bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-referred walk-in patients in the emergency department – who and why? Consultation determinants in a multicenter study of respiratory patients in Berlin, Germany
Authors: Holzinger Felix , Oslislo Sarah , Möckel Martin , Schenk Liane , Pigorsch Mareen , Heintze Christoph 
Published: September 2020

Abstract
Background
Emergency department (ED) consultations are on the rise, and frequently consultations by non-urgent patients have been held accountable. Self-referred walk-in (SRW) consulters supposedly represent a predominantly less urgent patient population. The EMACROSS study aimed to explore consultation determinants and motives in SRW patients with respiratory symptoms.

Methods
Multicenter survey of adult ED patients with respiratory complaints in eight emergency departments in central Berlin, Germany. Secondary hospital records data including diagnoses was additionally assessed. Characteristics of SRW and non-SRW patients were compared. Determinants of SRW consultation were evaluated by binary logistic regression. Consultation motives were analyzed descriptively. As a supplemental approach, network analysis (lasso-regularized mixed graphical model) was performed to explore connections between consultation determinants, consultation features and motives.

Results
Between June 2017 and November 2018, n = 472 participants were included, the median age was 55 years (range 18–96), 53.2% of patients were male and n = 185 cases (39.2%) were SRW consulters. The SRW group showed lower proportions of potentially severe (pneumonia and respiratory failure, p < 0.001, χ2 test) and chronic pulmonary conditions. Determinants of SRW consultation identified by logistic regression were younger age (p < 0.001), tertiary education (p = 0.032), being a first-generation migrant (p = 0.002) or tourist (p = 0.008), having no regular primary care provider (p = 0.036) and no chronic pulmonary illness (p = 0.017). The area under the curve (AUC) for the model was 0.79. Personal distress and access problems in ambulatory care were stated most frequently as consultation motives in the SRW group; network analysis showed the scarcity of associations between demographic and medical SRW determinants and motives triggering the actual decision to consult.

Conclusions
As to “who” consults, this study identified demographic and medical predictors of SRW utilization. The said markers seem only remotely connected to “why” people decide for SRW visits. To alleviate ED crowding by addressing frequent SRW consultation motives, interventions focused on the ability for symptom self-assessment and at better-accessible alternative care seem sensible.

Trial registration
German Clinical Trials Register (DRKS00011930); date: 2017/04/25.
Mechanical force-induced morphology changes in a human fungal pathogen
Authors: Puerner Charles , Kukhaleishvili Nino , Thomson Darren , Schaub Sebastien , Noblin Xavier , Seminara Agnese , Bassilana Martine , Arkowitz Robert A. 
Published: September 2020

Abstract
Background
The initial step of a number of human or plant fungal infections requires active penetration of host tissue. For example, active penetration of intestinal epithelia by Candida albicans is critical for dissemination from the gut into the bloodstream. However, little is known about how this fungal pathogen copes with resistive forces upon host cell invasion.

Results
In the present study, we have used PDMS micro-fabrication to probe the ability of filamentous C. albicans cells to penetrate and grow invasively in substrates of different stiffness. We show that there is a threshold for penetration that corresponds to a stiffness of ~ 200 kPa and that invasive growth within a stiff substrate is characterized by dramatic filament buckling, along with a stiffness-dependent decrease in extension rate. We observed a striking alteration in cell morphology, i.e., reduced cell compartment length and increased diameter during invasive growth, that is not due to depolarization of active Cdc42, but rather occurs at a substantial distance from the site of growth as a result of mechanical compression.

Conclusions
Our data reveal that in response to this compression, active Cdc42 levels are increased at the apex, whereas active Rho1 becomes depolarized, similar to that observed in membrane protrusions. Our results show that cell growth and morphology are altered during invasive growth, suggesting stiffness dictates the host cells that C. albicans can penetrate.
Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia
Authors: Shi Ce , Lan Wenjia , Wang Zhenkun , Yang Dongguang , Wei Jia , Liu Zhiyu , Teng Yueqiu , Gu Mengmeng , Yuan Tian , Cao Fenglin , Zhou Jin , Li Yang 
Published: September 2020

Abstract
Background
Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL.

Methods
ALL cell lines were treated with 1, 5 and 10 μM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model.

Results
ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression.

