bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive dynamic surface control using nonlinear disturbance observers for position tracking of electro-hydraulic servo systems
Authors: Sa Yunjie , Zhu Zhencai , Tang Yu , Li Xiang , Shen Gang
Published: August 2021

In this article, an adaptive dynamic surface control method with nonlinear disturbance observers is proposed for accurate position tracking of an electro-hydraulic servo system with unknown time-varying inner or external disturbances. The dynamic surface control approach adopted in the proposed controller is used to ameliorate the inherent complexity differentiation explosion of traditional backstepping method, which significantly simplifies the controller design process. The designed nonlinear disturbance observers are exploited to online estimate the inner or external disturbances of electro-hydraulic servo systems, and the performance degradation resulted from unknown time-varying disturbances is effectively suppressed. To further compensate for the system’s time-varying uncertain parameters, parameter adaptive updating laws are designed and combined in the proposed controller for accurate position tracking of electro-hydraulic servo systems. The closed-loop stability of the proposed controller is theoretically guaranteed by rigorous Lyapunov analysis. Comparative experimental results are carried out on a typical single-degree-of-freedom electro-hydraulic servo system, and the feasibility together with the superiority of the proposed controller is experimentally validated.
Prevalence, Symptoms, and Associated Factors of Chronic Constipation Among Older Adults in North-East of Peninsular Malaysia
Authors: Abdul Wahab Patimah , Mohd Yusoff Dariah , Abdul Kadir Azidah , Ali Siti Hawa , Yeong Yeh Lee
Published: August 2021

This study aimed to determine the prevalence, symptoms, and associated factors of chronic constipation among older adults in the North-East of Peninsular Malaysia. A cross-sectional study was conducted among older patients from four health clinics. A total of 400 older patients participated, with a mean age of 68.7 ( SD = 6.4) years. The prevalence of chronic constipation was 14.8%. The highest symptom reported was the inability to pass stool (98.3%). Chronic constipation was significantly associated with older age (OR = 2.97; 95% CI [1.17, 7.54]; p = .022), inadequate plain water intake per day (OR = 2.13; 95% CI [1.13, 4.02]; p = .020), hypertension (OR = 2.22; 95% CI [1.07, 4.61]; p = .033), and hyperlipidemia (OR = 2.52; 95% CI [1.24, 5.11]; p = .010). Identification of chronic constipation should be done as part of routine clinic visits, especially for older patients with cardiovascular disease.
A new progressive damage model for predicting the tensile behavior of the three-dimensional woven carbon/carbon composites using micromechanics method
Authors: Wei Kunlong , Shi Hongbin , Li Jiang , Tang Min
Published: August 2021

A new progressive damage model for the three-dimensional (3 D) woven carbon/carbon (C/C) composites is developed at fiber-matrix level using the micromechanics method. A woven architecture based Representative Volume Element (RVE) model composed of yarns, matrix and yarn/matrix interface is constructed, in which the manufacturing void defects are accounted for. The fiber-matrix concentric cylinder model is employed as a repeating unit cell to represent the yarn, and the matrix micro strain field is computed analytically by the micromechanics method. The maximum stain criteria is utilized for fiber longitudinal breakage, and the Von-Mises criterion is applied for the damage initiation of matrix in both intra-yarns and inter-yarns. The damaged fiber and matrix are modeled by the stiffness degradation method combined with exponential damage evolution equations. The zero thickness cohesive elements governed by bilinear traction-separation constitutive are adopted for yarn/matrix interfacial debonding behavior. The micro progressive damage and failure behavior of the 3 D woven C/C composites subjected to tension is implemented through a developed user-defined material subroutine in commercial software ABAQUS. The predicted stress-strain response is in a good agreement with experimental results. In addition, the effect of manufacturing void defects is also examined by the developed model.
Remote Ischemic Perconditioning Ameliorates Myocardial Ischemia and Reperfusion-Induced Coronary Endothelial Dysfunction and Aortic Stiffness in Rats
Authors: Szabó Petra Lujza , Dostal Christopher , Pilz Patrick Michael , Hamza Ouafa , Acar Eylem , Watzinger Simon , Mathew Shalett , Kager Gerd , Hallström Seth , Podesser Bruno K. , Kiss Attila
Published: August 2021

Background:

Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events.

Aim:

To explore whether remote ischemic perconditioning (RIPerc) protects against coronary and aorta endothelial dysfunction as well as aortic stiffness following AMI.

Methods:

Male OFA-1 rats were subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion either 3 or 28 days with or without RIPerc. Three groups: (1) sham operated (Sham, without LAD occlusion); (2) myocardial ischemia and reperfusion (MIR) and (3) MIR + RIPerc group with 3 cycles of 5 minutes of IR on hindlimb performed during myocardial ischemia were used. Assessment of vascular reactivity in isolated septal coronary arteries (non-occluded) and aortic rings as well as aortic stiffness was assessed by wire myography either 3 or 28 days after AMI, respectively. Markers of pro-inflammatory cytokines, adhesion molecules were assessed by RT-qPCR and ELISA.

