bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Out-of-Hour Admission and Short- and Long-Term Mortality in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis
Authors: Yu Yue-Yan , Zhao Bo-Wen , Ma Lan , Dai Xiao-Ce
Published: December 2021

Objectives: Out-of-hour admission (on weekends, holidays, and weekday nights) has been associated with higher mortality in patients with acute myocardial infarction (AMI). We conducted a meta-analysis to verify the association between out-of-hour admission and mortality (both short- and long-term) in AMI patients.

Design: This Systematic review and meta-analysis of cohort studies.

Data Sources: PubMed and EMBASE were searched from inception to 27 May 2021.

Eligibility Criteria for Selected Studies: Studies of any design examined the potential association between out-of-hour admission and mortality in AMI.

Data Extraction and Synthesis: In total, 2 investigators extracted the data and evaluated the risk of bias. Analysis was conducted using a random-effects model. The results are shown as odds ratios [ORs] with 95% confidence intervals (CIs). I2 value was used to estimate heterogeneity. Grading of Recommendations Assessment, Development, and Evaluation was used to assess the certainty of the evidence.

Results: The final analysis included 45 articles and 15,346,544 patients. Short-term mortality (defined as either in-hospital or 30-day mortality) was reported in 42 articles (15,340,220 patients). Out-of-hour admission was associated with higher short-term mortality (OR 1.04; 95%CI 1.02–1.05; I2 = 69.2%) but there was a significant statistical indication for publication bias (modified Macaskill's test P < 0.001). One-year mortality was reported in 10 articles (1,386,837 patients). Out-of-hour admission was also associated with significantly increased long-term mortality (OR 1.03; 95%CI 1.01–1.04; I2 = 66.6%), with no statistical indication of publication bias (p = 0.207). In the exploratory subgroup analysis, the intervention effect for short-term mortality was pronounced among patients in different regions (p = 0.04 for interaction) and socio-economic levels (p = 0.007 for interaction) and long-term mortality was pronounced among patients with different type of AMI (p = 0.0008 for interaction) or on different types of out-to-hour admission (p = 0.006 for interaction).

Conclusion: Out-of-hour admission may be associated with an increased risk of both short- and long-term mortality in AMI patients.

Trial Registration: PROSPERO (CRD42020182364).
Frequency-Domain Characteristics Response to Passive Exercise in Patients With Coronary Artery Disease
Authors: Zhang Xiaodong , Zhang Yahui
Published: December 2021

Purpose: The enhanced external counterpulsation (EECP), a kind of passive exercise, is a novel non-invasive therapy used to improve peripheral perfusion in patients with coronary artery disease (CAD). However, whether frequency-domain characteristics of peripheral hemodynamics may benefit from passive exercise needs to be verified.

Methods: We recruited 21 patients with CAD and 21 healthy controls in this study. Ultrasonic blood flow velocity spectrum in left carotid (LC) and right carotid (RC) common arteries, and right brachial (RB) and right femoral (RF) arteries was monitored using an ultrasonic Doppler. Frequency-domain characteristics before, during, and after passive exercise were extracted from ultrasonic spectrum images. The first and second peak amplitudes/frequencies (y1, y2, x1, x2) and power spectral energy ratio (PSER) in the 0–2.05 Hz/0.87 Hz (p5, p6) were calculated by fast Fourier transform and power spectrum density analysis.

Results: For the amplitude and frequency characteristics of the spectrum, y1 in the LC of patients with CAD was significantly decreased during exercise (p = 0.036), whereas, y2 was significantly decreased immediately after passive exercise (p = 0.038). Besides those, y1 only in the RC and RB of controls was significantly decreased during exercise. Immediately after exercise, y2 in the LC of control was significantly lower than at the baseline (p = 0.014). For the energy ratio characteristics of the spectrum, there was an opposite response in the two groups that p6 was significantly reduced and elevated in the LC of controls and in the RB of patients with CAD during exercise (both p < 0.05).

Conclusions: Passive exercise reduces amplitude and frequency characteristics of carotid arteries, while there was an opposite response of energy ratio characteristics in the LC and RB arteries to passive exercise between CAD patients and controls. Additionally, energy ratio characteristics of spectrum in the brachial artery were markedly elevated in CAD patients during passive exercise. Moreover, passive exercise only reduces amplitude characteristics of LC artery in the control group.
Investigation of Non-invasive Continuous Body Temperature Measurements in a Clinical Setting Using an Adhesive Axillary Thermometer (SteadyTemp®)
Authors: Boyer Johannes , Eckmann Jakob , Strohmayer Karl , Koele Werner , Federspiel Moritz , Schenk Michael , Weiss Gregor , Krause Robert
Published: December 2021

Since the human body reacts to a variety of different diseases with elevated body temperature, measurement of body temperature remains relevant in clinical practice. The absolute temperature value for fever definition is still arbitrary and depends on the measuring site, as well as underlying disease and individual factors. Hence, a simple threshold for fever definition is outdated and a definition which relies on the relative changes in the individual seems reasonable as it takes these individual factors into account. In this prospective multicentric study we validate an adhesive axillary thermometer (SteadyTemp®) which allows continuous non-invasive temperature measurements. It consists of a patch to measure temperature and a smartphone application to process and visualize gathered data. This article provides information of the new diagnostic possibilities when using this wearable device and where it could be beneficial. Furthermore, it discusses how to interpret the generated data and when it is not practical to use, based on its characteristics and physiological phenomena.
Is There a (Dis-)Fluency Effect in Learning With Handwritten Instructional Texts? Evidence From Three Studies
Authors: Beege Maik , Krieglstein Felix , Schneider Sascha , Nebel Steve , Rey Günter Daniel
Published: December 2021