Conclusions
The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.
Duplex Shiny app quantification of the sepsis biomarkers C-reactive protein and interleukin-6 in a fast quantum dot labeled lateral flow assay
Authors: Ruppert Christoph , Kaiser Lars , Jacob Lisa Johanna , Laufer Stefan , Kohl Matthias , Deigner Hans-Peter 
Published: September 2020

AbstractFast point-of-care (POC) diagnostics represent an unmet medical need and include applications such as lateral flow assays (LFAs) for the diagnosis of sepsis and consequences of cytokine storms and for the treatment of COVID-19 and other systemic, inflammatory events not caused by infection. Because of the complex pathophysiology of sepsis, multiple biomarkers must be analyzed to compensate for the low sensitivity and specificity of single biomarker targets. Conventional LFAs, such as gold nanoparticle dyed assays, are limited to approximately five targets—the maximum number of test lines on an assay. To increase the information obtainable from each test line, we combined green and red emitting quantum dots (QDs) as labels for C-reactive protein (CRP) and interleukin-6 (IL-6) antibodies in an optical duplex immunoassay. CdSe-QDs with sharp and tunable emission bands were used to simultaneously quantify CRP and IL-6 in a single test line, by using a single UV-light source and two suitable emission filters for readout through a widely available BioImager device. For image and data processing, a customized software tool, the MultiFlow-Shiny app was used to accelerate and simplify the readout process. The app software provides advanced tools for image processing, including assisted extraction of line intensities, advanced background correction and an easy workflow for creation and handling of experimental data in quantitative LFAs. The results generated with our MultiFlow-Shiny app were superior to those generated with the popular software ImageJ and resulted in lower detection limits. Our assay is applicable for detecting clinically relevant ranges of both target proteins and therefore may serve as a powerful tool for POC diagnosis of inflammation and infectious events.
Exoskeleton use in post-stroke gait rehabilitation: a qualitative study of the perspectives of persons post-stroke and physiotherapists
Authors: Vaughan-Graham Julie , Brooks Dina , Rose Lowell , Nejat Goldie , Pons Jose , Patterson Kara 
Published: September 2020

AbstractBackgroundWearable powered exoskeletons are a new and emerging technology developed to provide sensory-guided motorized lower limb assistance enabling intensive task specific locomotor training utilizing typical lower limb movement patterns for persons with gait impairments. To ensure that devices meet end-user needs it is important to understand and incorporate end-users perspectives, however research in this area is extremely limited in the post-stroke population. The purpose of this study was to explore in-depth, end-users perspectives, persons with stroke and physiotherapists, following a single-use session with a H2 exoskeleton.MethodsWe used a qualitative interpretive description approach utilizing semi-structured face to face interviews, with persons post-stroke and physiotherapists, following a 1.5 h session with a H2 exoskeleton.ResultsFive persons post-stroke and 6 physiotherapists volunteered to participate in the study. Both participant groups provided insightful comments on their experience with the exoskeleton. Four themes were developed from the persons with stroke participant data: (1) Adopting technology; (2) Device concerns; (3) Developing walking ability; and, (4) Integrating exoskeleton use. Five themes were developed from the physiotherapist participant data: (1) Developer-user collaboration; (2) Device specific concerns; (3) Device programming; (4) Patient characteristics requiring consideration; and, (5) Indications for use.ConclusionsThis study provides an interpretive understanding of end-users perspectives, persons with stroke and neurological physiotherapists, following a single-use experience with a H2 exoskeleton. The findings from both stakeholder groups overlap such that four over-arching concepts were identified including: (i) Stakeholder participation; (ii) Augmentation vs. autonomous robot; (iii) Exoskeleton usability; and (iv) Device specific concerns. The end users provided valuable perspectives on the use and design of the H2 exoskeleton, identifying needs specific to post-stroke gait rehabilitation, the need for a robust evidence base, whilst also highlighting that there is significant interest in this technology throughout the continuum of stroke rehabilitation.
Multisensory cueing facilitates naming in aphasia
Authors: Grechuta Klaudia , Rubio Ballester Belén , Espín Munné Rosa , Usabiaga Bernal Teresa , Molina Hervás Begoña , Mohr Bettina , Pulvermüller Friedemann , San Segundo Rosa Maria , Verschure Paul F. M. J. 
Published: September 2020

