bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pivotal Role of miRNA-21 in Myocardial Metabolic Flexibility in Response to Short- and Long-term High Glucose Treatment: Evidence in Human Cardiomyocyte Cell Line
Authors: Scisciola Lucia , Benedetti Rosaria , Chianese Ugo , Fontanella Rosaria Anna , Gaudio Nunzio Del , Marfella Raffaele , Surina Surina , Altucci Lucia , Barbieri Michelangela , Paolisso Giuseppe 
Published: March 2022

Abstract
BackgroundmiRNA-21 is a micro-RNA widely studied for its implications in several biological functions, including apoptosis, inflammation, fibrosis, and metabolism. Interestingly, miRNA-21 is a crucial regulator of developing cardiac diseases, but its role is controversial, and it is necessary to clarify its function in pathophysiological events of diabetic cardiomyopathy. In the present study we clarified the protective role of miRNA-21 at cardiac level and evaluated the involvement of miRNA-21 in high glucose induced-acute and chronic cardiac damage. MethodsHuman ventricular cardiac myoblasts AC16, treated and not with miR-21 inhibitor, were exposed to high glucose (33 mM) for 2 and 7 days, and the expression of fibrosis, inflammation, apoptosis, oxidative stress markers were assessed using western blotting. Further, cardiac energetic metabolism was evaluated by measuring both the expression of glucose transporters and regulators of lipids using western blotting analysis and key mitochondrial function parameters (oxygen consumption rate and proton production rate) using Seahorse technology.ResultsShort-term high glucose treatment induced a significant increase in miR-21 expression (p<0.05) that was associated with an increase in hydrogen ion flux and energy potential dissipation without any change in energy production or increase in the expression of genes involved in cellular damage. The reduction of miR-21 expression levels (p<0.05), observed after long-term (7 days) high glucose treatment, induced the activation of inflammation, apoptosis pathways and compromises mitochondrial function as demonstrated by the incapacity to answer energy demand and the impairment of physiological mitochondrial function (p<0.05).ConclusionIn human cardiomyocytes, the abundance of miR-21 takes part in the first defense mechanism against cardiac insult and its cardioprotective effect depends on the time of exposure to the injury. Moreover, miRNA-21regulates mitochondrial respiration and the ability of cells to select the most appropriate substrate for ATP production in a given environment.
Patient-specific assays based on whole-genome sequencing data to measure residual disease in children with acute lymphoblastic leukemia – a proof-of- concept study
Authors: Arthur C , Rezayee F , Mogensen N , Saft L , Rosenquist R , Nordenskjöld M , Harila-Saari A , Tham E , Barbany G 
Published: March 2022

Abstract
Risk-adapted treatment in acute lymphoblastic leukemia (ALL) relies on genetic information and measurable residual disease (MRD) monitoring. In this proof-of-concept study, DNA from diagnostic bone marrow from six children with ALL, without stratifying genetics or CNS involvement, underwent whole-genome sequencing to identify structural variants (SVs) in the leukemic blasts. Unique sequences generated by SVs were targeted with patient-specific droplet digital PCR assays, and genomic and cell-free DNA (cfDNA) from bone marrow, plasma and cerebrospinal fluid were analyzed longitudinally. The results indicate that this approach is a feasible option for accurate MRD quantification and that cfDNA may contribute valuable information regarding MRD and low-grade CNS involvement.
Activation of the Chemokine Receptor 3 Pathway Leads to a Better Response to Immune Checkpoint Inhibitors in Patients with Metastatic Urothelial Carcinoma
Authors: Feng Wenqin , Lin Anqi , Sun Le , Wei Ting , Ying Haoxuan , Zhang Jian , Luo Peng , Zhu Weiliang 
Published: March 2022

