bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring preconception signatures of metabolites in mothers with gestational diabetes mellitus using a non-targeted approach
Authors: Li Ling-Jun , Wang Ximeng , Chong Yap Seng , Chan Jerry Kok Yen , Tan Kok Hian , Eriksson Johan G. , Huang Zhongwei , Rahman Mohammad L. , Cui Liang , Zhang Cuilin
Published: March 2023

Background

Metabolomic changes during pregnancy have been suggested to underlie the etiology of gestational diabetes mellitus (GDM). However, research on metabolites during preconception is lacking. Therefore, this study aimed to investigate distinctive metabolites during the preconception phase between GDM and non-GDM controls in a nested case–control study in Singapore.

Methods

Within a Singapore preconception cohort, we included 33 Chinese pregnant women diagnosed with GDM according to the IADPSG criteria between 24 and 28 weeks of gestation. We then matched them with 33 non-GDM Chinese women by age and pre-pregnancy body mass index (ppBMI) within the same cohort. We performed a non-targeted metabolomics approach using fasting serum samples collected within 12 months prior to conception. We used generalized linear mixed model to identify metabolites associated with GDM at preconception after adjusting for maternal age and ppBMI. After annotation and multiple testing, we explored the additional predictive value of novel signatures of preconception metabolites in terms of GDM diagnosis.

Results

A total of 57 metabolites were significantly associated with GDM, and eight phosphatidylethanolamines were annotated using HMDB. After multiple testing corrections and sensitivity analysis, phosphatidylethanolamines 36:4 (mean difference β: 0.07; 95% CI: 0.02, 0.11) and 38:6 (β: 0.06; 0.004, 0.11) remained significantly higher in GDM subjects, compared with non-GDM controls. With all preconception signals of phosphatidylethanolamines in addition to traditional risk factors (e.g., maternal age and ppBMI), the predictive value measured by area under the curve (AUC) increased from 0.620 to 0.843.

Conclusions

Our data identified distinctive signatures of GDM-associated preconception phosphatidylethanolamines, which is of potential value to understand the etiology of GDM as early as in the preconception phase. Future studies with larger sample sizes among alternative populations are warranted to validate the associations of these signatures of metabolites and their predictive value in GDM.
Strategies to inTerrupt RAbies Transmission for the Elimination Goal by 2030 In China (STRATEGIC): a modelling study
Authors: Chen Qiulan , Liu Qiuping , Gong Chao , Yin Wenwu , Mu Di , Li Yu , Ding Shujun , Liu Yifang , Yang Hao , Zhou Shuwu , Chen Sa , Tao Zhongfa , Zhang Yanping , Tang Xun
Published: March 2023

Background

A global plan has been set to end human deaths from dog-mediated rabies by 2030 ("Zero-by-30"), but whether it could be achieved in some countries, such as China, remains unclear. Although elimination strategies through post-exposure prophylaxis (PEP) use, dog vaccination, and patient risk assessments with integrated bite case management (IBCM) were proposed to be cost-effective, evidence is still lacking in China. We aim to evaluate the future burdens of dog-mediated human rabies deaths in the next decade and provide quantitative evidence on the cost-effectiveness of different rabies-control strategies in China.

Methods

Based on data from China's national human rabies surveillance system, we used decision-analytic modelling to estimate dog-mediated human rabies death trends in China till 2035. We simulated and compared the expected consequences and costs of different combination strategies of the status quo, improved access to PEP, mass dog vaccination, and use of IBCM.

Results

The predicted human rabies deaths in 2030 in China will be 308 (95%UI: 214–411) and remain stable in the next decade under the status quo. The strategy of improved PEP access alone could only decrease deaths to 212 (95%UI: 147–284) in 2028, remaining unchanged till 2035. In contrast, scaling up dog vaccination to coverage of 70% could eliminate rabies deaths by 2033 and prevent approximately 3,265 (95%UI: 2,477–3,687) extra deaths compared to the status quo during 2024–2035. Moreover, with the addition of IBCM, the "One Health" approach through mass dog vaccination could avoid unnecessary PEP use and substantially reduce total cost from 12.53 (95%UI: 11.71–13.34) to 8.73 (95%UI: 8.09–9.85) billion US dollars. Even if increasing the total costs of IBCM from 100 thousand to 652.10 million US dollars during 2024–2035, the combined strategy of mass dog vaccination and use of IBCM will still dominate, suggesting the robustness of our results.

Conclusions

The combined strategy of mass dog vaccination and IBCM requires collaboration between health and livestock/veterinary sectors, and it could eliminate Chinese rabies deaths as early as 2033, with more deaths averted and less cost, indicating that adding IBCM could reduce unnecessary use of PEP and make the "One Health" rabies-control strategy most cost-effective.
Dose-dependent effect of canine lyophilized platelet on an in vitro hemodilution model
Authors: Kim Mu-Young , Han Hyun-Jung
Published: March 2023

