bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Developmental Eye Movement Test Does Not Detect Oculomotor Problems: Evidence from Children with Nystagmus
Authors: Tanke Nouk , Barsingerhorn Annemiek D. , Goossens Jeroen , Boonstra F. Nienke 
Published: August 2022

SIGNIFICANCE
The Developmental Eye Movement (DEM) test, a test purported to assess oculomotor skills, does not detect eye movement disorder in nystagmus syndromes. The test should not be used for the clinical evaluation of oculomotor disorders.

PURPOSE
The DEM test ratio compares a horizontal number naming subtest with a vertical one to identify oculomotor problems independent of a child's visual-verbal naming skills. Here, we tested the construct validity of this method by comparing scores of children with and without pathologic nystagmus. Such a nystagmus disturbs normal fixation and saccadic behavior because of the presence of involuntary rhythmic oscillations of the eyes. Therefore, if the ratio is indeed a comprehensive measure of oculomotor problems, children with nystagmus should show an increased ratio score.

METHODS
The DEM test performances of normally sighted children (n = 94), children with ocular visual impairments (VIo; n = 33), and children with cerebral visual impairment (n = 30) were analyzed using linear regression. Part of the children with VIo and cerebral visual impairment had either fusion maldevelopment nystagmus syndrome (n = 8) or infantile nystagmus syndrome (n = 20), whereas the others showed no pathologic nystagmus.

RESULTS
The times needed for the horizontal and vertical subtests were significantly different between children with normal vision, VIo, and cerebral visual impairment (P < .001). However, the presence of nystagmus did not add significantly to the horizontal and vertical times (P > .20), nor did it have an effect on the ratio (P > .10).

CONCLUSIONS
The DEM test ratio is not sensitive to fixation and saccade abnormalities associated with nystagmus, indicating that it does not have general construct validity to detect true eye movement disorders. Although not suitable for the evaluation of oculomotor disorders, the subtests do have clinical relevance in the diagnosis of cerebral visual impairment.
Identifying Operational Challenges and Solutions During the COVID-19 Response Among US Public Health Laboratories
Authors: Potter Christina , Kaushal Natasha , Wroblewski Kelly , Becker Scott , Nuzzo Jennifer B. 
Published: August 2022

Context:
The ability to diagnose and screen for infection is an important component of the US COVID-19 response and is facilitated by public health laboratories (PHLs). Anecdotal media reports and limited case studies have described some of the challenges faced by PHLs during the pandemic, particularly initial challenges related to developing and deploying tests to PHLs, but there has not been a systematic evaluation of the experience of PHLs during the pandemic.

Objective:
To document challenges and lessons learned experienced by local and state PHLs during the COVID-19 pandemic to support generation of best practices for current and future similar emergencies.

Design, Setting, and Participants:
From February to June 2021, researchers conducted 24 interviews with 68 leaders and staff representing 28 local and state PHLs across 27 states. Thematic analysis of interview content documented operational challenges and any identified solutions or preventive measures used or proposed.

Main Outcome Measures:
Analysis identified the following themes regarding challenges faced among PHLs: strategic decision making and determining the mandate of the PHL; political interference by jurisdictional leadership; federal mismanagement of the emergency; regulatory challenges; managing partnerships with other laboratories; acquisition of appropriate supplies; insufficient information systems; acquiring and retaining workforce; and difficulty accessing sufficient funding.

Results:
Within the identified themes, key informants provided further elaboration regarding how PHLs experienced, evaded, or solved these challenges. In addition, PHLs described how challenges evolved throughout the course of the COVID-19 pandemic and made proposals regarding how challenges could be prevented or further addressed in the future by laboratories or other decision makers and stakeholders.