Results:

MIR promotes impaired endothelial-dependent relaxation in septal coronary artery segments, increased aortic stiffness and adverse left ventricular remodeling. These changes were markedly attenuated in rats treated with RIPerc and associated with a significant decline in P-selectin, IL-6 and TNF-α expression either in infarcted or non-infarcted myocardial tissue samples.

Conclusions:

Our study for the first time demonstrated that RIPerc alleviates MIR-induced coronary artery endothelial dysfunction in non-occluded artery segments and attenuates aortic stiffness in rats. The vascular protective effects of RIPerc are associated with ameliorated inflammation and might therefore be caused by reduced inflammatory signaling.
Intraretinal, sub-retinal, and sub-retinal pigmented epithelium fluid in non-exudative age-related macular degeneration: follow-up with OCT imaging
Authors: Samanta Anindya , Jhingan Mahima , Arora Supriya , Singh Sumit , Tucci Davide , Cagini Carlo , Lupidi Marco , Chhablani Jay
Published: August 2021

Background/objectives:

To evaluate the presence and evolution of fluid in non-exudative age-related macular degeneration (AMD) through serial OCT.

Subjects/methods:

A retrospective analysis of eyes with non-exudative AMD with a minimum of 4 year follow-up was done. Parameters including intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid (SRPEF); subfoveal choroidal thickness (SFCT) and type of drusen were evaluated using optical coherence tomography (OCT) scans at baseline and follow up visits.

Results:

Seventy-two eyes (in 63 patients) were followed up for an average of 5.83 ± 2.17 years. A total of 26/72 (36%) and 29/65 (52%) of the non-exudative eyes had fluid during baseline and the last visit. Seven eyes (10%) out of 72 eyes converted into exudative AMD or neo-vascular AMD (nAMD) during the study period. SRPEF at baseline was most common fluid location for non-exudative eyes that eventually converted to nAMD.

Conclusion:

Non-exudative fluid including IRF, SRF, and SRPEF is seen in patients with non-exudative AMD with increasing incidence during long term follow-up.
To what extent do political parties utilize similar frames?
Authors: Bjarnøe Camilla
Published: August 2021

How parties compete by utilizing frames in the public debate is not well understood. A widespread understanding is that parties tend to compete by talking past each other, i.e. when they utilize dissimilar frames. This article relies on a unique data set of parties’ framing of four individual policy questions over two decades in Denmark to examine frame overlap, i.e. when parties adopt similar frames. Results show that parties utilize similar and dissimilar frames in the public debate. However, a high degree of frame similarity was generally found across parliamentary blocs (between the leading mainstream party from each bloc, their leading junior coalition partner, and the two blocs) and most often a very high degree of overlap was found within parliamentary blocs (between the leading mainstream party and its junior coalition partner). This result suggests a need to rethink thoroughly how to understand and study interaction among parties utilizing frames.
The moderating role of interest in politics and news consumption in the relationship between political ideology and beliefs about science and scientists in the United States
Authors: Hardy Bruce W. , Tallapragada Meghnaa
Published: August 2021

In the United States, an ideological and partisan divide in beliefs about science is well documented. In this study, we further examine this partisan divide and how this relationship is conditioned on levels of political interest and news consumption. Analyzing data from three nationally representative U.S. surveys, we replicate past research and find ideological divisions in evaluations of, and beliefs about, science and scientists. We then show that greater interest in politics and news consumption is more strongly related to positive beliefs about science and scientists among liberals than among moderates and conservatives.
An International, Multicenter Retrospective Observational Study to Assess Technical Success and Clinical Outcomes of Patients Treated with an Endovascular Aneurysm Sealing Device for Type III Endoleak
Authors: Zoethout Aleksandra C. , Ketting Shirley , Zeebregts Clark J. , Apostolou Dimitri , Mees Barend M.E. , Berg Patrick , Beyrouti Hazem El , De Vries Jean-Paul P.M. , Torella Francesco , Migliari Mattia , Silingardi Roberto , Reijnen Michel M.P.J.
Published: August 2021

Introduction:

Type III endoleaks post-endovascular aortic aneurysm repair (EVAR) warrant treatment because they increase pressure within the aneurysm sac leading to increased rupture risk. The treatment may be difficult with regular endovascular devices. Endovascular aneurysm sealing (EVAS) might provide a treatment option for type III endoleaks, especially if located near the flow divider. This study aims to analyze clinical outcomes of EVAS for type III endoleaks after EVAR.

Methods:

This is an international, retrospective, observational cohort study including data from 8 European institutions.

Results:

A total of 20 patients were identified of which 80% had a type IIIb endoleak and the remainder (20%) a type IIIa endoleak. The median time between EVAR and EVAS was 49.5 months (28.5–89). Mean AAA diameter prior to EVAS revision was 76.6±19.9 mm. Technical success was achieved in 95%, 1 patient had technical failure due to a postoperative myocardial infarction resulting in death. Mean follow-up was 22.8±15.2 months. During follow-up 1 patient had a type Ia endoleak, and 1 patient had a new type IIIa endoleak at an untreated location. There were 5 patients with aneurysm growth. Five patients underwent AAA-related reinterventions indications being: growth with type II endoleak (n=3), type Ia endoleak (n=1), and iliac aneurysm (n=1). At 1-year follow-up, the freedom from clinical failure was 77.5%, freedom from all-cause mortality 94.7%, freedom from aneurysm-related mortality 95%, and freedom from aneurysm-related reinterventions 93.8%.

