bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for severe adult-onset asthma: a multi-factor approach
Authors: Toppila-Salmi Sanna , Lemmetyinen Riikka , Chanoine Sebastien , Karjalainen Jussi , Pekkanen Juha , Bousquet Jean , Siroux Valérie
Published: July 2021

Background

The aim was to identify risk factors for severe adult-onset asthma.

Methods

We used data from a population-based sample (Adult Asthma in Finland) of 1350 patients with adult-onset asthma (age range 31–93 years) from Finnish national registers. Severe asthma was defined as self-reported severe asthma and asthma symptoms causing much harm and regular impairment and ≥ 1 oral corticosteroid course/year or regular oral corticosteroids or waking up in the night due to asthma symptoms/wheezing ≥ a few times/month. Sixteen covariates covering several domains (personal characteristics, education, lifestyle, early-life factors, asthma characteristics and multiple morbidities) were selected based on the literature and were studied in association with severe asthma using logistic regressions.

Results

The study population included 100 (7.4%) individuals with severe asthma. In a univariate analysis, severe asthma was associated with male sex, age, a low education level, no professional training, ever smoking, ≥ 2 siblings, ≥ 1 chronic comorbidity and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) (p < 0.05), and trends for association (p < 0.2) were observed for severe childhood infection, the presence of chronic rhinosinusitis with nasal polyps, and being the 1st child. The 10 variables (being a 1st child was removed due to multicollinearity) were thus entered in a multivariate regression model, and severe asthma was significantly associated with male sex (OR [95% CI] = 1.96 [1.16–3.30]), ever smoking (1.98 [1.11–3.52]), chronic comorbidities (2.68 [1.35–5.31]), NERD (3.29 [1.75–6.19]), and ≥ 2 siblings (2.51 [1.17–5.41]). There was a dose–response effect of the total sum of these five factors on severe asthma (OR [95% CI] = 2.30 [1.81–2.93] for each one-unit increase in the score).

Conclusions

Male sex, smoking, NERD, comorbidities, and ≥ 2 siblings were independent risk factors for self-reported severe asthma. The effects of these factors seem to be cumulative; each additional risk factor gradually increases the risk of severe asthma.
Literacy as part of professional knowing in a Swedish dental education
Authors: Lindberg Viveca , Jounger Sofia Louca , Christidis Maria , Christidis Nikolaos
Published: July 2021

Background

Academic reading and writing are seen as self-evident literacy competences in most contemporary higher educations, however, whether students also are introduced to professional literacy of relevance for dentistry during their education is a question. The purpose of this study is to analyze one of the Swedish dental programmes, with respect to its design, in relation to possible content of relevance for academic and professional literacy. Secondarily, to identify and analyze Swedish dental students’ writing in an academic setting, i.e. what these students are expected to read and write, and how they write.

Methods

Data, for this ethnographically inspired case-study, was produced by observations and audio-recordings of lectures, copies of teachers’ handouts and of volunteering students’ notes, and a multiple-choice-test. Data-analysis was made in five steps, starting with macro-level data, i.e. curriculum and syllabuses, followed by the syllabuses for the two observed modules, the teacher-provided material, analysis of the students’ notes, while in the fifth and final step, the results from the previous steps were compared, to find patterns of what students were expected to read and write, and what in the teacher-provided multimodal material that was emphasized in teachers’ talk.

Results

This study showed that students were engaged in several types of literacy events, such as reading, finding and watching videos on their learning platform, writing, and following instructions. The study also showed that there is a recurrent academic content comprised of anatomy, physiology and pathology, while the professional content comprised of patient communication and anamnesis. Further, an integrated content was found and was initiated in teacher-constructed PowerPoints and by student-questions. Note-taking patterns varied between individual students, but the general pattern for this group of students were the use of complementary notes. This type of note-taking was used to make available further descriptions of the teacher-constructed text in PowerPoints, but also an independent text describing pictures shown on teachers’ PowerPoints or the blackboard.

Conclusion

Findings from the present study reveal that students either copy text from teachers’ PowerPoint-slides, re-formulate text from teachers’ PowerPoint-slides, or write complementing text to teachers’ PowerPoint-slides. Further, the students individually choses type of note-taking based on situation. The study also revealed that the academic literacy – in the two modules during the fifth and sixth semesters of a dental education analyzed – mainly has a professional basis for reading, writing, and communication purposes. The study also showed that academic and professional literacy are closely connected through recurrent integration.
Creation of a novel simple heat mapping method for curriculum mapping, using pathology teaching as the exemplar
Authors: Clark Ryan , Bell Sarah , Roccisana Jennifer , Oien Karin A. , Sneddon Sharon F.
Published: July 2021

Background

The undergraduate five-year MBChB programme at the University of Glasgow has a high volume of pathology teaching integrated into the course. The ability to better understand what pathology is taught and when, so as to build a picture of the types and depth of pathology topics covered across the programme stages is crucial, especially in a spiral curriculum. A novel method of curriculum mapping, known as curriculum heat mapping, was developed as a way to visualise where and when topics are taught, in an easier to understand format.

