bluuebunny/crossref_metadata_2025 huggingface dataset:
A hybrid cost-sensitive ensemble for heart disease prediction
Authors: Zhenya Qi , Zhang Zuoru
Published: February 2021

Background

Heart disease is the primary cause of morbidity and mortality in the world. It includes numerous problems and symptoms. The diagnosis of heart disease is difficult because there are too many factors to analyze. What’s more, the misclassification cost could be very high.

Methods

A cost-sensitive ensemble method was proposed to improve the efficiency of diagnosis and reduce the misclassification cost. The proposed method contains five heterogeneous classifiers: random forest, logistic regression, support vector machine, extreme learning machine and k-nearest neighbor. T-test was used to investigate if the performance of the ensemble was better than individual classifiers and the contribution of Relief algorithm.

Results

The best performance was achieved by the proposed method according to ten-fold cross validation. The statistical tests demonstrated that the performance of the proposed ensemble was significantly superior to individual classifiers, and the efficiency of classification was distinctively improved by Relief algorithm.

Conclusions

The proposed ensemble gained significantly better results compared with individual classifiers and previous studies, which implies that it can be used as a promising alternative tool in medical decision making for heart disease diagnosis.
Mental health and diabetes self-management: assessing stakeholder perspectives from health centers in Northern Mexico
Authors: Aceves Benjamín , Ruiz Manuel , Ingram Maia , Denman Catalina , Garcia David O. , Madhivanan Purnima , Rosales Cecilia
Published: February 2021

Background

People living with diabetes have an increased risk of developing mental health issues. Mexico has observed a high prevalence of people living with diabetes suffering from mental health issues, such as anxiety and depression. Self-management programs have demonstrated promise in helping participants address and prevent not only physiological health complications but mental health issues as well. This qualitative study aimed to understand the mental health benefits of a diabetes self-management intervention for health centers in Northern Mexico and opportunities for improvement through assessing stakeholder perspectives.

Methods

Trained research staff used a semi-structured questionnaire guide to conduct all interviews and focus groups from February–May 2018. Individual interviews (n = 16) were conducted face-to-face at four health center sites among all health center directors and key staff located throughout the state of Sonora. One focus group (n = 41) was conducted at each of the four health centers among intervention participants. Directed content analysis was used to establish themes by understanding relationships, identifying similar experiences, and determining patterns across datasets.

Results

In total 57 health center directors, health center staff, and intervention participants were involved in the interviews and focus groups across the four health centers. Overall the analysis identified four themes throughout the data, two were categorized as benefits and two as improvements. The primary themes for participant benefits were an increase in self-efficacy and social support to manage their chronic conditions. These were evident from not only participant perspectives, but health staff observations. Conversely, increased family involvement, and increased mental health integration and services within diabetes care were identified themes for opportunities to improve the intervention to be more inclusive and holistic.

Conclusion

All stakeholders observed the benefits for intervention participants and opportunities for more inclusivity of the family and integration as well as an increase in mental health services. The themes identified demonstrated a need to more proactively enhance and utilize diabetes self-management as a means to improve mental health outcomes among people living with diabetes in Mexico. This is an opportunity to employ a more comprehensive approach to diabetes self-management, and integrate mental health services into overall diabetes care.

Trial registration

www.ClinicalTrials.gov, identifier: NCT02804698. Registered on June 17, 2016.
Lack of CD34 delays bacterial endotoxin-induced lung inflammation
Authors: Aulakh Gurpreet K. , Maltare Sushmita , Singh Baljit
Published: February 2021

Background

CD34, a pan-selectin binding protein when glycosylated, has been shown to be involved in leukocyte migration to the site of inflammation. However, only one report is available on the expression and role of CD34 in neutrophil recruitment during acute lung inflammation.

Methods

We proceeded to study the role of CD34 in lung neutrophil migration using mouse model of endotoxin induced acute lung inflammation and studied over multiple time points, in generic CD34 knock-out (KO) strain.

Results

While there was no difference in BAL total or differential leukocyte counts, lung MPO content was lower in LPS exposed KO compared to WT group at 3 h time-point (p = 0.0308). The MPO levels in CD34 KO mice begin to rise at 9 h (p = 0.0021), as opposed to an early 3 h rise in WT mice (p = 0.0001), indicating that KO mice display delays in lung neutrophil recruitment kinetics. KO mice do not loose endotoxin induced lung vascular barrier properties as suggested by lower BAL total protein at 3 h (p = 0.0452) and 24 h (p = 0.0113) time-points. Several pro-inflammatory cytokines and chemokines (TNF-α, IL-1β, KC, MIP-1α, IL-6, IL-10 and IL-12 p70 sub-unit; p < 0.05) had higher levels in WT compared to KO group, at 3 h. Lung immunofluorescence in healthy WT mice reveals CD34 expression in the bronchiolar epithelium, in addition to alveolar septa.