AbstractBackgroundImpaired naming is a ubiquitous symptom in all types of aphasia, which often adversely impacts independence, quality of life, and recovery of affected individuals. Previous research has demonstrated that naming can be facilitated by phonological and semantic cueing strategies that are largely incorporated into the treatment of anomic disturbances. Beneficial effects of cueing, whereby naming becomes faster and more accurate, are often attributed to the priming mechanisms occurring within the distributed language network.ObjectiveWe proposed and explored two novel cueing techniques: (1) Silent Visuomotor Cues (SVC), which provided articulatory information of target words presented in the form of silent videos, and (2) Semantic Auditory Cues (SAC), which consisted of acoustic information semantically relevant to target words (ringing for “telephone”). Grounded in neurophysiological evidence, we hypothesized that both SVC and SAC might aid communicative effectiveness possibly by triggering activity in perceptual and semantic language regions, respectively.MethodsTen participants with chronic non-fluent aphasia were recruited for a longitudinal clinical intervention. Participants were split into dyads (i.e., five pairs of two participants) and required to engage in a turn-based peer-to-peer language game using the Rehabilitation Gaming System for aphasia (RGSa). The objective of the RGSa sessions was to practice communicative acts, such as making a request. We administered SVCs and SACs in a pseudorandomized manner at the moment when the active player selected the object to be requested from the interlocutor. For the analysis, we compared the times from selection to the reception of the desired object between cued and non-cued trials.ResultsNaming accuracy, as measured by a standard clinical scale, significantly improved for all stimuli at each evaluation point, including the follow-up. Moreover, the results yielded beneficial effects of both SVC and SAC cues on word naming, especially at the early intervention sessions when the exposure to the target lexicon was infrequent.ConclusionsThis study supports the efficacy of the proposed cueing strategies which could be integrated into the clinic or mobile technology to aid naming even at the chronic stages of aphasia. These findings are consistent with sensorimotor accounts of language processing, suggesting a coupling between language, motor, and semantic brain regions.Trial registrationNCT02928822. Registered 30 May 2016.
GenoTypeMapper: graphical genotyping on genetic and sequence-based maps
Authors: Deblieck Mathieu , Fatiukha Andrii , Grundman Norbert , Merchuk-Ovnat Lianne , Saranga Yehoshua , Krugman Tamar , Pillen Klaus , Serfling Albrecht , Makalowski Wojciech , Ordon Frank , Perovic Dragan 
Published: September 2020

Abstract
Background
The rising availability of assemblies of large genomes (e.g. bread and durum wheat, barley) and their annotations deliver the basis to graphically present genome organization of parents and progenies on a physical scale. Genetic maps are a very important tool for breeders but often represent distorted models of the actual chromosomes, e.g., in centromeric and telomeric regions. This biased picture might lead to imprecise assumptions and estimations about the size and complexity of genetic regions and the selection of suitable molecular markers for the incorporation of traits in breeding populations or near-isogenic lines (NILs). Some software packages allow the graphical illustration of genotypic data, but to the best of our knowledge, suitable software packages that allow the comparison of genotypic data on the physical and genetic scale are currently unavailable.

Results
We developed a simple Java-based-software called GenoTypeMapper (GTM) for comparing genotypic data on genetic and physical maps and tested it for effectiveness on data of two NILs that carry QTL-regions for drought stress tolerance from wild emmer on chromosome 2BS and 7AS. Both NILs were more tolerant to drought stress than their recurrent parents but exhibited additional undesirable traits such as delayed heading time.