Methods

This method involved comparing the Glasgow curriculum to a pre-determined standard of what should be taught. In this case, The Royal College of Pathologists’ ‘Pathology Undergraduate Curriculum’ was used as a comparison of what a graduating doctor should know about pathology.

Results

Following the developed template, heat maps showcasing the range of pathology topics covered, and where they are covered, were developed for local use.

These heat maps provided a clear visual representation of where and when topics are taught, and how they cluster.

Conclusions

Heat mapping is a novel low-cost, high-input method of curriculum mapping. It requires a person to input the data which can take a long time for large curricula. There are no other upfront financial costs. It can be used in any area with a curriculum and an external or internal comparator. Examples of gold standard external comparators include validated national or international curricula.

Heat mapping can help integrated, spiral curriculum programmes to identify where core topics are taught throughout their course. The heat maps themselves successfully demonstrate the required information and are easy to interpret. The process of mapping, as well as the final heat map, can yield important information. This includes information about trends within the curriculum, areas for potential improvement in sessional design and a clearer understanding of the depth to which each topic is covered in each lecture.

Overall, it is a viable novel method, which has been successful locally and is easily transferable to other areas such as pharmacology.
Factors influencing the patient safety climate in intensive care units: cross-sectional study
Authors: de Lima Silva Nunes Ranielle , de Camargo Silva Ana Elisa Bauer , de Lima Juliana Carvalho , Carvalho Dayse Edwiges , Bernardes Cristina Alves , Sousa Tanielly Paula , Gimenes Fernanda Raphael Escobar , Pires Ana Claudia Andrade Cordeiro
Published: July 2021

Background

Measuring the patient safety climate of a health service provides important information about the safety status at a given time. This study aimed to determine the factors influencing the patient safety climate in Intensive Care Units.

Methods

An analytical and cross-sectional study conducted in 2017 and 2018 in two adult Intensive Care Units of a Brazilian Teaching Hospital. The Safety Attitudes Questionnaire instrument was applied with the multidisciplinary teams to determine the factors influencing the patient safety climate. Data were double entered into a database and processed using the R (version 3.5.0) statistical software. Position, central tendency and dispersion measures were taken and absolute and relative frequencies, mean and confidence intervals were calculated for the quantitative variables. Linear regression was performed to verify the effect of variables on the SAQ domains. Variables with a p-value of less than 0.25 were selected for multivariate analysis.

Results

A total of 84 healthcare providers participated in the study. The mean Safety Attitudes Questionnaire score was 59.5, evidencing a negative climate. The following factors influenced the safety climate: time since course completion, professional category, type of employment contract, complementary professional training, and weekly workload.

Conclusions

The factors identified indicate items for planning improvements in communication, teamwork, work processes, and management involvement, aiming to ensure care safety and construct a supportive safety climate.
Psychometric properities of the Polish version of clinical learning environment inventory
Authors: Bodys-Cupak Iwona
Published: July 2021

Background

Clinical experience is a crucial activity for nursing students. The way students` perceive clinical placement exerts an immense influence on the learning process. This study aims to test the psychometric properties of a 19-item version of the Clinical Learning Environment Inventory under Polish clinical conditions.

Method

For this study, Discriminant validity and Cronbach’s alpha reliabilities were computed. In order to measure content validity, the criterion validity Generalized Self Efficacy Scale and the Life Orientation Test - Revised were used.

Results

Cronbach’s Alpha for the Clinical Facilitator Support of Learning Scale and the Satisfaction with Clinical Placement scale is 0.949 and 0.901, respectively. The Spearman’s rank correlation coefficient indicates the existence of a positive correlation between the students’ satisfaction with clinical placement and their [overall] life optimism. Age correlates negatively with perceived teacher support and positively with satisfaction with clinical placement. The sense of self-efficacy correlates negatively with their satisfaction with clinical placement. Clinical Learning Environment Inventory − 19 could be a useful tool to evaluate the quality of the clinical learning process in Polish conditions.
Metagenome-wide association study of gut microbiome revealed potential microbial marker set for diagnosis of pediatric myasthenia gravis
Authors: Liu Peng , Jiang Yiqi , Gu Shanshan , Xue Yinping , Yang Hongxia , Li Yongzhao , Wang Yaxuan , Yan Congya , Jia Pei , Lin Xiaoting , Qi Guoyan
Published: July 2021

Background

Myasthenia gravis (MG) is an acquired immune-mediated disorder of the neuromuscular junction that causes fluctuating skeletal muscle weakness and fatigue. Pediatric MG and adult MG have many different characteristics, and current MG diagnostic methods for children are not quite fit. Previous studies indicate that alterations in the gut microbiota may be associated with adult MG. However, it has not been determined whether the gut microbiota are altered in pediatric MG patients.

