bluuebunny/crossref_metadata_2025 huggingface dataset:
The prevalence of multimorbidity and its association with physical activity and sleep duration in middle aged and elderly adults: a longitudinal analysis from China
Authors: He Li , Biddle Stuart J. H. , Lee John Tayu , Duolikun Nadila , Zhang Lin , Wang Zijie , Zhao Yang
Published: June 2021

Background

Preventing chronic disease is important in health policy in countries with significantly ageing populations. This study aims to examine the prevalence of chronic disease multimorbidity and its association with physical activity and sleep duration; and to understand whether physical activity modifies associations between sleep duration and multimorbidity.

Methods

We utilized longitudinal data of a nationally-representative sample from the China Health and Retirement Longitudinal Study (in year 2011 and 2015; N = 5321; 54.7% female; age ≥ 45 years old). Fourteen chronic diseases were used to measure multimorbidity (ten self-reported, and four by blood test). Participants were grouped into high, moderate, and low level based on self-reported frequencies and durations of physical activity with different intensities for at least 10 min at a time in a usual week. Poor and good sleepers were categorized according to average hours of actual sleep at each night during the past month. Panel data method of random-effects logistic regression model was applied to estimate the association of physical activity and sleep with multimorbidity, adjusting for social-demographic and behavioural confounders.

Results

From 2011 to 2015, the prevalence of multimorbidity increased from 52.2 to 62.8%. In 2015, the proportion of participants engaging in high, moderate, and low level of physical activity was 30.3, 24.4 and 45.3%, respectively, and 63.6% of adults had good sleep. For both genders, compared with good sleep, poor sleep was associated with higher odds of multimorbidity (OR = 1.527, 95% CI: 1.277, 1.825). Compared to the high-level group, participants with a low level of physical activity were significantly more likely to have multimorbidity (OR = 1.457, 95% CI: 1.277, 1.825), but associations were stronger among women. The relative excess risk due to interaction between poor sleep and moderate or low physical activity was positive but non-significant on multimorbidity.

Conclusions

The burden of multimorbidity was high in China. Low physical activity and poor sleep was independently and significantly associated with a higher likelihood of multimorbidity in women and both genders, separately. Physical activity could modify the association between sleep and multimorbidity.
Radiomic signature of the FOWARC trial predicts pathological response to neoadjuvant treatment in rectal cancer
Authors: Zhuang Zhuokai , Liu Zongchao , Li Juan , Wang Xiaolin , Xie Peiyi , Xiong Fei , Hu Jiancong , Meng Xiaochun , Huang Meijin , Deng Yanhong , Lan Ping , Yu Huichuan , Luo Yanxin
Published: June 2021

Background

We aimed to develop a radiomic model based on pre-treatment computed tomography (CT) to predict the pathological complete response (pCR) in patients with rectal cancer after neoadjuvant treatment and tried to integrate our model with magnetic resonance imaging (MRI)-based radiomic signature.

Methods

This was a secondary analysis of the FOWARC randomized controlled trial. Radiomic features were extracted from pre-treatment portal venous-phase contrast-enhanced CT images of 177 patients with rectal cancer. Patients were randomly allocated to the primary and validation cohort. The least absolute shrinkage and selection operator regression was applied to select predictive features to build a radiomic signature for pCR prediction (rad-score). This CT-based rad-score was integrated with clinicopathological variables using gradient boosting machine (GBM) or MRI-based rad-score to construct comprehensive models for pCR prediction. The performance of CT-based model was evaluated and compared by receiver operator characteristic (ROC) curve analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare CT-based rad-score, MRI-based rad-score and the combined rad-score.

Results

We developed a CT-based rad-score for pCR prediction and a gradient boosting machine (GBM) model was built after clinicopathological variables were incorporated, with improved AUCs of 0.997 [95% CI 0.990–1.000] and 0.822 [95% CI 0.649–0.995] in the primary and validation cohort, respectively. Moreover, we constructed a combined model of CT- and MRI-based radiomic signatures that achieve better AIC (75.49 vs. 81.34 vs.82.39) than CT-based rad-score (P = 0.005) and MRI-based rad-score (P = 0.003) alone did.

Conclusions

The CT-based radiomic models we constructed may provide a useful and reliable tool to predict pCR after neoadjuvant treatment, identify patients that are appropriate for a 'watch and wait' approach, and thus avoid overtreatment. Moreover, the CT-based radiomic signature may add predictive value to the MRI-based models for clinical decision making.
Uncharted waters: mesenchymal stem cell treatment for pediatric refractory rheumatic diseases; a single center case series
Authors: Wong Stephen C. , Medrano Leah C. , Hoftman Alice D. , Jones Olcay Y. , McCurdy Deborah K.
Published: June 2021

Background

With the advent of innovative therapies including biologics and Janus kinase inhibitors, children with rheumatic diseases are more likely to have improved outcomes. Despite these advances, some children do not respond, or they, or their parents fear adverse events and seek other alternatives. Increasingly, private companies are offering mesenchymal stem cells (MSC) as an alternative, which are described as natural therapies for rheumatic diseases, often insinuating them as a cure. MSC have immunomodulatory properties, and transplantation of these stem cells have been used to successfully treat immunologic conditions like graft-versus-host disease. Lately, MSC research in adult lupus has been encouraging, but the clinical trials are still underway and in most, MSC therapy is not a standalone treatment. This retrospective case series will highlight three cases of pediatric refractory autoimmune disease whose parents sought out and received MSC therapy as a self-decision without first seeking medical advice from our specialty. The three families felt that their children were improved and in two believed that their child was cured. MSC have the potential of beneficial immunomodulation and may be a powerful tool in the therapy of rheumatic disease, but well controlled clinical trials are necessary and should be designed and monitored by experts in childhood rheumatic disease.