The disfluency effect postulates that intentionally inserted desirable difficulties can have a beneficial effect on learning. Nevertheless, there is an ongoing discussion about the emergence of this effect since studies could not replicate this effect or even found opposite effects. To clarify boundary effects of the disfluency effect and to investigate potential social effects of disfluency operationalized through handwritten material, three studies (N1 = 97; N2 = 102; N3 = 103) were carried out. In all three experiments, instructional texts were manipulated in terms of disfluency (computerized font vs. handwritten font). Learning outcomes and cognitive load were measured in all experiments. Furthermore, metacognitive variables (Experiment 2 and 3) and social presence (Experiment 3) were measured. Results were ambiguous, indicating that element interactivity (complexity or connectedness of information within the learning material) of the learning material is a boundary condition that determines the effects of disfluency. When element interactivity is low, disfluency had a positive effect on learning outcomes and germane processes. When element interactivity increases, disfluency had negative impacts on learning efficiency (Experiment 2 and 3) and extraneous load (Experiment 3). In contrast to common explanations of the disfluency effect, a disfluent font had no metacognitive benefits. Social processes did not influence learning with disfluent material as well.
Altered Cortisol Metabolism Increases Nocturnal Cortisol Bioavailability in Prepubertal Children With Type 1 Diabetes Mellitus
Authors: Brossaud Julie , Corcuff Jean-Benoît , Vautier Vanessa , Bergeron Aude , Valade Aurelie , Lienhardt Anne , Moisan Marie-Pierre , Barat Pascal
Published: December 2021

Objective

Disturbances in the activity of the hypothalamus-pituitary-adrenal axis could lead to functional alterations in the brain of diabetes patients. In a later perspective of investigating the link between the activity of the hypothalamus-pituitary-adrenal axis and the developing brain in children with diabetes, we assessed here nocturnal cortisol metabolism in prepubertal children with type 1 diabetes mellitus (T1DM).

Methods

Prepubertal patients (aged 6–12 years) diagnosed with T1DM at least 1 year previously were recruited, along with matched controls. Nocturnal urine samples were collected, with saliva samples taken at awakening and 30 minutes after awakening. All samples were collected at home over 5 consecutive days with no detectable nocturnal hypoglycaemia. The State-Trait Anxiety Inventory (trait scale only) and Child Depression Inventory were also completed. Glucocorticoid metabolites in the urine, salivary cortisol (sF) and cortisone (sE) were measured by liquid chromatography–tandem mass spectrometry. Metabolic data were analysed by logistic regression, adjusting for sex, age, BMI and trait anxiety score.

Results

Urine glucocorticoid metabolites were significantly lower in T1DM patients compared to controls. 11β-hydroxysteroid dehydrogenase type 1 activity was significantly higher, while 11β-hydroxysteroid dehydrogenase type 2, 5(α+β)-reductase and 5α-reductase levels were all lower, in T1DM patients compared to controls. There was a significant group difference in delta sE level but not in delta sF level between the time of awakening and 30 minutes thereafter.

Conclusions

Our findings suggest that altered nocturnal cortisol metabolism and morning HPA axis hyperactivity in children with T1DM leads to greater cortisol bioavailability and lower cortisol production as a compensatory effect. This altered nocturnal glucocorticoid metabolism when cortisol production is physiologically reduced and this HPA axis hyperactivity question their impact on brain functioning.
Research on Time-Varying Two-Way Spillover Effects Between Carbon and Energy Markets: Empirical Evidence From China
Authors: Qiao Sen , Zhao Chen Xi , Zhang Kai Quan , Ren Zheng Yu
Published: December 2021

With the improvement of China’s carbon emission trading system, the spillover effect between carbon and energy markets is becoming more and more prominent. This paper selects four representative pilot carbon markets, including Beijing (BEA), Guangdong (GDEA), Hubei (HBEA) and Shanghai (SHEA). And three representative energy markets, including Crude Oil Futures (SC), power index (L11655) and China Securities new energy index (NEI). Combining the rolling window technology with DY spillover index, set a 50-weeks rolling window to measure the spillover index, and deeply analyze the time-varying two-way spillover effect between China’s carbon and energy markets. The results show that the spillover effect between China’s carbon and energy markets has significant time variability and two-way asymmetry. The time-varying spillover effect of different carbon pilot markets on the energy market has regional heterogeneity. The volatility spillover effect of Beijing and Shanghai carbon markets mainly comes from the crude oil futures market, Guangdong carbon market mainly comes from the new energy market, and Hubei carbon market mainly comes from crude oil and electricity market. The above research results contribute to the prevention of potential risk spillover between carbon and energy markets, which can promote the establishment of China’s unified carbon market and the prevention of systemic financial risks in energy market.
Fam20C Overexpression Predicts Poor Outcomes and is a Diagnostic Biomarker in Lower-Grade Glioma
Authors: Feng Jing , Zhou Jinping , Zhao Lin , Wang Xinpeng , Ma Danyu , Xu Baoqing , Xie Feilai , Qi Xingfeng , Chen Gang , Zhao Hu , Wu Junxin
Published: December 2021