Methods

Our study recruited 53 pediatric MG patients and 46 age- and gender-matched healthy controls (HC). We sequenced the fecal samples of recruited individuals using whole-genome shotgun sequencing and analyzed the data with in-house bioinformatics pipeline.

Results

We built an MG disease classifier based on the abundance of five species, Fusobacterium mortiferum, Prevotella stercorea, Prevotella copri, Megamonas funiformis, and Megamonas hypermegale. The classifier obtained 94% area under the curve (AUC) in cross-validation and 84% AUC in the independent validation cohort. Gut microbiome analysis revealed the presence of human adenovirus F/D in 10 MG patients. Significantly different pathways and gene families between MG patients and HC belonged to P. copri, Clostridium bartlettii, and Bacteroides massiliensis. Based on functional annotation, we found that the gut microbiome affects the production of short-chain fatty acids (SCFAs), and we confirmed the decrease in SCFA levels in pediatric MG patients via serum tests.

Conclusions

The study indicated that altered fecal microbiota might play vital roles in pediatric MG’s pathogenesis by reducing SCFAs. The microbial markers might serve as novel diagnostic methods for pediatric MG.
Identification of autophagy-related risk signatures for the prognosis, diagnosis, and targeted therapy in cervical cancer
Authors: Meng Dan , Jin Hua , Zhang Xing , Yan Wenjing , Xia Qianqian , Shen Siyuan , Xie Shuqian , Cui Mengjing , Ding Bo , Gu Yun , Wang Shizhi
Published: July 2021

Background

To rummage autophagy-related prognostic, diagnostic, and therapeutic biomarkers in cervical cancer (CC).

Methods

The RNA-sequence and clinical information were from the TCGA and GTEx databases. We operated Cox regression to determine signatures related to overall survival (OS) and recurrence-free survival (RFS) respectively. The diagnostic and therapeutic effectiveness of prognostic biomarkers were further explored.

Results

We identified nine (VAMP7, MTMR14, ATG4D, KLHL24, TP73, NAMPT, CD46, HGS, ATG4C) and three risk signatures (SERPINA1, HSPB8, SUPT20H) with prognostic values for OS and RFS respectively. Six risk signatures (ATG4C, ATG4D, CD46, TP73, SERPINA1, HSPB8) were selected for qPCR. We screened five prognostic signatures(ATG4C, CD46, HSPB8, MTMR14, NAMPT) with diagnostic function through the GEO database. Correlation between our models and treatment targets certificated the prognostic score provided a reference for precision medicine.

Conclusions

We constructed OS and RFS prognostic models in CC. Autophagy-related risk signatures might serve as diagnostic and therapeutic biomarkers.
Identification and validation of lncRNAs involved in m6A regulation for patients with ovarian cancer
Authors: Zheng Jianfeng , Guo Jialu , Cao Benben , Zhou Ying , Tong Jinyi
Published: July 2021

Background

Both N6-methyladenosine (m6A) modification and lncRNAs play an important role in the carcinogenesis and cancer inhibition of ovarian cancer (OC). However, lncRNAs involved in m6A regulation (LI-m6As) have never been reported in OC. Herein, we aimed to identify and validate a signature based on LI-m6A for OC.

Methods

RNA sequencing profiles with corresponding clinical information associated with OC and 23 m6A regulators were extracted from TCGA. The Pearson correlation coefficient (PCC) between lncRNAs and 23 m6A regulators (|PCC|> 0.4 and p < 0.01) was calculated to identify LI-m6As. The LI-m6As with significant prognostic value were screened based on univariate Cox regression analysis to construct a risk model by LASSO Cox regression. Gene Set Enrichment Analysis (GSEA) was implemented to survey the biological functions of the risk groups. Several clinicopathological characteristics were utilized to evaluate their ability to predict prognosis, and a nomogram was constructed to evaluate the accuracy of survival prediction. Besides, immune microenvironment, checkpoint, and drug sensitivity in the two risk groups were compared using comprehensive algorithms. Finally, real-time qPCR analysis and cell counting kit-8 assays were performed on an alternative lncRNA, CACNA1G-AS1.

Results

The training cohort involving 258 OC patients and the validation cohort involving 111 OC patients were downloaded from TCGA. According to the PCC between the m6A regulators and lncRNAs, 129 LI-m6As were obtained to perform univariate Cox regression analysis and then 10 significant prognostic LI-m6As were identified. A prognostic signature containing four LI-m6As (AC010894.3, ACAP2-IT1, CACNA1G-AS1, and UBA6-AS1) was constructed according to the LASSO Cox regression analysis of the 10 LI-m6As. The prognostic signature was validated to show completely opposite prognostic value in the two risk groups and adverse overall survival (OS) in several clinicopathological characteristics. GSEA indicated that differentially expressed genes in disparate risk groups were enriched in several tumor-related pathways. At the same time, we found significant differences in some immune cells and chemotherapeutic agents between the two groups. An alternative lncRNA, CACNA1G-AS1, was proven to be upregulated in 30 OC specimens and 3 OC cell lines relative to control. Furthermore, knockdown of CACNA1G‐AS1 was proven to restrain the multiplication capacity of OC cells.