Case presentation

Three children with three different rheumatic diseases; systemic lupus erythematosus, mixed connective tissue disease and juvenile idiopathic arthritis were under the care of pediatric rheumatology at a large, tertiary-care, teaching institution. Multiple non-biologic and biologic disease-modifying anti-rheumatic drugs failed to significantly decrease disease activity, and as a result, the families chose to undergo MSC therapy. After transplantation, all children improved per patient and parent report and tapered off conventional immunosuppressive drugs. No serious adverse events occurred in these three patients.

Conclusion

The three cases presented in this report reflect comparable beneficial outcomes and minimal risks published in adult studies. These were not controlled studies, however, and benefit was reported rather than documented. These cases suggest that MSC transplantation may prove a promising adjunctive treatment option; however, further research, development of standardized infusion therapy protocols, and well-designed monitored clinical trials are essential.
Enhancing organizational readiness for implementation: constructing a typology of readiness-development strategies using a modified Delphi process
Authors: Vax Sigal , Farkas Marianne , Russinova Zlatka , Mueser Kim T. , Drainoni Mari-Lynn
Published: June 2021

Background

Knowledge about the development of organizational readiness for implementation (ORI) is limited. ORI, referred to as the willingness and capacity of all relevant stakeholders to change practice, is critical for increasing the adoption rate of evidence-based practices and improving implementation outcomes. However, no methodology currently guides ORI’s enhancement or addresses differences in readiness needs across an organization. This study used the transtheoretical model (TTM) as a framework for classifying a well-established compilation of implementation strategies into three readiness stages: pre-contemplation, contemplation, and preparation.

Methods

A modified Delphi method was used to establish consensus among a panel of purposefully selected research and field implementation experts. The Delphi process involved three rounds of online questionnaires. The third round also included a live video discussion to clarify definitions in an effort to increase consensus among experts.

Results

Of the 73 strategies reviewed, the experts identified 75% (n= 55) as relevant for pre-implementation and reached a high-level agreement on the assignment of 7% (n= 5) of the strategies to the pre-contemplation stage (ORI-1), 25% (n= 18) to the contemplation stage (ORI-2), and 52% (n= 38) to the preparation stage (ORI-3). Several strategies were identified as relevant to more than one stage.

Conclusions

Participating experts were able to reach high-level agreement on the relevance of specific sets of implementation strategies to each of the three ORI stages. The lowest number of strategies was assigned to ORI-1 and the highest number to ORI-3. Given the overlap of strategies across ORI stages, there is a need to better understand the specific utilization of such strategies at different stages. Future studies are needed to empirically evaluate the relevance and applicability of this expert-informed typology based on implementers’ experiences in the field.
Model to predict cause‐specific mortality in patients with olfactory neuroblastoma: a competing risk analysis
Authors: Liu Lipin , Zhong Qiuzi , Zhao Ting , Chen Dazhi , Xu Yonggang , Li Gaofeng
Published: June 2021

Purpose

The main objective of this study was to evaluate the cumulative incidence of cause-specific mortality and other causes of mortality for patients with olfactory neuroblastoma (ONB). The secondary aim was to model the probability of cause-specific death and build a competing risk nomogram to predict cause-specific mortality for this disease.

Methods

Patients with ONB from 1975 to 2016 were identified from the Surveillance, Epidemiology, and End Results database. We estimated the cumulative incidence function (CIF) for cause-specific mortality and other causes of mortality, and constructed the Fine and Gray’s proportional subdistribution hazard model, as well as a competing-risk nomogram based on Fine and Gray’s model, to predict the probability of cause-specific mortality for patients with ONB.

Results

After data selection, 826 cases were included for analysis. Five-year cumulative incidence of cause-specific mortality was 19.5% and cumulative incidence of other causes of mortality was 11.3%. Predictors of cause-specific mortality for ONB included tumor stage, surgery and chemotherapy. Age was most strongly predictive of other causes of mortality: patients aged > 60 years exhibited subdistribution hazard ratios of 1.063 (95 % confidence interval [CI] 1.05–1.08; p = 0.001). The competing risk nomogram for cause-specific mortality was well-calibrated, and had good discriminative ability (concordance index = 0.79).

Conclusions

We calculated the CIF of cause-specific mortality and other causes of mortality in patients with the rare malignancy ONB. We also built the first competing risk nomogram to provide useful individualized predictive information for patients with ONB.
Patient and hospital factors associated with 30-day readmissions after coronary artery bypass graft (CABG) surgery: a systematic review and meta-analysis
Authors: Shawon Md Shajedur Rahman , Odutola Michael , Falster Michael O. , Jorm Louisa R.
Published: June 2021

Background

Readmission after coronary artery bypass graft (CABG) surgery is associated with adverse outcomes and significant healthcare costs, and 30-day readmission rate is considered as a key indicator of the quality of care. This study aims to: quantify rates of readmission within 30 days of CABG surgery; explore the causes of readmissions; and investigate how patient- and hospital-level factors influence readmission.