Glioma is a relatively low aggressive brain tumor. Although the median survival time of patients for lower-grade glioma (LGG) was longer than that of patients for glioblastoma, the overall survival was still short. Therefore, it is urgent to find out more effective molecular prognostic markers. The role of the Fam20 kinase family in different tumors was an emerging research field. However, the biological function of Fam20C and its prognostic value in brain tumors have rarely been reported. This study aimed to evaluate the value of Fam20C as a potential prognostic marker for LGG. A total of 761 LGG samples (our cohort, TCGA and CGGA) were included to investigate the expression and role of Fam20C in LGG. We found that Fam20C was drastically overexpressed in LGG and was positively associated with its clinical progression. Kaplan-Meier analysis and a Cox regression model were employed to evaluate its prognostic value, and Fam20C was found as an independent risk factor in LGG patients. Gene set enrichment analysis also revealed the potential signaling pathways associated with Fam20C gene expression in LGG; these pathways were mainly enriched in extracellular matrix receptor interactions, cell adhesion, cell apoptosis, NOTCH signaling, cell cycle, etc. In summary, our findings provide insights for understanding the potential role of Fam20C and its application as a new prognostic biomarker for LGG.
The Importance of Genomic Literacy and Education in Nursing
Authors: Majstorović Dijana , Barišić Anita , Štifanić Mauro , Dobrača Igor , Vraneković Jadranka
Published: December 2021

Genetic discoveries and technological advances have been changing nursing care delivery, which modifies the roles and practices of nursing in society. Although the need for education of nurses in the field of genomics has been recognized in the 1960s, many countries still have no clear guidelines in this field of education and training. The purpose of this study was to evaluate current genomics content in the curriculum of undergraduate and graduate programs of studies in nursing in Croatia, and to measure the genomic literacy of Croatian undergraduate nursing students through assessing participants’ understanding of genomic concepts most critical to nursing practice. The curriculum of undergraduate and graduate programs of nursing classes of 2020/2021 were independently analyzed by the authors. For measuring the knowledge of essential genomic concepts among nurses, a Genomic Nursing Concept Inventory (GNCI©) instrument was employed. Results indicate that the current genomics content, for undergraduate and graduate nursing programs in Croatia, is inadequate and not concordant among universities. Moreover, the genomic literacy of Croatian undergraduate students (Undergraduate program 10) was found to be low. Scores across respondents ranged from 3 to 22 (out of possible 31), with a mean scale score 9.8 (SD 5.3) (31.6% correct). We can conclude that the curriculum for undergraduate and graduate programs of Studies in nursing should be revised to implement the latest genomic practices and approaches to genomics education while nurses should acquire an adequate level of genomic literacy in order to produce desired outcomes of competency in nursing practice.
Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China
Authors: Kong Lingrong , Li Shaojun , Zhao Zhenhua , Feng Jun , Chen Guangquan , Liu Lina , Tang Weiqin , Li Suqing , Li Feifei , Han Xiujuan , Wu Di , Zhang Haichuan , Sun Luming , Kong Xiangdong
Published: December 2021

Noninvasive prenatal diagnosis (NIPD) of single-gene disorders has recently become the focus of clinical laboratories. However, reports on the clinical application of NIPD of Duchenne muscular dystrophy (DMD) are limited. This study aimed to evaluate the detection performance of haplotype-based NIPD of DMD in a real clinical environment. Twenty-one DMD families at 7–12 weeks of gestation were prospectively recruited. DNA libraries of cell-free DNA from the pregnant and genomic DNA from family members were captured using a custom assay for the enrichment of DMD gene exons and spanning single-nucleotide polymorphisms, followed by next-generation sequencing. Parental haplotype phasing was based on family linkage analysis, and fetal genotyping was inferred using the Bayes factor through target maternal plasma sequencing. Finally, the entire experimental process was promoted in the local clinical laboratory. We recruited 13 complete families, 6 families without paternal samples, and 2 families without probands in which daughter samples were collected. Two different maternal haplotypes were constructed based on family members in all 21 pedigrees at as early as 7 gestational weeks. Among the included families, the fetal genotypes of 20 families were identified at the first blood collection, and a second blood collection was performed for another family due to low fetal concentration. The NIPD result of each family was reported within 1 week. The fetal fraction in maternal cfDNA ranged from 1.87 to 11.68%. In addition, recombination events were assessed in two fetuses. All NIPD results were concordant with the findings of invasive prenatal diagnosis (chorionic villus sampling or amniocentesis). Exon capture and haplotype-based NIPD of DMD are regularly used for DMD genetic diagnosis, carrier screening, and noninvasive prenatal diagnosis in the clinic. Our method, haplotype-based early screening for DMD fetal genotyping via cfDNA sequencing, has high feasibility and accuracy, a short turnaround time, and is inexpensive in a real clinical environment.
Treatment With Cladribine Selects IFNγ+IL17+ T Cells in RRMS Patients – An In Vitro Study
Authors: Dobreanu Minodora , Manu Doina Ramona , Mănescu Ion Bogdan , Gabor Manuela Rozalia , Huţanu Adina , Bărcuţean Laura , Bălaşa Rodica
Published: December 2021

Background

Multiple sclerosis (MS) is an incurable autoimmune disease mediated by a heterogeneous T cell population (CD3+CD161+CXCR3−CCR6+IFNγ−IL17+, CD3+CXCR3+CCR6+IFNγ+IL17+, and CD3+CXCR3+IFNγ+IL17− phenotypes) that infiltrates the central nervous system, eliciting local inflammation, demyelination and neurodegeneration. Cladribine is a lymphocyte-depleting deoxyadenosine analogue recently introduced for MS therapy as a Disease Modifying Drug (DMD). Our aim was to establish a method for the early identification and prediction of cladribine responsiveness among MS patients.