The transfusion of stored platelets has emerged as an efficient method for treating dogs with thrombocytopenia. However, the availability of fresh platelets is limited in veterinary medicine due to demanding storage conditions. Lyophilized platelets have long shelf lives and can be easily stored, increasing their accessibility for thrombocytopenic dogs. Due to the lack of research and information on the dose effect, canine lyophilized platelets are used at a clinical dosage without research-based evidence. This study was to evaluate the dose effect of lyophilized canine platelets on blood coagulability. Three different concentrations of lyophilized canine platelets were added to in vitro hemodilution blood model, increasing the platelet count by 25, 50, and 100 × 106/ml and coagulation profiles were analyzed. The coagulability was evaluated via the plasma fibrinogen concentration, coagulation time, thromboelastography (TEG), and platelet function analyzer (PFA). Higher concentrations of lyophilized platelets showed dose-dependent association with decreased aPTT and R-time of TEG and increased alpha angle and MA of TEG. These results showed the potential that the higher dose of canine lyophilized platelets better improve blood coagulability than the standard dose and provided the basis for further safety and clinical studies.
GAS6-AS1, a long noncoding RNA, functions as a key candidate gene in atrial fibrillation related stroke determined by ceRNA network analysis and WGCNA
Authors: Li Rui-bin , Yang Xiao-hong , Zhang Ji-dong , Cui Wei
Published: March 2023

Background

Stroke attributable to atrial fibrillation (AF related stroke, AFST) accounts for 13 ~ 26% of ischemic stroke. It has been found that AFST patients have a higher risk of disability and mortality than those without AF. Additionally, it’s still a great challenge to treat AFST patients because its exact mechanism at the molecular level remains unclear. Thus, it’s vital to investigate the mechanism of AFST and search for molecular targets of treatment. Long non-coding RNAs (lncRNAs) are related to the pathogenesis of various diseases. However, the role of lncRNAs in AFST remains unclear. In this study, AFST-related lncRNAs are explored using competing endogenous RNA (ceRNA) network analysis and weighted gene co-expression network analysis (WGCNA).

Methods

GSE66724 and GSE58294 datasets were downloaded from GEO database. After data preprocessing and probe reannotation, differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) between AFST and AF samples were explored. Then, functional enrichment analysis and protein-protein interaction (PPI) network analysis of the DEMs were performed. At the meantime, ceRNA network analysis and WGCNA were performed to identify hub lncRNAs. The hub lncRNAs identified both by ceRNA network analysis and WGCNA were further validated by Comparative Toxicogenomics Database (CTD).

Results

In all, 19 DELs and 317 DEMs were identified between the AFST and AF samples. Functional enrichment analysis suggested that the DEMs associated with AFST were mainly enriched in the activation of the immune response. Two lncRNAs which overlapped between the three lncRNAs identified by the ceRNA network analysis and the 28 lncRNAs identified by the WGCNA were screened as hub lncRNAs for further validation. Finally, lncRNA GAS6-AS1 turned out to be associated with AFST by CTD validation.

Conclusion

These findings suggested that low expression of GAS6-AS1 might exert an essential role in AFST through downregulating its downstream target mRNAs GOLGA8A and BACH2, and GAS6-AS1 might be a potential target for AFST therapy.
Development and validation of cuproptosis-related lncRNA signatures for prognosis prediction in colorectal cancer
Authors: Pang Lin , Wang Qingqing , Wang Lingxiao , Hu Zhen , Yang Chong , Li Yiqun , Wang Zhenqi , Li Yaoping
Published: March 2023

Background

Cuproptosis, a novel form of programmed cell death, plays an essential role in various cancers. However, studies of the function of cuproptosis lncRNAs (CRLs) in colorectal cancer (CRC) remain limited. Thus, this study aims to identify the cuprotosis-related lncRNAs (CRLs) in CRC and to construct the potential prognostic CRLs signature model in CRC.

Methods

First, we downloaded RNA-Seq data and clinical information of CRC patients from TCGA database and obtained the prognostic CRLs based on typical expression analysis of cuproptosis-related genes (CRGs) and univariate Cox regression. Then, we constructed a prognostic model using the Least Absolute Shrinkage and Selection Operator algorithm combined with multiple Cox regression methods (Lasso-Cox). Next, we generated Kaplan–Meier survival and receiver operating characteristic curves to estimate the performance of the prognostic model. In addition, we also analysed the relationships between risk signatures and immune infiltration, mutation, and drug sensitivity. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT -PCR) to verify the prognostic model.

Result

Lasso-Cox analysis revealed that four CRLs, SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, were related to CRC prognosis. Receiver operating characteristic (ROC) and Kaplan–Meier analysis curves indicated that this model performs well in prognostic predictions of CRC patients. The DCA results also showed that the model included four gene signatures was better than the traditional model. In addition, GO and KEGG analyses revealed that DE-CRLs are enriched in critical signalling pathway, such as chemical carcinogenesis-DNA adducts and basal cell carcinoma. Immune infiltration analysis revealed significant differences in immune infiltration cells between the high-risk and low-risk groups. Furthermore, significant differences in somatic mutations were noted between the high-risk and low-risk groups. Finally, we also validated the expression of four CRLs in FHCs cell lines and CRC cell lines using qRT-PCR.