Conclusions:
While fellow laboratories and political leadership may gain inspiration from creative solutions employed by PHLs, recognition of long-standing gaps related to funding, laboratory workforce, and consideration of laboratory needs in preparedness policies must be addressed for future large-scale outbreaks.
Quality Improvement Initiative Increasing Early Discharges From an Acute Care Cardiology Unit for Cardiac Surgery and Cardiology Patients–Associated With Reduced Hospital Length of Stay
Authors: Colyer Jessica , Ring Lisa , Gallagher Sarah , Mullenholz Mary , Robison Jan , Rigney-Radford Kathleen , Harahsheh Ashraf S. 
Published: August 2022

Introduction:
Discharging patients from the acute care setting is complex and requires orchestration of many clinical and technical processes. Focusing on timely discharges improves throughput by off-loading ICUs and coordinating safe outpatient transitions. Our data review demonstrated most discharges occurred later in the day. We sought to improve our discharge times for cardiology and cardiovascular surgery (CVS) patients in our 26-bed inpatient acute care cardiology unit (ACCU). We aimed to increase the number of discharges between 6 am and 12 pm for cardiology and CVS patients on ACCU from 5 to 10 patients per month over 6 months and sustain.

Methods:
We performed a simplified Failure Mode Effect Analysis on the discharge process and identified improvement opportunities. Our key drivers centered around education, documentation, and planning. Our interventions included: staff education, communication of discharge expectations, daily quality board rounds, hospital-wide collaboration emphasizing conditional discharges, and hospital information technology (IT) improvements. We utilized statistical process control charts to analyze the data.

Results:
Discharges between 6 am, and 12 pm increased from a baseline of 5 (8%) to 12 (18%) patients per month with a centerline shift. Our process measures demonstrated appropriate conditional discharge usage linked to earlier discharges. Upgrades to our EMR, documentation further increased our timely discharges. Our efforts resulted in a 22% reduction in hospital length of stay from 11.2 to 8.7 days without increased readmission rates suggesting that improved efficiency did not impact care quality.

Conclusion:
We successfully show how multidisciplinary collaboration and systems-based improvement can increase the number of safe, early discharges.
Computational modelling of the crushing of carbon fibre-reinforced polymer composites
Authors: Falzon Brian G. 
Published: August 2022

The use of lightweight carbon fibre-reinforced polymer (CFRP) composites in transportation vehicles has necessitated the need to guarantee that these new materials and their structures are able to deliver a sufficient level of crashworthiness to ensure passenger safety. Unlike their metallic counterparts, which absorb energy primarily through plastic deformation, CFRPs absorb energy through a complex interaction of damage mechanisms involving matrix (polymer) cracking, fibre/matrix debonding, fibre pull-out/kinking/fracture, delamination and inter/intralaminar friction. CFRP is primarily deployed as a laminate and can potentially deliver a higher specific energy absorption than metals. Translating this capability to a structural scale requires careful design and is dependent on geometry, fibre architecture, laminate stacking sequence and damage initiation strategies for optimal uniform crushing. Consequently, the design of crashworthy CFRP structures currently entails extensive physical testing which is expensive and time consuming. This paper reports on progress and challenges in the development of a finite-element computational capability for simulating the crushing of composites for crashworthiness assessments, with the aim of reducing the burden of physical testing. It addresses the ‘tyranny of scales’ in modelling structures constructed of CFRP composites. Intrinsic to this capability is the acquisition of reliable material data for the damage model, in particular interlaminar and intralaminar fracture toughness values. While quasi-static values can be obtained with a reasonable level of confidence, results achieved through dynamic testing are still the subject of debate and the relationship between fracture toughness and strain rate has yet to be satisfactorily resolved.
This article is part of the theme issue ‘Nanocracks in nature and industry’.
Adhesion and wear of diamond: formation of nanocracks and adhesive craters of torn out material
Authors: Borodich Feodor M. , Galanov Boris A. , Grigoriev Oleg N. 
Published: August 2022

Mechanical transformation of rough diamonds into brilliant ones is usually achieved by polishing using microsized abrasive diamond particles. It is shown that in addition to formation of periodic pattern of ‘partial’ Hertzian cone cracks on the diamond surface, nano-sized domains (50–150 nm in diameter) of crumbled material are observed. Because these domains are located in the centres of the regions (250–500 nm in diameter) partially surrounded by the Hertzian cone cracks, where the stresses are close to the stress field of hydrostatic compression, the material removal cannot be explained by creation of tensile or shear cracks. It is argued that the creation of these domains of crumbled material is due to adhesive interactions between sliding diamond particles and the diamond surface. Employing a two-term law of friction, the scheme of ultimate equilibrium between the particle and the surface is presented. The distributions of contact stresses are calculated for two approaches: (i) the extended Johnson–Kendall–Roberts model and (ii) the ‘soft’ model of adhesive contact. Thus, adhesion between the sliding diamond particle and the surface leads to creation of periodic pattern of the crumbling domains with the steps 500–1000 nm and adhesive tearing out of the material from the domains.
This article is part of the theme issue ‘Nanocracks in nature and industry’.
COGNITION AND INFLUENCING FACTORS OF HOSPICE CARE AMONG NURSING UNDERGRADUATES
Authors: Zhang Rui-ting 
Published: August 2022

