bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association study reveals the genetic architecture for calcium accumulation in grains of hexaploid wheat (Triticum aestivum L.)
Authors: Shi Xia , Zhou Zhengfu , Li Wenxu , Qin Maomao , Yang Pan , Hou Jinna , Huang Fangfang , Lei Zhensheng , Wu Zhengqing , Wang Jiansheng
Published: May 2022

Background

Hexaploid wheat (Triticum aestivum L.) is a leading cereal crop worldwide. Understanding the mechanism of calcium (Ca) accumulation in wheat is important to reduce the risk of human micronutrient deficiencies. However, the mechanisms of Ca accumulation in wheat grain are only partly understood.

Results

Here, a genome-wide association study (GWAS) was performed to dissect the genetic basis of Ca accumulation in wheat grain using an association population consisting of 207 varieties, with phenotypic data from three locations. In total, 11 non-redundant genetic loci associated with Ca concentration were identified and they explained, on average, 9.61–26.93% of the phenotypic variation. Cultivars containing more superior alleles had increased grain Ca concentrations. Notably, four non-redundant loci were mutually verified by different statistical models in at least two environments, indicating their stability across different environments. Four putative candidate genes linked to Ca accumulation were revealed from the stable genetic loci. Among them, two genes, associated with the stable genetic loci on chromosomes 4A (AX-108912427) and 3B (AX-110922471), encode the subunits of V-type Proton ATPase (TraesCS4A02G428900 and TraesCS3B02G241000), which annotated as the typical generators of a proton gradient that might be involved in Ca homeostasis in wheat grain.

Conclusion

To identify genetic loci associated with Ca accumulation, we conducted GWAS on Ca concentrations and detected 11 genetic loci; whereas four genetic loci were stable across different environments. A genetic loci hot spot exists at the end of chromosome 4A and associated with the putative candidate gene TraesCS4A02G428900. The candidate gene TraesCS4A02G428900 encodes V-type proton ATPase subunit e and highly expressed in wheat grains, and it possibly involved in Ca accumulation. This study increases our understanding of the genetic architecture of Ca accumulation in wheat grains, which is potentially helpful for wheat Ca biofortification pyramid breeding.
Efficacy of using tidal volume challenge to improve the reliability of pulse pressure variation reduced in low tidal volume ventilated critically ill patients with decreased respiratory system compliance
Authors: Xu Yujun , Guo Jun , Wu Qin , Chen Junjun
Published: May 2022

Background

The prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was proposed to be unreliable in low tidal volume (Vt) ventilation. It was suggested that changes in PPV obtained by transiently increasing Vt to 8 ml/kg accurately predicted fluid responsiveness even in subjects receiving low Vt. We assessed whether the changes in PPV induced by a Vt challenge predicted fluid responsiveness in our critically ill subjects ventilated with low Vt 6 ml/kg.

Methods

This study is a prospective single-center study. PPV and other parameters were measured at a Vt of 6 mL/kg, 8 mL/kg, and after volume expansion. The prediction accuracy of PPV and other parameters for fluid responsiveness before and after tidal volume challenge was also analyzed using receiver operating characteristic (ROC) curves.

Results

Thirty-one of the 76 subjects enrolled in the study were responders (41%). Respiratory system compliance of all subjects decreased significantly (26 ± 4.3). The PPV values were significantly higher in the responder group than the non-responder group before (8.8 ± 2.7 vs 6.8 ± 3.1) or after (13.0 ± 1.7 vs 8.5 ± 3.0) Vt challenge. In the receiver operating characteristic curve (ROC) analysis, PPV6 showed unsatisfactory predictive capability with an area under the curve (AUC) of 0.69 (95%CI, 0.57–0.79, p = 0.002) at a Vt of 6 mL/kg. PPV8 andΔPPV6–8 showed good predictive capability with an AUC of 0.90 (95% CI, 0.81–0.96, p < 0.001) and 0.90 (95% CI, 0.80–0.95, P < 0.001) respectively. The corresponding cutoff values were 11% for PPV8 and 2% for ΔPPV6–8.

Conclusions

PPV shows a poor operative performance as a predictor of fluid responsiveness in critically ill subjects ventilated with a tidal volume of 6 mL/ kg. Vt challenge could improve the predictive accuracy of PPV to a good but not excellent extent when respiratory system compliance decreased significantly.
Gitelman syndrome with normocalciuria – a case report
Authors: Flisiński Mariusz , Skalska Ewa , Mączyńska Barbara , Butt-Hussaim Natalia , Sobczyńska-Tomaszewska Agnieszka , Haus Olga , Manitius Jacek
Published: May 2022

Background

Gitelman Syndrome (GS) is a hereditary tubulopathy associated with a biallelic inactivating mutations of the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT). The typical clinical manifestation is a hypokalemic metabolic alkalosis with significant hypomagnesemia, and low urinary calcium excretion. Hypocalciuria is widely believed to be a hallmark of GS that distinguishes it from Barter’s syndrome, presenting as hypercalciuria. The pathomechanism of hypocalciuria in GS is not fully elucidated. Up to date, a clinical course of GS with normocalciuria has been reported only in men, while women have a milder course of the disease with typical hypocalciuria, which is believed as the result of sex hormone. Additionally, there is a growing evidence that calcium channels of the distal nephron could be regulated by a variety of hormones, including aldosterone (Aldo).