Conclusion:

The EVAS relining can be safely performed to treat type III endoleaks with an acceptable technical success rate, a low 30-day mortality rate and no secondary ruptures at short-term follow-up. The relatively low clinical success rates, related to reinterventions and AAA enlargement, highlight the need for prolonged follow-up.
Time to Say Goodbye: A Duration Analysis of the Determinants of Coach Dismissals and Quits in Major League Soccer
Authors: Semmelroth Dirk
Published: August 2021

This study investigates the determinants of voluntary and involuntary head coach turnovers using a large dataset of some 6,500 coach-game observations from Major League Soccer over 2004–2019. The duration analysis results show that team performance related to expected playoff qualification and performance expectations matter for both types of separations. Moreover, the findings reveal that coach reputation decreases dismissal probabilities, while coach age increases quit rates. The results of this study will be of particular interest to Major League Soccer team owners and managers as well as for business management outside the sports industry.
The Effectiveness of Lapatinib in HER2-Positive Metastatic Breast Cancer Patients Pretreated With Multiline Anti-HER2 Treatment: A Retrospective Study in China
Authors: Wang Xinzhao , Wang Lin , Yu Qian , Liu Zhaoyun , Li Chao , Wang Fukai , Yu Zhiyong
Published: August 2021

Background:

The aim of this study was to evaluate the effectiveness of lapatinib in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.

Methods:

We retrospectively reviewed the medical records of patients who received lapatinib for salvage treatment at any line setting from January 1, 2007 to August 31, 2019 at Shandong Cancer Hospital and Institute.

Results:

A total of 115 (89.1%) patients were included in the study. In the overall cohort, the median disease-free survival (DFS) was 19.0 months; the median progression-free survival (PFS), 6.3 months; and median overall survival (OS), 88.0 months, with 32.2% of patients alive at 5 years. In the second line setting, the median PFS among trastuzumab, lapatinib, and trastuzumab plus lapatinib were 4.2 months, 5.2 months, and 7.3 months, respectively ( P = 0.004). No significant differences between the median PFSs and OSs of the different line salvage treatments with lapatinib was observed (all P > 0.05). For brain metastasis patients, the median PFSs in first line, second line, and more than 3 lines were 7.2 months, 4.5 months, and 6.3 months, respectively.

Conclusions:

Our findings suggest that patients would benefit more from trastuzumab plus lapatinib than from lapatinib or trastuzumab alone for second line treatment in the advanced stages of the disease. Lapatinib could be used as an alternative selection for HER2-positive metastasic breast cancer patients when there is disease progression after trastuzumab or pyrotinib treatment, which is used as part of China’s national health insurance.
Stopping the COVID-19 pandemic in dental offices: A review of SARS-CoV-2 transmission and cross-infection prevention
Authors: Hartig Maya , Stephens Carley , Foster Aaron , Fontes Douglas , Kinzel Michael , García-Godoy Franklin
Published: August 2021

Due to the essential role of dentists in stopping the COVID-19 pandemic, the purpose of this review is to help dentists to detect any weaknesses in their disinfection and cross-contamination prevention protocols, and to triage dental treatments to meet the needs of patients during the pandemic. We used PRISMA to identify peer-reviewed publications which supplemented guidance from the center for disease control about infection control and guidelines for dentists. Dentists must triage dental treatments to meet the needs of patients during the pandemic. The ongoing pandemic has changed the practice of dentistry forever, the changes make it more cumbersome, time-consuming, and costly due to the possible pathways of transmission and mitigation steps needed to prevent the spread of COVID-19. Dental chairside rapid tests for SARS-CoV-2 are urgently needed. Until then, dentists need to screen patients for COVID-19 even though 75% of people with COVID-19 have no symptoms. Despite the widespread anxiety and fear of the devastating health effects of COVID-19, only 61% of dentists have implemented a change to their treatment protocols. As an urgent matter of public health, all dentists must identify the additional steps they can take to prevent the spread of COVID-19. The most effective steps to stop the pandemic in dental offices are to; vaccinate all dentists, staff, and patients; triage dental treatments for patients, separate vulnerable patients, separate COVID-19 patients, prevent cross-contamination, disinfect areas touched by patients, maintain social distancing, and change personal protective equipment between patients.
Tendon Transection Healing Can Be Improved With Adipose-Derived Stem Cells Cultured With Growth Differentiation Factor 5 and Platelet-Derived Growth Factor
Authors: Fitzgerald Michael J. , Mustapich Taylor , Liang Haixiang , Larsen Christopher G. , Nellans Kate W. , Grande Daniel A.
Published: August 2021

Background:

As hand surgeons, tendon injuries and lacerations are a particularly difficult problem to treat, as poor healing potential and adhesions hamper optimal recovery. Adipose-derived stem cells (ADSCs) have been shown to aid in rat Achilles tendon healing after a puncture defect, and this model can be used to study tendon healing in the upper extremity. We hypothesized that ADSCs cultured with growth differentiation factor 5 (GDF5) and platelet-derived growth factor (PDGF) would improve tendon healing after a transection injury.