Methods

We conducted systematic searches (until June 2020) of PubMed and Embase databases to retrieve observational studies that investigated readmission after CABG. Random effect meta-analysis was used to estimate rates and predictors of 30-day post-CABG readmission.

Results

In total, 53 studies meeting inclusion criteria were identified, including 8,937,457 CABG patients. The pooled 30-day readmission rate was 12.9% (95% CI: 11.3–14.4%). The most frequently reported underlying causes of 30-day readmissions were infection and sepsis (range: 6.9–28.6%), cardiac arrythmia (4.5–26.7%), congestive heart failure (5.8–15.7%), respiratory complications (1–20%) and pleural effusion (0.4–22.5%). Individual factors including age (OR per 10-year increase 1.12 [95% CI: 1.04–1.20]), female sex (OR 1.29 [1.25–1.34]), non-White race (OR 1.15 [1.10–1.21]), not having private insurance (OR 1.39 [1.27–1.51]) and various comorbidities were strongly associated with 30-day readmission rates, whereas associations with hospital factors including hospital CABG volume, surgeon CABG volume, hospital size, hospital quality and teaching status were inconsistent.

Conclusions

Nearly 1 in 8 CABG patients are readmitted within 30 days and the majority of these are readmitted for noncardiac causes. Readmission rates are strongly influenced by patients’ demographic and clinical characteristics, but not by broadly defined hospital characteristics.
Characteristics and possible mechanisms of 46, XY differences in sex development caused by novel compound variants in NR5A1 and MAP3K1
Authors: Cheng Yiping , Chen Jing , Zhou Xinli , Yang Jiangfei , Ji Yiming , Xu Chao
Published: June 2021

Background

Dozens of genes are involved in 46, XY differences in sex development (DSD). Notably, about 3/4 of patients cannot make a clear etiology diagnosis and single gene variant identified cannot fully explain the clinical heterogeneity of 46, XY DSD.

Materials and methods

We conducted a systematic clinical analysis of a 46, XY DSD patient, and applied whole-exome sequencing for the genetic analysis of this pedigree. The identified variants were analyzed by bioinformatic analysis and in vitro studies were performed in human embryonic kidney 293T (HEK-293T) cells which were transiently transfected with wild type or variant NR5A1 and MAP3K1 plasmid. Furthermore, protein production of SRY-box transcription factor 9 (SOX9) was analyzed in cell lysates.

Results

A novel NR5A1 variant (c.929A > C, p. His310Pro) and a rare MAP3K1 variant (c.2282T > C, p. Ile761Thr) were identified in the proband, whereas the proband's mother and sister who only carry rare MAP3K1 variant have remained phenotypically healthy to the present. These two variants were predicted to be pathogenic by bioinformatic analysis. In vitro, NR5A1 variant decreased the SOX9 production by 82.11% compared to wild type NR5A1, while MAP3K1 variant had little effect on the SOX9 production compared to wild type MAP3K1. Compared to wild type NR5A1 transfection, the SOX9 production of cells transfected with both wild type plasmids decreased by about 17.40%. Compared to variant NR5A1 transfection, the SOX9 production of cells transfected with both variant plasmids increased by the 36.64%.

Conclusions

Our findings suggested the novel compound variants of NR5A1 and MAP3K1 can alter the expression of SOX9 and ultimately lead to abnormality of sex development.
Outcome of L-DEP regimen for treatment of pediatric chronic active Epstein–Barr virus infection
Authors: Ma Honghao , Zhang Liping , Wei Ang , Yang Jun , Wang Dong , Zhang Qing , Zhao Yunze , Chen Sitong , Lian Hongyun , Zhang Li , Zhou Chunju , Qin Maoquan , Li Zhigang , Wang Tianyou , Zhang Rui
Published: June 2021

Purpose

We intended to investigate the clinical features of paediatric patients with chronic active Epstein–Barr virus infection (CAEBV) and to examine the effectiveness of the L-DEP regimen before haematopoietic stem cell transplantation (HSCT).

Methods

A retrospective analysis was performed on 35 patients with CAEBV at Beijing Children’s Hospital from January 2016 to January 2020. The efficacy and adverse events of the L-DEP regimen were evaluated.