Methods

An experimental model was designed to study the cytotoxic and immunomodulatory effect of cladribine. T cell subsets of naïve relapsing-remitting MS (RRMS) patients were analyzed ex vivo and in vitro comparatively to healthy controls (HC). Surviving cells were stimulated with rh-interleukin-2 for up to 14days. Cell proliferation and immunophenotype changes were analyzed after maximal (phorbol myristate acetate/ionomycin/monensin) and physiological T-cell receptor (CD3/CD28) activation, using multiparametric flow cytometry and xMAP technology.

Results

Ex vivo CD161+Th17 cells were increased in RRMS patients. Ex vivo to in vitro phenotype shifts included: decreased CD3+CCR6+ and CD3+CD161+ in all subjects and increased CD3+CXCR3+ in RRMS patients only; Th17.1 showed increased proliferation vs Th17 in all subjects; CD3+IL17+ and CD3+IFNγ+IL17+ continued to proliferate till day 14, CD3+IFNγ+ only till day 7. Regarding cladribine exposure: RRMS CD3+ cells were more resistant compared to HC; treated CD3+ cells proliferated continuously for up to 14 days, while untreated cells only up to 7 days; both HC/RRMS CD3+CXCR3+ populations increased from baseline till day 14; in RRMS patients vs HC, IL17 secretion from cladribine-treated cells increased significantly, in line with the observed proliferation of CD3+IL17+ and CD3+IFNγ+IL17+ cells; in both HC/RRMS, cladribine led to a significant increase in CD3+IFNγ+ cells at day 7 only, having no further effect at day14. IFNγ and IL17 secreted in culture media decreased significantly from ex vivo to in vitro.

Conclusions

CD3+ subtypes showed different responsiveness due to selectivity of cladribine action, in most patients leading to in vitro survival/proliferation of lymphocyte subsets known as pathogenic in MS. This in vitro experimental model is a promising tool for the prediction of individual responsiveness of MS patients to cladribine and other DMDs.
Development and Clinical Validation of Novel 8-Gene Prognostic Signature Associated With the Proportion of Regulatory T Cells by Weighted Gene Co-Expression Network Analysis in Uterine Corpus Endometrial Carcinoma
Authors: Liu Jinhui , Geng Rui , Yang Sheng , Shao Fang , Zhong Zihang , Yang Min , Ni Senmiao , Cai Lixin , Bai Jianling
Published: December 2021

Background

Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with low survival rate and poor prognosis. The traditional clinicopathological staging is insufficient to estimate the prognosis of UCEC. It is necessary to select a more effective prognostic signature of UCEC to predict the prognosis and immunotherapy effect of UCEC.

Methods

CIBERSORT and weighted correlation network analysis (WGCNA) algorithms were combined to screen modules related to regulatory T (Treg) cells. Subsequently, univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the genes in key modules. The difference in overall survival (OS) between high- and low-risk patients was analyzed by Kaplan–Meier analysis. The Tregs-related risk signature (TRRS) was screened by uni- and multivariate Cox analyses. Afterward, we analyzed the expression difference of TRRS and verified its ability to predict the prognosis of UCEC and the effect of immunotherapy.

Results

Red module has the highest correlation with Tregs among all clustered modules. Pathways enrichment indicated that the related processes of UCEC were primarily associated to the immune system. Eight genes (ZSWIM1, NPRL3, GOLGA7, ST6GALNAC4, CDC16, ITPK1, PCSK4, and CORO1B) were selected to construct TRRS. We found that this TRRS is a significantly independent prognostic factor of UCEC. Low-risk patients have higher overall survival than high-risk patients. The immune status of different groups was different, and tumor-related pathways were enriched in patients with higher risk score. Low-risk patients are more likely take higher tumor mutation burden (TMB). Meanwhile, they are more sensitive to chemotherapy than patients with high-risk score, which indicated a superior prognosis. Immune checkpoints such as PD-1, CTLA4, PD-L1, and PD-L2 all had a higher expression level in low-risk group. TRRS expression really has a relevance with the sensitivity of UCEC patients to chemotherapeutic drugs.