Methods:

Rat Achilles tendons were transected and then left either unrepaired or repaired. Both groups were treated with a hydrogel alone, a hydrogel with ADSCs, or a hydrogel with ADSCs that were cultured with GDF5 and PDGF prior to implantation. Tissue harvested from the tendons was evaluated for gene expression of several genes known to play an important role in successful tendon healing. Histological examination of the tendon healing was also performed.

Results:

In both repaired and unrepaired tendons, those treated with ADSCs cultured with GDF5/PDGF prior to implantation showed the best tendon fiber organization, the smallest gaps, and the most organized blood vessels. Treatment with GDF5/PDGF increased expression of the protenogenesis gene SOX9, promoted cell-to-cell connections, improved cellular proliferation, and enhanced tissue remodeling.

Conclusions:

Adipose-derived stem cells cultured with GDF5/PDGF prior to implantation can promote tendon repair by improving cellular proliferation, tenogenesis, and vascular infiltration. This effect results in a greater degree of organized tendon healing.
Challenges and opportunities in point-of-care ultrasound: A qualitative exploration of respiratory physiotherapists’ experiences of lung ultrasound training and its adoption in critical care
Authors: Hayward Simon , Innes Sue , Smith Mike
Published: August 2021

Introduction

Diagnostic lung ultrasound (LUS) is gaining popularity among respiratory physiotherapists as an imaging modality to aid pulmonary assessments, guide intervention selection, and monitor the efficacy of chosen interventions. The ability of respiratory physiotherapists to incorporate LUS into their clinical practice is influenced by multiple factors to adoption and implementation. The aim of this study was to explore the experiences of senior respiratory physiotherapists who have attempted to adopt and implement LUS into their clinical practice in critical care. It is hoped these experiences will inform the development of educational and adoption strategies for the future implementation of LUS.

Methods

Following a national call out, eight senior critical care respiratory physiotherapists were purposively selected to be interviewed using semi-structured questions exploring their varied experiences of LUS adoption into clinical practice in critical care. The transcribed data were thematically analysed.

Results

Five main themes emerged from the participants’ responses: (i) support for physiotherapists using LUS, (ii) knowledge and understanding of LUS evidence, (iii) governance, (iv) physiotherapists’ motivation to use LUS, and (v) resources. Quotes for each of the five themes are given as exemplars.

Conclusion

Participants reported a range of factors that influenced their ability to adopt and implement LUS into practice several were enabling, and others were barriers to progress. Online Appendix 1 contains recommendations from the authors to help guide managers and clinicians wishing to adopt LUS into respiratory physiotherapy services and patient pathways.
Heart rate monitoring of the endurance runner during high intensity interval training: Influence of device used on training functions
Authors: Ruiz-Alias Santiago A , García-Pinillos Felipe , Soto-Hermoso Víctor M , Ruiz-Malagón Emilio J
Published: August 2021

Photoplethysmography (PPG) heart rate devices are greatly affected by the motion artifacts of running. As a result, their application in training load systems and effort control strategies based on heart rate (HR) could be debatable. In 2019, Polar applied some new features on their PPG devices to improve their accuracy. Thus, the purpose of this study was to determine the level of agreement between the new PPG system Polar Precision Prime™ and the chest strap Polar H10 (reference system) in the HR monitoring during an interval running protocol. A group of 37 long distance runners completed an interval running protocol of 10 min composed of five 1-min trials with an active break of 1-min between each trial. An excellent reliability (ICC > 0.9) was obtained for the entire interval running protocol with the lowest values in the first 2 min (ICC = 0.960–0.949), slight differences between intensities (ICC = 0.992–0.986), and a reduction of the observed tendency (ICC > 0.9) when the Edwards quantification model was applied (ICC = 0.877–0.967). The Bland-Altman plots with the final HR values of each trial establish a systematic bias (<1 bpm) for all intervals with a random error (<4 bpm), except in the first trial which had a higher random error (6.85 bpm). In conclusion, the innovations applied in the new PPG system provide the accuracy required for use in diverse functions, including endurance running.
Case report: Flattening of the tectal plate in obstructive hydrocephalus with auto-ventriculostomy
Authors: Städt Michael , Holtmannspötter Markus , Schwab Johannes , Eff Florian , Voit-Höhne Heinz
Published: August 2021

Background

Obstructive hydrocephalus in adulthood can be caused by stenosis in the aqueductal area. Chronic changes lead to a dilatation of the lateral ventricles and ballooning of infratentorial recesses. In rare cases a rupture of the floor of the third ventricle (so-called spontaneous ventriculostomy) has been described in the literature. Case presentation: We present two cases of chronic obstructive hydrocephalus due to aqueductal stenosis in adult patients. Magnetic resonance imaging included phase-contrast-imaging and revealed significant flow through the floor of the third ventricle in keeping with spontaneous ventriculostomy. In addition to other typical changes associated with chronic hydrocephalus, a distinct flattening of the tectal plate could be identified in one case.