Conclusion

The signature composed of SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, which has better performance in predicting colorectal cancer prognosis and are promising biomarkers for prognosis prediction of CRC.
Effects of gastroesophageal reflux disease treatment with proton pump inhibitors on the risk of acute exacerbation and pneumonia in patients with COPD
Authors: Kang Jieun , Lee Rugyeom , Lee Sei Won
Published: March 2023

Background

Gastroesophageal reflux disease (GERD) has been suggested as a risk factor for acute exacerbation of chronic obstructive pulmonary disease (COPD). However, it remains undetermined whether proton pump inhibitor (PPI) treatment reduces the risk of exacerbation or affects the risk of pneumonia. This study aimed to evaluate the risks of both exacerbation and pneumonia following PPI treatment for GERD in patients with COPD.

Methods

This study used a reimbursement database of the Republic of Korea. Patients aged ≥ 40 years with COPD as a main diagnosis and who received PPI treatment for GERD at least for 14 consecutive days between January 2013 and December 2018 were included in the study. A self-controlled case series analysis was conducted to calculate the risk of moderate and severe exacerbation and pneumonia.

Results

A total of 104,439 patients with prevalent COPD received PPI treatment for GERD. The risk of moderate exacerbation was significantly lower during the PPI treatment than at baseline. The risk of severe exacerbation increased during the PPI treatment but significantly decreased in the post-treatment period. Pneumonia risk was not significantly increased during the PPI treatment. The results were similar in patients with incident COPD.

Conclusions

The risk of exacerbation was significantly reduced after PPI treatment compared with the non-treated period. Severe exacerbation may increase due to uncontrolled GERD but subsequently decrease following PPI treatment. There was no evidence of an increased risk of pneumonia.
National, subnational and risk attributed burden of chronic respiratory diseases in Iran from 1990 to 2019
Authors: Heidari-Foroozan Mahsa , Aryan Alisam , Esfahani Zahra , Shahrbaf Mohammad Amin , Moghaddam Sahar Saeedi , Keykhaei Mohammad , Ghasemi Erfan , Rashidi Mohammad-Mahdi , Rezaei Nazila , Ghamari Seyyed-Hadi , Abbasi-Kangevari Mohsen , Fateh Sahar Mohammadi , Farzi Yousef , Rezaei Negar , Larijani Bagher
Published: March 2023

Introduction

Data on the distribution of the burden of diseases is vital for policymakers for the appropriate allocation of resources. In this study, we report the geographical and time trends of chronic respiratory diseases (CRDs) in Iran from 1990 to 2019 based on the Global burden of the Disease (GBD) study 2019.

Methods

Data were extracted from the GBD 2019 study to report the burden of CRDs through disability-adjusted life years (DALYs), mortality, incidence, prevalence, Years of Life lost (YLL), and Years Lost to Disability (YLD). Moreover, we reported the burden attributed to the risk factors with evidence of causation at national and subnational levels. We also performed a decomposition analysis to determine the roots of incidence changes. All data were measured as counts and age-standardized rates (ASR) divided by sex and age group.

Results

In 2019, the ASR of deaths, incidence, prevalence, and DALYs attributed to CRDs in Iran were 26.9 (23.2 to 29.1), 932.1 (799.7 to 1091.5), 5155.4 (4567.2 to 5859.6) and 587,911 (521,418 to 661,392) respectively. All burden measures were higher in males than females, but in older age groups, CRDs were more incident in females than males. While all crude numbers increased, all ASRs except for YLDs decreased over the studied period. Population growth was the main contributor to the changes in incidence at a national and subnational levels. The ASR of mortality in the province (Kerman) with the highest death rate (58.54 (29.42 to 68.73) was four times more than the province (Tehran) with the lowest death rate (14.52 (11.94 to 17.64)). The risk factors which imposed the most DALYs were smoking (216 (189.9 to 240.8)), ambient particulate matter pollution (117.9 (88.1 to 149.4)), and high body mass index (BMI) (57 (36.3 to 81.8)). Smoking was also the main risk factor in all provinces.

Conclusion

Despite the overall decrease in ASR of burden measures, the crude counts are rising. Moreover, the ASIR of all CRDs except asthma is increasing. This suggests that the overall incidence of CRDs will continue to grow in the future, which calls for immediate action to reduce exposure to the known risk factors. Therefore, expanded national plans by policymakers are essential to prevent the economic and human burden of CRDs.
Dietary patterns, lung function and asthma in childhood: a longitudinal study
Authors: Talaei Mohammad , Emmett Pauline M. , Granell Raquel , Tabatabaeian Hossein , Northstone Kate , Bergström Anna , Shaheen Seif O.
Published: March 2023

Background

Longitudinal epidemiological data are scarce examining the relationship between dietary patterns and respiratory outcomes in childhood. We investigated whether three distinct dietary patterns in mid-childhood were associated with lung function and incident asthma in adolescence.

Methods

In the Avon Longitudinal Study of Parents and Children, ‘processed’, ‘traditional’, and ‘health-conscious’ dietary patterns were identified using principal components analysis from food frequency questionnaires at 7 years of age. Post-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25–75% of FVC (FEF25–75) were measured at 15.5 years and were transformed to z-scores based on the Global Lung Function Initiative curves. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years.