Conclusions

Based on the four LI-m6As (AC010894.3, ACAP2-IT1, CACNA1G-AS1, and UBA6-AS1), the risk model we identified can independently predict the OS and therapeutic value of OC. CACNA1G‐AS1 was preliminarily proved to be a malignant lncRNA.
High burden of anemia among pregnant women in Tanzania: a call to address its determinants
Authors: Sunguya Bruno F. , Ge Yue , Mlunde Linda , Mpembeni Rose , Leyna Germana , Huang Jiayan
Published: July 2021

Background

Anemia in pregnancy is behind a significant burden of maternal mortality and poor birth outcomes globally. Efforts to address it need evidence on trends and its pertinent factors as they vary from one area to another.

Methods

We pooled data of 23,203 women of reproductive age whose hemoglobin levels were measured from two Tanzania Demographic and Health Surveys (TDHS). Of them, 2,194 women were pregnant. Analyses employed descriptive analyses to determine the burden of anemia, its characteristics, and severity; GIS mapping to determine the regional changes of anemia between 2005 and 2015; and logistic regression to determine the remaining determinants of anemia among pregnant women using Stata 15.

Results

The burden of anemia among pregnant women in Tanzania has remained unprecedently high, and varies between regions. There was no significant decline of anemia in general between the two periods after adjusting for individual, households, reproductive, and child characteristics [AOR = 0.964, 95% CI = 0.774–1.202, p = 0.747). Anemia is currently prevalent in 57% of pregnant women in Tanzania. The prevalence is more likely to be higher among women aged 15–19 years than those aged between 20–34 years. It is more likely to be prevalent among those within large families, with no formal education, food insecurity, lack of health insurance, had no antimalaria during pregnancy, and had low frequency of ANC attendance. On the other hand, delivery in a health facility may be potentially protective against anemia.

Conclusions

Anemia in pregnancy remained persistently high and prevalent among 57% of pregnant women in Tanzania. Efforts to address anemia are crucial and need to be focused in regions with increasing burden of anemia among pregnant women. It is imperative to address important risk factors such as food insecurity, strengthening universal health coverage, empowering women of reproductive age with education and especially nutritional knowledge and advocating for early antenatal booking, attendance, and facility delivery.
Optimizing the maximum reported cluster size in the spatial scan statistic for survival data
Authors: Lee Sujee , Moon Jisu , Jung Inkyung
Published: July 2021

Background

The spatial scan statistic is a useful tool for cluster detection analysis in geographical disease surveillance. The method requires users to specify the maximum scanning window size or the maximum reported cluster size (MRCS), which is often set to 50% of the total population. It is important to optimize the maximum reported cluster size, keeping the maximum scanning window size at as large as 50% of the total population, to obtain valid and meaningful results.

Results

We developed a measure, a Gini coefficient, to optimize the maximum reported cluster size for the exponential-based spatial scan statistic. The simulation study showed that the proposed method mostly selected the optimal MRCS, similar to the true cluster size. The detection accuracy was higher for the best chosen MRCS than at the default setting. The application of the method to the Korea Community Health Survey data supported that the proposed method can optimize the MRCS in spatial cluster detection analysis for survival data.

Conclusions

Using the Gini coefficient in the exponential-based spatial scan statistic can be very helpful for reporting more refined and informative clusters for survival data.
Factors associated with opioid overdose during medication-assisted treatment: How can we identify individuals at risk?
Authors: Au Vivian Y. O. , Rosic Tea , Sanger Nitika , Hillmer Alannah , Chawar Caroul , Worster Andrew , Marsh David C. , Thabane Lehana , Samaan Zainab
Published: July 2021

Background

Due to the loss of tolerance to opioids during medication-assisted treatment (MAT), this period may represent a time of heightened risk for overdose. Identifying factors associated with increased risk of overdose during treatment is therefore paramount to improving outcomes. We aimed to determine the prevalence of opioid overdoses in patients receiving MAT. Additionally, we explored factors associated with opioid overdose during MAT and the association between length of time enrolled in MAT and overdose.

Methods

Data were collected prospectively from 2360 participants receiving outpatient MAT in Ontario, Canada. Participants were divided into three groups by overdose status: no history of overdose, any lifetime history of overdose, and emergency department visit for opioid overdose in the last year. We used a multivariate multinomial regression model to assess demographic and clinical factors associated with overdose status.

Results

Twenty-four percent of participants reported a lifetime history of overdose (n = 562), and 8% reported an emergency department (ED) visit for opioid overdose in the last year (n = 179). Individuals with a recent ED visit for opioid overdose were in treatment for shorter duration (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.87, 0.97,p = 0.001). Individuals with a lifetime or recent history of overdose were more likely to be younger in age (OR 0.93, 95% CI 0.89, 0.98,p = 0.007 and OR 0.84, 95% CI 0.77, 0.92,p < 0.001, respectively), report more physical symptoms (OR 1.02, 95% CI 1.01, 1.03,p = 0.005 and OR 1.03, 95% CI 1.01, 1.05,p = 0.005, respectively), and had higher rates of non-prescription benzodiazepine use (OR 1.87, 95% CI 1.32, 2.66,p < 0.001 and OR 2.34, 95% CI 1.43, 3.81,p = 0.001, respectively) compared to individuals with no history of overdose.