Conclusion

We present two cases of spontaneous ventriculostomy in patients with chronic hydrocephalus. To our knowledge, flattening of the tectal plate has not yet been described in the literature and may be caused by continuous cerebrospinal fluid-pulsation.
Patient-reported utilization patterns of endometriosis medications in Europe: Real-world results from the non-interventional VIPOS study
Authors: Becker Kerstin , Heinemann Klaas , Imthurn Bruno , Marions Lena , Moehner Sabine , von Stockum Sophia , Gerlinger Christoph , Serrani Marco , Faustmann Thomas
Published: August 2021

Introduction:

Women with endometriosis require individualized, long-term treatment. Analyzing prescription choices, medication switches, discontinuations, and breaks can describe real-world treatment patterns and optimize pathways for women. To our knowledge, the Visanne Post-approval Observational Study (VIPOS) is the largest real-world, non-interventional study examining the safety of hormonal treatments for the routine clinical management of endometriosis. We present data from VIPOS on endometriosis drug utilization patterns, including treatment discontinuation due to treatment failure.

Methods:

VIPOS was a prospective, long-term, controlled, non-interventional cohort study in six European countries (Germany, Switzerland, Russia, Poland, Ukraine, and Hungary) conducted between 2010 and 2018. Women self-reported medical and gynecological history and symptoms and treatment information via comprehensive questionnaires.

Results:

Overall, 27,840 women were enrolled via gynecologists or specialized centers. Inter-country variance in treatment prescription patterns suggests the influence of differential management strategies and guidelines on prescribing behavior and diagnostic methods. Most enrolled women were receiving combined hormonal contraceptives. Women receiving dienogest 2 mg or gonadotropin-releasing hormone agonists more often had a surgical diagnosis of endometriosis compared to other treatments, while most women receiving combined hormonal contraceptives, other progestins or danazol had a symptom-based diagnosis. Although treatment changes during follow-up were common, only 4733 discontinuations out of 42,342 treatment starts were reported due to side effects or treatment ineffectiveness.

Conclusion:

VIPOS provides valuable insights into the considerable inter-country variance in endometriosis treatment prescription and potential role of differing management guidelines and practices strategies. Findings presented here suggest the need greater alignment of clinical practice to optimize patient management.
Multilayer sheets for thermoforming non thermoformable polymers
Authors: Wittmann Lisa-Maria , Drummer Dietmar
Published: August 2021

Multilayer sheets were used for thermoforming non thermoformable polymers in order to face the challenge of semi-crystalline polymers like low melt-stiffness. Mono- and 2-layer sheets consisting of different polypropylene (PP) homopolymers were extruded on a twin screw extruder. The PP viscosity as was measured by melt flow rate (MFR) 3 g/10 min., 12 g/10 min., 22 g/10 min. and 50 g/10 min. The layer ratio was varied between the equal layer ratio (A50/B50) of the individual layers and the low (A30/B70) or high viscosity ratio (A70/B30). The extrusion results show that for extreme viscosity differences (MFR3 and MFR50), the critical layer ratios known from the literature are only valid to a limited extent. The critical viscosity ratio < 4, which is known from the literature, is much lower here and should be less than 3.

The investigation of thermoformability on laboratory scale of the extruded PP sheets with different viscosities showed that the low viscous layer position has only a marginal influence on the general thermoformability. Thermoforming of materials that are not thermoformable, with a storage modulus of less than 10³ Pa and a ratio between storage and loss modulus (tan δ) greater than 1, becomes possible using a multilayer sheet independant of the layer ratio. If the layer with higher viscosity acts as a stabilizing layer, thermoforming is possible.
Novel NPM1 exon 5 mutations and gene fusions leading to aberrant cytoplasmic nucleophosmin in AML
Authors: Martelli Maria Paola , Rossi Roberta , Venanzi Alessandra , Meggendorfer Manja , Perriello Vincenzo Maria , Martino Giovanni , Spinelli Orietta , Ciurnelli Raffaella , Varasano Emanuela , Brunetti Lorenzo , Ascani Stefano , Quadalti Corinne , Cardinali Valeria , Mezzasoma Federica , Gionfriddo Ilaria , Milano Francesca , Pacini Roberta , Tabarrini Alessia , Bigerna Barbara , Albano Francesco , Specchia Giorgina , Vetro Calogero , Di Raimondo Francesco , Annibali Ombretta , Avvisati Giuseppe , Rambaldi Alessandro , Falzetti Franca , Tiacci Enrico , Sportoletti Paolo , Haferlach Torsten , Haferlach Claudia , Falini Brunangelo
Published: August 2021