Results

In multivariable-adjusted models, the ‘health-conscious’ pattern was positively associated with FEV1 (regression coefficient comparing top versus bottom quartile of pattern score 0.16, 95% CI 0.01 to 0.31, P for trend 0.04) and FVC (0.18, 95% CI 0.04 to 0.33, P for trend 0.02), while the ‘processed’ pattern was negatively associated with FVC (− 0.17, 95% CI − 0.33 to − 0.01, P for trend 0.03). Associations between the ‘health-conscious’ and ‘processed’ patterns and lung function were modified by SCGB1A1 and GPX4 gene polymorphisms. We found no evidence of an association between the ‘traditional’ pattern and lung function, nor between any pattern and FEF25–75 or incident asthma.

Conclusions

A ‘health-conscious’ diet in mid-childhood was associated with higher subsequent lung function, while a diet high in processed food was associated with lower lung function.
Pseudomonas aeruginosa isolation is an important predictor for recurrent hemoptysis after bronchial artery embolization in patients with idiopathic bronchiectasis: a multicenter cohort study
Authors: Wang Le-Le , Lu Hai-Wen , Li Ling-Ling , Gao Yong-Hua , Xu Yu-Hua , Li Hong-Xiao , Xi Yun-Zhu , Jiang Fu-Sheng , Ling Xue-Feng , Wei Wei , Li Fa-Jiu , Mao Bei , Jiang Sen , Xu Jin-Fu
Published: March 2023

Background

Nearly half of bronchiectasis patients receiving bronchial artery embolization (BAE) still have recurrent hemoptysis, which may be life-threatening. Worse still, the underlying risk factors of recurrence remain unknown.

Methods

A retrospective cohort was conducted of patients with idiopathic bronchiectasis who received BAE from 2015 to 2019 at eight centers. Patients were followed up for at least 24 months post BAE. Based on the outcomes of recurrent hemoptysis and recurrent severe hemoptysis, a Cox regression model was used to identify risk factors for recurrence.

Results

A total of 588 individuals were included. The median follow-up period was 34.0 months (interquartile range: 24.3–53.3 months). The 1-month, 1-year, 2-year, and 5-year cumulative recurrent hemoptysis-free rates were 87.2%, 67.5%, 57.6%, and 49.4%, respectively. The following factors were relative to recurrent hemoptysis: 24-h sputum volume (hazard ratio [HR] = 1.99 [95% confidence interval [95% CI]: 1.25–3.15, p = 0.015]), isolation of Pseudomonas aeruginosa (HR = 1.50 [95% CI: 1.13–2.00, p = 0.003]), extensive bronchiectasis (HR = 2.00 [95% CI: 1.29–3.09, p = 0.002]), and aberrant bronchial arteries (AbBAs) (HR = 1.45 [95% CI: 1.09–1.93, p = 0.014]). The area under the receiver operating characteristic curve of the nomogram was 0.728 [95% CI: 0.688–0.769].

Conclusions

Isolation of Pseudomonas aeruginosa is an important independent predictor of recurrent hemoptysis. The clearance of Pseudomonas aeruginosa might effectively reduce the hemoptysis recurrence rate.
No increased prevalence of autoantibodies neutralizing type I IFNs in idiopathic pulmonary fibrosis patients
Authors: Philippot Quentin , Bastard Paul , Puel Anne , Casanova Jean-Laurent , Cobat Aurélie , Laouénan Cédric , Tardivon Coralie , Crestani Bruno , Borie Raphael
Published: March 2023

SARS-CoV2 infection has a poor prognosis in patients affected of idiopathic pulmonary fibrosis (IPF). Autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) are found in the blood of at least 15% of patients with life-threatening COVID-19 pneumonia. Because of the elevated prevalence of some auto-Abs in IPF patients, we hypothesize that the prevalence of auto-Abs neutralizing type I IFNs might be increased in the IPF population and then explained specific poor outcome after COVID-19. We screened the plasma of 247 consecutive IPF patients for the presence of auto-Abs neutralizing type I IFNs. Three patients displayed auto-Abs neutralizing type I IFNs. Among them, the only patient with documented SARS-CoV-2 infection experienced life threatening COVID-19 pneumonia. The prevalence of auto-Abs neutralizing type I IFNs in this cohort of IPF patients was not significantly different from the one of the general population. Overall, this study did not suggest any association between auto-Abs neutralizing type I IFNs and IPF.
Association of the triglyceride–glucose index with coronary artery disease complexity in patients with acute coronary syndrome
Authors: Xiong Shiqiang , Chen Qiang , Long Yu , Su Hong , Luo Yan , Liu Hanxiong , Chen Yingzhong , Feng Qiao , Peng Xiufen , Jiang Maoling , Yu Xiuqiong , Zhang Zhen , Cai Lin
Published: March 2023

Aim

The triglyceride–glucose (TyG) index has been shown to be an independent predictor for the progression and prognosis of coronary artery disease (CAD). Whether the TyG index predicts the severity of CAD in patients presenting with acute coronary syndrome (ACS) remains unknown.

Methods

A total of 1,007 individuals presenting with ACS undergoing coronary angiography were stratified according to the tertiles of the TyG index and The Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score ≤ 22 versus SYNTAX score > 22). CAD complexity was determined by the SYNTAX score.