Conclusion

We developed and validated a TRRS to estimate the prognosis and reflect the immune status of UCEC, which could accurately assess the prognosis of patients with UCEC and supply personalized treatments for them.
Transcriptional Profiling of Mouse Eosinophils Identifies Distinct Gene Signatures Following Cellular Activation
Authors: Dolitzky Avishay , Shapira Guy , Grisaru-Tal Sharon , Hazut Inbal , Avlas Shmulik , Gordon Yaara , Itan Micahl , Shomron Noam , Munitz Ariel
Published: December 2021

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis to host defense and cancer. Eosinophils have been studied mostly in the context of Type 2 inflammatory responses such as those found in allergy. Nonetheless, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ. Recent data suggest that the pleotropic roles of eosinophils are due to heterogeneous responses to environmental cues. Despite this, the activation profile of eosinophils, in response to various stimuli is yet to be defined. To better understand the transcriptional spectrum of eosinophil activation, we exposed eosinophils to Type 1 (e.g. IFN-γ, E. coli) vs. Type 2 (e.g. IL-4) conditions and subjected them to global RNA sequencing. Our analyses show that IL-4, IFN-γ, E. coli and IFN-γ in the presence of E. coli (IFN-γ/E. coli)-stimulated eosinophils acquire distinct transcriptional profiles, which polarize them towards what we termed Type 1 and Type 2 eosinophils. Bioinformatics analyses using Gene Ontology based on biological processes revealed that different stimuli induced distinct pathways in eosinophils. These pathways were confirmed using functional assays by assessing cytokine/chemokine release (i.e. CXCL9, CCL24, TNF-α and IL-6) from eosinophils following activation. In addition, analysis of cell surface markers highlighted CD101 and CD274 as potential cell surface markers that distinguish between Type 1 and Type 2 eosinophils, respectively. Finally, the transcriptome signature of Type 1 eosinophils resembled that of eosinophils that were obtained from mice with experimental colitis whereas the transcriptome signature of Type 2 eosinophils resembled that of eosinophils from experimental asthma. Our data demonstrate that eosinophils are polarized to distinct “Type 1” and “Type 2” phenotypes following distinct stimulations. These findings provide fundamental knowledge regarding the heterogeneity of eosinophils and support the presence of transcriptional differences between Type 1 and Type 2 cells that are likely reflected by their pleotropic activities in diverse disease settings.
Systemic Immune Activation and Responses of Irradiation to Different Metastatic Sites Combined With Immunotherapy in Advanced Non-Small Cell Lung Cancer
Authors: Wu Min , Liu Jie , Wu Shihao , Liu Jingru , Wu Hui , Yu Jinming , Meng Xue
Published: December 2021

Purpose

Considering the limited data, we aimed to identify the greatest immune activation irradiated site of common metastases and response to immune checkpoint inhibitors simultaneously in non-small cell lung cancer (NSCLC).

Methods

A total of 136 patients with advanced NSCLC who had received radiation to a primary or metastatic solid tumor were enrolled. We recorded blood cell counts in three time periods, before, during, and after radiotherapy (RT), and derived some blood index ratios including monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). The delta-IBs were calculated as medio-IBs ÷ pre-IBs − 1. We analyzed the changes before and during RT using Spearman rank correlation test, Kruskal–Wallis rank sum test, and logistic regression analyzing their correlation with efficacy.

Results

The medians of delta-MLR and delta-PLR were both the lowest while the median of delta-L was the highest in brain. Therapeutic effect evaluation showed that the objective response rate (ORR) of 48.65% (18/37) in the brain irradiation group was the highest, compared with 17.07% (7/41) in bone and 41.94% (13/31) in lung.

Conclusions

In this study, results suggested that irradiation to brain has the best immune activation effect and patient outcome compared with other organs in NSCLC, and when the earlier-line ICIs were combined with RT, a better patient outcome was reached. Prospective studies are also necessary to provide more convincing evidence and standards for clinical irradiation metastases selection.
Kinematics of Articulated Planar Linkages
Authors: Zhao Jing-Shan , Wei Song-Tao
Published: December 2021

This paper proposes a kinematics algorithm in screw coordinates for articulated linkages. As the screw consists of velocity and position variables of a joint, the solutions of the forward and inverse velocities are the functions of position coordinates and their time derivatives. The most prominent merit of this kinematic algorithm is that we only need the first order numerical differential interpolation for computing the acceleration. To calculate the displacement, we also only need the first order numerical integral of the velocity. This benefit stems from the screw the coordinates of which are velocity components. Both the forward and the inverse kinematics have the similar calculation process in this method. Through examples of planar open-chain linkage, single closed-chain linkage and multiple closed-chain linkage, the kinematics algorithm is validated. It is particularly fit for developing numerical programmers for forward and inverse kinematics in the same procedures, including the velocity, displacement and acceleration which provide the fundamental information for dynamics of the linkage.
Clinical Features and Risk Factors Analysis for Hemorrhage in Adults on ECMO
Authors: Hu Wenwen , Zhang Jing , Wang Meifang , Chen Wei , Chai Lin , Leung Elaine Lai-Han , Tang Yijun
Published: December 2021

Background: The use of extracorporeal membrane oxygenation (ECMO) to support critically ill patients with cardiorespiratory dysfunction has increased over the last decades. However, hemorrhagic complications occur frequently during ECMO support, and this has a significant impact on morbidity and mortality. Thus, this study aimed to identify the risk factors for hemorrhage in patients receiving ECMO.

Methods: Our retrospective study included 60 patients, who were admitted to the Taihe Hospital in Shiyan City, Hubei Province, China from February 2017 to October 2020. About 18 patients developed hemorrhagic complications, and 42 patients did not demonstrate such complications. Data regarding patient demography, laboratory tests, and clinical manifestations prior to ECMO were collected to analyze their clinical features. Univariable and multivariable logistic analyses were used to explore the risk factors for hemorrhage in adults on ECMO. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the binary logistic model. The amount of blood transfusions was compared between the two groups, and the activated partial thromboplastin time (APTT), platelet count, and hemoglobin level before the initiation of ECMO.