Case presentation

We present the case of a 28-year-old Caucasian woman with asymptomatic, chronic hypokalemia, hypomagnesemia, hypochloremic alkalosis and normal urinary calcium excretion. A high renin levels with normal concentration of Aldo in serum have also been found. The values of blood pressure were low. Based on genetic studies, two heterozygous mutations in the trans position were confirmed: c.2186G>T (p.Gly729Val) and c.1247G>C (p.Cys416Ser) in the SLC12A3 gene, which ultimately confirmed the diagnosis of GS.

Conclusions

We report here the first case of genetically confirmed GS manifested as normocalciuria in a Caucasian woman. Thus, our result does not confirm a role of sex hormones on the level of calciuria. Based on the results of normal Aldo concentration despite high renin level in our patient, we hypothesized that Aldo may be connecting with the level of urinary calcium excretion in patients with the GS.
Application of machine learning methods for predicting infant mortality in Rwanda: analysis of Rwanda demographic health survey 2014–15 dataset
Authors: Mfateneza Emmanuel , Rutayisire Pierre Claver , Biracyaza Emmanuel , Musafiri Sanctus , Mpabuka Willy Gasafari
Published: May 2022

Background

Extensive research on infant mortality (IM) exists in developing countries; however, most of the methods applied thus far relied on conventional regression analyses with limited prediction capability. Advanced of Machine Learning (AML) methods provide accurate prediction of IM; however, there is no study conducted using ML methods in Rwanda. This study, therefore, applied Machine Learning Methods for predicting infant mortality in Rwanda. 

Methods

A cross-sectional study design was conducted using the 2014–15 Rwanda Demographic and Health Survey. Python software version 3.8 was employed to test and apply ML methods through Random Forest (RF), Decision Tree, Support Vector Machine and Logistic regression. STATA version 13 was used for analysing conventional methods. Evaluation metrics methods specifically confusion matrix, accuracy, precision, recall, F1 score, and Area under the Receiver Operating Characteristics (AUROC) were used to evaluate the performance of predictive models.

Results

Ability of prediction was between 68.6% and 61.5% for AML. We preferred with the RF model (61.5%) presenting the best performance. The RF model was the best predictive model of IM with accuracy (84.3%), recall (91.3%), precision (80.3%), F1 score (85.5%), and AUROC (84.2%); followed by decision tree model with model accuracy (83%), recall (91%), precision (79%), F1 score (84.67%) and AUROC(82.9%), followed by support vector machine with model accuracy (68.6%), recall (74.9%), precision(67%), F1 score (70.73%) and AUROC (68.6%) and last was a logistic regression with the low accuracy of prediction (61.5%), recall (61.1%), precision (62.2%), F1 score (61.6%) and AUROC (61.5%) compared to other predictive models. Our predictive models showed that marital status, children ever born, birth order and wealth index are the 4 top predictors of IM.

Conclusions

In developing a predictive model, ML methods are used to classify certain hidden information that could not be detected by traditional statistical methods. Random Forest was classified as the best classifier to be used for the predictive models of IM.
An analysis of age-standardized suicide rates in Muslim-majority countries in 2000-2019
Authors: Lew Bob , Lester David , Kõlves Kairi , Yip Paul S. F. , Chen Ying-Yeh , Chen Won Sun , Hasan M. Tasdik , Koenig Harold G. , Wang Zhi Zhong , Fariduddin Muhamad Nur , Zeyrek-Rios Emek Yuce , Chan Caryn Mei Hsien , Mustapha Feisul , Fitriana Mimi , Dolo Housseini , Gönültaş Burak M. , Dadfar Mahboubeh , Davoudi Mojtaba , Abdel-Khalek Ahmed M. , Chan Lai Fong , Siau Ching Sin , Ibrahim Norhayati
Published: May 2022

Background

This study examines the 20-year trend of suicide in 46 Muslim-majority countries throughout the world and compares their suicide rates and trends with the global average. Ecological-level associations between the proportion of the Muslim population, the age-standardized suicide rates, male-to-female suicide rate ratio, and the Human Development Index (HDI) in 2019 were examined.

Methods

Age-standardized suicide rates were extracted from the WHO Global Health Estimates database for the period between 2000 and 2019. The rates in each country were compared with the age-standardized global average during the past 20 years. The countries were further grouped according to their regions/sub-regions to calculate the regional and sub-regional weighted age-standardized suicide rates involving Muslim-majority countries. Correlation analyses were conducted between the proportion of Muslims, age-standardized suicide rate, male: female suicide rate ratio, and the HDI in all countries. Joinpoint regression was used to analyze the age-standardized suicide rates in 2000-2019.

Results

The 46 countries retained for analysis included an estimated 1.39 billion Muslims from a total worldwide Muslim population of 1.57 billion. Of these countries, eleven (23.9%) had an age-standardized suicide rate above the global average in 2019. In terms of regional/sub-regional suicide rates, Muslim-majority countries in the Sub-Saharan region recorded the highest weighted average age-standardized suicide rate of 10.02/100,000 population, and Southeastern Asia recorded the lowest rate (2.58/100,000 population). There were significant correlations between the Muslim population proportion and male-to-female rate ratios (r=-0.324, p=0.028), HDI index and age-standardized suicide rates (r=-0.506, p<0.001), and HDI index and male-to-female rate ratios (r=0.503, p<0.001) in 2019. Joinpoint analysis revealed that seven Muslim-majority countries (15.2%) recorded an increase in the average annual percentage change regarding age-standardized suicide rates during 2000-2019.