Results

After adjusting for multiple confounding factors, the TyG index was still an independent risk factor for mid/high SYNTAX scores (SYNTAX score > 22, OR 2.6452, 95% CI 1.9020–3.6786, P < 0.0001). Compared with the lowest tertile of the TyG (T1) group, the risk for a mid/high SYNTAX score in the T2 and T3 groups was 2.574-fold higher (OR, 2.574; 95% CI 1.610–4.112; P < 0.001) and 3.732-fold higher (OR, 3.732; 95% CI 2.330–5.975; P < 0.001), respectively. Furthermore, there was a dose‒response relationship between the TyG index and the risk of complicated CAD (SYNTAX score > 22; nonlinear P = 0.200). The risk for a mid/high SYNTAX score in the T2 and T3 groups was significantly higher in normoglycemia, prediabetes mellitus, and diabetes mellitus subgroups.

Conclusions

A higher TyG index was associated with the presence of a higher coronary anatomical complexity (SYNTAX score > 22) in ACS patients, irrespective of diabetes mellitus status. The TyG index might serve as a noninvasive predictor of CAD complexity in ACS patients and could potentially influence the management and therapeutic approach.
Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction
Authors: Gonzalez Jimmy , Bates Benjamin A. , Setoguchi Soko , Gerhard Tobias , Dave Chintan V.
Published: March 2023

Background

No study has compared the cardiovascular outcomes for sodium–glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)—which also have cardiovascular benefits—in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction.

Methods

Medicare fee-for-service data (2013–2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting.

Results

Among HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses.

Conclusions

Bias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.
PNPLA3 rs738409 risk genotype decouples TyG index from HOMA2-IR and intrahepatic lipid content
Authors: Nádasdi Ákos , Gál Viktor , Masszi Tamás , Somogyi Anikó , Firneisz Gábor
Published: March 2023

Background

Recent reports suggested a different predictive value for TyG index compared to HOMA-IR in coronary artery calcification (CAC) and other atherosclerotic outcomes, despite that both indices are proposed as surrogate markers of insulin resistance. We hypothesized a key role for liver pathology as an explanation and therefore assessed the relationship among the two indices and the intrahepatic lipid content stratified byPNPLA3rs738409 genotypes as a known non-alcoholic fatty liver disease (NAFLD) genetic risk.

Methods

Thirty-nine women from a prior GDM-genetic study were recalled withPNPLA3rs738409CCandGGgenotypes for metabolic phenotyping and to assess hepatic triglyceride content (HTGC). 75 g OGTT was performed, fasting lipid, glucose, insulin levels and calculated insulin resistance indices (TyG and HOMA2-IR) were used. HTGC was measured by MR based methods. Mann–Whitney-U, χ2and for the correlation analysis Spearman rank order tests were applied.

Results

ThePNPLA3rs738409 genotype had a significant effect on the direct correlation between the HOMA2-IR and TyG index: the correlation (R = 0.52, p = 0.0054) found in theCCgroup was completely abolished in those with theGG(NAFLD) risk genotype. In addition, the HOMA2-IR correlated with HTGC in the entire study population (R = 0.69, p < 0.0001) and also separately in both genotypes (CCR = 0.62, p = 0.0006,GG: R = 0.74, p = 0.0058). In contrast, the correlation between TyG index and HTGC was only significant in rs738409CCgenotype group (R = 0.42, p = 0.0284) but not inGGgroup. A similar pattern was observed in the correlation between TG and HTGC (CC: R = 0.41, p = 0.0335), when the components of the TyG index were separately assessed.

Conclusions

PNPLA3rs738409 risk genotype completely decoupled the direct correlation between two surrogate markers of insulin resistance: TyG and HOMA2-IR confirming our hypothesis. The liver lipid content increased in parallel with the HOMA2-IR independent of genotype, in contrast to the TyG index where the risk genotype abolished the correlation. This phenomenon seems to be related to the nature of hepatic fat accumulation and to the different concepts establishing the two insulin resistance markers.
CT-derived fractional flow reserve for prediction of major adverse cardiovascular events in diabetic patients
Authors: Lan Ziting , Ding Xiaoying , Yu Yarong , Yu Lihua , Yang Wenli , Dai Xu , Ling Runjianya , Wang Yufan , Yang Wenyi , Zhang Jiayin
Published: March 2023

Objectives

To investigate the prognostic value of computed tomography fractional flow reserve (CT-FFR) in patients with diabetes and to establish a risk stratification model for major adverse cardiac event (MACE).

Methods

Diabetic patients with intermediate pre-test probability of coronary artery disease were prospectively enrolled. All patients were referred for coronary computed tomography angiography and followed up for at least 2 years. In the training cohort comprising of 957 patients, two models were developed: model1 with the inclusion of clinical and conventional imaging parameters, model2 incorporating the above parameters + CT-FFR. An internal validation cohort comprising 411 patients and an independent external test cohort of 429 patients were used to validate the proposed models.

Results

1797 patients (mean age: 61.0 ± 7.0 years, 1031 males) were finally included in the present study. MACE occurred in 7.18% (129/1797) of the current cohort during follow- up. Multivariate Cox regression analysis revealed that CT-FFR ≤ 0.80 (hazard ratio [HR] = 4.534, p < 0.001), HbA1c (HR = 1.142, p = 0.015) and low attenuation plaque (LAP) (HR = 3.973, p = 0.041) were the independent predictors for MACE. In the training cohort, the Log-likelihood test showed statistical significance between model1 and model2 (p < 0.001). The C-index of model2 was significantly larger than that of model1 (C-index = 0.82 [0.77–0.87] vs. 0.80 [0.75–0.85], p = 0.021). Similar findings were found in internal validation and external test cohorts.