Conclusion

Thus, given CD34′s pan-selectin affinity, and expression in the bronchiolar epithelium as well as alveolar septa, our study points towards a role of CD34 in lung neutrophil recruitment but not alveolar migration, cytokine expression and lung inflammation.
UTRN inhibits melanoma growth by suppressing p38 and JNK/c-Jun signaling pathways
Authors: Zhou Sitong , Ouyang Wen , Zhang Xi , Liao Lexi , Pi Xiaobing , Yang Ronghua , Mei Baiqiang , Xu Huaiyuan , Xiang Shijian , Li Jiehua
Published: February 2021

Background

Utrophin(UTRN), as a tumor suppressor gene, is involved in various cancer progression. The function of UTRN in the melanoma process and the related molecular mechanisms are still unclear. Herein, we studied the function of UTRN in melanoma growth and the relevant molecular mechanisms.

Methods

Using the GEO database and UCSC Xena project, we compared the expression of UTRN in non-cancerous and melanoma tissues. Immunohistochemistry (IHC) staining, qRT-PCR and Western Blot (WB) were performed to evaluate UTRN expression in clinical samples. A total of 447 cases with UTRN expression data, patient characteristics and survival data were extracted from TCGA database and analyzed. After stable transduction and single cell cloning, the proliferation ability of A375 human melanoma cells was analyzed by Cell Counting Kit‑8 (CCK) and 5‑ethynyl‑2′‑deoxyuridine (EdU) incorporation assays. GSEA was performed to predict the mechanism by which UTRN regulated melanoma growth. Then WB analysis was used to assess the protein expression levels of pathway signaling in overexpression (EXP) melanoma cells. Epac activator 8-pCPT-2′-O-Me-cAMP was then used to evaluate the proliferation ability by activation of p38 and JNK/c-Jun signaling pathways.

Results

Data from GEO and UCSC Xena project indicated that UTRN expression was decreased in melanoma. Experiment on clinical samples further confirmed our finding. TCGA results showed that a reduced expression of UTRN in 447 melanoma samples was associated with advanced clinical characteristics (T stage, Clark level, ulceration), shorter survival time and poorer prognosis. In addition, up-regulated UTRN expression inhibited melanoma cell proliferation when compared to control group. MAPK signaling pathway was presented in both KEGG and BioCarta databases by using GSEA tool. WB results confirmed the down-regulated expression of p38, JNK1 and c-Jun in EXP group when compared to control group. Epac activator 8-pCPT-2′-O-Me-cAMP treatment could partially rescue proliferation of tumor cells.

Conclusion

We have demonstrated that reduced UTRN predicted poorer prognosis and UTRN inhibited melanoma growth via p38 and JNK1/c-Jun pathways. Therefore, UTRN could serve as a tumor suppressor and novel prognostic biomarker for melanoma patients.
Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern Uganda by high‐resolution melt analysis
Authors: Kassaza Kennedy , Long Anna C. , McDaniels Jennifer M. , Andre Mharlove , Fredrickson Wasswa , Nyehangane Dan , Orikiriza Patrick , Operario Darwin J. , Bazira Joel , Mwanga-Amumpaire Juliet A. , Moore Christopher C. , Guler Jennifer L. , Boum Yap
Published: February 2021

Background

Chloroquine (CQ) resistance is conferred by mutations in the Plasmodium falciparum CQ resistance transporter (pfcrt). Following CQ withdrawal for anti-malarial treatment, studies across malaria-endemic countries have shown a range of responses. In some areas, CQ sensitive parasites re-emerge, and in others, mutant haplotypes persist. Active surveillance of resistance mutations in clinical parasites is essential to inform treatment regimens; this effort requires fast, reliable, and cost-effective methods that work on a variety of sample types with reagents accessible in malaria-endemic countries.

Methods

Quantitative PCR followed by High-Resolution Melt (HRM) analysis was performed in a field setting to assess pfcrt mutations in two groups of clinical samples from Southwestern Uganda. Group 1 samples (119 in total) were collected in 2010 as predominantly Giemsa-stained slides; Group 2 samples (125 in total) were collected in 2015 as blood spots on filter paper. The Rotor-Gene Q instrument was utilized to assess the impact of different PCR-HRM reagent mixes and the detection of mixed haplotypes present in the clinical samples. Finally, the prevalence of the wild type (CVMNK) and resistant pfcrt haplotypes (CVIET and SVMNT) was evaluated in this understudied Southwestern region of Uganda.

Results

The sample source (i.e. Giemsa-stained slides or blood spots) and type of LCGreen-based reagent mixes did not impact the success of PCR-HRM. The detection limit of 10− 5 ng and the ability to identify mixed haplotypes as low as 10 % was similar to other HRM platforms. The CVIET haplotype predominated in the clinical samples (66 %, 162/244); however, there was a large regional variation between the sample groups (94 % CVIET in Group 1 and 44 % CVIET in Group 2).

Conclusions

The HRM-based method exhibits the flexibility required to conduct reliable assessment of resistance alleles from various sample types generated during the clinical management of malaria. Large regional variations in CQ resistance haplotypes across Southwestern Uganda emphasizes the need for continued local parasite genotype assessment to inform anti-malarial treatment policies.
Clinicopathologic characteristics, metastasis-free survival, and skeletal-related events in 628 patients with skeletal metastases in a tertiary orthopedic and trauma center
Authors: Herget Georg , Saravi Babak , Schwarzkopf Eugenia , Wigand Mara , Südkamp Norbert , Schmal Hagen , Uhl Markus , Lang Gernot
Published: February 2021

Background

Skeletal-related events (SREs) due to bone metastases (BM) significantly impact the morbidity and mortality of cancer patients. The present study sought to investigate clinicopathological characteristics, metastasis-free survival (MFS), and SREs in patients referred to a tertiary orthopedic and trauma center.