Conclusions

Most Muslim-majority countries had lower age-standardized suicide rates than the global average, which might reflect religious belief and practice or due to Muslim laws in their judicial and social structure which may lead to underreporting. This finding needs further in-depth country and region-specific study with regard to its implication for public policy.
United for health to improve urban food environments across five underserved communities: a cross-sector coalition approach
Authors: Payán Denise D. , Lewis LaVonna B. , Illum Jacqueline , Hawkins Breanna , Sloane David C.
Published: May 2022

Background

Cross-sector coalitions can be a powerful vehicle to promote adoption and implementation of evidence-based programs and policies across diverse racial/ethnic communities with a high chronic disease burden. Few studies have examined coalition composition, function, or capacity to promote learning among members.

Methods

We used a mixed methods approach to examine the United for Health coalition’s implementation of multiple food environment interventions across five low-income communities of color in Los Angeles, California (USA). At the coalition-level, key measures included the collaborative environment, membership characteristics, process and structure, communication, resources, strengths, challenges/barriers, and community impact. At the organizational- and individual-levels, we collected data on participation, leadership development, intraorganizational change, perceived benefits, and learning outcomes.

Findings

Overall, the United for Health coalition produced five community gardens, three pop-up produce markets, and one farmers’ market; members also expanded Electronic Benefits Transfer (EBT) access at three existing farmers’ markets. Findings indicate early coalition strengths included having a mutual purpose, which was maintained throughout the study period. Coalition participation and engagement was consistently high, while coalition and inter-organizational communication improved over time. Strengths were membership diversity and the availability of learning opportunities. Benefits included leadership development and strategic alignment across organizations. Members demonstrated an increased awareness of the importance of culturally adapted interventions and knowledge of community health planning topics. Key implementation challenges were a lack of resources and social context barriers.

Conclusions

Examining coalition function and maturation in a real-world context reveals important lessons for scholars and practitioners committed to addressing nutrition-related health disparities in marginalized and historically underserved communities. Future work should investigate the sustainability of externally funded cross-sector coalitions after funding ceases.
Bereaved parents’ perspectives on their child’s end-of-life care: connecting a self-report questionnaire and interview data from the nationwide Paediatric End-of-LIfe CAre Needs in Switzerland (PELICAN) study
Authors: Zimmermann Karin , Marfurt-Russenberger Katrin , Cignacco Eva , Bergstraesser Eva
Published: May 2022

Background

Paediatric Palliative Care (PPC) focuses on ensuring the best possible quality of life for the child and his/her family by extending beyond the physical domain into psychosocial and spiritual wellbeing. A deep understanding of what is important to parents is crucial in guiding the further evaluation and improvement of PPC and end-of-life (EOL) care services. Much can be learned from specific positive and negative experiences of bereaved parents with the EOL care of their child. This report builds upon a questionnaire survey as part of the national Paediatric End-of-LIfe CAre Needs in Switzerland (PELICAN) study.

Methods

One part of the PELICAN study was set up to assess and explore the parental perspectives on their child’s EOL care. Interview data were used to explain the extremely positive and negative results of a quantitative survey in an explanatory sequential mixed-methods approach. Data integration occurred at different points: during sampling of the interview participants, when designing the interview guide and during analysis. A narrative approach was applied to combine the qualitative results reported here with the already published quantitative survey results.

Results

Eighteen mothers (60%) and twelve fathers (40%) participated in 20 family interviews. All parents reported having both positive and negative experiences during their child’s illness and EOL, which was characterised by many ups and downs. The families transitioned through phases with a prospect of a cure for some children as well as setbacks and changing health status of the child which influenced prognosis, leading to the challenge of making extremely difficult decisions. Severely negative experiences still haunted and bothered the parents at the time when the interview took place.

Conclusions

A deep understanding of the perspectives and needs of parents going through the devastating event of losing a child is important and a prerequisite to providing compassionate care. This complex care needs to recognise and respond to the suffering not only of the child but of the parents and the whole family. Communication and shared decision-making remain pivotal, as do still improvable elements of care that should build on trustful relationships between families and healthcare professionals.
Ursolic acid-enriched kudingcha extract enhances the antitumor activity of bacteria-mediated cancer immunotherapy
Authors: Xu Haixia , Piao Linghua , Liu Xiande , Jiang Sheng-nan
Published: May 2022

Background

Bacteria-mediated cancer immunotherapy (BCI) robustly stimulates the immune system and represses angiogenesis, but tumor recurrence and metastasis commonly occur after BCI. The natural product Ilex kudingcha C. J Tseng enriched with ursolic acid has anti-cancer activity and could potentially augment the therapeutic effects of BCI. The objective of the present study was to determine potential additive effects of these modalities.

Methods

We investigated the anti-cancer activity of KDCE (Kudingcha extract) combined with S.t△ppGpp in the mice colon cancer models.

Results

In the present study, KDCE combined with S.t△ppGpp BCI improved antitumor therapeutic efficacy compared to S.t△ppGpp or KDCE alone. KDCE did not prolong bacterial tumor-colonizing time, but enhanced the antiangiogenic effect of S.t△ppGpp by downregulatingVEGFR2. We speculated that KDCE-induced VEGFR2 downregulation is associated with FAK/MMP9/STAT3 axis but not AKT or ERK.