Conclusions

A considerable number of patients enrolled in MAT have experienced overdose. Our study highlights that there are identifiable factors associated with a patient’s overdose status that may represent areas for intervention. In particular, longer duration in MAT is associated with a decreased risk of overdose.
5-aza-2′-deoxycitidine inhibits cell proliferation, extracellular matrix formation and Wnt/β-catenin pathway in human uterine leiomyomas
Authors: Carbajo-García María Cristina , Corachán Ana , Segura-Benitez Marina , Monleón Javier , Escrig Julia , Faus Amparo , Pellicer Antonio , Cervelló Irene , Ferrero Hortensia
Published: July 2021

Background

Uterine leiomyoma is a benign tumor with unclear pathogenesis and inaccurate treatment. This tumor exhibits altered DNA methylation related to disease progression. DNMT inhibitors as 5-aza-2′-deoxycytidine (5-aza-CdR), have been suggested to treat tumors in which DNA methylation is altered. We aimed to evaluate whether DNA methylation reversion with 5-aza-CdR reduces cell proliferation and extracellular matrix (ECM) formation in uterine leiomyoma cells to provide a potential treatment option.

Methods

Prospective study using uterine leiomyoma and adjacent myometrium tissues and human uterine leiomyoma primary (HULP) cells (n = 16). In tissues, gene expression was analyzed by qRT-PCR and DNMT activity by ELISA. Effects of 5-aza-CdR treatment on HULP cells were assessed by CellTiter, western blot, and qRT-PCR.

Results

DNMT1 gene expression was higher in uterine leiomyoma vs myometrium. Similarly, DNMT activity was greater in uterine leiomyoma and HULP cells (6.5 vs 3.8 OD/h/mg; 211.3 vs 63.7 OD/h/mg, respectively). After 5-aza-CdR treatment on HULP cells, cell viability was reduced, significantly so at 10 μM (85.3%). Treatment with 10 μM 5-aza-CdR on HULP cells significantly decreased expression of proliferation marker PCNA (FC = 0.695) and of ECM proteins (COLLAGEN I FC = 0.654; PAI-1, FC = 0.654; FIBRONECTIN FC = 0.733). 5-aza-CdR treatment also decreased expression of Wnt/β-catenin pathway final targets, including WISP1 protein expression (10 μM, FC = 0.699), c-MYC gene expression (2 μM, FC = 0.745 and 10 μM, FC = 0.728), and MMP7 gene expression (5 μM, FC = 0.520 and 10 μM, FC = 0.577).

Conclusions

5-aza-CdR treatment inhibits cell proliferation, ECM formation, and Wnt/β-catenin signaling pathway targets in HULP cells, suggesting that DNA methylation inhibition is a viable therapeutic target in uterine leiomyoma.
Dissecting immune cell stat regulation network reveals biomarkers to predict ICB therapy responders in melanoma
Authors: Wang Jingwen , Li Feng , Xu Yanjun , Zheng Xuan , Zhang Chunlong , Hu Congxue , Xu Yingqi , Mi Wanqi , Li Xia , Zhang Yunpeng
Published: July 2021

Background

Immunotherapy is a revolutionary strategy in cancer therapy, but the resistance of which is one of the important challenges. Detecting the regulation of immune cells and biomarkers concerning immune checkpoint blockade (ICB) therapy is of great significance.

Methods

Here, we firstly constructed regulation networks for 11 immune cell clusters by integrating biological pathway data and single cell sequencing data in metastatic melanoma with or without ICB therapy. We then dissected these regulation networks and identified differently expressed genes between responders and non-responders. Finally, we trained and validated a logistic regression model based on ligands and receptors in the regulation network to predict ICB therapy response.

Results

We discovered the regulation of genes across eleven immune cell stats. Functional analysis indicated that these stat-specific networks consensually enriched in immune response corrected pathways and highlighted antigen processing and presentation as a core pathway in immune cell regulation. Furthermore, some famous ligands like SIRPA, ITGAM, CD247and receptors like CD14, IL2 and HLA-G were differently expressed between cells of responders and non-responders. A predictive model of gene sets containing ligands and receptors performed accuracy prediction with AUCs above 0.7 in a validation dataset suggesting that they may be server as biomarkers for predicting immunotherapy response.

Conclusions

In summary, our study presented the gene–gene regulation landscape across 11 immune cell clusters and analysis of these networks revealed several important aspects and immunotherapy response biomarkers, which may provide novel insights into immune related mechanisms and immunotherapy response prediction.
CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma
Authors: Zhao Haoqi , Wang Lan , Wang Shufang , Chen Xihua , Liang Min , Zhang Xin , Wang Jiedong , Xu Xiangbo
Published: July 2021

Background

Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified.