Conclusion

CT-FFR was a strong independent predictor for MACE in diabetic cohort. The model incorporating CT-FFR, LAP and HbA1c yielded excellent performance in predicting MACE.
ncRNAs-mediated overexpression of STIL predict unfavorable prognosis and correlated with the efficacy of immunotherapy of hepatocellular carcinoma
Authors: Xu Longwen , Zhang Shirong , Feng Jinteng , Tan Deli , Sun Hong , Guo Hui
Published: March 2023

Background

STIL centriolar assembly protein (STIL) is a cytoplasmic protein implicated in cellular growth and proliferation as well as chromosomal stability, which abnormal condition affected tumor immunity and tumor progression. However, the role of STIL in the biological mechanism of hepatocellular carcinoma (HCC) remains unclear.

Methods

Comprehensive bioinformatic approaches, in vitro functional assays, and validation were conducted to elucidate the oncogenic value of STIL in HCC.

Results

In the present study, we found that STIL may serve as an independent prognostic indicator and a potential oncogene in HCC. Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA) showed that upregulated expression of STIL was positively associated with pathways enriched in the cell cycle and DNA damage response. Subsequently, we identified several non-coding RNAs (ncRNAs) accounting for the upregulation of STIL expression using a combination of in silico bioinformatics approaches (including expression analysis, correlation analysis, and survival analysis). Finally, CCNT2-AS1/SNHG1-has-miR-204-5p-STIL axis was screened out as the most potential upstream ncRNA-related pathway of STIL in HCC. Moreover, STIL expression is highly associated with the infiltration of immune cells, the expression of immune checkpoints, as well as the survival benefit of immunotherapy/chemotherapy.

Conclusions

Our study discloses that ncRNAs-mediated overexpression of STIL independently predicted poor prognosis and correlated with the efficacy of PD-1-targeted immunotherapy in HCC.
Hypoxia-responsive circular RNA circAAGAB reduces breast cancer malignancy by activating p38 MAPK and sponging miR-378 h
Authors: Lee Kuan-Yi , Liu Chia-Ming , Chen Li-Han , Lee Chien-Yueh , Lu Tzu-Pin , Chuang Li-Ling , Lai Liang-Chuan
Published: March 2023

Background

Breast cancer is a prevalent disease in women, with high prevalence worldwide. The hypoxic microenvironment of solid tumors develops during the progress of carcinogenesis and leads to greater malignancy and treatment resistance. Recently, accumulating evidence indicates that non-coding RNAs, such as circular RNAs (circRNAs), play a pivotal role in altering cellular functions. However, the underlying mechanisms of circRNAs in breast cancer are still unclear. Therefore, the purpose of this study was to investigate the role of a tumor-suppressive circRNA, circAAGAB, in breast cancer by assuming down-regulation of circAAGAB under hypoxia and the properties of a tumor suppressor.

Methods

Firstly, circAAGAB was identified from expression profiling by next generation sequencing. Next, the stability of circAAGAB increased by interacting with the RNA binding protein FUS. Moreover, cellular and nuclear fractionation showed that most circAAGAB resided in the cytoplasm and that it up-regulated KIAA1522, NKX3-1, and JADE3 by sponging miR-378 h. Lastly, the functions of circAAGAB were explored by identifying its down-stream genes using Affymetrix microarrays and validated by in vitro assays.

Results

The results showed that circAAGAB reduced cell colony formation, cell migration, and signaling through p38 MAPK pathway, as well as increased radiosensitivity.

Conclusion

These findings suggest that the oxygen-responsive circAAGAB acts as a tumor suppressor in breast cancer, and may contribute to the development of a more specific therapeutic regimen for breast cancer.
Trends of insecticide resistance monitoring in mainland Tanzania, 2004–2020
Authors: Tungu Patrick , Kabula Bilali , Nkya Theresia , Machafuko Pendael , Sambu Edward , Batengana Bernard , Sudi Wema , Derua Yahaya A. , Mwingira Victor , Masue Denis , Malima Robert , Kitojo Chonge , Serbantez Naomi , Reaves Erik J. , Mwalimu Charles , Nhiga Samwel L. , Ally Mohamed , Mkali Humphrey R. , Joseph Joseph J. , Chan Adeline , Ngondi Jeremiah , Lalji Shabbir , Nyinondi Ssanyu , Eckert Erin , Reithinger Richard , Magesa Stephen , Kisinza William N.
Published: March 2023

Background

Insecticide resistance is a serious threat to the continued effectiveness of insecticide-based malaria vector control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This paper describes trends and dynamics of insecticide resistance and its underlying mechanisms from annual resistance monitoring surveys on Anopheles gambiae sensu lato (s.l.) populations conducted across mainland Tanzania from 2004 to 2020.

Methods

The World Health Organization (WHO) standard protocols were used to assess susceptibility of the wild female An. gambiae s.l. mosquitoes to insecticides, with mosquitoes exposed to diagnostic concentrations of permethrin, deltamethrin, lambdacyhalothrin, bendiocarb, and pirimiphos-methyl. WHO test papers at 5× and 10× the diagnostic concentrations were used to assess the intensity of resistance to pyrethroids; synergist tests using piperonyl butoxide (PBO) were carried out in sites where mosquitoes were found to be resistant to pyrethroids. To estimate insecticide resistance trends from 2004 to 2020, percentage mortalities from each site and time point were aggregated and regression analysis of mortality versus the Julian dates of bioassays was performed.