Methods

Data were retrieved from electronic health records (n=628). Survival curves were estimated utilizing the Kaplan–Meier method. The Cox regression model was used to determine factors influencing MFS based on estimated hazard ratios (HRs).

Results

Breast (55.8%) and lung (18.2%), and lung (32.9%) and prostate (16.8%) cancer were the most common cancer types in our cohort in women and men, respectively. Fifteen percent of patients presented with BM as the first manifestation of tumor disease, 23% had metastasis diagnosis on the same day of primary tumor diagnosis or within 3 months, and 62% developed BM at least 3 months after primary tumor diagnosis. Osteolytic BM were predominant (72.3%) and most commonly affecting the spine (23%). Overall median MFS was 45 months (32 (men) vs. 53 (women) months). MFS was shortest in the lung (median 15 months, 95% CI 8.05–19) and longest in breast cancer (median 82 months, 95% CI 65.29–94). Age (≥ 60 vs. < 60 years) and primary cancer grading of ≥2 vs. 1 revealed prognostic relevance.

Conclusion

Women with breast or lung cancer, men with lung or prostate cancer, age ≥60 years, male sex, and primary cancer grading ≥2 are associated with increased risk for MBD. Intensified follow-up programs may reduce the risk of SREs and associated morbidity and mortality.
Hypofibrinogenemia is associated with a high degree of risk in infectious diseases: a post-hoc analysis of post-marketing surveillance of patients with disseminated intravascular coagulation treated with thrombomodulin alfa
Authors: Kawasugi Kazuo , Wada Hideo , Honda Goichi , Kawano Noriaki , Uchiyama Toshimasa , Madoiwa Seiji , Takezako Naoki , Suzuki Kei , Seki Yoshinobu , Ikezoe Takayuki , Iba Toshiaki , Okamoto Kohji
Published: February 2021

Background

In patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value. The relationship between hypofibrinogenemia and outcomes of DIC in infectious diseases has thus remained unclear.

Methods

We analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level < 1.5 g/L.

Results

Hypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly higher in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower for infectious disease patients with DIC with hypofibrinogenemia than for those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases.

Conclusions

Hypofibrinogenemia among infectious disease patients with DIC may reflect increased consumption of fibrinogen due to accelerated coagulation reactions, while hypofibrinogenemia among hematological disease patients with DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.
Promoting the integrated community case management of pneumonia in children under 5 years in Nigeria through the proprietary and patent medicine vendors: a cost-effectiveness analysis
Authors: Okafor Charles E. , Ekwunife Obinna I. , Nduaguba Sabina O.
Published: February 2021

Background

While evidence-based recommendations for the management pneumonia in under-5-year-olds at the community level with amoxicillin dispersible tablets (DT) were made by the World Health Organisation, initiatives to promote the integrated community case management (iCCM) of pneumonia through the proprietary and patent medicine vendors (PPMVs) have been poorly utilized in Nigeria, possibly due to low financial support and perceived benefit. This study provides costs, benefits and cost-effectiveness estimates and implications of promoting the iCCM through the PPMVs’ education and support. The outcome of this study will help inform healthcare decisions in Nigeria.

Methods

This study was a cost-effectiveness analysis using a simulation-based Markov model. Two approaches were compared, the ‘no promotion’ and the ‘promotion’ scenarios. The health outcomes include disability-adjusted life years averted and severe pneumonia hospitalisation cost averted. The costs were expressed in 2019 US dollars.

Results

The promotion of iCCM through the PPMVs was very cost effective with an incremental cost-effectiveness ratio of US$143.77 (95% CI US$137.42–150.50)/DALY averted. The promotion will prevent 28,359 cases of severe pneumonia hospitalisation with an estimated healthcare cost of US$390,578. It will also avert 900 deaths in a year.

Conclusion

Promoting the iCCM for the treatment of pneumonia in children under 5 years through education and support of the PPMVs holds promise to harness the benefits of amoxicillin DT and provide a high return on investment. A nationwide promotion exercise should be considered especially in remote areas of the country.
Niclosamide suppresses the expansion of follicular helper T cells and alleviates disease severity in two murine models of lupus via STAT3
Authors: Jang Se Gwang , Lee Jaeseon , Hong Seung-Min , Song Young-Seok , Kim Min Jun , Kwok Seung-Ki , Cho Mi-La , Park Sung-Hwan
Published: February 2021

Background

Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (TFH) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to TFH cells. Niclosamide is an anti-helminthic drug used to treat parasitic infections but also exhibits a therapeutic effect on autoimmune diseases due to its potential immune regulatory effects. In this study, we examined whether niclosamide treatment could relieve lupus-like autoimmunity by modulating the differentiation of TFH cells in two murine models of lupus.