Methods

The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting.

Results

CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002.

Conclusion

These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.
APOE genotype dependent molecular abnormalities in the cerebrovasculature of Alzheimer’s disease and age-matched non-demented brains
Authors: Ojo Joseph O. , Reed Jon M. , Crynen Gogce , Vallabhaneni Prashanthi , Evans James , Shackleton Benjamin , Eisenbaum Maximillian , Ringland Charis , Edsell Anastasia , Mullan Michael , Crawford Fiona , Bachmeier Corbin
Published: July 2021

Cerebrovascular dysfunction is a hallmark feature of Alzheimer's disease (AD). One of the greatest risk factors for AD is the apolipoprotein E4 (E4) allele. The APOE4 genotype has been shown to negatively impact vascular amyloid clearance, however, its direct influence on the molecular integrity of the cerebrovasculature compared to other APOE variants (APOE2 and APOE3) has been largely unexplored. To address this, we employed a 10-plex tandem isobaric mass tag approach in combination with an ultra-high pressure liquid chromatography MS/MS (Q-Exactive) method, to interrogate unbiased proteomic changes in cerebrovessels from AD and healthy control brains with different APOE genotypes. We first interrogated changes between healthy control cases to identify underlying genotype specific effects in cerebrovessels. EIF2 signaling, regulation of eIF4 and 70S6K signaling and mTOR signaling were the top significantly altered pathways in E4/E4 compared to E3/E3 cases. Oxidative phosphorylation, EIF2 signaling and mitochondrial dysfunction were the top significant pathways in E2E2 vs E3/E3cases. We also identified AD-dependent changes and their interactions with APOE genotype and found the highest number of significant proteins from this interaction was observed in the E3/E4 (192) and E4/E4 (189) cases. As above, EIF2, mTOR signaling and eIF4 and 70S6K signaling were the top three significantly altered pathways in E4 allele carriers (i.e. E3/E4 and E4/E4 genotypes). Of all the cerebrovascular cell-type specific markers identified in our proteomic analyses, endothelial cell, astrocyte, and smooth muscle cell specific protein markers were significantly altered in E3/E4 cases, while endothelial cells and astrocyte specific protein markers were altered in E4/E4 cases. These proteomic changes provide novel insights into the longstanding link between APOE4 and cerebrovascular dysfunction, implicating a role for impaired autophagy, ER stress, and mitochondrial bioenergetics. These APOE4 dependent changes we identified could provide novel cerebrovascular targets for developing disease modifying strategies to mitigate the effects of APOE4 genotype on AD pathogenesis.
Giardia duodenalis extracellular vesicles regulate the proinflammatory immune response in mouse macrophages in vitro via the MAPK, AKT and NF-κB pathways
Authors: Zhao Panpan , Cao Lili , Wang Xiaocen , Li Jianhua , Dong Jingquan , Zhang Nan , Li Xin , Li Shan , Sun Min , Zhang Xichen , Liang Min , Pu Xudong , Gong Pengtao
Published: July 2021

Background

Giardia duodenalis is an extracellular protozoan parasite that causes giardiasis in mammals. The presentation of giardiasis ranges from asymptomatic to severe diarrhea, and the World Health Organization lists it in the Neglected Diseases Initiative. Extracellular vesicles (EVs) are a key mediator of intracellular communication. Although previous studies have shown that G. intestinalis can regulate a host’s innate immune response, the role of G. intestinalis EVs (GEVs) in triggering a G. intestinalis-induced innate immune response remains to be further explored.

Methods

In this study, GEVs, G. intestinalis and GEVs + G. intestinalis were inoculated into macrophages, respectively. The transcription and secretion levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α), were measured using real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs). The phosphorylation levels of the MAPK, AKT and NF-κB signaling pathways in GEV-stimulated mouse macrophages were examined using western blotting and immunofluorescence methods. The roles of activated pathways in the GEV-triggered inflammatory response were determined using inhibition assays, western blotting and ELISAs.

Results

The results showed that pretreatment with GEVs enhanced with G. intestinalis (GEVs + G. intestinalis) induced IL-1β, IL-6 and TNF-α transcription and secretion from mouse macrophages compared to stimulation with either GEVs or G. intestinalis alone. Inoculation of mouse macrophages with GEVs upregulated the phosphorylation levels of the p38 MAPK, p44/42 MAPK (Erk1/2), AKT and NF-κB signaling pathways and led to the nuclear translocation of NF-κB p65. Blocking the activated p38, Erk and NF-κB signaling pathways significantly downregulated the secretion of proinflammatory cytokines, and blocking the activated AKT signaling pathway demonstrated reverse effects.

Conclusions

The results of this study reveal that GEVs can enhance G. intestinalis-induced inflammatory response levels in mouse macrophages through activation of the p38, ERK and NF-κB signaling pathways. The role of GEVs in regulating host cell immune responses may provide insights into exploring the underlying mechanisms in G. intestinalis–host interactions.