Conclusions

Ursolic acid-enriched KDCE enhances the antitumor activity of BCI, which could be mediated by VEGFR2 downregulation and subsequent suppression of angiogenesis. Therefore, combination therapy with S.t△ppGpp and KDCE is a potential cancer therapeutic strategy.
Fusing pre-trained convolutional neural networks features for multi-differentiated subtypes of liver cancer on histopathological images
Authors: Dong Xiaogang , Li Min , Zhou Panyun , Deng Xin , Li Siyu , Zhao Xingyue , Wu Yi , Qin Jiwei , Guo Wenjia
Published: May 2022

Liver cancer is a malignant tumor with high morbidity and mortality, which has a tremendous negative impact on human survival. However, it is a challenging task to recognize tens of thousands of histopathological images of liver cancer by naked eye, which poses numerous challenges to inexperienced clinicians. In addition, factors such as long time-consuming, tedious work and huge number of images impose a great burden on clinical diagnosis. Therefore, our study combines convolutional neural networks with histopathology images and adopts a feature fusion approach to help clinicians efficiently discriminate the differentiation types of primary hepatocellular carcinoma histopathology images, thus improving their diagnostic efficiency and relieving their work pressure. In this study, for the first time, 73 patients with different differentiation types of primary liver cancer tumors were classified. We performed an adequate classification evaluation of liver cancer differentiation types using four pre-trained deep convolutional neural networks and nine different machine learning (ML) classifiers on a dataset of liver cancer histopathology images with multiple differentiation types. And the test set accuracy, validation set accuracy, running time with different strategies, precision, recall and F1 value were used for adequate comparative evaluation. Proved by experimental results, fusion networks (FuNet) structure is a good choice, which covers both channel attention and spatial attention, and suppresses channel interference with less information. Meanwhile, it can clarify the importance of each spatial location by learning the weights of different locations in space, then apply it to the study of classification of multi-differentiated types of liver cancer. In addition, in most cases, the Stacking-based integrated learning classifier outperforms other ML classifiers in the classification task of multi-differentiation types of liver cancer with the FuNet fusion strategy after dimensionality reduction of the fused features by principle component analysis (PCA) features, and a satisfactory result of 72.46% is achieved in the test set, which has certain practicality.
The role of retinoid-related orphan receptor-α in cigarette smoke-induced autophagic response
Authors: Kim Hak-Su , An Chang Hyeok , Teller Danielle , Moon Su-Jin , Hwang Gi Won , Song Jin Woo
Published: May 2022

Background

Retinoid-related orphan receptor-α (RORα) and autophagy dysregulation are involved in the pathophysiology of chronic obstructive pulmonary disease (COPD), but little is known regarding their association. We investigated the role of RORα in COPD-related autophagy.

Methods

The lung tissues and cells from a mouse model were analyzed for autophagy markers by using western blot analysis and transmission electron microscopy.

Results

Cigarette smoke increased the LC3-II level and decreased the p62 level in whole lung homogenates of a chronic cigarette smoking mouse model. Although cigarette smoke did not affect the levels of p62 in Staggerer mutant mice (RORαsg/sg), the baseline expression levels of p62 were significantly higher than those in wild type (WT) mice. Autophagy was induced by cigarette smoke extract (CSE) in Beas-2B cells and in primary fibroblasts from WT mice. In contrast, fibroblasts from RORαsg/sg mice failed to show CSE-induced autophagy and exhibited fewer autophagosomes, lower LC3-II levels, and higher p62 levels than fibroblasts from WT mice. Damage-regulated autophagy modulator (DRAM), a p53-induced modulator of autophagy, was expressed at significantly lower levels in the fibroblasts from RORαsg/sg mice than in those from WT mice. DRAM knockdown using siRNA in Beas-2B cells inhibited CSE-induced autophagy and cell death. Furthermore, RORα co-immunoprecipitated with p53 and the interaction increased p53 reporter gene activity.

Conclusions

Our findings suggest that RORα promotes autophagy and contributes to COPD pathogenesis via regulation of the RORα-p53-DRAM pathway.
Harm reduction calls to action from young people who use drugs on the streets of Vancouver and Lisbon
Authors: Canêdo Joana , Sedgemore Kali-olt , Ebbert Kelly , Anderson Haleigh , Dykeman Rainbow , Kincaid Katey , Dias Claudia , Silva Diana ,   Youth Health Advisory Council, Charlesworth Reith , Knight Rod , Fast Danya
Published: May 2022

Vancouver, Canada, and Lisbon, Portugal, are both celebrated for their world-leading harm reduction policies and programs and regarded as models for other cities contending with the effects of increasing levels of drug use in the context of growing urban poverty. However, we challenge the notion that internationally celebrated places like Lisbon and Vancouver are meeting the harm reduction needs of young people who use drugs (YPWUD; referring here to individuals between the ages of 14 and 29). In particular, the needs of YPWUD in the context of unstable housing, homelessness, and ongoing poverty—a context which we summarize here as “street involvement”—are not being adequately met. We are a group of community and academic researchers and activists working in Vancouver, Lisbon, and Pittsburgh. Most of us identify as YPWUD and have lived and living experience with the issues described in this comment. We make several calls to action to support the harm reduction needs of YPWUD in the context of street involvement in and beyond our settings.
Surgical resection for esophageal adenosquamous carcinoma: an analysis of 56 cases
Authors: Chen Shao-bin , Liu Di-tian , Chen Yu-ping
Published: May 2022

Background

Esophageal adenosquamous carcinoma (EASC) is a rare disease. The biological behavior and treatment of this malignancy are not well studied.