Methods

10-week-old MRL/lpr mice were orally administered with 100 mg/kg of niclosamide or with 0.5% methylcellulose (MC, vehicle) daily for 7 weeks. TLR7 agonist, resiquimod was topically applied to an ear of 8-week-old C57BL/6 mice 3 times a week for 5 weeks. And they were orally administered with 100 mg/kg of niclosamide or with 0.5% MC daily for 5 weeks. Every mouse was analyzed for lupus nephritis, proteinuria, autoantibodies, immune complex, immune cell subsets at the time of the euthanization.

Results

Niclosamide treatment greatly improved proteinuria, anti-dsDNA antibody levels, immunoglobulin subclass titers, histology of lupus nephritis, and C3 deposition in MRL/lpr and R848-induced mice. In addition, niclosamide inhibited the proportion of TFH cells and PCs in the spleens of these animals, and effectively suppressed differentiation of TFH-like cells and expression of associated genes in vitro.

Conclusions

Niclosamide exerted therapeutic effects on murine lupus models by suppressing TFH cells and plasma cells through STAT3 inhibition.
Activities of daily living with bionic arm improved by combination training and latching filter in prosthesis control comparison
Authors: Paskett Michael D. , Brinton Mark R. , Hansen Taylor C. , George Jacob A. , Davis Tyler S. , Duncan Christopher C. , Clark Gregory A.
Published: February 2021

Background

Advanced prostheses can restore function and improve quality of life for individuals with amputations. Unfortunately, most commercial control strategies do not fully utilize the rich control information from residual nerves and musculature. Continuous decoders can provide more intuitive prosthesis control using multi-channel neural or electromyographic recordings. Three components influence continuous decoder performance: the data used to train the algorithm, the algorithm, and smoothing filters on the algorithm’s output. Individual groups often focus on a single decoder, so very few studies compare different decoders using otherwise similar experimental conditions.

Methods

We completed a two-phase, head-to-head comparison of 12 continuous decoders using activities of daily living. In phase one, we compared two training types and a smoothing filter with three algorithms (modified Kalman filter, multi-layer perceptron, and convolutional neural network) in a clothespin relocation task. We compared training types that included only individual digit and wrist movements vs. combination movements (e.g., simultaneous grasp and wrist flexion). We also compared raw vs. nonlinearly smoothed algorithm outputs. In phase two, we compared the three algorithms in fragile egg, zipping, pouring, and folding tasks using the combination training and smoothing found beneficial in phase one. In both phases, we collected objective, performance-based (e.g., success rate), and subjective, user-focused (e.g., preference) measures.

Results

Phase one showed that combination training improved prosthesis control accuracy and speed, and that the nonlinear smoothing improved accuracy but generally reduced speed. Phase one importantly showed simultaneous movements were used in the task, and that the modified Kalman filter and multi-layer perceptron predicted more simultaneous movements than the convolutional neural network. In phase two, user-focused metrics favored the convolutional neural network and modified Kalman filter, whereas performance-based metrics were generally similar among all algorithms.

Conclusions

These results confirm that state-of-the-art algorithms, whether linear or nonlinear in nature, functionally benefit from training on more complex data and from output smoothing. These studies will be used to select a decoder for a long-term take-home trial with implanted neuromyoelectric devices. Overall, clinical considerations may favor the mKF as it is similar in performance, faster to train, and computationally less expensive than neural networks.
The relationship between 2019-nCoV and psychological distress among parents of children with autism spectrum disorder
Authors: Wang Luxi , Li Dexin , Pan Shixu , Zhai Jinhe , Xia Wei , Sun Caihong , Zou Mingyang
Published: February 2021

Objectives

The psychological distress caused by COVID-19 may be pronounced among the parents of children with autism spectrum disorder (ASD). This study aimed to investigate psychological distress among parents of children with ASD during the COVID-19 pandemic.

Methods

A total of 1764 parents of children with ASD and 4962 parents of typically developing (TD) children were recruited. The participants completed an online survey which contained demographic information, the impact due to COVID-19 crisis, resilience, coping styles, anxiety and depression. Hierarchical linear regression was used to assess the contributions of these variables to anxiety and depression.

Results

After adjusting for demographic variables, the following factors were associated with parents’ anxiety and depression symptoms: (i) Whether or not the participants had a child with ASD; (ii) resilience; (iii) coping strategies, and; (iv) the impact due to COVID-19. Among these, the psychological stress caused by COVID-19 played the most important role in parental anxiety (β = 0.353) and depression (β = 0.242) symptoms. Parents of children with ASD had lower levels of resilience and positive coping, and used more negative coping strategies than parents of TD children. Among all participants, 8.0 and 24.2% of parents had symptoms of anxiety and depression, respectively. Compared to parents of TD children, more parents of children with ASD exhibited symptoms of anxiety and depression (12.2% vs. 6.6%; 31.0% vs. 21.7%, respectively).