Results: Logistic analysis showed that a longer duration of ECMO support, higher APTT, and lower platelet count prior to ECMO were independent risk factors for hemorrhage in adults on ECMO. In addition, we found that the cannula site was the most common bleeding site. Most bleeding events occurred within the first 3 days of ECMO therapy. After the ECMO initiation, APTT was prolonged while the platelet count and hemoglobin levels were decreased. The amount of blood transfusion was significantly higher in the hemorrhage group than in the non-hemorrhage group.

Conclusions: Clinicians should evaluate the risk of hemorrhage based on the coagulation function of patients, underlying disease, and the duration of ECMO support. In the first 3 days during ECMO support, special attention should be given to the cannula site, mucosal, and dermal regions, and digestive tract to detect any signs of hemorrhage. Moreover, increasing the platelet count transfusion threshold and accurately determining the amount of blood transfusion required may prevent bleeding events.
Red Blood Cell Classification Based on Attention Residual Feature Pyramid Network
Authors: Song Weiqing , Huang Pu , Wang Jing , Shen Yajuan , Zhang Jian , Lu Zhiming , Li Dengwang , Liu Danhua
Published: December 2021

Clinically, red blood cell abnormalities are closely related to tumor diseases, red blood cell diseases, internal medicine, and other diseases. Red blood cell classification is the key to detecting red blood cell abnormalities. Traditional red blood cell classification is done manually by doctors, which requires a lot of manpower produces subjective results. This paper proposes an Attention-based Residual Feature Pyramid Network (ARFPN) to classify 14 types of red blood cells to assist the diagnosis of related diseases. The model performs classification directly on the entire red blood cell image. Meanwhile, a spatial attention mechanism and channel attention mechanism are combined with residual units to improve the expression of category-related features and achieve accurate extraction of features. Besides, the RoI align method is used to reduce the loss of spatial symmetry and improve classification accuracy. Five hundred and eighty eight red blood cell images are used to train and verify the effectiveness of the proposed method. The Channel Attention Residual Feature Pyramid Network (C-ARFPN) model achieves an mAP of 86%; the Channel and Spatial Attention Residual Feature Pyramid Network (CS-ARFPN) model achieves an mAP of 86.9%. The experimental results indicate that our method can classify more red blood cell types and better adapt to the needs of doctors, thus reducing the doctor's time and improving the diagnosis efficiency.
Predictive Potential of Flow Cytometry Crossmatching in Deceased Donor Kidney Transplant Recipients Subjected to Peritransplant Desensitization
Authors: Osickova Klara , Hruba Petra , Kabrtova Katerina , Klema Jiri , Maluskova Jana , Slavcev Antonij , Slatinska Janka , Marada Tomas , Böhmig Georg A. , Viklicky Ondrej
Published: December 2021

Recipient sensitization is a major risk factor of antibody-mediated rejection (ABMR) and inferior graft survival. The predictive effect of solid-phase human leukocyte antigen antibody testing and flow cytometry crossmatch (FCXM) in the era of peritransplant desensitization remains poorly understood. This observational retrospective single-center study with 108 donor-specific antibody (DSA)-positive deceased donor kidney allograft recipients who had undergone peritransplant desensitization aimed to analyze variables affecting graft outcome. ABMR rates were highest among patients with positive pretransplant FCXM vs. FCXM-negative (76 vs. 18.7%, p < 0.001) and with donor-specific antibody mean fluorescence intensity (DSA MFI) > 5,000 vs. <5,000 (54.5 vs. 28%, p = 0.01) despite desensitization. In univariable Cox regression, FCXM positivity, retransplantation, recipient gender, immunodominant DSA MFI, DSA number, and peak panel reactive antibodies were found to be associated with ABMR occurrence. In multivariable Cox regression adjusted for desensitization treatment (AUC = 0.810), only FCXM positivity (HR = 4.6, p = 0.001) and DSA number (HR = 1.47, p = 0.039) remained significant. In conclusion, our data suggest that pretransplant FCXM and DSA number, but not DSA MFI, are independent predictors of ABMR in patients who received peritransplant desensitization.
Impact of Computer-Assisted System on the Learning Curve and Quality in Esophagogastroduodenoscopy: Randomized Controlled Trial
Authors: Huang Li , Liu Jun , Wu Lianlian , Xu Ming , Yao Liwen , Zhang Lihui , Shang Renduo , Zhang Mengjiao , Xiong Qiutang , Wang Dawei , Dong Zehua , Xu Youming , Li Jia , Zhu Yijie , Gong Dexin , Wu Huiling , Yu Honggang
Published: December 2021

Background and Aims: To investigate the impact of the computer-assisted system on esophagogastroduodenoscopy (EGD) training for novice trainees in a prospective randomized controlled trial.

Methods: We have constructed a computer-aided system (CAD) using retrospective images based on deep learning which could automatically monitor the 26 anatomical landmarks of the upper digestive tract and document standard photos. Six novice trainees were allocated and grouped into the CAD group and control group. Each of them took the training course, pre and post-test, and EGD examination scored by two experts. The CAD group was trained with the assistance of the CAD system and the control group without.