Methods

Data from 56 patients with EASC who underwent esophagectomy were retrospectively analyzed and compared with 5028 patients with esophageal squamous cell carcinoma (ESCC). The impact of clinicopathological factors on the survival of patients with EASC was analyzed. The survival differences between patients with EASC and ESCC were also compared.

Results

There were 43 males and 13 females with a mean age of 59.7 ± 1.3 years (range, 39–79 years). Only 1 of the 43 patients who received preoperative esophagoscopic biopsy was diagnosed with EASC. The median survival time for patients with EASC was 32.0 months, and the 1-, 3-, and 5-year overall survival rates were 78.3%, 46.1%, and 29.6%, respectively. Resection margin, pN category, and adjuvant chemotherapy were found to be independent predictors. After 1:1 propensity score matching, the 5-year overall survival rate of 29.6% for patients with EASC was similar to that of 42.5% for patients with ESCC (P = 0.179).

Conclusions

EASC is a rare disease and is easily misdiagnosed by esophagoscopic biopsy. The prognosis of EASC was similar to that of ESCC. Postoperative adjuvant chemotherapy may improve the survival of patients with EASC after esophagectomy.
Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid arthritis by bioinformatics analysis
Authors: Wang Jiaqian , Xue Yuan , Zhou Liang
Published: May 2022

Background

Spondyloarthritis (SpA) and rheumatoid arthritis (RA) are chronic autoimmune diseases, but they are usually difficult to distinguish in the early stage of the diseases. The purpose of this study is to explore the differences of immune mechanism and diagnostic markers through bioinformatics analysis.

Methods

First, microarray datasets from patients with SpA, RA and normal controls were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between groups were identified in R software. Functional and pathway enrichment of DEGs were analyzed by David database. Then, we screened the hub genes using Cytoscape plugin, and constructed the protein–protein interaction (PPI) network and heatmap of hub genes. After that, CIBERSORT was used to evaluate the differences and connections of immune cells in SpA and RA, and screened out diagnostic markers. Correlation analysis was used to analyze the relationship between immune cells and diagnostic markers. Finally, quantitative real-time polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of immunodiagnostic markers.

Results

We obtained three datasets, from which we can see that the functional enrichment of DEGs is mainly in cell chemotaxis, lymphocyte activation, primary immunodeficiency and other immune responses. The difference of immune cells between SpA, RA and normal control was concentrated in B, T lymphocytes cells, macrophages and dendritic cells. C19orf12 + S1PR3 is most associated with these immune cells and S1PR3 can be used as a diagnostic marker of this kind of immune diseases. In addition, MZB1 + XIST is closely related to T cells, NK cells and dendritic cells, and is expected to be used as a marker to distinguish the two diseases.

Conclusion

Although the clinical manifestations of SpA and RA are similar, the pathogenesis is different. The screening of immune cells and diagnostic markers provides a more accurate target for the treatment of this kind of diseases.
Single-cell N6-methyladenosine regulator patterns guide intercellular communication of tumor microenvironment that contribute to colorectal cancer progression and immunotherapy
Authors: Gao Yuzhen , Wang Hao , Chen Shipeng , An Rui , Chu Yadong , Li Guoli , Wang Yanzhong , Xie Xinyou , Zhang Jun
Published: May 2022

Background

N6-methyladenosine (m6A) RNA methylation plays a critical role in key genetic events for various cancers; yet, how m6A functions within the tumor microenvironment (TME) remains to be elucidated.

Methods

A total of 65,362 single cells from single-cell RNA-seq data derived from 33 CRC tumor samples were analyzed by nonnegative matrix factorization (NMF) for 23 m6A RNA methylation regulators. CRC and Immunotherapy cohorts from public repository were used to determine the prognosis and immune response of TME clusters.

Results

The fibroblasts, macrophages, T and B cells were respectively grouped into 4 to 5 subclusters and then classified according to various biological processes and different marker genes. Furthermore, it revealed that the m6A RNA methylation regulators might be significantly related to the clinical and biological features of CRC, as well as the pseudotime trajectories of main TME cell types. Bulk-seq analysis suggested that these m6A-mediated TME cell subclusters had significant prognostic value for CRC patients and distinguished immune response for patients who underwent ICB therapy, especially for the CAFs and macrophages. Notably, CellChat analysis revealed that RNA m6A methylation-associated cell subtypes of TME cells manifested diverse and extensive interaction with tumor epithelial cells. Further analysis showed that ligand-receptor pairs, including MIF −  (CD74 + CXCR4), MIF −  (CD74 + CD44), MDK–NCL and LGALS9 − CD45, etc. mediated the communication between m6A associated subtypes of TME cells and tumor epithelial cells.