Conclusions

During the COVID-19 pandemic, parents experienced varying levels of anxiety and depression, particularly, parents of children with ASD. More specific attention should be paid to parental mental health and long-term effective intervention programs, that are targeted towards parents of children with ASD, and such programs should be promoted around China in the wake of the COVID-19 crisis.
Changing behaviour, ‘more or less’: do implementation and de-implementation interventions include different behaviour change techniques?
Authors: Patey Andrea M. , Grimshaw Jeremy M. , Francis Jill J.
Published: February 2021

Background

Decreasing ineffective or harmful healthcare practices (de-implementation) may require different approaches than those used to promote uptake of effective practices (implementation). Few psychological theories differentiate between processes involved in decreasing, versus increasing, behaviour. However, it is unknown whether implementation and de-implementation interventions already use different approaches. We used the behaviour change technique (BCT) taxonomy (version 1) (which includes 93 BCTs organised into 12 groupings) to investigate whether implementation and de-implementation interventions for clinician behaviour change use different BCTs.

Methods

Intervention descriptions in 181 articles from three systematic reviews in the Cochrane Library were coded for (a) implementation versus de-implementation and (b) intervention content (BCTs) using the BCT taxonomy (v1). BCT frequencies were calculated and compared using Pearson’s chi-squared (χ2), Yates’ continuity correction and Fisher’s exact test, where appropriate. Identified BCTs were ranked according to frequency and rankings for de-implementation versus implementation interventions were compared and described.

Results

Twenty-nine and 25 BCTs were identified in implementation and de-implementation interventions respectively. Feedback on behaviour was identified more frequently in implementation than de-implementation (Χ2(2, n=178) = 15.693, p = .000057). Three BCTs were identified more frequently in de-implementation than implementation: Behaviour substitution (Χ2(2, n=178) = 14.561, p = .0001; Yates’ continuity correction); Monitoring of behaviour by others without feedback (Χ2(2, n=178) = 16.187, p = .000057; Yates’ continuity correction); and Restructuring social environment (p = .000273; Fisher’s 2-sided exact test).

Conclusions

There were some significant differences between BCTs reported in implementation and de-implementation interventions suggesting that researchers may have implicit theories about different BCTs required for de-implementation and implementation. These findings do not imply that the BCTs identified as targeting implementation or de-implementation are effective, rather simply that they were more frequently used. These findings require replication for a wider range of clinical behaviours. The continued accumulation of additional knowledge and evidence into whether implementation and de-implementation is different will serve to better inform researchers and, subsequently, improve methods for intervention design.
Clinical feasibility of deep learning-based auto-segmentation of target volumes and organs-at-risk in breast cancer patients after breast-conserving surgery
Authors: Chung Seung Yeun , Chang Jee Suk , Choi Min Seo , Chang Yongjin , Choi Byong Su , Chun Jaehee , Keum Ki Chang , Kim Jin Sung , Kim Yong Bae
Published: February 2021

Background

In breast cancer patients receiving radiotherapy (RT), accurate target delineation and reduction of radiation doses to the nearby normal organs is important. However, manual clinical target volume (CTV) and organs-at-risk (OARs) segmentation for treatment planning increases physicians’ workload and inter-physician variability considerably. In this study, we evaluated the potential benefits of deep learning-based auto-segmented contours by comparing them to manually delineated contours for breast cancer patients.

Methods

CTVs for bilateral breasts, regional lymph nodes, and OARs (including the heart, lungs, esophagus, spinal cord, and thyroid) were manually delineated on planning computed tomography scans of 111 breast cancer patients who received breast-conserving surgery. Subsequently, a two-stage convolutional neural network algorithm was used. Quantitative metrics, including the Dice similarity coefficient (DSC) and 95% Hausdorff distance, and qualitative scoring by two panels from 10 institutions were used for analysis. Inter-observer variability and delineation time were assessed; furthermore, dose-volume histograms and dosimetric parameters were also analyzed using another set of patient data.

Results

The correlation between the auto-segmented and manual contours was acceptable for OARs, with a mean DSC higher than 0.80 for all OARs. In addition, the CTVs showed favorable results, with mean DSCs higher than 0.70 for all breast and regional lymph node CTVs. Furthermore, qualitative subjective scoring showed that the results were acceptable for all CTVs and OARs, with a median score of at least 8 (possible range: 0–10) for (1) the differences between manual and auto-segmented contours and (2) the extent to which auto-segmentation would assist physicians in clinical practice. The differences in dosimetric parameters between the auto-segmented and manual contours were minimal.

Conclusions

The feasibility of deep learning-based auto-segmentation in breast RT planning was demonstrated. Although deep learning-based auto-segmentation cannot be a substitute for radiation oncologists, it is a useful tool with excellent potential in assisting radiation oncologists in the future.

Trial registration Retrospectively registered.
Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses
Authors: Al-Zayed Zayed , Al-Rijjal Roua A. , Al-Ghofaili Lamya , BinEssa Huda A. , Pant Rajeev , Alrabiah Anwar , Al-Hussainan Thamer , Zou Minjing , Meyer Brian F. , Shi Yufei
Published: February 2021

Background

Hereditary Multiple Exostoses (HME), also known as Multiple Osteochondromas (MO) is a rare genetic disorder characterized by multiple benign cartilaginous bone tumors, which are caused by mutations in the genes for exostosin glycosyltransferase 1 (EXT1) and exostosin glycosyltransferase 2 (EXT2). The genetic defects have not been studied in the Saudi patients.

Aim of study

We investigated mutation spectrum of EXT1 and EXT2 in 22 patients from 17 unrelated families.