Results

The median age of the 35 patients was 7.0 years old (range 2.5–17.5 years). Twenty-eight patients achieved a clinical response (80.0%, 22 in clinical CR, 6 in clinical PR) after L-DEP. In terms of virological response, 7 patients (20%) were assessed as having virological CR, and 23 patients (65.7%) had virological PR. Finally, 29 patients underwent allo-HSCT. The median survival time was 18 months (2–50 months). The 3-year overall survival rates in patients treated with chemotherapy only (n = 6) and chemotherapy followed by HSCT (n = 25) were 33.3% and 75.4%, respectively. After L-DEP 1st treatment and L-DEP 2nd treatment, the EBV-DNA loads in blood and plasma were significantly reduced compared with those before chemotherapy (median: 4.29 × 105 copies/ml vs. 1.84 × 106 copies/ml, Mann–Whitney U: P = 0.0004; 5.00 × 102 copies/ml vs. 3.17 × 103 copies/ml, Mann–Whitney U; P = 0.003; 2.27 × 105 copies/ml vs. 1.84 × 106 copies/ml, P = 0.0001; 5.00 × 102 copies/ml vs. 3.17 × 103 copies/ml, P = 0.003). Compared with the liver and spleen size before chemotherapy, the size of the liver and spleen shrank significantly after L-DEP 2nd (median 3.8 cm vs. 1.9 cm, P = 0.003; 3.8 cm vs. 0 cm, P < 0.008). In addition, after L-DEP treatment, there was no difference in the clinical or virological response rate regardless of HLH status (clinical response: 77.3% vs. 84.6%, P = 0.689; virological response: 90.9% vs. 76.9%, P = 0.337).

Conclusion

The L-DEP regimen is an effective therapy in CAEBV for bridging to allo-HSCT.
CircPVT1 promotes proliferation of lung squamous cell carcinoma by binding to miR-30d/e
Authors: Shi Jie , Lv Xin , Zeng Lizhong , Li Wei , Zhong Yujie , Yuan Jingyan , Deng Shanshan , Liu Boxuan , Yuan Bo , Chen Yang , Ming Zongjuan , Yang Xia , Fang Ping , Yang Shuanying , Chen Guoan
Published: June 2021

Background

Circular RNAs (circRNAs) are a new type of extensive non-coding RNAs that regulate the activation and progression of different human diseases, including cancer. However, information on the underlying mechanisms and clinical significance of circRNAs in lung squamous cell carcinoma (LUSC) remains scant.

Methods

The expression profile of RNAs in 8 LUSC tissues, and 9 healthy lung tissues were assayed using RNA sequencing (RNA-seq) techniques. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to profile the expression of circPVT1 and its relationship with the prognosis of LUSC, i.e., survival analysis. Moreover, in vitro and in vivo experiments were performed to evaluate the impacts of circPVT1 on the growth of tumors. RNA pull-down tests, mass spectrometry, dual-luciferase reporter assessment, and RNA immune-precipitation tests were further conducted to interrogate the cross-talk between circPVT1, HuR, or miR-30d/e in LUSC.

Results

Our data showed that circPVT1 was upregulated in LUSC tissues, serum, and cell lines. LUSC patients with higher circPVT1 expression exhibited shorter survival rates. The in vivo and in vitro data revealed that circPVT1 promotes the proliferation of LUSC cells. Additionally, mechanistic analysis showed that HuR regulated circPVT1. On the other hand, circPVT1 acted as a competing endogenous RNA (ceRNA) of miR-30d and miR-30e in alleviating the suppressive influences of miR-30d and miR-30e on its target cyclin F (CCNF).

Conclusion

CircPVT1 promotes LUSC progression via HuR/circPVT1/miR-30d and miR-30e/CCNF cascade. Also, it acts as a novel diagnostic biomarker or treatment target of individuals diagnosed with LUSC.
Successful experimental infant baboon model for childhood cryptosporidiosis studies
Authors: Jillani Ngalla E. , Nyachieo Atunga , Chai Daniel C. , Nyariki James Nyabuga
Published: June 2021

Background

Cryptosporidiosis causes high morbidity and mortality in children under 2 years of age globally. The lack of an appropriate animal model that mimics the pathogenesis of disease in humans has hampered the development and testing of potential therapeutic options. This study aimed to develop and validate an infant baboon infection model of cryptosporidiosis.

Methods

Eighteen immunocompetent weaned infant baboons aged 12 to 16 months were used. The animals were n = 3 controls and three experimental groups of n = 5 animals each inoculated with Cryptosporidium parvum oocysts as follows: group 1: 2 × 104, group 2: 2 × 105, group 3: 2 × 106 followed by daily fecal sampling for oocyst evaluation. Blood sampling for immunological assay was done on the day of infection and weekly thereafter until the end of the experiment, followed by necropsy and histopathology. Statistical analysis was performed using R, SPSS, and GraphPad Prism software. Analysis of variance (ANOVA) and Bonferroni post hoc tests were used for comparison of the means, with p < 0.05 considered as a significant difference. Correlation coefficient and probit analysis were also performed.

Results

In all experimental animals but not controls, the onset of oocyst shedding occurred between days 2 and 4, with the highest oocyst shedding occurring between days 6 and 28. Histological analysis revealed parasite establishment only in infected animals. Levels of cytokines (TNF-α, IFN-γ, and IL-10) increased significantly in experimental groups compared to controls.

Conclusion

For developing a reproducible infant baboon model, 2 × 104 oocysts were an effective minimum quantifiable experimental infection dose.

Graphic abstract
Poor vector competence of the human flea, Pulex irritans, to transmit Yersinia pestis
Authors: Miarinjara Adélaïde , Bland David M. , Belthoff James R. , Hinnebusch B. Joseph
Published: June 2021

Background

The human flea, Pulex irritans, is widespread globally and has a long association with humans, one of its principal hosts. Its role in plague transmission is still under discussion, although its high prevalence in plague-endemic regions and the presence of infected fleas of this species during plague outbreaks has led to proposals that it has been a significant vector in human-to-human transmission in some historical and present-day epidemiologic situations. However, based on a limited number of studies, P. irritans is considered to be a poor vector and receives very little attention from public health policymakers. In this study we examined the vector competence of P. irritans collected from foxes and owls in the western United States, using a standard protocol and artificial infection system.