Nucleophosmin (NPM1) mutations in acute myeloid leukemia (AML) affect exon 12, but also sporadically affect exons 9 and 11, causing changes at the protein C-terminal end (tryptophan loss, nuclear export signal [NES] motif creation) that lead to aberrant cytoplasmic NPM1 (NPM1c+), detectable by immunohistochemistry. Combining immunohistochemistry and molecular analyses in 929 patients with AML, we found non–exon 12 NPM1 mutations in 5 (1.3%) of 387 NPM1c+ cases. Besides mutations in exons 9 (n = 1) and 11 (n = 1), novel exon 5 mutations were discovered (n = 3). Another exon 5 mutation was identified in an additional 141 patients with AML selected for wild-type NPM1 exon 12. Three NPM1 rearrangements (NPM1/RPP30, NPM1/SETBP1, NPM1/CCDC28A) were detected and characterized among 13 979 AML samples screened by cytogenetic/fluorescence in situ hybridization and RNA sequencing. Functional studies demonstrated that in AML cases, new NPM1 proteins harbored an efficient extra NES, either newly created or already present in the fusion partner, ensuring its cytoplasmic accumulation. Our findings support NPM1 cytoplasmic relocation as critical for leukemogenesis and reinforce the role of immunohistochemistry in predicting AML-associated NPM1 genetic lesions. This study highlights the need to develop new assays for molecular diagnosis and monitoring of NPM1-mutated AML.
Bleeding diathesis in mice lacking JAK2 in platelets
Authors: Eaton Nathan , Subramaniam Saravanan , Schulte Marie L. , Drew Caleb , Jakab David , Haberichter Sandra L. , Weiler Hartmut , Falet Hervé
Published: August 2021

The tyrosine kinase JAK2 is a critical component of intracellular JAK/STAT cytokine signaling cascades that is prevalent in hematopoietic cells, such as hematopoietic stem cells and megakaryocytes (MKs). Individuals expressing the somatic JAK2 V617F mutation commonly develop myeloproliferative neoplasms (MPNs) associated with venous and arterial thrombosis, a leading cause of mortality. The role of JAK2 in hemostasis remains unclear. We investigated the role of JAK2 in platelet hemostatic function using Jak2fl/fl Pf4-Cre (Jak2Plt−/−) mice lacking JAK2 in platelets and MKs. Jak2Plt−/− mice developed MK hyperplasia and splenomegaly associated with severe thrombocytosis and bleeding. This notion was supported by failure to occlude in a ferric chloride carotid artery injury model and by a cremaster muscle laser-induced injury assay, in which Jak2Plt−/− platelets failed to form stable thrombi. Jak2Plt−/− platelets formed thrombi poorly after adhesion to type 1 collagen under arterial shear rates. Jak2Plt−/− platelets spread poorly on collagen under static conditions or on fibrinogen in response to the collagen receptor GPVI-specific agonist, collagen-related peptide (CRP). After activation with collagen, CRP, or the CLEC-2 agonist rhodocytin, Jak2Plt−/− platelets displayed decreased α-granule secretion and integrin αIIbβ3 activation or aggregation, but showed normal responses to thrombin. Jak2Plt−/− platelets had impaired intracellular signaling when activated via GPVI, as assessed by tyrosine phosphorylation. Together, the results show that JAK2 deletion impairs platelet immunoreceptor tyrosine-based activation motif signaling and hemostatic function in mice and suggest that aberrant JAK2 signaling in patients with MPNs affects GPVI signaling, leading to hemostatic platelet function.
A future without drivers? Comparing users', urban planners' and developers' assumptions, hopes, and concerns about autonomous vehicles
Authors: Strömberg Helena , Ramos Érika Martins Silva , Karlsson MariAnne , Johansson Mikael , Ekman Fredrick , Bligård Lars-Ola , Bergstad Cecilia Jakobsson
Published: August 2021

Aim

This study identifies and compares perceptions of autonomous vehicle (AV) implementation among three Swedish stakeholder groups: Future Users, Urban Planners, and Developers.

Method

Semi-structured comparative focus groups were conducted separately with each of the three groups of stakeholders and the transcripts were analysed in broad themes using thematic analysis.

Results

Assumptions, hopes, concerns, and direction of development were the main themes that emerged from the analysis. Assumptions included electrification of vehicles, changes in travel demand, and the need for regulations; Hopes included the idea that AVs will contribute to a more accessible and safer transport system; Concerns included overtrust in AV technology, a possible detrimental impact on the city in the form of congestion and higher demand for investments in infrastructure that could outcompete other modes of transport; and Direction of development and their own role, where the need for collaboration between stakeholders and implementation of AVs in connection with society’s needs were emphasised.

Conclusions

AVs were seen to lead to both positive and negative consequences depending on implementation and the development of society. The study shows that dialogue between different stakeholders is lacking but it is desired for the inclusive implementation of AVs.
Step-free railway station access in the UK: the value of inclusive design
Authors: Swift Antony , Cheng Long , Loo Becky P. Y. , Cao Mengqiu , Witlox Frank
Published: August 2021

Background

Despite substantial investment in step-free access at UK railway stations, persons with reduced mobility (PRMs) continue to travel less than their able-bodied counterparts and little is known about the value of step-free access. This research examines the benefits of step-free access and its relationship with rail usage among PRMs, and the wider benefits of railway station accessibility.