Methods

Genomic DNA was extracted from peripheral leucocytes. The coding regions and intron–exon boundaries of both EXT1 and EXT2 genes were screened for mutations by PCR-sequencing analysis. Gross deletions were analyzed by MLPA analysis.

Results

EXT1 mutations were detected in 6 families (35%) and 3 were novel mutations: c.739G > T (p. E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25). EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1. Five patients from different families had no family history and carried de novo mutations (29%, 5/17). No EXT1 and EXT2 mutations were found in the remaining four families. In total, EXT1 and EXT2 mutations were found in 77% (13/17) of Saudi HME patients.

Conclusion

EXT1 and EXT2 mutations contribute significantly to the pathogenesis of HME in the Saudi population. In contrast to high mutation rate in EXT 1 (65%) and low mutation rate in EXT2 (25%) in other populations, the frequency of EXT2 mutations are much higher (41%) and comparable to that of EXT1 among Saudi patients. De novo mutations are also common and the six novel EXT1/EXT2 mutations further expands the mutation spectrum of HME.
Long-term health-related quality of life and burden of disease after intensive care: development of a patient-reported outcome measure
Authors: Malmgren Johan , Waldenström Ann-Charlotte , Rylander Christian , Johannesson Elias , Lundin Stefan
Published: February 2021

Background

ICU survivorship includes a diverse burden of disease. Current questionnaires used for collecting information about health-related problems and their relation to quality of life lack detailed questions in several areas relevant to ICU survivors. Our aim was to construct a provisional questionnaire on health-related issues based on interviews with ICU survivors and to test if this questionnaire was able to show differences between ICU survivors and a control group.

Methods

Thirty-two ICU survivors were identified at a post-ICU clinic and interviewed at least six months after ICU discharge. Using an established qualitative methodology from oncology, all dysfunctions and disabilities were extracted, rephrased as questions and compiled into a provisional questionnaire. In a second part, this questionnaire was tested on ICU survivors and controls. Inclusion criteria for the ICU survivors were ICU stay at least 72 h with ICU discharge six months to three years prior to the study. A non-ICU-treated control group was obtained from the Swedish Population Register, matched for age and sex. Eligible participants received an invitation letter and were contacted by phone. If willing to participate, they were sent the questionnaire. Descriptive statistics were applied.

Results

Analysis of the interviews yielded 238 questions in 13 domains: cognition, fatigue, physical health, pain, psychological health, activities of daily living, sleep, appetite and alcohol, sexual health, sensory functions, gastrointestinal functions, urinary functions and work life. In the second part, 395 of 518 ICU survivors and 197 of 231 controls returned a completed questionnaire, the response rates being 76.2% and 85.3%, respectively. The two groups differed significantly in 13 of 22 comorbidities. ICU survivors differed in a majority of questions (p ≤ 0.05) distributed over all 13 domains compared with controls.

Conclusions

This study describes the development of a provisional questionnaire to identify health-related quality of life issues and long-term burden of disease after intensive care. The questionnaire was answered by 395 ICU survivors. The questionnaire could identify that they experience severe difficulties in a wide range of domains compared with a control group.

Trial registry ClinicalTrials.gov Ref# NCT 02767180
Interplay between severities of COVID-19 and the gut microbiome: implications of bacterial co-infections?
Authors: Chhibber-Goel Jyoti , Gopinathan Sreehari , Sharma Amit
Published: February 2021

COVID-19 is an acute respiratory distress syndrome and is often accompanied by gastrointestinal symptoms. The SARS-CoV-2 has been traced not only in nasopharyngeal and mid-nasal swabs but also in stool and rectal swabs of COVID-19 patients. The gut microbiota is important for an effective immune response as it ensures that unfavorable immune reactions in lungs and other vital organs are regulated. The human gut-lung microbiota interplay provides a framework for therapies in the treatment and management of several pulmonary diseases and infections. Here, we have collated data from COVID-19 studies, which suggest that bacterial co-infections as well as the gut-lung cross talk may be important players in COVID-19 disease prognosis. Our analyses suggests a role of gut microbiome in pathogen infections as well as in an array of excessive immune reactions during and post COVID-19 infection recovery period.
Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn’s disease
Authors: Hu Shijia , Png Eileen , Gowans Michelle , Ong David E. H. , de Sessions Paola Florez , Song Jie , Nagarajan Niranjan
Published: February 2021

Background

This study aims to characterize, the gut and oral microbiome in Asian subjects with Crohn’s disease (CD) using whole genome shotgun sequencing, thereby allowing for strain-level comparison.

Methods

A case–control study with age, sex and ethnicity matched healthy controls was conducted. CD subjects were limited to well-controlled patients without oral manifestations. Fecal and saliva samples were collected for characterization of gut and oral microbiome respectively. Microbial DNA were extracted, libraries prepared and sequenced reads profiled. Taxonomic diversity, taxonomic association, strain typing and microbial gene pathway analyses were conducted.