Conclusions

Taken together, our study firstly revealed the m6A methylation mediated intercellular communication of the tumor microenvironment in the regulation of tumor growth and antitumor immunomodulatory processes.
CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling
Authors: Zhu Lili , Yang Xiaobei , Feng Jingyu , Mao Jian , Zhang Qidong , He Mengru , Mi Yang , Mei Yingwu , Jin Ge , Zhang Haifeng
Published: May 2022

Objective

Knowledge of the role of CYP2E1 in hepatocarcinogenesis is largely based on epidemiological and animal studies, with a primary focus on the role of CYP2E1 in metabolic activation of procarcinogens. Few studies have directly assessed the effects of CYP2E1 on HCC malignant phenotypes.

Methods

The expression of CYP2E1 in HCC tissues was determined by qRT-PCR, western blotting and immunohistochemistry. Overexpression of CYP2E1 in HCC cell was achieved by lentivirus transfection. The function of CYP2E1 were detected by CCK-8, wound healing, transwell assays, xenograft models and pulmonary metastasis model. TOP/FOPFlash reporter assay, western blotting, functional rescue experiments, Co-immunoprecipitation and reactive oxygen species detection were conducted to reveal the underlying mechanism of the tumor suppressive role of CYP2E1.

Results

CYP2E1 expression is down-regulated in HCC tissues, and this downregulation was associated with large tumor diameter, vascular invasion, poor differentiation, and shortened patient survival time. Ectopic expression of CYP2E1 inhibits the proliferation, invasion and migration and epithelial-to-mesenchymal transition of HCC cells in vitro, and inhibits tumor formation and lung metastasis in nude mice. Mechanistic investigations show that CYP2E1 overexpression significantly inhibited Wnt/β-catenin signaling activity and decreased Dvl2 expression in HCC cells. An increase in Dvl2 expression restored the malignant phenotype of HCC cells. Notably, CYP2E1 promoted the ubiquitin-mediated degradation of Dvl2 by strengthening the interaction between Dvl2 and the E3 ubiquitin ligase KLHL12 in CYP2E1-stable HCC cells. CYP2E1-induced ROS accumulation was a critical upstream event in the Wnt/β-Catenin pathway in CYP2E1-overexpressing HCC cells.

Conclusions

These results provide novel insight into the role of CYP2E1 in HCC and the tumor suppressor role of CYP2E1 can be attributed to its ability to manipulate Wnt/Dvl2/β-catenin pathway via inducing ROS accumulation, which provides a potential target for the prevention and treatment of HCC.

Graphical Abstract
Enhanced DNA and RNA pathogen detection via metagenomic sequencing in patients with pneumonia
Authors: He Yukun , Fang Kechi , Shi Xing , Yang Donghong , Zhao Lili , Yu Wenyi , Zheng Yali , Xu Yu , Ma Xinqian , Chen Li , Xie Yu , Yu Yan , Wang Jing , Gao Zhancheng
Published: May 2022

Background

Metagenomic next-generation sequencing (mNGS) is an important supplement to conventional tests for pathogen detections of pneumonia. However, mNGS pipelines were limited by irregularities, high proportion of host nucleic acids, and lack of RNA virus detection. Thus, a regulated pipeline based on mNGS for DNA and RNA pathogen detection of pneumonia is essential.

Methods

We performed a retrospective study of 151 patients with pneumonia. Three conventional tests, culture, loop-mediated isothermal amplification (LAMP) and viral quantitative real-time polymerase chain reaction (qPCR) were conducted according to clinical needs, and all samples were detected using our optimized pipeline based on the mNGS (DNA and RNA) method. The performances of mNGS and three other tests were compared. Human DNA depletion was achieved respectively by MolYsis kit and pre-treatment using saponin and Turbo DNase. Three RNA library preparation methods were used to compare the detection performance of RNA viruses.

Results

An optimized mNGS workflow was built, which had only 1-working-day turnaround time. The proportion of host DNA in the pre-treated samples decreased from 99 to 90% and microbiome reads achieved an approximately 20-fold enrichment compared with those without host removal. Meanwhile, saponin and Turbo DNase pre-treatment exhibited an advantage for DNA virus detection compared with MolYsis. Besides, our in-house RNA library preparation procedure showed a more robust RNA virus detection ability. Combining three conventional methods, 76 (76/151, 50.3%) cases had no clear causative pathogen, but 24 probable pathogens were successfully detected in 31 (31/76 = 40.8%) unclear cases using mNGS. The agreement of the mNGS with the culture, LAMP, and viral qPCR was 60%, 82%, and 80%, respectively. Compared with all conventional tests, mNGS had a sensitivity of 70.4%, a specificity of 72.7%, and an overall agreement of 71.5%.

Conclusions

A complete and effective mNGS workflow was built to provide timely DNA and RNA pathogen detection for pneumonia, which could effectively remove the host sequence, had a higher microbial detection rate and a broader spectrum of pathogens (especially for viruses and some pathogens that are difficult to culture). Despite the advantages, there are many challenges in the clinical application of mNGS, and the mNGS report should be interpreted with caution.
Entropy as the main justification for research in medical ethics
Authors: Zarzavadjian Le Bian Alban , Pantel Louis , Tresallet Christophe , Mamzer Marie-France
Published: May 2022

Ethics is an unconventional field of research for a surgeon, as ethics in surgery owns several specificities and surgery is considered an aggressive specialty. Therefore, the interest of research in medical ethics is sometimes unclear.

In this short essay, we discussed the interest of research in medical ethics using a comparison to thermodynamics and mainly, entropy. During the transformation of a figure from one state to another, some energy is released or absorbed; yet, a part of this energy is wasted because of “unordered” (and unsuccessful) reactions: it is Entropy.

