bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling of differentially expressed circulating exosomal microRNAs among patients with coronary artery disease
Authors: Hao Wen-Rui , Hong Hong-Jye , Cheng Chun-Yao , Cheng Tzu-Hurng , Liu Ju-Chi , Wang Yi-Chih , Chen Jin-Jer 
Published: March 2023

Abstract
Coronary artery disease (CAD) is the leading cause of death in developed countries. Studies have indicated that ischemic tissues may release exosome-carried microRNAs (miRNAs) into circulation. miRNAs are a class of small, endogenous, noncoding RNAs that regulate the expression of multiple target genes at the posttranscriptional level on the basis of sequences that are complementary to target mRNA molecules. However, the prognostic role of exosomal miRNAs in CAD remains unclear. In this study, we compared the profiles of circulating exosomal miRNA expression in patients with angiographically assessed absent and well-developed collateral vessels. A total of 109 patients who underwent coronary angiography were recruited, including 31 patients with CAD and well-developed collateral circulation, 44 patients with no collateral flow (as indicated by their Rentrop scores), and 34 patients with patent coronary arteries (control group). miRNAs were then extracted from exosomes collected from peripheral blood and amplified, and a miRNA microarray system was used to profile the expression of these miRNAs in the exosomes. Subsequently, the effects of specific miRNAs on angiogenesis were identified in vitro. On the basis of the array data, miRNAs with high differential expression ratios along with Grade 0–2 collateral flow were selected. Among patients with adequate collateral perfusion, the top five overexpressed candidate miRNA markers were miR-29a, miR-592, miR-518e, miR-32, and miR-766. Similarly, among patients with no collateral flow, the top five overexpressed miRNAs were miR-300, miR-576-3p, miR-642, miR-620, and miR-1255a. As a next step, the angiogenic ability and proangiogenic signaling pathway of two specific angiogenesis-related miRNAs (i.e., miR-300 and miR-29a) with high differential expression ratios were determined. According to the microarray data and study results, miRNAs with high expression levels can be used as biomarkers to distinguish between types of collateral circulation in patients with CAD and can be used in diagnostic or prognostic applications for high-risk patients with CAD. These findings may serve as a reference for the development of noninvasive and cost-effective approaches aimed at identifying the high risk of CAD and for the development of novel therapeutic targets for vascular diseases, including CAD with impaired collateral angiogenesis.
Sustained released of microRNA-99b-3p abundant exosomes derived from adipose stem cell encapsulated with hydrogel microparticles (HMPs) for long-term osteoarthritis treatment
Authors: Yin Zhaowei , Pan Shaowei , Shi Chen , Wu Guanfu , Feng Yan , Qin Chaoren , Zhang Jing , Yu Ziyi , Liang Bin , Gui Jianchao 
Published: March 2023

Abstract
Adipose derived stem cells (ADSCs) have the potential to attenuate osteoarthritis (OA); however, complications such as immune rejection and tumour formation limit their application. Exosomes (Exos)-mediated acellular therapy is promising in alleviating OA. This study aims to confirm whether ADSC-exos derived from infrapatellar fat pad (IPFP, ExosIPFP) are more suitable for ameliorating OA than ADSC-exos derived from subcutaneous fat (ScAT, ExoScAT) in vitro and in DMM models. Then, we investigated the regulatory mechanism by which the two kinds of Exos inhibit extracellular matrix (ECM) degradation in OA. ADSCs were successfully isolated and Exos were then obtained. ExosIPFP exhibited better attenuated effects on osteoarthritic chondrocytes in vitro and in vivo than ExoScAT. Small RNA sequencing was performed and the results shown that miR-99b-3p was upregulated in ExosIPFP. In vitro experiments confirmed that ADAMTS4 is a direct downstream target of miR-99b-3p. Over-expression miR-99b-3p in ExosScAT (ExosScAT-99b-3p) indicated that miR-99b-3p serves a positive role for OA treatment by inhibiting ADAMTS4 expression both in vitro and in vivo. In addition, hydrogel microparticles (HMPs) system was prepared by microfluidic technology, and confirmed the beneficial results for long-term therapeutic by continuous release of Exos. Take together, these results suggest that the therapeutic effects of ADSC-Exos may vary according to differential expression of miRNAs. Exosomal miR-99b-3p may act as a promising therapeutic strategy for OA, in addition, the injectable HMPs act as a sustained local drug release system, therefore representing great potential for treating OA and other diseases.
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes and Exosome-Liposome Hybrids as Nanocarriers for Delivering Cas9-GFP Plasmid to Embryonic Kidney Cells
Authors: Gharehchelou Behnaz , Mehrarya Mehrnoush , Vosough Massoud , Arjmand Sareh , Uskoković Vuk , Siadat Seyed Omid Ranaei , Karima Saeed , Sefidbakht Yahya 
Published: March 2023