Methods

Wild-caught fleas were maintained in the laboratory and infected by allowing them to feed on human or rat blood containing 2 × 108 to 1 × 109Y. pestis/ml. The fleas were then monitored periodically for infection rate and bacterial load, mortality, feeding rate, bacterial biofilm formation in the foregut (proventricular blockage), and ability to transmit Y. pestis after their single infectious blood meal.

Results

P. irritans were susceptible to infection, with more than 30% maintaining high bacterial loads for up to 20 days. Transmission during this time was infrequent and inefficient, however. Consistent with previous studies, a low level of early-phase transmission (3 days after the infectious blood meal) was detected in some trials. Transmission at later time points was also sporadic, and the incidence of proventricular blockage, required for this mode of transmission, was low in fleas infected using rat blood and never occurred in fleas infected using human blood. The highest level of blockage and transmission was seen in fleas infected using rat blood and allowed to feed intermittently rather than daily, indicating that host blood and feeding frequency influence vector competence.

Conclusions

Our results affirm the reputation of P. irritans as a feeble vector compared to rodent flea species examined similarly, and its vector competence may be lower when infected by feeding on bacteremic human blood.

Graphic abstract
Comparison of mitochondrial genome and development of specific PCR primers for identifying two scuticociliates, Pseudocohnilembus persalinus and Uronema marinum
Authors: Huang Yu-Xi , Wang Sen , Gao Yan-Qi , Chen Jie-Hu , Wang Xiu-Li , Li Rui-Jun
Published: June 2021

Background

Pseudocohnilembus persalinusandUronema marinum(Ciliophora, Scuticociliatia), as parasitic scuticociliatid ciliates, were isolated fromScophthalmus maximusandTakifugu rubripes, respectively, in our previous studies. These ciliates are morphologically very similar; hence, it is difficult to identify specific scuticociliate species using traditional classification methods for performing taxonomic research and disease control studies.

Methods

We annotated the mitochondrial genomes of these two scuticociliates on the basis of previous sequencing, including analyses of nucleotide composition, codon usage, Ka/Ks, and p-distance. We also compared the nucleotide and amino acid similarity of the mitochondrial genomes ofP. persalinus,U. marinum, and other 12 related ciliates, and a phylogenetic tree was constructed using 16 common genes. We chose thenad4andnad7genes to design specific PCR primers for identification.

Results

P. persalinusandU. marinumwere found to have a close evolutionary relationship. Although codon preferences were similar, differences were observed in the usage of codons such as CGA, CGC, and GTC. Both Ka/Ks and p-distance were less than 1. Except foryejR,ymf57,ymf67, andymf75, the amino acid sequence similarity betweenP. persalinusandU. marinumwas greater than 50%.

Conclusions

The mitochondrial genomes ofP. persalinusandU. marinumwere thoroughly compared to provide a reference for disease prevention and control. The specific PCR primers enabled us to identifyP. persalinusandU. marinumrapidly and accurately at the molecular level, thus providing a basis for classification and identification.

Graphic abstract
Conservation and diversity of the eukaryotic SAGA coactivator complex across kingdoms
Authors: Chen Ying-Jiun C. , Dent Sharon Y. R.
Published: June 2021

The SAGA complex is an evolutionarily conserved transcriptional coactivator that regulates gene expression through its histone acetyltransferase and deubiquitylase activities, recognition of specific histone modifications, and interactions with transcription factors. Multiple lines of evidence indicate the existence of distinct variants of SAGA among organisms as well as within a species, permitting diverse functions to dynamically regulate cellular pathways. Our co-expression analysis of genes encoding human SAGA components showed enrichment in reproductive organs, brain tissues and the skeletal muscle, which corresponds to their established roles in developmental programs, emerging roles in neurodegenerative diseases, and understudied functions in specific cell types. SAGA subunits modulate growth, development and response to various stresses from yeast to plants and metazoans. In metazoans, SAGA further participates in the regulation of differentiation and maturation of both innate and adaptive immune cells, and is associated with initiation and progression of diseases including a broad range of cancers. The evolutionary conservation of SAGA highlights its indispensable role in eukaryotic life, thus deciphering the mechanisms of action of SAGA is key to understanding fundamental biological processes throughout evolution. To illuminate the diversity and conservation of this essential complex, here we discuss variations in composition, essentiality and co-expression of component genes, and its prominent functions across Fungi, Plantae and Animalia kingdoms.
STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease
Authors: Yu Ya-Li , Chen Meng , Zhu Hua , Zhuo Ming-Xing , Chen Ping , Mao Yu-Juan , Li Lian-Yun , Zhao Qiu , Wu Min , Ye Mei
Published: June 2021

Background

The aetiology of inflammatory bowel disease (IBD) is related to genetics and epigenetics. Epigenetic regulation of the pathogenesis of IBD has not been well defined. Here, we investigated the role of H3K27ac events in the pathogenesis of IBD. Based on previous ChIP-seq and RNA-seq assays, we studied signal transducer and activator of transcription 1 (STAT1) as a transcription factor (TF) and investigated whether the STAT1–EP300–H3K27ac axis contributes to the development of IBD. We performed ChIP-PCR to investigate the interaction between STAT1 and H3K27ac, and co-IP assays were performed to investigate the crosstalk between STAT1 and EP300.