Abstract
Immune checkpoint inhibitors (ICIs) have made important breakthrough in anti-tumor therapy, however, no single biomarker can accurately predict their efficacy. Studies have found that tumor microenvironment is a key factor for determining the response to ICI therapy. Cytokine receptor 3 (C-X-C Motif Chemokine Receptor 3, CXCR3) pathway has been reported to play an important role in the migration, activation, and response of immune cells. We analyzed survival data, genomics, and clinical data from patients with metastatic urothelial carcinoma (mUC) who received ICI treatment to explore the relationship between CXCR3 pathway activation and the effectiveness of ICIs. The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort and six other cohorts receiving ICI treatment were used for mechanism exploration and validation. In the ICI cohort, we performed univariate and multivariate COX analyses and discovered that patients in the CXCR3-high group were more sensitive to ICI treatment. A Kaplan-Meier analysis demonstrated that patients in the high CXCR3-high group had a better prognosis than those in the CXCR3-low group (P=0.0001, Hazard Ratio=0.56; 95% CI: 0.42−0.75). CIBERSORT analysis found that mUC patients in the CXCR3-high group had higher levels of activated CD8+ T cells, M1 macrophages, and activated NK cells and less regulatory T cell (Treg) infiltration. Immunogenicity analysis showed the CXCR3-high group had higher tumor neoantigen burden (TNB). Our study suggests that CXCR3 pathway activation may be a novel predictive biomarker for the effectiveness of immunotherapy in mUC patients.
PreCoF: Counterfactual Explanations for Fairness
Authors: Goethals Sofie , Martens David , Calders Toon 
Published: March 2022

Abstract
This paper studies how counterfactual explanations can be used to assess the fairness of a model. Using machine learning for high-stakes decisions is a threat to fairness as these models can amplify bias present in the dataset, and there is no consensus on a universal metric to detect this. The appropriate metric and method to tackle the bias in a dataset will be case-dependent, and it requires insight into the nature of the bias first. We aim to provide this insight by integrating explainable AI (XAI) research with the fairness domain. More specifically, apart from being able to use (Predictive) Counterfactual Explanations to detect explicit bias when the model is directly using the sensitive attribute, we show that it can also be used to detect implicit bias when the model does not use the sensitive attribute directly but does use other correlated attributes leading to a substantial disadvantage for a protected group. We call this metric $PreCoF$, or Predictive Counterfactual Fairness. Our experimental results show that our metric succeeds in detecting occurrences of implicit bias in the model by assessing which attributes are more present in the explanations of the protected group compared to the unprotected group. These results could help policymakers decide on whether this discrimination is justified or not.
High Glucose-Induced ROS-Accumulation in Zebrafish Larvae Leads to Mitochondria- Mediated Apoptosis
Authors: Li Yaoqi , Chen Qianqian , Liu Yinai , Bi Liuliu , Jin Libo , Xu Ke , Peng Renyi 
Published: March 2022

Abstract
In recent decades, diabetes mellitus has become a major chronic disease threatening human health worldwide, and the age of patients tends to be younger; however, the pathogenesis remains unclear, resulting in many difficulties in its treatment. As an ideal model animal, zebrafish can simulate the processes of human diabetes well. In this study, we successfully established a model of diabetic zebrafish larvae in a previous work. Furthermore, transcriptome analysis was completed, and the results suggested that 10.59% of differentially expressed genes (DEGs) related to the apoptosis pathway need to be considered. Then, glucose-induced developmental toxicity, reactive oxygen species (ROS) accumulation, antioxidant system function, apoptosis and mitochondrial dysfunction were measured in zebrafish larvae. We hope that this study will provide valuable reference information for type 2 juvenile diabetes treatment.
Microstructures and Mechanical Properties of Non-thinning and Penetrating Friction Stir Welded 2219-T6 Aluminum Alloy
Authors: Li Dongrui , Liu Huijie , Chen Siping , Du Shuaishuai , Hu Yanying , Li Xuanmo , Gao Yisong 
Published: March 2022