Results: Both groups achieved great improvements in EGD skills. The CAD group received a higher examination grading score in the EGD examination (72.83 ± 16.12 vs. 67.26 ± 15.64, p = 0.039), especially in the mucosa observation (26.40 ± 6.13 vs. 24.11 ± 6.21, p = 0.020) and quality of collected images (7.29 ± 1.09 vs. 6.70 ± 1.05). The CAD showed a lower blind spot rate (2.19 ± 2.28 vs. 3.92 ± 3.30, p = 0.008) compared with the control group.

Conclusion: The artificial intelligence assistant system displayed assistant capacity on standard EGD training, and assisted trainees in achieving a learning curve with high operation quality, which has great potential for application.

Clinical Trial Registration: This trial is registered at https:/clinicaltrials.gov/, number NCT04682821.
A Six-Step Model for Developing Competency Frameworks in the Healthcare Professions
Authors: Batt Alan , Williams Brett , Rich Jessica , Tavares Walter
Published: December 2021

Competency frameworks are developed for a variety of purposes, including describing professional practice and informing education and assessment frameworks. Despite the volume of competency frameworks developed in the healthcare professions, guidance remains unclear and is inconsistently adhered to (perhaps in part due to a lack of organizing frameworks), there is variability in methodological choices, inconsistently reported outputs, and a lack of evaluation of frameworks. As such, we proposed the need for improved guidance. In this paper, we outline a six-step model for developing competency frameworks that is designed to address some of these shortcomings. The six-steps comprise [1] identifying purpose, intended uses, scope, and stakeholders; [2] theoretically informed ways of identifying the contexts of complex, “real-world” professional practice, which includes [3] aligned methods and means by which practice can be explored; [4] the identification and specification of competencies required for professional practice, [5] how to report the process and outputs of identifying such competencies, and [6] built-in strategies to continuously evaluate, update and maintain competency framework development processes and outputs. The model synthesizes and organizes existing guidance and literature, and furthers this existing guidance by highlighting the need for a theoretically-informed approach to describing and exploring practice that is appropriate, as well as offering guidance for developers on reporting the development process and outputs, and planning for the ongoing maintenance of frameworks.
CalmBelt: Rapid SARS-CoV-2 Genome Characterization for Outbreak Tracking
Authors: Yingtaweesittikul Hatairat , Ko Karrie , Abdul Rahman Nurdyana , Tan Shireen Yan Ling , Nagarajan Niranjan , Suphavilai Chayaporn
Published: December 2021

Background: The ongoing COVID-19 pandemic is a global health crisis caused by the spread of SARS-CoV-2. Establishing links between known cases is crucial for the containment of COVID-19. In the healthcare setting, the ability to rapidly identify potential healthcare-associated COVID-19 clusters is critical for healthcare worker and patient safety. Increasing sequencing technology accessibility has allowed routine clinical diagnostic laboratories to sequence SARS-CoV-2 in clinical samples. However, these laboratories often lack specialized informatics skills required for sequence analysis. Therefore, an on-site, intuitive sequence analysis tool that enables clinical laboratory users to analyze multiple genomes and derive clinically relevant information within an actionable timeframe is needed.

Results: We propose CalmBelt, an integrated framework for on-site whole genome characterization and outbreak tracking. Nanopore sequencing technology enables on-site sequencing and construction of draft genomes for multiple SARS-CoV-2 samples within 12 h. CalmBelt's interactive interface allows users to analyse multiple SARS-CoV-2 genomes by utilizing whole genome information, collection date, and additional information such as predefined potential clusters from epidemiological investigations. CalmBelt also integrates established SARS-CoV-2 nomenclature assignments, GISAID clades and PANGO lineages, allowing users to visualize relatedness between samples together with the nomenclatures. We demonstrated multiple use cases including investigation of potential hospital transmission, mining transmission patterns in a large outbreak, and monitoring possible diagnostic-escape.

Conclusions: This paper presents an on-site rapid framework for SARS-CoV-2 whole genome characterization. CalmBelt interactive web application allows non-technical users, such as routine clinical laboratory users in hospitals to determine SARS-CoV-2 variants of concern, as well as investigate the presence of potential transmission clusters. The framework is designed to be compatible with routine usage in clinical laboratories as it only requires readily available sample data, and generates information that impacts immediate infection control mitigations.
The Clinical Value of Explainable Deep Learning for Diagnosing Fungal Keratitis Using in vivo Confocal Microscopy Images
Authors: Xu Fan , Jiang Li , He Wenjing , Huang Guangyi , Hong Yiyi , Tang Fen , Lv Jian , Lin Yunru , Qin Yikun , Lan Rushi , Pan Xipeng , Zeng Siming , Li Min , Chen Qi , Tang Ningning
Published: December 2021

Background: Artificial intelligence (AI) has great potential to detect fungal keratitis using in vivo confocal microscopy images, but its clinical value remains unclarified. A major limitation of its clinical utility is the lack of explainability and interpretability.

Methods: An explainable AI (XAI) system based on Gradient-weighted Class Activation Mapping (Grad-CAM) and Guided Grad-CAM was established. In this randomized controlled trial, nine ophthalmologists (three expert ophthalmologists, three competent ophthalmologists, and three novice ophthalmologists) read images in each of the conditions: unassisted, AI-assisted, or XAI-assisted. In unassisted condition, only the original IVCM images were shown to the readers. AI assistance comprised a histogram of model prediction probability. For XAI assistance, explanatory maps were additionally shown. The accuracy, sensitivity, and specificity were calculated against an adjudicated reference standard. Moreover, the time spent was measured.