Graphical abstract
Identification and prediction of difficult-to-treat rheumatoid arthritis patients in structured and unstructured routine care data: results from a hackathon
Authors: Messelink Marianne A. , Roodenrijs Nadia M. T. , van Es Bram , Hulsbergen-Veelken Cornelia A. R. , Jong Sebastiaan , Overmars L. Malin , Reteig Leon C. , Tan Sander C. , Tauber Tjebbe , van Laar Jacob M. , Welsing Paco M. J. , Haitjema Saskia
Published: July 2021

Background

The new concept of difficult-to-treat rheumatoid arthritis (D2T RA) refers to RA patients who remain symptomatic after several lines of treatment, resulting in a high patient and economic burden. During a hackathon, we aimed to identify and predict D2T RA patients in structured and unstructured routine care data.

Methods

Routine care data of 1873 RA patients were extracted from the Utrecht Patient Oriented Database. Data from a previous cross-sectional study, in which 152 RA patients were clinically classified as either D2T or non-D2T, served as a validation set. Machine learning techniques, text mining, and feature importance analyses were performed to identify and predict D2T RA patients based on structured and unstructured routine care data.

Results

We identified 123 potentially new D2T RA patients by applying the D2T RA definition in structured and unstructured routine care data. Additionally, we developed a D2T RA identification model derived from a feature importance analysis of all available structured data (AUC-ROC 0.88 (95% CI 0.82–0.94)), and we demonstrated the potential of longitudinal hematological data to differentiate D2T from non-D2T RA patients using supervised dimension reduction. Lastly, using data up to the time of starting the first biological treatment, we predicted future development of D2TRA (AUC-ROC 0.73 (95% CI 0.71–0.75)).

Conclusions

During this hackathon, we have demonstrated the potential of different techniques for the identification and prediction of D2T RA patients in structured as well as unstructured routine care data. The results are promising and should be optimized and validated in future research.
Switching from TNFα inhibitor to tacrolimus as maintenance therapy in rheumatoid arthritis after achieving low disease activity with TNFα inhibitors and methotrexate: 24-week result from a non-randomized, prospective, active-controlled trial
Authors: Jung Sang Youn , Koh Jung Hee , Kim Ki-Jo , Park Yong-Wook , Yang Hyung-In , Choi Sung Jae , Lee Jisoo , Choi Chan-Bum , Kim Wan-Uk
Published: July 2021

Background

Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX).

Methods

This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period.

Results

In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01–1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated.

Conclusion

This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks.

Trial registration

Korea CDC CRIS, KCT0005868. Registered 4 February 2021—retrospectively registered
Autoimmune pulmonary alveolar proteinosis successfully treated with lung lavage in an adolescent patient: a case report
Authors: Alasiri Abdalla Mohmed , Alasbali Reem Abdullah , Alaqil Meaad Ali , Alahmari Aishah Marei , Alshamrani Nouf Dagash , Badri Rabab Nasir
Published: July 2021

Background

Pulmonary alveolar proteinosis is a rare interstitial lung disease characterized by accumulating surfactant materials in the alveoli. The autoimmune form is by far the most common in adults, while in the pediatric age group, the vast majority of cases are congenital. We report a case of an adolescent patient diagnosed with autoimmune pulmonary alveolar proteinosis, which is unusual in this age group.

Case presentation

A-15 year-old Saudi male presented to the emergency department with a history of shortness of breath and low oxygen saturation. High-resolution computed tomography of his chest showed a global crazy-paving pattern. Autoantibodies against granulocyte-macrophage colony-stimulating factor were detected in his serum. A diagnosis of the autoimmune form of pulmonary alveolar proteinosis was confirmed after excluding other possible causes. The patient improved after he underwent whole lung lavage under general anesthesia, and he was independent of oxygen therapy after 6 months of follow-up.

Conclusion

The autoimmune form of pulmonary alveolar proteinosis is rare in the pediatric age group and should be considered when no apparent cause of this disease was found. Whole lung lavage should be the first treatment modality offered in this setting with close follow-up and monitoring.
Timestamp-aligning and keyword-biasing end-to-end ASR front-end for a KWS system
Authors: Shi Gui-Xin , Zhang Wei-Qiang , Wang Guan-Bo , Zhao Jing , Chai Shu-Zhou , Zhao Ze-Yu
Published: July 2021