This “wasted energy” exists in Medical practice and justifies research in Medical ethics.
3D chromatin architecture and transcription regulation in cancer
Authors: Deng Siwei , Feng Yuliang , Pauklin Siim
Published: May 2022

Chromatin has distinct three-dimensional (3D) architectures important in key biological processes, such as cell cycle, replication, differentiation, and transcription regulation. In turn, aberrant 3D structures play a vital role in developing abnormalities and diseases such as cancer. This review discusses key 3D chromatin structures (topologically associating domain, lamina-associated domain, and enhancer–promoter interactions) and corresponding structural protein elements mediating 3D chromatin interactions [CCCTC-binding factor, polycomb group protein, cohesin, and Brother of the Regulator of Imprinted Sites (BORIS) protein] with a highlight of their associations with cancer. We also summarise the recent development of technologies and bioinformatics approaches to study the 3D chromatin interactions in gene expression regulation, including crosslinking and proximity ligation methods in the bulk cell population (ChIA-PET and HiChIP) or single-molecule resolution (ChIA-drop), and methods other than proximity ligation, such as GAM, SPRITE, and super-resolution microscopy techniques.
Incidence of diabetes and its predictors in the Greater Beirut Area: a five-year longitudinal study
Authors: Nasrallah Mona P. , Elbejjani Martine , Nasreddine Lara , Chami Hassan , Ismaeel Hussein , Fleifel Mohamad , Al Zahraa Chokor Fatima , Tamim Hani
Published: May 2022

Background

Type 2 Diabetes (T2D) remains a world epidemic. Obtaining accurate estimates of its incidence and their predictors will aid in targeting preventive measures, allocating resources, and strategizing its management. The Middle East North Africa region has high T2D prevalence and rates of rise. Few incidence studies exist for the region, and none from Lebanon. The current study objective was to determine diabetes incidence and diabetes predictors in a community-based Lebanese sample. A secondary objective was to describe the metabolic control over time in adults with preexisting diabetes.

Methods

This is a five-year (2014–2019) follow-up study on a random sample of 501 residents of the Greater Beirut area. Out of 478 people eligible to participate in the follow-up study, 198 returned (response rate 39.5%). Assessment included medical history, anthropometric measures, food frequency, sleep, and lifestyle questionnaires. Laboratory data included glycemic indices (fasting glucose and HbA1C) and other biological markers. The diagnosis of probable diabetes (PD) was based on one abnormal test for either fasting glucose ≥ 126 mg/dL or HbA1C ≥ 6.5% or having history of diabetes.

Results

The incidence of diabetes was 17.2 (95% CI 9.6–28.7) per 1000 person-years. Cardiometabolic risk factors independently associated with diabetes were: older age, higher BMI, family history of diabetes, metabolic syndrome, higher CRP and triglyceride level; whereas an independent predictor of diabetes was previous BMI.

In addition, the 42 participants with preexisting diabetes had worsening of their metabolic profile over a five-year period.

Conclusions

The incidence of diabetes was high as compared to some reported world rates, and in line with the high prevalence in the MENA region. The risk was highest in those with positive family history and the presence of the metabolic syndrome or its components. Preventive measures should particularly target participants with that specific risk profile. This becomes particularly important when observing that metabolic control gets worse over time in individuals with diabetes.
Emotional competences in vocational education and training: state of the art and guidelines for interventions
Authors: Sauli Florinda , Wenger Matilde , Fiori Marina
Published: May 2022

Interventions in emotional competences and scientific studies of emotional competence are flourishing in the educational context. However, we find very few programs in Europe involving emotional interventions in vocational education and training (VET) and a dearth of scientific contributions. Our purpose with this paper is twofold: a) we provide the state of the art on existing international scientific publications about emotional training interventions in VET and a summary of existing programs at the European level; b) by relying on the analysis of relevant cases in the educational literature, we provide guidelines about how scientifically-based interventions in emotional competences in VET could be developed. Ultimately, our goal is to open a discussion of emotional training as a novel domain of research for VET scholars and practitioners, and of how emotional competences could be introduced in a vocational curriculum.
Left thoracoscopic approach in the supine position for torsion of the residual esophagus after esophagectomy: a case report
Authors: Yamaguchi Kazuya , Haruki Shigeo , Sakano Masayoshi , Suzuki Kunihito , Miura Akinori
Published: May 2022

Background

Anastomotic stenosis can occur after esophagectomy and gastric tube reconstruction. The effective surgical treatment for refractory anastomotic stenosis, which seems difficult to resolve with endoscopic treatment, has not been established. We report a case of refractory stenosis due to esophageal torsion in which reconstructive surgery was possible using a left thoracoscopic approach in the supine position.