Results: Both forms of algorithmic assistance increased the accuracy and sensitivity of competent and novice ophthalmologists significantly without reducing specificity. The improvement was more pronounced in XAI-assisted condition than that in AI-assisted condition. Time spent with XAI assistance was not significantly different from that without assistance.

Conclusion: AI has shown great promise in improving the accuracy of ophthalmologists. The inexperienced readers are more likely to benefit from the XAI system. With better interpretability and explainability, XAI-assistance can boost ophthalmologist performance beyond what is achievable by the reader alone or with black-box AI assistance.
Associations of TFEB Gene Polymorphisms With Cognitive Function in Rural Chinese Population
Authors: Wei Yanfei , Liu Shuzhen , Cai Jiansheng , Tang Xu , Zhang Junling , Xu Min , Liu Qiumei , Wei Chunmei , Mo Xiaoting , Huang Shenxiang , Lin Yinxia , Mai Tingyu , Tan Dechan , Luo Tingyu , Gou Ruoyu , Lu Huaxiang , Qin Jian , Zhang Zhiyong
Published: December 2021

Background: The study aimed to investigate the relationship between transcription factor EB (TFEB) gene polymorphisms, including their haplotypes, and the cognitive functions of a selected population in Gongcheng County, Guangxi.

Methods: A case-control study approach was used. The case group comprised 339 individuals with cognitive impairment, as assessed by their Mini-Mental State Examination scores; the control population also comprised 339 individuals who were matched by sex and age (± 5 years) in a 1:1 ratio. TFEB gene polymorphisms were genotyped in 678 participants (190 men and 488 women, aged 30–91 years) by using the Sequenom MassARRAY platform.

Results: Multifactorial logistic regression analysis showed that in the dominant model, the risk of developing cognitive impairment was 1.547 times higher in cases with the TFEB rs14063A allele (AG + AA) than in those with the GG genotype (adjusted odds ratio [OR] = 1.547, Bonferroni correction confidence interval = 1.021–2.345). Meanwhile, the presence of the TFEB rs1062966T allele (CT + TT) was associated with a lower risk of cognitive impairment in comparison with the presence of the CC genotype (adjusted OR = 0.636, Bonferroni correction confidence interval = 0.405–0.998). In the co-dominant model, the risk of developing cognitive impairment was 1.553 times higher in carriers of the TFEB rs14063AG genotype than in carriers of the GG genotype (adjusted OR = 1.553, Bonferroni correction confidence interval = 1.007–2.397). After the Bonferroni correction and adjustment for confounding factors, the association of TFEB rs1062966 with cognitive function persisted in the analyses stratified by education level. Ethnically stratified analysis showed a significant association between TFEB rs1062966 and cognitive function in the Yao population. The multilocus linkage disequilibrium analysis indicated that the identified single nucleotide polymorphisms were not inherited independently. The haplotype analysis suggested that the rs14063A–rs1062966C–rs2278068C–rs1015149T haplotype of the TFEB gene increased the risk of cognitive impairment (P < 0.05) and that the rs14063G–rs1062966T–rs2278068C–rs1015149C haplotype was associated with a reduced risk of cognitive impairment (P < 0.05).

Conclusion:TFEB rs1062966 polymorphisms and their rs14063A–rs1062966C–rs2278068C–rs1015149T and rs14063G–rs1062966T–rs2278068C–rs1015149C haplotypes are genetic factors that may affect cognitive function among the rural Chinese population.
Intravenous Thrombolysis After Reversal of Dabigatran With Idarucizumab in Acute Ischemic Stroke: A Case Report
Authors: Xie Dan , Wang Xuefan , Li Yao , Chen Ruiling , Zhao Yingying , Xu Chunling , Zhang Qian , Zhang Yongbo
Published: December 2021

Background: As there is a growing concern about the cerebral embolism events secondary to non-valvular atrial fibrillation (NVAF), novel oral anticoagulant (NOAC) has been more and more widely used as an anticoagulation treatment for the prevention of stroke. However, in the face of life-threatening bleeding or emergency surgery/treatment, NOAC-related antagonists such as idarucizumab need to be urgently used to reverse the NOAC. Using recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis for acute ischemic stroke requires a time window of 4.5 h. This case reports rt-PA intravenous thrombolysis after reversal of dabigatran anticoagulation with idarucizumab in patients with acute ischemic stroke.

Case Presentation: We report the case of 62-year-old Chinese female with NVAF treated with dabigatran 110 mg twice daily, and missed a dose on the eve of the stroke. The patient presented with acute ischemic stroke causing the angle of mouth deviated to right side and left limb weakness in the early morning of the next day. However, the last dosing time of dabigatran was between 24 and 48 h, the patients were given rt-PA intravenous thrombolysis after reversal of dabigatran anticoagulation with idarucizumab, while any potential relative contraindication had been excluded by means of laboratory test and CT scan in the hospitalization services. National Institute of Health stroke scale (NIHSS) score was reduced from 4 to 1, and the patient was discharged after 2 weeks.

Conclusion: Our case report adds to the evidence that idarucizumab administration is safe and effective in the setting of patients with atrial fibrillation treated with dabigatran who develop acute ischemic stroke requiring rt-PA intravenous thrombolysis.