Methods

These issues are explored through a mixed methods approach. Semi-structured interviews with ten key organisations were undertaken, as was an analysis of Senior/Disabled Persons Railcard data from 17 railway stations in Buckinghamshire, each with varying levels of step-free accessibility.

Results

The results show that the benefits of step-free access extend beyond benefits at the individual level typically associated with those limited to PRMs, and demonstrate the potential to positively affect the society at large economically, environmentally, and socially. The findings also show a positive correlation between the level of step-free accessibility at a railway station and the percentage of PRMs using it.

Conclusions

This research argues that government and interested stakeholders should commit to expanding the number and coverage of step-free stations throughout the UK. They should ensure that the appraisal process for investment in step-free accessibility appropriately captures both user and non-user benefits.
Generalist camouflage can be more successful than microhabitat specialisation in natural environments
Authors: Briolat Emmanuelle Sophie , Arenas Lina María , Hughes Anna E. , Liggins Eric , Stevens Martin
Published: August 2021

Background

Crypsis by background-matching is a critical form of anti-predator defence for animals exposed to visual predators, but achieving effective camouflage in patchy and variable natural environments is not straightforward. To cope with heterogeneous backgrounds, animals could either specialise on particular microhabitat patches, appearing cryptic in some areas but mismatching others, or adopt a compromise strategy, providing partial matching across different patch types. Existing studies have tested the effectiveness of compromise strategies in only a limited set of circumstances, primarily with small targets varying in pattern, and usually in screen-based tasks. Here, we measured the detection risk associated with different background-matching strategies for relatively large targets, with human observers searching for them in natural scenes, and focusing on colour. Model prey were designed to either ‘specialise’ on the colour of common microhabitat patches, or ‘generalise’ by matching the average colour of the whole visual scenes.

Results

In both the field and an equivalent online computer-based search task, targets adopting the generalist strategy were more successful in evading detection than those matching microhabitat patches. This advantage occurred because, across all possible locations in these experiments, targets were typically viewed against a patchwork of different microhabitat areas; the putatively generalist targets were thus more similar on average to their various immediate surroundings than were the specialists.

Conclusions

Demonstrating close agreement between the results of field and online search experiments provides useful validation of online citizen science methods commonly used to test principles of camouflage, at least for human observers. In finding a survival benefit to matching the average colour of the visual scenes in our chosen environment, our results highlight the importance of relative scales in determining optimal camouflage strategies, and suggest how compromise coloration can succeed in nature.
Variable clinical characteristics and laboratory results in five patients with Chinese Good's syndrome (thymoma and hypogammaglobulinemia): an 8-year retrospective analysis in a university hospital in China
Authors: Ni Jinyao , Zhang Junwu , Chen Yanxia , Wang Weizhong , Liu Jinlin
Published: August 2021

Background

Good's syndrome (GS) is a rare secondary immunodeficiency disease presenting as thymoma and hypogammaglobulinemia. Due to its rarity, the diagnosis of GS is often missed.

Methods

We used the hospital information system to retrospectively screen thymoma and hypogammaglobulinemia patients at the First Affiliated Hospital of Wenzhou Medical University from Apr 2012 to Apr 2020. The clinical, laboratory, treatment, and outcome data for these patients were collected and analyzed.

Results

Among the 181 screened thymoma patients, 5 thymoma patients with hypogammaglobulinemia were identified; 3 patients had confirmed diagnoses of GS, and the other 2 did not have a diagnosis of GS recorded in the hospital information system. A retrospective review of the clinical characteristics, laboratory results, and follow-up data for these 2 undiagnosed patients confirmed the diagnosis of GS. All 5 GS patients presented with pneumonia, 2 patients presented with recurrent skin abscesses, 2 patients presented with recurrent cough and expectoration, 1 patient presented with recurrent oral lichen planus and diarrhea, and 1 patient presented with tuberculosis and granulomatous epididymitis. In the years after the diagnosis of hypogammaglobulinemia with mild symptoms, all 5 patients had received irregular intravenous immunoglobulin (IVIG) treatment. As the course of the disease progressed, the clinical symptoms of all patients worsened, but the symptoms were partly resolved with IVIG in these patients. However, 4 patients died due to comorbidities.