Case presentation

A 72-year-old man who underwent thoracoscopic subtotal esophagectomy and retrosternal gastric tube reconstruction for esophageal cancer 6 months previously presented to us. Postoperative endoscopy revealed that the residual esophagus was twisted approximately 360°, just above the anastomotic site. Conservative endoscopic treatment failed to improve the condition due to severe passage obstruction, and reconstructive surgery was repeated. Surgery was performed in the supine position using a left thoracoscopic approach. The entire circumferences of the gastric tube and residual esophagus were dissected from the inferior mediastinum to the top of the sternum, with focus on preserving the right gastroepiploic vein and gastric-tube wall. Subsequently, laparoscopic surgery was performed to remove the gastric tube from the thoracoabdominal junction. After separating the esophagus on the oral side of the torsion from the left cervical wound, the abdomen was opened, the gastric tube was pulled out through the abdominal wound, and adhesions in the abdominal cavity were peeled off to raise the gastric tube cranially via the retrosternal route. An end-to-side anastomosis was performed using a circular stapler, and the esophageal torsion and previous anastomosis were resected. Oral intake was resumed on the 7th postoperative day, and the patient was discharged on the 38th day.

Conclusions

After subtotal esophagectomy and retrosternal gastric tube reconstruction, the left thoracoscopic approach is one of the most minimally invasive approaches and is especially useful for preserving the right gastroepiploic artery and veins and for mobilizing the gastric tube wall.
The EORTC QLU-C10D discrete choice experiment for cancer patients: a first step towards patient utility weights
Authors: Gamper Eva-Maria , King Madeleine T. , Norman Richard , Loth Fanny L. C. , Holzner Bernhard , Kemmler Georg ,   the EORTC Quality of Life Group^
Published: May 2022

Background

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Utility-Core 10 Dimensions (QLU-C10D) is a novel cancer-specific preference-based measure (PBM) for which value sets are being developed for an increasing number of countries. This is done by obtaining health preferences from the respective general population. There is an ongoing discussion if instead patients suffering from the disease in question should be asked for their preferences. We used the QLU-C10D valuation survey, originally designed for use in the general population, in a sample of cancer patients in Austria to assess the methodology’s acceptability and applicability in this target group before obtaining QLU-C10D patient preferences.

Methods

The core of the QLU-C10D valuation survey is a discrete choice experiment in which respondents are asked to give preferences for certain health states (described by a relatively large number of 10 quality of life domains) and an associated survival time. They therewith are asked to trade off quality of life against life time. As this might be a very burdensome task for cancer patients undergoing treatment, a cognitive interview was conducted in a pilot sample to assess burden and potential additional needs for explanation in order to be able to use the DCE for the development of QLU-C10D patient preferences. In addition, responses to general feedback questions on the survey were compared against responses from a matched control group from the already completed Austrian general population valuation survey.

Results

We included 48 patients (mean age 59.9 years; 46% female). In the cognitive interview, the majority indicated that their experience with the survey was positive (85%) and overall clarity as good (90%). In response to the general feedback questions, patients rated the presentation of the health states less clear than matched controls (p = 0.008). There was no difference between patients and the general population concerning the difficulty in choosing between the health states (p = 0.344).

Conclusion

Despite the relatively large number of DCE domains the survey was manageable for patients and allows going on with the QLU-C10D patient valuation study.
Behavioral symptoms among children and adolescents with attention deficit hyperactivity disorder during COVID-19 outbreak: a retrospective prospective cohort study
Authors: Abdel Fattah Nelly R. , Yousef Amira Mohamed , Mohamed Amany Elshabrawy , Amin Shimaa Ibrahim
Published: May 2022

Background

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental conditions in children, and with the coronavirus pandemic, ADHD children now pose obvious challenges. This retrospective prospective cohort study was conducted on 150 ADHD children and adolescents that had previously attended the child unit of the Psychiatry Department, Zagazig University Hospitals, Sharkia, Egypt, and diagnosed as ADHD patients using the research diagnostic criteria of DSM-5 which administrated by experienced psychiatrists and evaluated by The Arabic version of Conner’s Parent Rating Scale Revised-short version (CPRS-48) before the onset of COVID-19 pandemic. We collected the other data of the study by applying an Arabic language questionnaire which included the data related to the COVID -19 pandemic and the Arabic version of CPRS-48 by which we reevaluated the behavioral symptoms of the subjects who participated in the study during COVID-19 pandemic. This research aimed to evaluate the behavioral symptoms among ADHD children and adolescents and detect the change in these symptoms during the COVID-19 pandemic by comparing them before and during the pandemic.

Results

One hundred fifty ADHD children were included in the study with a mean age of 10 years old. The male gender was predominant and represented 76.7% of the sample. Ninety percent were living in urban areas with more low social class (50%), 84.7% of parents were married, 60% of the family member of our subjects had COVID-19 while 12% lost one or more of their relative by the pandemic (64.7%). The fathers continued working as normal, while 40.7% of the mothers stopped working because of COVID-19. 62.7% of the parents were verbally and physically abusive to their children. Unfortunately, 100% of the subjects stopped attending their behavioral therapy center, 96.0% stopped their Follow up with a psychiatrist, and 55% stopped complying with their medications. As we presumed, we found a statistically significant change in the behavioral and psychological symptoms measured by Conner’s Parent Rating Scale Revised-short version (CPRS-48) during the COVID-19 pandemic compared to the period before. The worsening of the symptoms was associated with age, sex, residency, social class, father and mother present working and couple status, having positive cases or losses of COVID-19 among family members, and patient maltreatment.

Conclusions

To conclude, this study suggests that the lockdown caused by the COVID-19 pandemic has worsened symptoms in a significant number of children and adolescents with ADHD, which needs clinical attention. Moreover, the patients’ psychiatric follow-up and compliance with their medications were markedly affected. Additionally, the lockdown has also led to an increase in the abusive behavior of the parents towards their children.