Results

Lymphocyte cytosolic protein 2 (LCP2) and TNF-α‐inducible protein 2 (TNFAIP2) are target genes of STAT1. p-STAT1 binds to the enhancer loci of the two genes where H3K27ac is enriched, and EP300 subsequently binds to regulate their expression. In mice with dextran sulfate sodium (DSS)-induced acute colitis, an EP300 inhibitor significantly inhibited colitis.

Conclusions

p-STAT1 and EP300 promote TNFAIP2 and LCP2 expression through an increase in H3K27ac enrichment on their enhancers and contribute to the pathogenesis of chronic inflammation.

Graphic abstract
T-staging pulmonary oncology from radiological reports using natural language processing: translating into a multi-language setting
Authors: Nobel J. Martijn , Puts Sander , Weiss Jakob , Aerts Hugo J. W. L. , Mak Raymond H. , Robben Simon G. F. , Dekker André L. A. J.
Published: June 2021

Background

In the era of datafication, it is important that medical data are accurate and structured for multiple applications. Especially data for oncological staging need to be accurate to stage and treat a patient, as well as population-level surveillance and outcome assessment. To support data extraction from free-text radiological reports, Dutch natural language processing (NLP) algorithm was built to quantify T-stage of pulmonary tumors according to the tumor node metastasis (TNM) classification. This structuring tool was translated and validated on English radiological free-text reports. A rule-based algorithm to classify T-stage was trained and validated on, respectively, 200 and 225 English free-text radiological reports from diagnostic computed tomography (CT) obtained for staging of patients with lung cancer. The automated T-stage extracted by the algorithm from the report was compared to manual staging. A graphical user interface was built for training purposes to visualize the results of the algorithm by highlighting the extracted concepts and its modifying context.

Results

Accuracy of the T-stage classifier was 0.89 in the validation set, 0.84 when considering the T-substages, and 0.76 when only considering tumor size. Results were comparable with the Dutch results (respectively, 0.88, 0.89 and 0.79). Most errors were made due to ambiguity issues that could not be solved by the rule-based nature of the algorithm.

Conclusions

NLP can be successfully applied for staging lung cancer from free-text radiological reports in different languages. Focused introduction of machine learning should be introduced in a hybrid approach to improve performance.
CT appearances, patterns of progression, and follow-up of COVID-19: evaluation on thin-section CT
Authors: Guan Chun-Shuang , Lv Zhi-Bin , Li Jing-Jing , Du Yan-Ni , Chen Hui , Cui Tao , Guo Ning , Chen Bu-Dong , Xie Ru-Ming
Published: June 2021

Background

To retrospectively analyze CT appearances and progression pattern of COVID-19 during hospitalization, and analyze imaging findings of follow-up on thin-section CT.

Methods

CT findings of 69 patients with COVID-19 were evaluated on initial CT, peak CT, and pre-discharge CT. CT pattern were divided into four types on CT progression. Lesion percentage of pulmonary lobe (lobe score) was graded. Correlation analysis was made between scores and intervals. 53 patients were followed up by CT.

Results

Among 69 patients, 33.3% exhibited improvement pattern, 65.2% peak pattern, 1.5% deterioration pattern, and 0% fluctuation pattern. The lobe scores were positively correlated with most of intervals. It was more common to observe consolidation, pleural thickening and pleural effusion on the peak CT, and irregular line and reticulation on pre-discharge CT. The peak-initial interval were shortened when the initial CT with consolidation and pleural thickening. The intervals were extended when the irregular lines appeared on peak CT and reticulation on pre-discharge CT. Among 53 follow-up patients, 37.7% showed normal chest CT, and 62.3% showed viral pneumonia remained that mainly included GGO (100.0%) and irregular lines (33.3%).

Conclusions

COVID-19 displayed different appearances on CT as progressing. The peak pattern was the most common progression pattern. The CT appearances showed closely related to the intervals. The COVID-19 pneumonia can be remained or completely absorbed on CT with follow-up.
SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats
Authors: Huang Wei , Qu Mingjia , Li Lu , Liu Tao , Lin Miaoman , Yu Xiaobing
Published: June 2021

Background

How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances.

Methods

We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats,

Results

In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI).

Conclusions

In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.
Adipose-derived mesenchymal stromal cell-derived exosomes promote tendon healing by activating both SMAD1/5/9 and SMAD2/3
Authors: Liu Hengchen , Zhang Mingzhao , Shi Manyu , Zhang Tingting , Lu Wenjun , Yang Shulong , Cui Qingbo , Li Zhaozhu
Published: June 2021

Background

The use of adipose-derived mesenchymal stromal cell-derived exosomes (ADSC-Exos) may become a new therapeutic method in biomedicine owing to their important role in regenerative medicine. However, the role of ADSC-Exos in tendon repair has not yet been evaluated. Therefore, we aimed to clarify the healing effects of ADSC-Exos on tendon injury.