Conclusion

GS should be investigated as a possible diagnosis in thymoma patients who present with hypogammaglobulinemia, especially those with recurrent opportunistic infections, recurrent skin abscesses, chronic diarrhea, or recurrent lichen planus.
Fatal septic shock due to Capnocytophaga canimorsus bacteremia masquerading as COVID-19 pneumonia - a case report
Authors: Meyer Eva Christina , Alt-Epping Sabine , Moerer Onnen , Büttner Benedikt
Published: August 2021

Background

Capnocytophaga canimorsus (C. canimorsus) infections are rare and usually present with unspecific symptoms, which can eventually end in fatal septic shock and multiorgan failure. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related coronavirus disease 2019 (COVID-19), on the other hand, is predominantly characterized by acute respiratory failure, although other organ complications can occur. Both infectious diseases have in common that hyperinflammation with a cytokine storm can occur. While microbial detection of C. canimorsus in blood cultures can take over 48 h, diagnosis of SARS-CoV-2 is facilitated by a widely available rapid antigen diagnostic test (Ag-RDT) the results of which are available within half an hour. These Ag-RDT results are commonly verified by a nucleic acid amplification test (NAAT), whose results are only available after a further 24 h.

Case presentation

A 68-year-old male patient with the diagnosis of COVID-19 pneumonia was referred to our Intensive Care Unit (ICU) from another hospital after testing positive on an Ag-RDT. While the initial therapy was focused on COVID-19, the patient developed a fulminant septic shock within a few hours after admission to the ICU, unresponsive to maximum treatment. SARS-CoV-2 NAATs were negative, but bacteremia of C. canimorsus was diagnosed post-mortem. Further anamnestic information suggest that a small skin injury caused by a dog leash or the subsequent contact of this injury with the patient’s dog could be the possible point of entry for these bacteria.

Conclusion

During the acute phase of hyperinflammation and cytokine storm, laboratory results can resemble both, sepsis of bacterial origin or SARS-CoV-2. This means that even in the light of a global SARS-CoV-2 pandemic, where this diagnosis provides the most salient train of thoughts, differential diagnoses must be considered. Ag-RDT can contribute to early detection of a SARS-CoV-2 infection, but false-positive results may cause fixation errors with severe consequences for patient outcome.
Dynamics of the COVID-19 epidemic in Ireland under mitigation
Authors: Cazelles Bernard , Nguyen-Van-Yen Benjamin , Champagne Clara , Comiskey Catherine
Published: August 2021

Background

In Ireland and across the European Union the COVID-19 epidemic waves, driven mainly by the emergence of new variants of the SARS-CoV-2 have continued their course, despite various interventions from governments. Public health interventions continue in their attempts to control the spread as they wait for the planned significant effect of vaccination.

Methods

To tackle this challenge and the observed non-stationary aspect of the epidemic we used a modified SEIR stochastic model with time-varying parameters, following Brownian process. This enabled us to reconstruct the temporal evolution of the transmission rate of COVID-19 with the non-specific hypothesis that it follows a basic stochastic process constrained by the available data. This model is coupled with Bayesian inference (particle Markov Chain Monte Carlo method) for parameter estimation and utilized mainly well-documented Irish hospital data.

Results

In Ireland, mitigation measures provided a 78–86% reduction in transmission during the first wave between March and May 2020. For the second wave in October 2020, our reduction estimation was around 20% while it was 70% for the third wave in January 2021. This third wave was partly due to the UK variant appearing in Ireland. In June 2020 we estimated that sero-prevalence was 2.0% (95% CI: 1.2–3.5%) in complete accordance with a sero-prevalence survey. By the end of April 2021, the sero-prevalence was greater than 17% due in part to the vaccination campaign. Finally we demonstrate that the available observed confirmed cases are not reliable for analysis owing to the fact that their reporting rate has as expected greatly evolved.

Conclusion

We provide the first estimations of the dynamics of the COVID-19 epidemic in Ireland and its key parameters. We also quantify the effects of mitigation measures on the virus transmission during and after mitigation for the three waves. Our results demonstrate that Ireland has significantly reduced transmission by employing mitigation measures, physical distancing and lockdown. This has to date avoided the saturation of healthcare infrastructures, flattened the epidemic curve and likely reduced mortality. However, as we await for a full roll out of a vaccination programme and as new variants potentially more transmissible and/or more infectious could continue to emerge and mitigation measures change silent transmission, challenges remain.
Associations of immunological features with COVID-19 severity: a systematic review and meta-analysis
Authors: Zhang Zhicheng , Ai Guo , Chen Liping , Liu Shunfang , Gong Chen , Zhu Xiaodong , Zhang Chunli , Qin Hua , Hu Junhui , Huang Jinjin
Published: August 2021

Background

COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity.

Methods

We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature.

Results

A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3+ T cell (× 106, MD, − 413.87; 95%CI, − 611.39 to − 216.34), CD4+ T cell (× 106, MD, − 203.56; 95%CI, − 277.94 to − 129.18), CD8+ T cell (× 106, MD, − 128.88; 95%CI, − 163.97 to − 93.79), B cell (× 106/L; MD, − 23.87; 95%CI, − 43.97 to − 3.78) and NK cell (× 106/L; MD, − 57.12; 95%CI, − 81.18 to − 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 106, MD, − 0.13; 95%CI, − 1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, − 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, − 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, − 0.49 to 0.60), IL-4 (pg/ml; MD, − 0.03; 95%CI, − 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, − 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, − 2.88 to 4.75).

Conclusion

Our meta-analysis revealed significantly lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients.