; 0.05).

Conclusion:
In this study, a lack of pectoralis muscle enhancement by MRI did not exclude pathologic muscle invasion by breast cancers abutting the muscle.

Advances in knowledge:
Knowledge of the likelihood of pectoralis muscle involvement for breast cancers abutting the pectoralis muscle on MRI may guide accurate interpretation and definition of the posterior extent of disease.
On the paradigm of modern education
Authors: Repnikova Valentina , Garnov Andrey , Bykova O. 
Published: December 2020

Digitalization, the transition to a knowledge economy, requires a restructuring of the education system. The existing education system does not meet the realities of the country's development, but it also contributes to the modernization of technologies, the definition of a high status among the country's economic leaders. Adaptation of education to the changing conditions of the world economic system is required. Additional education can make the transformation of the education system smoother without jeopardizing national technological development, accelerating these changes and becoming an instrument for meeting the demands of labor market professionals.
Economic changes in the context of the transformation of a knowledge-based society require restructuring the education system, creating new professional skills and training specialists who can acquire and use new knowledge in rapidly changing situations.
Americans’ perceptions of privacy and surveillance in the COVID-19 pandemic
Authors: Zhang Baobao , Kreps Sarah , McMurry Nina , McCain R. Miles 
Published: December 2020

Objective
To study the U.S. public’s attitudes toward surveillance measures aimed at curbing the spread of COVID-19, particularly smartphone applications (apps) that supplement traditional contact tracing.

Method
We deployed a survey of approximately 2,000 American adults to measure support for nine COVID-19 surveillance measures. We assessed attitudes toward contact tracing apps by manipulating six different attributes of a hypothetical app through a conjoint analysis experiment.

Results
A smaller percentage of respondents support the government encouraging everyone to download and use contact tracing apps (42%) compared with other surveillance measures such as enforcing temperature checks (62%), expanding traditional contact tracing (57%), carrying out centralized quarantine (49%), deploying electronic device monitoring (44%), or implementing immunity passes (44%). Despite partisan differences on a range of surveillance measures, support for the government encouraging digital contact tracing is indistinguishable between Democrats (47%) and Republicans (46%), although more Republicans oppose the policy (39%) compared to Democrats (27%). Of the app features we tested in our conjoint analysis experiment, only one had statistically significant effects on the self-reported likelihood of downloading the app: decentralized data architecture increased the likelihood by 5.4 percentage points.

Conclusion
Support for public health surveillance policies to curb the spread of COVID-19 is relatively low in the U.S. Contact tracing apps that use decentralized data storage, compared with those that use centralized data storage, are more accepted by the public. While respondents’ support for expanding traditional contact tracing is greater than their support for the government encouraging the public to download and use contact tracing apps, there are smaller partisan differences in support for the latter policy.