Methods

The adipose-derived mesenchymal stromal cells (ADSCs) and tendon stem cells (TSCs) were isolated from the subcutaneous fat and tendon tissues of Sprague-Dawley rats, respectively, and exosomes were isolated from ADSCs. The proliferation and migration of TSCs induced by ADSC-Exos were analyzed by EdU, cell scratch, and transwell assays. We used western blot to analyze the tenogenic differentiation of TSCs and the role of the SMAD signaling pathways. Then, we explored a new treatment method for tendon injury, combining exosome therapy with local targeting using a biohydrogel. Immunofluorescence and immunohistochemistry were used to detect the expression of inflammatory and tenogenic differentiation after tendon injury, respectively. The quality of tendon healing was evaluated by hematoxylin-eosin (H&E) staining and biomechanical testing.

Results

ADSC-Exos could be absorbed by TSCs and promoted the proliferation, migration, and tenogenic differentiation of these cells. This effect may have depended on the activation of the SMAD2/3 and SMAD1/5/9 pathways. Furthermore, ADSC-Exos inhibited the early inflammatory reaction and promoted tendon healing in vivo.

Conclusions

Overall, we demonstrated that ADSC-Exos contributed to tendon regeneration and provided proof of concept of a new approach for treating tendon injuries.
LigTMap: ligand and structure-based target identification and activity prediction for small molecular compounds
Authors: Shaikh Faraz , Tai Hio Kuan , Desai Nirali , Siu Shirley W. I.
Published: June 2021

Target prediction is a crucial step in modern drug discovery. However, existing experimental approaches to target prediction are time-consuming and costly. Here, we introduce LigTMap, an online server with a fully automated workflow that can identify protein targets of chemical compounds among 17 classes of therapeutic proteins extracted from the PDBbind database. It combines ligand similarity search with docking and binding similarity analysis to predict putative targets. In the validation experiment of 1251 compounds, targets were successfully predicted for more than 70% of the compounds within the top-10 list. The performance of LigTMap is comparable to the current best servers SwissTargetPrediction and SEA. When testing with our newly compiled compounds from recent literature, we get improved top 10 success rate (66% ours vs. 60% SwissTargetPrediction and 64% SEA) and similar top 1 success rate (45% ours vs. 51% SwissTargetPrediction and 41% SEA). LigTMap directly provides ligand docking structures in PDB format, so that the results are ready for further structural studies in computer-aided drug design and drug repurposing projects. The LigTMap web server is freely accessible at https://cbbio.online/LigTMap. The source code is released on GitHub (https://github.com/ShirleyWISiu/LigTMap) under the BSD 3-Clause License to encourage re-use and further developments.
Machine type communications: key drivers and enablers towards the 6G era
Authors: Mahmood Nurul Huda , Böcker Stefan , Moerman Ingrid , López Onel A. , Munari Andrea , Mikhaylov Konstantin , Clazzer Federico , Bartz Hannes , Park Ok-Sun , Mercier Eric , Saidi Selma , Osorio Diana Moya , Jäntti Riku , Pragada Ravikumar , Annanperä Elina , Ma Yihua , Wietfeld Christian , Andraud Martin , Liva Gianluigi , Chen Yan , Garro Eduardo , Burkhardt Frank , Liu Chen-Feng , Alves Hirley , Sadi Yalcin , Kelanti Markus , Doré Jean-Baptiste , Kim Eunah , Shin JaeSheung , Park Gi-Yoon , Kim Seok-Ki , Yoon Chanho , Anwar Khoirul , Seppänen Pertti
Published: June 2021

The recently introduced 5G New Radio is the first wireless standard natively designed to support critical and massive machine type communications (MTC). However, it is already becoming evident that some of the more demanding requirements for MTC cannot be fully supported by 5G networks. Alongside, emerging use cases and applications towards 2030 will give rise to new and more stringent requirements on wireless connectivity in general and MTC in particular. Next generation wireless networks, namely 6G, should therefore be an agile and efficient convergent network designed to meet the diverse and challenging requirements anticipated by 2030. This paper explores the main drivers and requirements of MTC towards 6G, and discusses a wide variety of enabling technologies. More specifically, we first explore the emerging key performance indicators for MTC in 6G. Thereafter, we present a vision for an MTC-optimized holistic end-to-end network architecture. Finally, key enablers towards (1) ultra-low power MTC, (2) massively scalable global connectivity, (3) critical and dependable MTC, and (4) security and privacy preserving schemes for MTC are detailed. Our main objective is to present a set of research directions considering different aspects for an MTC-optimized 6G network in the 2030-era.
Shortest link scheduling in wireless networks under the Rayleigh fading model
Authors: Huang Baogui , Yu Jiguo , Ma Chunmei , Li Fengyin , Li Guangshun
Published: June 2021