Results

The study recruited 25 subjects with CD and 25 healthy controls. The oral microbe Streptococcus salivarius was found to be enriched and of concordant strains in the gut and oral microbiome of Crohn’s disease subjects. This was more likely in CD subjects with higher Crohn’s Disease Activity Index (184.3 ± 2.9 vs 67.1 ± 82.5, p = 0.012) and active disease status (Diarrhoea/abdominal pain/blood-in-stool/fever and fatigue) (p = 0.016). Gut species found to be significantly depleted in CD compared to control (Relative abundance: Median[Range]) include: Faecalibacterium prausnitzii (0.03[0.00–4.56] vs 13.69[5.32–18.71], p = 0.010), Roseburia inulinivorans (0.00[0.00–0.03] vs 0.21[0.01–0.53], p = 0.010) and Alistipes senegalensis (0.00[0.00–0.00] vs 0.00[0.00–0.02], p = 0.029). While Clostridium nexile (0.00[0.00–0.12] vs 0.00[0.00–0.00], p = 0.038) and Ruminococcus gnavus (0.43[0.02–0.33] vs 0.00[0.00–0.13], p = 0.043) were found to be enriched. C. nexile enrichment was not found in CD subjects of European descent. Microbial arginine (Linear-discriminant-analysis: 3.162, p = 0.001) and isoprene (Linear-discriminant-analysis: 3.058, p < 0.001) pathways were found at a higher relative abundance level in gut microbiome of Crohn’s disease.

Conclusions

There was evidence of ectopic gut colonization by oral bacteria, especially during the active phase of CD. Previously studied gut microbial differences were detected, in addition to novel associations which could have resulted from geographical/ethnic differences to subjects of European descent. Differences in microbial pathways provide possible targets for microbiome modification.
Intestinal organoids in farm animals
Authors: Beaumont Martin , Blanc Fany , Cherbuy Claire , Egidy Giorgia , Giuffra Elisabetta , Lacroix-Lamandé Sonia , Wiedemann Agnès
Published: February 2021

In livestock species, the monolayer of epithelial cells covering the digestive mucosa plays an essential role for nutrition and gut barrier function. However, research on farm animal intestinal epithelium has been hampered by the lack of appropriate in vitro models. Over the past decade, methods to culture livestock intestinal organoids have been developed in pig, bovine, rabbit, horse, sheep and chicken. Gut organoids from farm animals are obtained by seeding tissue-derived intestinal epithelial stem cells in a 3-dimensional culture environment reproducing in vitro the stem cell niche. These organoids can be generated rapidly within days and are formed by a monolayer of polarized epithelial cells containing the diverse differentiated epithelial progeny, recapitulating the original structure and function of the native epithelium. The phenotype of intestinal organoids is stable in long-term culture and reflects characteristics of the digestive segment of origin. Farm animal intestinal organoids can be amplified in vitro, cryopreserved and used for multiple experiments, allowing an efficient reduction of the use of live animals for experimentation. Most of the studies using livestock intestinal organoids were used to investigate host-microbe interactions at the epithelial surface, mainly focused on enteric infections with viruses, bacteria or parasites. Numerous other applications of farm animal intestinal organoids include studies on nutrient absorption, genome editing and bioactive compounds screening relevant for agricultural, veterinary and biomedical sciences. Further improvements of the methods used to culture intestinal organoids from farm animals are required to replicate more closely the intestinal tissue complexity, including the presence of non-epithelial cell types and of the gut microbiota. Harmonization of the methods used to culture livestock intestinal organoids will also be required to increase the reproducibility of the results obtained in these models. In this review, we summarize the methods used to generate and cryopreserve intestinal organoids in farm animals, present their phenotypes and discuss current and future applications of this innovative culture system of the digestive epithelium.
Regularity criterion for 3D nematic liquid crystal flows in terms of finite frequency parts in $\dot{B}_{\infty,\infty }^{-1}$
Authors: Chen Xiaoli , Cheng Haiyan
Published: February 2021

In this paper, we establish the regularity criterion for the weak solution of nematic liquid crystal flows in three dimensions when the $L^{\infty }(0,T;\dot{B}_{\infty,\infty }^{-1})$

L
∞

(
0
,
T
;

B
˙

∞
,
∞

−
1

)
-norm of a suitable low frequency part of $(u,\nabla d)$
(
u
,
∇
d
)
is bounded by a scaling invariant constant and the initial data $(u_{0},\nabla d_{0})$
(

u
0

,
∇

d
0

)
. Our result refines the corresponding one in (Liu and Zhao in J. Math. Anal. Appl. 407:557-566, 2013) and that in (Ri in Nonlinear Anal. TMA 190:111619, 2020).
On some new double dynamic inequalities associated with Leibniz integral rule on time scales
Authors: El-Deeb A. A. , Rashid Saima
Published: February 2021

In 2020, El-Deeb et al. proved several dynamic inequalities. It is our aim in this paper to give the retarded time scales case of these inequalities. We also give a new proof and formula of Leibniz integral rule on time scales. Beside that, we also apply our inequalities to discrete and continuous calculus to obtain some new inequalities as special cases. Furthermore, we study boundedness of some delay initial value problems by applying our results as application.
Clinical and microbiological characteristics of nosocomial, healthcare-associated, and community-acquired Klebsiella pneumoniae infections in Guangzhou, China
Authors: Le Tingting , Wang Ling , Zeng Chaoying , Fu Leiwen , Liu Zhihua , Hu Jing
Published: February 2021

Background

Klebsiella pneumoniae(K. pneumoniae) is a common pathogen associated with hospital and community-onset infections. This study aimed to compare the clinical and microbiological characteristics of nosocomial, healthcare-associated (HCA), and community-acquired (CA)K. pneumoniaeinfections.