Abstract
In the conventional friction stir welding (CFSW) process, a certain size spindle tilting angle and shoulder plunge depth were applied in order to obtain high-quality welds. However, what was the reason for the thinning phenomenon of weld and thus the weakening of weld bearing capacity? The reduction of spindle tilting angle and shoulder plunge depth was likely to cause the welding tool not being able to reach the weld root, and thus it was engendered for the kissing bond or the absence of complete penetration. In the present study, a novel welding tool with large-size shoulder and Archimedes spiral groove was designed in order to achieve non-thinning and lack of kissing bond welds. The microstructures and mechanical properties of the joints obtained by the Non-thinning and Penetrating Friction Stir Welding (NTPFSW) and the Penetrating Friction Stir Welding (PFSW) had been analyzed in detail. Compared with PFSW, NTPFSW had a narrow shoulder affected zone. The stir zones (SZ) obtained by the PFSW and NTPFSW were both composed of fine equiaxed grains. The grains in the upper part of NTPFSW joint were larger in size and the number of precipitates (θ’ phase) was less. NTPFSW completely eliminated weld thinning phenomenon and the tensile properties were improved.
Characterization Of Danube Swabian Population Samples On A High-Resolution Genome-Wide Basis
Authors: Bánfai Zsolt , Kövesdi Erzsébet , Sümegi Katalin , Büki Gergely , Szabó András , Magyari Lili , Ádám Valerián , Pálos Ferenc , Miseta Attila , Kásler Miklós , Melegh Béla 
Published: March 2022

Abstract
Background: German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans came to Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150-year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Danube Swabian individuals living in the Dunaszekcső-Bár area, Danube side villages in Southwest Hungary. Based on self-declaration they did not admix with other ethnic groups for 3-6 succeeding generations. Using Illumina Infinium 720K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples.Results: Haplotype-based analyses like identity by descent and homozygosity by descent analyses show that the investigated Danube Swabians remained isolated from other ethnic groups which was supported by the D-statistics results. According to our results, the investigated Danube Swabian individuals do not possess detectable recent admixture, and our results suggest that their main source of ancestry can be traced back to the region of Germany. Conclusions: This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns.
Associated Maternal And Fetal Factors Of Fetal Congenital Heart Diseases Diagnosed By Fetal Echocardiography
Authors: Ruan Yanping , Xie Zan , Liu Xiaowei , He Yihua 
Published: March 2022

Abstract
Objective: Current studies have suggested that fetal congenital heart diseases (CHDs) are caused by various factors. However, few data is available with respect to the aspect in China. This study aimed to detect associated maternal and fetal factors of fetal CHD in a large sample in China.Study Design: Pregnant women who underwent fetal echocardiography (N=5024) were recruited in our hospital between May 2018 and September 2019. Of these, 875 pregnant women had fetuses with CHD. The maternal sociodemographic and lifestyle characteristics and some fetal factors were obtained. We used forward stepwise logistic regression analysis to assess the associations of fetal CHD with various factors.Results: Among the fetal CHD group (N=875), critical CHDs account for 27%, of which Tetralogy of Fallot is the most (7.1%), followed by coarctation of aorta (4.0%), Double-outlet right ventricle (2.9%). The forward stepwise logistic regression models revealed that gravidity (OR=1.32, 95%CI 1.21-1.43, P=0.000), upper respiratory tract infection during early pregnancy (OR=1.30, 95%CI 1.04-1.63, P=0.021), mental stress during early pregnancy (OR=2.87, 95%CI 1.35-5.92, P=0.006), single umbilical artery (OR=2.46, 95%CI 1.24-4.85, P=0.010), and parental smoking (OR=1.20, 95%CI 1.00-1.45, P=0.048) are positively associated with an increased risk of fetal CHD.Conclusion: We identified two maternal factors and two fetal factors positively associated with fetal CHD.. These findings suggest that it is important to strengthen healthcare and prenatal counseling for women with these factors.
Interpeduncular Cistern Intrathecal Targeted Drug Delivery for Intractable Postherpetic Neuralgia: A Case Report
Authors: Fu Feng , Jiang Xianfeng , Gong Lei , Yun Chen , Tang Fengwu 
Published: March 2022