Many shortest link scheduling algorithms adopt non-fading SINR interference model, which assumes that the received signal power will always remain determinate as long as the transmission power of the corresponding sender is fixed. In fact, because environment always influences the propagation of radio signals, the received signal power is by no means a certain value. Rayleigh fading is a statistical model for radio signals propagation. It assumes that the strength of a signal on a receiver is a random variable, varying with the Rayleigh distribution. This paper proposes a shortest link scheduling algorithm under the Rayleigh fading model (SLSRF). The SLSRF partitions the wireless network area into hexagons and colors the hexagons with three different colors such that two neighboring hexagons have different colors. The senders of the links scheduled simultaneously are arranged in hexagons with the same color. The correctness of the SLSRF is proved through theoretical analysis, and the efficiency is illustrated by elaborate simulations. Our simulation results demonstrate that the schedule delay of SLSRF is less than that of some results under the non-fading SINR interference model. Furthermore, we extend the SLSRF to a distributed version, which is suitable for large wireless networks.
Energy-efficient resource management for OFDM modulated bidirectional relaying with quality-of-service constraint
Authors: Ji Xiaodong , Qian Chong , Huang Chenhao , Ye Shu
Published: June 2021

This paper addressed the energy-efficient resource management problem of an amplify-and-forward relay-assisted bidirectional relay system under a quality-of-service (QoS) constraint. The objective is to develop a holistic resource management algorithm for joint implementation of relay selection, power adaptation and bit-rate management for optimal energy efficiency (EE). A three-stage approach is proposed to solve the energy-efficient resource management problem. At stage 1 (stage of power management), a per-subcarrier energy-efficient problem is investigated, leading to a power adaptation algorithm for maximizing the system EE and ensuring the required level of the system QoS. Within the framework of the power adaptation algorithm and by exploiting spatial diversity of multiple-relay channels, distributed relay selection is investigated at stage 2 (stage of relay management). Next, the bit-rate management problem is tackled at stage 3, namely assigning bit rate to different subcarriers to maximize the system EE further. Finally, summarizing the results achieved at the three stages, a novel EE technology combined with relay selection, bit-rate management and power adaptation is developed. Simulation results validated the correctness and the efficiency of the proposed algorithm. It is shown that the proposed algorithm can significantly reduce the total transmit power of the system while ensuring the required system QoS.
A probiotic has differential effects on allergic airway inflammation in A/J and C57BL/6 mice and is correlated with the gut microbiome
Authors: Casaro Mateus B. , Thomas Andrew M. , Mendes Eduardo , Fukumori Claudio , Ribeiro Willian R. , Oliveira Fernando A. , Crisma Amanda R. , Murata Gilson M. , Bizzarro Bruna , Sá-Nunes Anderson , Setubal Joao C. , Mayer Marcia P. A. , Martins Flaviano S. , Vieira Angélica T. , Antiorio Ana T. F. B. , Tavares-de-Lima Wothan , Camara Niels O. S. , Curi Rui , Dias-Neto Emmanuel , Ferreira Caroline M.
Published: June 2021

The phenotypes of allergic airway diseases are influenced by the interplay between host genetics and the gut microbiota, which may be modulated by probiotics. We investigated the probiotic effects on allergic inflammation in A/J and C57BL/6 mice. C57BL/6 mice had increased gut microbiota diversity compared to A/J mice at baseline. Acetate producer probiotics differentially modulated and altered the genus abundance of specific bacteria, such as Akkermansia and Allistipes, in mouse strains. We induced airway inflammation followed by probiotic treatment and found that only A/J mice exhibited decreased inflammation, and the beneficial effects of probiotics in A/J mice were partially due to acetate production. To understand the relevance of microbial composition colonization in the development of allergic diseases, we implanted female C57BL/6 mice with A/J embryos to naturally modulate the microbial composition of A/J mice, which increased gut microbiota diversity and reduced eosinophilic inflammation in A/J. These data demonstrate the central importance of microbiota to allergic phenotype severity.
Interspecific competition in germination of bird-dispersed seeds in a habitat with sparse tree vegetation in South Africa
Authors: Vukeya L. R. , Mokotjomela T. M. , Malebo N. J. , Oke S.
Published: June 2021

Background

By transporting and scarifying the seeds during ingestion, avian frugivores reduce the competition with siblings, and may improve the germination which is critical for dispersal effectiveness and population recruitment. However, generally, there is limited knowledge on how deposited seeds interact/compete in the new microsite. We tested the hypothesis that the bird-dispersed seeds benefit from improved germination after their passage through the bird’s gut; and we investigated the potential impact of seed density on competition at the microsites by determining whether seed density and species diversity influence germination in the Free State Province, South Africa.

Results

Overall, the results partly supported the hypothesis. Germination trials with defecated seeds of five plant species compared with the manually depulped seeds showed that only Searsia lancea had significantly higher seed germination success and improved germination speed after passage through the bird gut while Ziziphus mucronata only benefited rapid germination. There was a significant correlation between seed size and the germination of bird-ingested seeds except in Olea subsp. africana possibly due to possession of extremely hard protective seed cover. Seed competition experiments pointed to Z. mucronata and O. subsp. africana having significant germination performance that was positively correlated to seed density and seed size while Ehretia rigida did not germinate at all. Seed species diversity in the germination trays did not have a significant impact since the seeds of two former plant species consistently displayed significantly higher germination across the competition levels.

Conclusions

We conclude that different plant species respond differently to seed ingestion by birds, and that further long-term tests for germination physiological responses of the seeds’ samples used in this study are required since poor germination observed in other tree/shrub species cannot be attributed to competition solely.