Methods

Clinical data were extracted from electronic medical records and analyzed retrospectively. Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) production were determined for all identified strains. Carbapenemase and ESBL genes were amplified by PCR. Genotyping of carbapenem-resistantK. pneumoniae(CRKP) and ESBL-producing strains was performed by pulsed-field gel electrophoresis (PFGE).

Results

Of 379 K. pneumoniaeinfections, 98 (25.9%) were nosocomial, 195 (51.5%) were healthcare-associated, and 86 (22.6%) were community-acquired. Hematological malignancy (OR = 4.467), and hypertension (OR = 2.08) and cerebral vascular disease (OR = 2.486) were associated with nosocomial and HCA infections respectively, when compared to CA infections. Overall, the incidence of antimicrobial resistance for the majority of agents tested was similar between nosocomial and HCA infections (P > 0.05) and both groups had a higher incidence than CA infections (P < 0.05). Moreover, 95.1% (78/82) of CRKP strains were isolated from the nosocomial and HCA groups. TheblaKPCwas the most prevalent carbapenemase gene among CRKP strains (80.5%, 66/82). ESBL-producing strains were prevalent among nosocomial (40.8%), HCA (35.9%) and CA groups (24.4%). TheblaCTX-M-9-groupandblaCTX-M-1-groupgenes were predominant in nosocomial (65.0%) and CA strains (66.7%), respectively. PFGE results showed ESBL-producing and CRKP strains were genetically diverse. Identical PFGE profiles were observed among HCA and nosocomial strains.

Conclusions

Nosocomial and HCAK. pneumoniaeinfections presented similar clinical features and antimicrobial resistance, and both two types of infections were different to CA infections. CRKP and ESBL-producing strains were disseminated mainly in HCA and nosocomial groups, and showed a clonal diversity. The cross transmission of CRKP was existed among HCA and nosocomial patients. This finding suggests that similar empirical therapy should be considered for patients with nosocomial and HCAK. pneumoniaeinfections and bacterial resistance surveillance of these infections is necessary.
What impact does maths anxiety have on university students?
Authors: Khasawneh Eihab , Gosling Cameron , Williams Brett
Published: February 2021

Background

Maths anxiety is defined as a feeling of tension and apprehension that interferes with maths performance ability, the manipulation of numbers and the solving of mathematical problems in a wide variety of ordinary life and academic situations. Our aim was to identify the facilitators and barriers of maths anxiety in university students.

Method

A scoping review methodology was used in this study. A search of databases including: Cumulative Index of Nursing and Allied Health Literature, Embase, Scopus, PsycInfo, Medline, Education Resources Information Centre, Google Scholar and grey literature. Articles were included if they addressed the maths anxiety concept, identified barriers and facilitators of maths anxiety, had a study population comprised of university students and were in Arabic or English languages.

Results and discussion

After duplicate removal and applying the inclusion criteria, 10 articles were included in this study. Maths anxiety is an issue that effects many disciplines across multiple countries and sectors. The following themes emerged from the included papers: gender, self-awareness, numerical ability, and learning difficulty. The pattern in which gender impacts maths anxiety differs across countries and disciplines. There was a significant positive relationship between students’ maths self-efficacy and maths performance and between maths self-efficacy, drug calculation self-efficacy and drug calculation performance.

Conclusion

Maths anxiety is an issue that effects many disciplines across multiple countries and sectors. Developing anxiety toward maths might be affected by gender; females are more prone to maths anxiety than males. Maths confidence, maths values and self-efficacy are related to self-awareness. Improving these concepts could end up with overcoming maths anxiety and improving performance.
Trans-synaptic spreading of alpha-synuclein pathology through sensory afferents leads to sensory nerve degeneration and neuropathic pain
Authors: Ferreira Nelson , Gonçalves Nádia Pereira , Jan Asad , Jensen Nanna Møller , van der Laan Amelia , Mohseni Simin , Vægter Christian Bjerggaard , Jensen Poul Henning
Published: February 2021

Pain is a common non-motor symptom of Parkinson’s disease (PD), with current limited knowledge of its pathophysiology. Here, we show that peripheral inoculation of mouse alpha-synuclein (α-Syn) pre-formed fibrils, in a transgenic mouse model of PD, elicited retrograde trans-synaptic spreading of α-Syn pathology (pSer129) across sensory neurons and dorsal nerve roots, reaching central pain processing regions, including the spinal dorsal horn and the projections of the anterolateral system in the central nervous system (CNS). Pathological peripheral to CNS propagation of α-Syn aggregates along interconnected neuronal populations within sensory afferents, was concomitant with impaired nociceptive response, reflected by mechanical allodynia, reduced nerve conduction velocities (sensory and motor) and degeneration of small- and medium-sized myelinated fibers. Our findings show a link between the transneuronal propagation of α-Syn pathology with sensory neuron dysfunction and neuropathic impairment, suggesting promising avenues of investigation into the mechanisms underlying pain in PD.