Results

Percentage of sites with pyrethroid resistance increased from 0% in 2004 to more than 80% in the 2020, suggesting resistance has been spreading geographically. Results indicate a strong negative association (p = 0.0001) between pyrethroids susceptibility status and survey year. The regression model shows that by 2020 over 40% of An. gambiae mosquitoes survived exposure to pyrethroids at their respective diagnostic doses. A decreasing trend of An. gambiae susceptibility to bendiocarb was observed over time, but this was not statistically significant (p = 0.8413). Anopheles gambiae exhibited high level of susceptibility to the pirimiphos-methyl in sampled sites.

Conclusions

Anopheles gambiae Tanzania’s major malaria vector, is now resistant to pyrethroids across the country with resistance increasing in prevalence and intensity and has been spreading geographically. This calls for urgent action for efficient malaria vector control tools to sustain the gains obtained in malaria control. Strengthening insecticide resistance monitoring is important for its management through evidence generation for effective malaria vector control decision.
Effectiveness of community case management of malaria on severe malaria and inpatient malaria deaths in Zambia: a dose–response study using routine health information system data
Authors: Ashton Ruth A. , Hamainza Busiku , Lungu Chris , Rutagwera Marie-Reine I. , Porter Travis , Bennett Adam , Hainsworth Michael , Burnett Sarah , Silumbe Kafula , Slater Hannah , Eisele Thomas P. , Miller John M.
Published: March 2023

Background

Community case management of malaria (CCM) has been expanded in many settings, but there are limited data describing the impact of these services in routine implementation settings or at large scale. Zambia has intensively expanded CCM since 2013, whereby trained volunteer community health workers (CHW) use rapid diagnostic tests and artemether-lumefantrine to diagnose and treat uncomplicated malaria.

Methods

This retrospective, observational study explored associations between changing malaria service point (health facility or CHW) density per 1000 people and severe malaria admissions or malaria inpatient deaths by district and month in a dose–response approach, using existing routine and programmatic data. Negative binomial generalized linear mixed-effect models were used to assess the impact of increasing one additional malaria service point per 1000 population, and of achieving Zambia’s interim target of 1 service point per 750 population. Access to insecticide-treated nets, indoor-residual spraying, and rainfall anomaly were included in models to reduce potential confounding.

Results

The study captured 310,855 malaria admissions and 7158 inpatient malaria deaths over 83 districts (seven provinces) from January 2015 to May 2020. Total CHWs increased from 43 to 4503 during the study period, while health facilities increased from 1263 to 1765. After accounting for covariates, an increase of one malaria service point per 1000 was associated with a 19% reduction in severe malaria admissions among children under five (incidence rate ratio [IRR] 0.81, 95% confidence interval [CI] 0.75–0.87, p < 0.001) and 23% reduction in malaria deaths among under-fives (IRR 0.77, 95% CI 0.66–0.91). After categorizing the exposure of population per malaria service point, there was evidence for an effect on malaria admissions and inpatient malaria deaths among children under five only when reaching the target of one malaria service point per 750 population.

Conclusions

CCM is an effective strategy for preventing severe malaria and deaths in areas such as Zambia where malaria diagnosis and treatment access remains challenging. These results support the continued investment in CCM scale-up in similar settings, to improve access to malaria diagnosis and treatment.
Two decades of capacity building to support global malaria control and elimination: retrospective and prospective international trainings in Jiangsu Institute of Parasitic Diseases, China, 2002–2021
Authors: Liang Cheng , Ke Xuedan , Cao Yuanyuan , Wang Weiming , Yang Mengmeng , Wang Jie , Hugo Cecilia T. , Ortega Leonard , Gonzales Glenda , Zhu Guoding , Cao Jun
Published: March 2023

Background

Malaria is still one of the major infectious diseases affecting human health, and the World Health Organization (WHO) has attached special importance to malaria-related technical training for its global elimination efforts. The Jiangsu Institute of Parasitic Diseases (JIPD), designated as a WHO Collaborating Centre for Research and Training on Malaria Elimination, has conducted numerous international malaria training programmes during the last 2 decades.

Methods

A retrospective analysis of international training programmes organized and facilitated by JIPD in China since 2002 was conducted. A web-based questionnaire was designed to gather respondents’ basic information, evaluation of course topics, methodology, trainers, and facilitators, course impact, and suggestions for future trainings. Individuals who participated in the training courses from 2017 to 2019 were invited to participate in this assessment.

Results

Since 2002, JIPD has conducted 62 malaria-related international trainings attended by 1935 participants from 85 countries, covering 73% of malaria endemic countries. Of 752 participants enrolled, 170 responded to the online survey. A majority of respondents (160/170, 94.12%) gave a high evaluation of the training, with an average score of 4.52 (5 maximum score). Also, survey respondents gave a 4.28 score on “knowledge and skills gained in the training useful for the national malaria programme”, 4.52 on “topics appropriate to their professional needs”, and 4.52 on “knowledge and skills gained in the training useful to their career”. Surveillance and response was the most important topic discussed and field visit was the most effective method of training. For future training programmes, with increasing length of training, more field visits and demonstration, improving language barrier, and sharing experience were what the respondents requested most.