Many end-to-end approaches have been proposed to detect predefined keywords. For scenarios of multi-keywords, there are still two bottlenecks that need to be resolved: (1) the distribution of important data that contains keyword(s) is sparse, and (2) the timestamps of the detected keywords are inaccurate. In this paper, to alleviate the first issue and further improve the performance of the end-to-end ASR front-end, we propose the biased loss function for guiding the recognizer to pay more attention to the speech segments containing the predefined keywords. As for the second issue, we solve this problem by modifying the force alignment applied to the end-to-end ASR front-end. To get the frame-level alignment, we utilize a Gaussian Mixture Model-Hidden Markov Model (GMM-HMM) based acoustic model (AM) for auxiliary. The proposed system is evaluated in the OpenSAT20 held by the National Institute of Standards and Technology (NIST). The performance of our end-to-end KWS system is comparable to the conventional hybrid KWS system, sometimes even slightly better. With fusion results of the end-to-end and conventional KWS systems, we won the first prize in the KWS track. On the dev dataset (a part of SAFE-T corpus), the system outperforms the baseline by a large margin, i.e., our system with GMM-HMM aligner has a lower segmentation-aware word error rates (relatively 7.9–19.2% decrease) and higher overall Actual term-weighted values (relatively 3.6–11.0% increase), which demonstrates the effectiveness of the proposed method. For more precise alignments, we can use DNN-based AM as alignmentor at the cost of more computation.
Lie symmetry and μ-symmetry methods for nonlinear generalized Camassa–Holm equation
Authors: Jafari H. , Goodarzi K. , Khorshidi M. , Parvaneh V. , Hammouch Z.
Published: July 2021

In this paper, a Lie symmetry method is used for the nonlinear generalized Camassa–Holm equation and as a result reduction of the order and computing the conservation laws are presented. Furthermore,μ-symmetry andμ-conservation laws of the generalized Camassa–Holm equation are obtained.
TMEM263: a novel candidate gene implicated in human autosomal recessive severe lethal skeletal dysplasia
Authors: Mohajeri Mahsa Sadat Asl , Eslahi Atieh , Khazaii Zeinab , Moradi Mohammad Reza , Pazhoomand Reza , Farrokhi Shima , Feizabadi Masoumeh Heidari , Alizadeh Farzaneh , Mojarrad Majid
Published: July 2021

Introduction

Skeletal dysplasia is a common, clinically and genetically heterogeneous disorder in the human population. An increasing number of different genes are being identified causing this disorder. We used whole exome sequencing (WES) for detection of skeletal dysplasia causing mutation in a fetus affected to severe lethal skeletal dysplasia.

Patient

Fetus was assessed by ultrasonography in second trimester of pregnancy. He suffers from severe rhizomelic dysplasia and also pathologic shortening of ribs. WES was applied to finding of causal mutation. Furthermore, bioinformatics analysis was performed to predict mutation impact.

Results

Whole exome sequencing (WES) identified a homozygous frameshift mutation in the TMEM263 gene in a fetus with severe lethal skeletal dysplasia. Mutations of this gene have been previously identified in dwarf chickens, but this is the first report of involvement of this gene in human skeletal dysplasia. This gene plays a key role in the growth hormone signaling pathway.

Conclusion

TMEM263 can be considered as a new gene responsible for skeletal dysplasia. Given the complications observed in the affected fetus, the mutation of this gene appears to produce much more intense complications than that found in chickens and is likely to play a more important role in bone development in human.
Rapid standardized operating rooms (RAPSTOR) in thyroid and parathyroid surgery
Authors: Ernst Hannah , Sowerby Leigh , Sahovaler Axel , Macneil Danielle , Nichols Anthony , Yoo John , Hilsden Richard , Strychowsky Julie , Fung Kevin
Published: July 2021

Objective

To evaluate the impact of a high efficiency rapid standardized OR (RAPSTOR) for hemithyroid/parathyroid surgery using standardized equipment sets (SES) and consecutive case scheduling (CCS) on turnover times (TOT), average case volumes, patient outcomes, hospital costs and OR efficiency/stress.

Methods

Patients requiring hemithyroidectomy (primary or completion) or unilateral parathyroidectomy in a single surgeon's practice were scheduled consecutively with SES. Retrospective control groups were classified as sequential (CS) or non-sequential (CNS). A survey regarding OR efficiency/stress was administered. Phenomenography and descriptive statistics were conducted for time points, cost and patient outcome variables. Hospital cost minimization analysis was performed.

Results

The mean TOT of RAPSTOR procedures (16 min; n = 27) was not significantly different than CS (14 min, n = 14) or CNS (17 min, n = 6). Mean case number per hour was significantly increased in RAPSTOR (1.2) compared to both CS (0.9; p < 0.05) and CNS (0.7; p < 0.05). Average operative time was significantly reduced in RAPSTOR (32 min; n = 28) compared to CNS (48 min; p < 0.05) but not CS (33 min; p = 0.06). Time to discharge was reduced in RAPSTOR (595 min) compared to CNS (1210 min, p < 0.05). There was no difference in complication rate between all groups ( p = 0.27). Survey responses suggested improved efficiency, teamwork and workflow. Furthermore, there is associated decrease in direct operative costs for RAPSTOR vs. CS.

Conclusion

A high efficiency standardized OR for hemithyroid and parathyroid surgery using SES and CCS is associated with improved efficiency and, in this study, led to increased capacity at reduced cost without compromising patient safety.

Level of evidence

Level 2.

Graphical Abstract