Conclusions
In this article, we illustrate that the software easily allows users to display and identify additional chromosomal introgressions in both NILs originating from the wild emmer parent. The ability to detect and diminish linkage drag can be of particular interest for pre-breeding purposes and the developed software is a well-suited tool in this respect. The software is based on a simple allele-matching algorithm between the offspring and parents of a crossing scheme. Despite this simple approach, GTM seems to be the only software that allows us to analyse, illustrate and compare genotypic data of offspring of different crossing schemes with up to four parents in two different maps. So far, up to 500 individuals with a maximum number of 50,000 markers can be examined with the software. The main limitation that hampers the performance of the software is the number of markers that are examined in parallel. Since each individual must be analysed separately, a maximum of ten individuals can currently be displayed in a single run. On a computer with an Intel five processor of the 8th generation, GTM can reliably either analyse a single individual with up to 12,000 markers or ten individuals with up to 3,600 markers in less than five seconds. Future work aims to improve the performance of the software so that more complex crossing schemes with more parents and more markers can be analysed.
COVID-19: an update and cardiac involvement
Authors: Alwaqfi Nizar R. , Ibrahim Khalid S. 
Published: September 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through angiotensin converting enzyme 2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, and also causing acute cardiac injury and chronic damage to the cardiovascular system. The purpose of this review is primarily reviewing the COVID-19 disease, including pathogen, clinical features, diagnosis, and treatment with particular attention to cardiovascular involvement based on the current evidence. COVID-19 remains a threat to global public health. The associated extra-pulmonary manifestations and their prolonged consequences are frequently overlooked. Pre-existing cardiovascular disease or acute cardiac complications may contribute to adverse early clinical outcome. At the moment, there is no specific treatment for COVID-19, but multiple randomized controlled trials (RCT) are being conducted. New supportive therapies are being evaluated with promising results.
Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer
Authors: Xu Tie , Zeng Yulan , Shi Linli , Yang Qin , Chen Yeshan , Wu Gang , Li Guiling , Xu Shuangbing 
Published: September 2020

AbstractBackgroundNEK2, a serine/threonine kinase involved in mitosis, has been found to function in chromosome instability, tumor progression and metastasis, but its role in cervical cancer radioresistance remains unknown.MethodsWe detected the protein levels of NEK2 in cervical carcinoma tissues and paired paracarcinoma tissues by immunohistochemistry. The roles of NEK2 in oncogenesis were examined using cell growth and colony formation assays, EdU assay, apoptosis assay as well as in vivo mouse model. γ-H2AX and Rad51 foci formation, neutral comet assay and clonogenic cell survival assay were applied to determine the radiosensitivity of cervical cancer cells. RNA-seq was performed to identify the downstream effector of NEK2. The gene expression levels were measured by Real-time PCR.ResultsWe report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer tissues. Furthermore, we provided evidence that depletion of NEK2 impairs oncogenesis and enhances radiosensitivity in cervical cancer. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression.ConclusionsOur results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.
Consistency and variability in human performance during simulate infant CPR: a reliability study
Authors: Almeida Debora , Clark Carol , Jones Michael , McConnell Phillip , Williams Jonathan 
Published: September 2020

Abstract
Background
Positive outcomes from infant cardiac arrest depend on the effective delivery of resuscitation techniques, including good quality infant cardiopulmonary resuscitation (iCPR) However, it has been established that iCPR skills decay within weeks or months after training. It is not known if the change in performance should be considered true change or inconsistent performance. The aim of this study was to investigate consistency and variability in human performance during iCPR.

Methods
An experimental, prospective, observational study conducted within a university setting with 27 healthcare students (mean (SD) age 32.6 (11.6) years, 74.1% female). On completion of paediatric basic life support (BLS) training, participants performed three trials of 2-min iCPR on a modified infant manikin on two occasions (immediately after training and after 1 week), where performance data were captured. Main outcome measures were within-day and between-day repeated measures reliability estimates, determined using Intraclass Correlation Coefficients (ICCs), Standard Error of Measurement (SEM) and Minimal Detectable Change (MDC95%) for chest compression rate, chest compression depth, residual leaning and duty cycle along with the conversion of these into quality indices according to international guidelines.

Results
A high degree of reliability was found for within-day and between-day for each variable with good to excellent ICCs and narrow confidence intervals. SEM values were low, demonstrating excellent consistency in repeated performance. Within-day MDC values were low for chest compression depth and chest compression rate (6 and 9%) and higher for duty cycle (15%) and residual leaning (22%). Between-day MDC values were low for chest compression depth and chest compression rate (3 and 7%) and higher for duty cycle (21%) and residual leaning (22%). Reliability reduced when metrics were transformed in quality indices.

Conclusion
iCPR skills are highly repeatable and consistent, demonstrating that changes in performance after training can be considered skill decay. However, when the metrics are transformed in quality indices, large changes are required to be confident of real change.