Conclusion

JIPD, as a professional institute for malaria control, has conducted a great quantity of training in the past 20 years, providing training opportunities to both malaria and non-malaria endemic countries globally. For future training, survey respondents’ suggestions will be considered to provide a more effective capacity building activity to better contribute to global malaria elimination.
Effects of maternal antenatal treatment with two doses of azithromycin added to monthly sulfadoxine-pyrimethamine for the prevention of low birth weight in Burkina Faso: an open-label randomized controlled trial
Authors: Lingani Moussa , Zango Serge H. , Valéa Innocent , Samadoulougou Sékou , Somé Georges , Sanou Maïmouna , Kaboré Berenger , Rouamba Toussaint , Sorgho Herman , Tahita Marc C. , Derra Karim , Dramaix Michèle , Tinto Halidou , Donnen Philippe , Robert Annie
Published: March 2023

Background

Exposure during pregnancy to malaria and sexually-transmitted infections is associated with adverse birth outcomes including low birth weight (LBW). This study aimed at assessing if the adjunction of two doses of azithromycin to sulfadoxine-pyrimethamine for the intermittent preventive treatment of malaria in pregnancy can reduce LBW.

Methods

A two parallel-groups, open-label randomized controlled trial involving pregnant women (16 to 35 years of age and 12 to 24 weeks of gestation as confirmed by last menstrual period or fundal height) was conducted in rural Burkina Faso. Women were assigned in a 1:1 ratio either to use azithromycin (1 g daily for 2 days) during the second and third trimesters of pregnancy plus monthly sulfadoxine-pyrimethamine (1500/75 mg) (SPAZ) (intervention) or to continue using a monthly sulfadoxine-pyrimethamine (1500/75 mg) (SP) (control). Primary outcome was a LBW (birth weight measured within 24 h after birth < 2500 g). Secondary outcomes including stillbirth, preterm birth or miscarriage are reported together with safety data.

Results

A total of 992 pregnant women underwent randomization (496 per group) and 898 (90.5%) valid birth weights were available (450 in SPAZ and 448 in SP). LBW incidence was 8.7% (39/450) in SPAZ and 9.4% (42/448) in controls (p-value = 0.79). Compared with controls, pregnant women with SPAZ showed a risk ratio (RR) of 1.16 (95% confidence interval (CI 0.64–2.08]) for preterm births, 0.75 (95% CI 0.17–3.35) for miscarriage and 0.64 (95% CI 0.25–1.64) for stillbirths. No treatment-related serious adverse events (SAEs) have been observed, and there was no significant difference in the number of SAEs (13.5% [67/496] in SPAZ, 16.7% [83/496] in SP, p-value = 0.18) or AEs (17.1% [85/496] in SPAZ, 18.8% [93/496] in SP, p-value = 0.56).

Conclusion

Adequate prevention regimen with monthly sulfadoxine-pyrimethamine given to all pregnant women has been proved to reduce the risk of LBW in malaria endemic areas. Adding azithromycin to the regimen does not offer further benefits, as far as women receive a malaria prevention regimen early enough during pregnancy.

Trial registration Pan African Clinical Trial Registry (https://pactr.samrc.ac.za/Search.aspx): PACTR201808177464681. Registered 21 August 2018.
Mapping current and future thermal limits to suitability for malaria transmission by the invasive mosquito Anopheles stephensi
Authors: Ryan Sadie J. , Lippi Catherine A. , Villena Oswaldo C. , Singh Aspen , Murdock Courtney C. , Johnson Leah R.
Published: March 2023

Background

Anopheles stephensi is a malaria-transmitting mosquito that has recently expanded from its primary range in Asia and the Middle East, to locations in Africa. This species is a competent vector of both Plasmodium falciparum and Plasmodium vivax malaria. Perhaps most alarming, the characteristics of An. stephensi, such as container breeding and anthropophily, make it particularly adept at exploiting built environments in areas with no prior history of malaria risk.

Methods

In this paper, global maps of thermal transmission suitability and people at risk (PAR) for malaria transmission by An. stephensi were created, under current and future climate. Temperature-dependent transmission suitability thresholds derived from recently published species-specific thermal curves were used to threshold gridded, monthly mean temperatures under current and future climatic conditions. These temperature driven transmission models were coupled with gridded population data for 2020 and 2050, under climate-matched scenarios for future outcomes, to compare with baseline predictions for 2020 populations.

Results

Using the Global Burden of Disease regions approach revealed that heterogenous regional increases and decreases in risk did not mask the overall pattern of massive increases of PAR for malaria transmission suitability with An. stephensi presence. General patterns of poleward expansion for thermal suitability were seen for both P. falciparum and P. vivax transmission potential.

Conclusions

Understanding the potential suitability for An. stephensi transmission in a changing climate provides a key tool for planning, given an ongoing invasion and expansion of the vector. Anticipating the potential impact of onward expansion to transmission suitable areas, and the size of population at risk under future climate scenarios, and where they occur, can serve as a large-scale call for attention, planning, and monitoring.