AbstractObjectiveTo investigate the current cognition of hospice care among nursing undergraduates, and analyze the influencing factors affecting their cognition, so as to provide suggestions for improving the cognition of hospice care among nursing undergraduates.Methods290 nursing undergraduates were selected for an online questionnaire survey. The questionnaire includes general information, hospice care knowledge, and hospice care attitude.ResultsThe mean score of the hospice care knowledge questionnaire is 9.68±4.73, and the mean score of the attitude questionnaire is 62.59±7.29. The influencing factors of hospice care cognition of nursing undergraduates are gender, age, religious belief, the only child, internship experience, grade, source of death experience, death talk at home, and access to hospice care knowledge.ConclusionNursing undergraduates’ lack of knowledge of hospice care, and hospice care attitude is more positive, suggesting that nursing undergraduates should strengthen hospice care education according to the influencing factors, call for government support, in order to further improve nursing undergraduates’ hospice care cognition status.
High throughput steady-state enzyme kinetics measured in a parallel droplet generation and absorbance detection platform
Authors: Neun Stefanie , van Vliet Liisa , Hollfelder Florian , Gielen Fabrice 
Published: August 2022

ABSTRACTMicrofluidic water-in-oil emulsion droplets are becoming a mainstay of experimental biology, where they replace the classical test tube. In most applications (e.g. in ultrahigh throughput directed evolution) the droplet content is identical for all compartmentalized assay reactions. When emulsion droplets are used for kinetics or other functional assays, though, concentration dependencies (e.g. of initial rates for Michaelis-Menten plots) are required. Droplet-on-demand systems satisfy this need but extracting large amounts of data is challenging. Here we introduce a multiplexed droplet absorbance detector which, coupled to semi-automated droplet generation, forms a tubing-based droplet-on-demand system able to generate and extract quantitative datasets from defined concentration gradients across multiple series of droplets for multiple time points. The emergence of product is detected by reading the absorbance of the droplet sets at multiple, adjustable time points (reversing the flow direction after each detection, so that the droplets pass a line scan camera multiple times). Detection multiplexing allows absorbance values at twelve distinct positions to be measured and enzyme kinetics are recorded for label-free concentration gradients (composed of about 60 droplets each, covering as many concentrations). With a throughput of around 8640 data points per hour, a 10-fold improvement compared to the previously reported single point detection method is achieved. In a single experiment, twelve full datasets of high-resolution and high accuracy Michaelis-Menten kinetics were determined to demonstrate the potential for enzyme characterization for glycosidase substrates covering a range in enzymatic hydrolysis of seven orders of magnitude in kcat/KM. The straightforward set-up, high throughput, excellent data quality, wide dynamic range that allows coverage of diverse activities suggest that this system may serve as a miniaturized spectrophotometer to for detailed analysis of study clones emerging from large-scale combinatorial experiments.Abstract Figure
JBrowse 2: A modular genome browser with views of synteny and structural variation
Authors: Diesh Colin , Stevens Garrett J , Xie Peter , De Jesus Martinez Teresa , Hershberg Elliot A. , Leung Angel , Guo Emma , Dider Shihab , Zhang Junjun , Bridge Caroline , Hogue Gregory , Duncan Andrew , Morgan Matthew , Flores Tia , Bimber Benjamin N. , Haw Robin , Cain Scott , Buels Robert M. , Stein Lincoln D. , Holmes Ian H. 
Published: August 2022