Abstract
BackgroundIntractable Postherpetic Neuralgia(PHN) can be difficult to manage though receiving aggressive multimodal therapies. Patients who experience uncontrolled refractory PHN on head despite conservative treatment may benefit greatly from intrathecal drug delivery system （IDDS）. For craniofacial neuropathic pain，the traditional approach has been to place the intrathecal catheter tip usually below the level of cranial nerve root entry zones, which may lead to an insufficient analgesic effect.Case presentationHerein, we describe a 69-year-old male had a one-year history of PHN after developing a vesicular rash in the ophthalmic division of cranial nerve V (trigeminal nerve) distribution. The pain was rated 7-8 at rest and 9-10 of breakthrough pain(BTP) on an numeric rating scale(NRS). Despite receiving aggressive multimodal therapies including large doses of oral analgesics and Sphenopalatine Ganglion Block (SGB), with no relief of his pain, and subsequently the patient elected to pursue an implantable IDDS with the catheter tip placed at the interpeduncular cistern. The frequency of BTP episodes was also decreased. The patient’s continuous daily dose was adjusted to 0.032 mg/day after 3 months of follow-up and stop 5 months later.ConclusionThe use of interpeduncular cistern intrathecal infusion with low dose of opioids by IDDS may present an effective alternative in the management of severe PHN and other forms of neuropathic-associated craniofacial pain.
Evaluation of genes and molecular pathways involved in the development of cardiovascular disease in preeclampsia patients: biological system and bioinformatics analysis approach
Authors: Amirlatifi Shahrzad , Pazoki Mahboubeh , Amrovani Mehran , ghezelbash Shima , Dastyar Fatemeh 
Published: March 2022

Abstract
Background: Hypertension in preeclampsia (PE) is one of the most important complications in these patients, which increases the risk of cardiovascular disease (CVD). Bioinformatics analysis can identify the signaling pathways, genes and microRNAs involved in the development of CVD due to hypertension; it can also reduce the risk of developing PE by providing appropriate target therapies.Method: In this study, after collecting data and determining the gene list, changes in gene expression in patients with severe and non-severe forms of PE were compared. Protein-Protein interaction (PPI) and pathway enrichment analysis were also used to evaluate the common genes and pathways between the two cited forms of PE. Result: FGF, TNF, Adherent junction, metabolic signaling pathway, GATA3-mediated activation pathways of Th2, EGF / EGFR signaling pathway and Rab GTPase among the most important signaling pathways are effective in CVD development. HLTF, SUMO1, KDR, SNRPD3, DERL2, VCP, EIF4B, NOTCH1, SOCS3, CBL, ICAM-1, ITGB2, STRN, MEF2A and PTPRC are the most important genes and miR-3135-3P, miR-505, miR-6088, miR-451, miR-4637-3P, miR-1281-3P, miR-4304-3P, miR-323-3P, miR-3150-3p.1, miR-4718, miR-151-5p, miR-3117-5p.2, miR-3613, miR-1278- 3P, miR-4467, miR-4730 , miR-190b-3p , miR-610-5p, miR-3648-3p , miR-4796-3p, miR-2277-3P, miR-325, miR- 6807-3p , miR-551a-3p, and miR-3131-3P have been also effective in the development of CVD by hypertension in PE patients. Conclusion: Finally, it was concluded that identification of common signaling pathways, genes and microRNAs between severe and non-severe forms of PE can be effective to design preventive and treatment strategies for CVD caused by hypertension.
Ignition of Small Molecule Inhibitors in Friedreich's Ataxia with Explainable Artificial Intelligence
Authors: Kırboğa Kevser Kübra , Küçüksille Ecir Uğur , Köse Utku 
Published: March 2022