AbstractWe present JBrowse 2, a general-purpose genome annotation browser offering enhanced visualization of complex structural variation and evolutionary relationships. JBrowse 2 retains the core features of the open-source JavaScript genome browser JBrowse while adding new views for synteny, dotplots, breakpoints, gene fusions, and whole-genome overviews. The software readily allows users to share sessions, open multiple genomes or views, and navigate quickly between these views. It can be embedded in a web page, used as a standalone desktop application, or run from Jupyter notebooks or R sessions. Using a plugin framework, developers can create new data adapters, track types, and visualizations. These improvements are enabled by a ground-up redesign of the JBrowse architecture using modern web technology. We describe application functionality, use cases, performance benchmarks, and implementation notes for web administrators and developers.
Fat Extract Modulates Calcium Signaling and Protects Against Hyperactive Osteoclastogenesis in Bone Remodeling with Antioxidant Capacity
Authors: Yang Yiqi , Xu Mingming , Kan Tianyou , Wang Yao , Zhang Shuhong , Deng Mingwu , Zhang Wenjie , Li Hanjun , Yu Zhifeng 
Published: August 2022

AbstractOsteoclasts are cells which are primarily involved in bone remodeling and osteolytic bone diseases. Hyperactive osteoclastogenesis leads to pathological bone loss and microarchitectural deterioration, particularly in postmenopausal osteoporosis. However, given the limitations of current first-line osteoclast inhibitors, there is an urgent need for a novel antiresorptive agent with higher efficiency and fewer side effects. Cell-free fat extract (CEFFE) is the liquid fraction obtained from human adipose tissues, which are enriched with a variety of cytokines and growth factors. This study aims to explore its pharmaceutical effect on hyperactive osteoclast formation in vivo and in vitro. CEFFE exhibits excellent potentials to attenuate osteoclast-associated bone loss in an ovariectomy (OVX) mouse model and to inhibit RANKL-induced osteoclastogenesis in primary bone marrow-derived monocytes. Furthermore, the cationic protein fraction of CEFFE (CEFFE-Cation) is identified as the main inhibitory component in osteoclast formation assay. Excessive reactive oxygen species (ROS) production is the main cause of osteoclast overactivation. According to LC-MS/MS analysis, the CEFFE-Cation fraction mainly consists of various antioxidant enzymes, extracellular matrix, and secreted cytokines, which endow it with a superior antioxidant capacity. Ca2+ signaling contributes to osteoclast maturation. In addition to scavenging ROS, CEFFE-Cation is also capable of mitigating Ca2+ oscillation, calcineurin activation, and subsequent NFATc1 nuclear translocation during osteoclastogenesis. Overall, this study elucidates the promising translational potential of CEFFE as a next-generation personalized antiresorptive agent for osteolytic bone disease treatment.
Constraints and trade-offs shape the evolution of T cell search strategies
Authors: Wortel Inge M N , Textor Johannes 
Published: August 2022

AbstractTwo decades of in vivo imaging have revealed how diverse the shapes and motion patterns of migrating T cells can be. This finding has sparked the notion of “search strategies”: T cells may have evolved ways to search for antigen efficiently and might even adapt their motion to the task at hand. Mathematical models have indeed confirmed that observed T-cell migration patterns resemble a theoretical optimum in several contexts; for example, frequent turning, stop-and-go motion, or alternating short and long motile runs have all been interpreted as deliberately tuned behaviours, optimising the cell’s chance of finding antigen. But the same behaviours could also arise simply because T cells can’t follow a straight, regular path through the tight spaces they navigate. Even if T cells can be shown to follow a theoretically optimal pattern, the question remains: has that pattern truly been evolved for this particular searching task, or does it merely reflect how the cell’s migration machinery and surroundings constrain motion paths?We here examine to what extent cells can evolve search strategies when faced with realistic constraints. Using a cellular Potts model (CPM), where motion arises from interactions between intracellular dynamics, cell shape, and a constraining environment, we simulate an evolutionary process in which cells “optimise” a simple task: explore as much area as possible. We find that cells evolve several motility characteristics previously attributed to search optimisation, even though these features were not beneficial for the task given here. Our results stress that “optimal” search strategies do not always stem from evolutionary adaptation: instead, they may be the inevitable side effects of interactions between cell shape, intracellular actin dynamics, and the diverse environments T cells face in vivo.
DLC3/Cv-c function in testis development in humans and Drosophila: implication for variants of sex development
Authors: Sotillos Sol , von der Decken Isabel , Mercadé Ivan Domenech , Srinivasan Sriraksha , Vanni Stefano , Nef Serge , Biason-Lauber Anna , Gutiérrez Daniel Rodríguez , Hombría James C-G 
Published: August 2022

AbstractIdentifying genes affecting gonad development is essential to understand the mechanisms causing Variants/Differences in Sex Development. Recently, a DLC3 mutation was associated with male gonadal dysgenesis in 46,XY DSD patients. We show that Cv-c, the Drosophila ortholog of DLC3, is also required to maintain testis integrity during fly development. We found that Cv-c and human DLC3 can perform the same function in fly embryos, as flies with wild type but not mutated DLC3 rescue gonadal dysgenesis, suggesting a functional conservation. Expression of different Cv-c protein variants demonstrated that the StART domain mediates the Cv-c function in the male gonad, independently from the GAP domain activity. This work demonstrates a role for DLC3/Cv-c in male gonadogenesis and highlights a novel StART-mediated function required for gonadal mesoderm-germ cell interaction during testis development.Significance StatementAssociating rare human genetic variants to specific conditions is complex. An amino acid change in the StART domain of the RhoGAP DLC3 protein has been found in female DSD patients with a 46,XY male karyotype. We present a second DSD patient with a mutation in the same region and show that the Cv-c/DLC3 homolog is also required in Drosophila testis. In cv-c mutant embryos the testis mesodermal cells display various defects: the testes are unable to retain the germ cells due to their abnormal ensheathment by mesodermal cells and the mesodermal sheet of cells surrounding the testis is discontinuous resulting in the liberation of the germ cells outside the gonad. Defects can be rescued by gonadal expression of Cv-c or DLC3 but not by the patients’ DLC3 protein variant. Testis development requires the StART lipid binding domain but not the GAP domain, revealing a novel function of this RhoGAP family.
Lipid Desaturation Regulates the Balance between Self-renewal and Differentiation in Mouse Blastocyst-derived Stem Cells
Authors: Thomas Mannully Chanchal , Bruck-Haimson Reut , Zacharia Anish , Orih Paul , Shehadeh Alaa , Saidemberg Daniel , Kogan Natalya M , Alfandary Sivan , Serruya Raphael , Dagan Arie , Petit Isabelle , Moussaieff Arieh 
Published: August 2022

ABSTRACTStem cells are defined by their ability to self-renew and to differentiate, both shown in multiple studies to be regulated by metabolic processes. To decipher metabolic signatures of self-renewal in blastocyst-derived stem cells, we compared early differentiating embryonic stem cells (ESCs) and their extra-embryonic counterparts - trophoblast (T)SCs to their self-renewing counterparts. A metabolomics analysis pointed to the desaturation of fatty acyl chains as a metabolic signature of differentiating blastocyst-derived SCs via the upregulation of delta-6 desaturase (D6D; FADS2) and delta-5 desaturase (D5D; FADS1), key enzymes in the biosynthesis of polyunsaturated fatty acids (PUFAs). The inhibition of D6D or D5D by specific inhibitors or SiRNA retained stemness in ESCs and TSCs, and attenuated endoplasmic reticulum (ER) stress-related apoptosis. D6D inhibition upregulated stearoyl-CoA desaturase-1 (Scd1) in ESCs, essential to maintain ER homeostasis. In TSCs, however, D6D inhibition downregulated Scd1. TSCs show higherScd1mRNA expression and high levels of monounsaturated fatty acyl chain products in comparison to ESCs. Addition of oleic acid – the product of Scd1 (essential for ESCs), to culture medium, was detrimental to TSCs. Interestingly, TSCs express a high molecular mass variant of Scd1 protein, hardly expressed by ESCs. Taken together, our data point to lipid desaturation as a metabolic regulator of the balance between differentiation and self-renewal of ESCs and TSCs. They point to lipid polydesaturation as a driver of differentiation in both cell types. In contrast, mono unsaturated fatty acids (MUFAs), known to be essential for ESCs are detrimental to TSCs.