Abstract
Iron (Fe) chelating medicines and Histone deacetylase (HDAC) inhibitors are two therapy options for hereditary Friedreich's Ataxia that have been shown to improve clinical results (FA). Fe chelation molecules can be used to minimize the quantity of stored Fe, and HDAC inhibitors can be used to boost the expression of the Frataxin (FXN) gene in the process of enhancing FA. A complete quantitative structure-activity relationship (QSAR) search of inhibitors from the ChEMBL database is reported in this paper, which includes 437 compounds for Fe chelation and 1,354 compounds for HDAC inhibitors. For further investigation, the IC50 was chosen as the unit of bioactivity, and following data refinement, a final dataset of 436 and 1,163 compounds for Fe chelation and HDAC inhibition, respectively, was produced. The Random Forest (RF) technique was used to generate models, and the models created using the PubChem fingerprint were the strongest of the 12 fingerprint kinds, hence that feature was chosen for interpretation. The results showed the importance of properties related to nitrogen-containing functional groups and aromatic rings. As a result, we explained the effect of the molecular fingerprints used on the models and therefore the effects on possible drugs that can be developed for FA with artificial intelligence (XAI), which can be explained through SHAP (Shapley Additive Explanations) values. Model scripts and fingerprinting methods are also available at https://github.com/tissueandcells/XAI.
Conflict, Epidemic And Faith Communities: The Reconfiguration Of Church-State Relations During The Fight Against Covid-19 In North-Eastern DR Congo
Authors: Kangamina Sadiki , Falisse Jean-Benoit , Baba Amuda , Grant Liz , Pearson Nigel , Way Yossa , Wild-Wood Emma 
Published: March 2022

Abstract
Background: understanding and improving access to essential services in (post)-conflict settings requires paying particular attention to the actors who occupy the space left ‘empty’ by weak or deficient State institutions. Religious institutions often play a fundamental role among these actors and typically benefit from high trust capital, a rare resource in so-called ‘fragile’ States. While part of the literature has looked at the role faith organisations can play to mobilise and sensitise communities during emergencies, our focus is on a different, essential dimension: the reconfiguration of the relationship between religion and health authorities impelled by health crises.Methods: we analyse observations, interviews, and focus group discussions with 21 leaders from eight different religious categories in Ituri province in 2020-2021.Results: we show how faith institutions handled the Covid-19 lockdown period, notably by using and redeploying structures at the grassroots level but also by responding to health authorities’ call for support. New actors usually not associated with the health system, such as revivalist churches, got involved. The closure of worship places during the lockdown shocked all faith leaders; some saw it as a test of faith while others criticised inconsistent State measures, but, ultimately, most were inclined to follow and support health authorities. Such experience was, however, often one of frustration and feeling unheard. The interviewed religious leaders, especially those whose congregations were not previously involved in healthcare provision, felt that they were doing a favour to the State and the health authorities. Such service is at the level of community-level awareness-raising, but also, crucially, leaders were aware that by publicly committing themselves against Covid-19, they were participating in an effort to depoliticise Covid-19 in a context where the response to past epidemics, especially Ebola, is highly contentious. Conclusions: in the short run, depoliticization may help address health emergencies, but in the longer run and in the absence of a credible space for discussion, it may affect the constructive criticism of health system responses and health system strengthening. The faith leaders’ frustration with the ‘collaboration’ with health authorities (especially for the new actors) also limits its long-term potential.
A 16th Century Escherichia Coli Draft Genome Associated with an Opportunistic Bile Infection
Authors: Long George , Klunk Jeniffer , Duggan Ana , Tapson Madeline , Giuffra Valentina , Gazzè Lavinia , Fornaciari Antonio , Duchene Sebastian , Fornaciari Gino , Clermont Olivier , Denamur Erick , Golding Brian , Poinar Hendrik 
Published: March 2022

Abstract
Escherichia coli – one of the most characterized bacteria and a major public health concern – remains invisible across the temporal landscape. Here, we present the meticulous reconstruction of the first ancient E. coli genome from a 16th century gallstone from an Italian mummy with chronic cholecystitis. We isolated ancient DNA and reconstructed the ancient E. coli genome. It consisted of one chromosome of 4446 genes and two putative plasmids with 52 genes. The E. coli strain belonged to the phylogroup A and an exceptionally rare sequence type 4995. The Type VI secretion system component genes appears to be horizontally acquired from Klebsiella aerogenes, however we could not identify any pathovar specific genes were detected nor any antibiotic resistances. A sepsis mouse assay performed using a closely related contemporary E. coli strain was avirulent. Our reconstruction of this ancient E. coli helps paint a more complete picture of the burden of opportunistic infections of the past.