Abstract
Exosomes are natural membrane-enclosed nanovesicles (30–150 nm) involved in cell-cell communication. Recently, they have garnered considerable interest as nanocarriers for the controlled transfer of therapeutic agents to cells. Here, exosomes were derived from bone marrow mesenchymal stem cells (BM-MSCs) using three different isolation methods, and the size exclusion chromatography (SEC) led to the isolation with the highest purity. The limitation of using pure exosomes for encapsulating large nucleic acids was then addressed by the development of exosome-liposome hybrids. The efficiency of these hybrids to transfer the Cas9-green fluorescent protein plasmid (pCas9-GFP) into the human embryonic kidney 293T (HEK293T) cells were evaluated compared to the pure exosomes. The method of combining exosomes with liposomes (freeze-thaw vs. direct mixing) was proved to be more decisive in determining the size of the vesicular hybrids. In contrast, the ionic nature of the liposomes (lipoplex vs. cationic) in these hybrids was proved to be more important in determining the transfection efficiency. Both Cas9-GFP-loaded exosomes and exosome-liposome hybrids were taken up well by the HEK293T and were able to transfect them with their plasmid loads; however, the pure exosome and then the vesicular hybrids incorporating lipoplex transfected the cells more efficiently than those containing cationic liposomes.
Invasive pancreatic cystic neoplasm with favorable prognosis: A large retrospective cohort study over two decades
Authors: song yanjing , li zhe , Cui Hongyuan , xu jingyong , Song Jinghai 
Published: March 2023

Abstract
Purposes: Invasive pancreatic cystic neoplasms (iPCNs) are an uncommon and biologically heterogeneous group of aggressive neoplasms. We aimed to investigate the clinicopathological characteristics of iPCN patients, and to develop nomograms for individual survival prediction after radical surgery. Methods: Data of patients diagnosed with iPCN between 2000 and 2018 from the SEER database were retrieved. The differences of clinical outcomes were evaluated using Kaplan-Meier analysis. Nomograms were proposed based on Cox regression model and internally validated by C-index, AUC value, and calibration plot. Results: A total of 7777 iPCN patients were enrolled. Most neoplasms were advanced, with 63.1% at stage IV. The 3-year OS and CSS rates in surgical patients were as follows: 45.7% and 50.1% for invasive IPMN, 54.8% and 59.3% for invasive MCN, 97.8% and 98.2% for invasive SPN, 88.9% and 88.9% for invasive SCN. Subgroup analyses showed no clinical benefit from chemotherapy or radiotherapy in lymph node-negative iPCN patients who underwent surgery. The following variables associated with OS and CSS were identified: age, race, chemotherapy, radiotherapy, histologic type, pathological grade, regional nodes examined, and T, N, and M stage. The nomograms had good discrimination and calibration by internal validation, with AUC value of 0.800 for 3-year OS and 0.814 for 3-year CSS. Conclusion: Our study showed that the prognosis of iPCN patients was significantly better than PDAC patients. The proposed nomograms demonstrated substantially better discrimination and calibration.
ACE2 (angiotensin converting enzyme) polymorphisms and susceptibility of severe SARS- CoV-2 in subset of Pakistani population
Authors: Sidhwani Santosh Kumar , Mirza Talat , Khatoon Ambrina , Shaikh Fouzia , Khan Rizma , Shaikh Omer Ahmed , Nashwan Abdulqadir J. 
Published: March 2023

Abstract
Science is digging for the varied presentation of COVID-19 patients exposed to the same risk factors, and medical conditions may be influenced by the presence of polymorphic genetic variants. This study investigated the link between ACE2 gene polymorphisms and the severity of SARS-Cov-2. This cross-sectional study recruited COVID-19 PCR-positive patients by consecutive sampling from Ziauddin Hospital from April to September 2020. DNA was extracted from whole blood, followed by gene amplification and Sanger’s sequencing. Most of the patients, 77: 53.8%, were serious. Males were higher (80; 55.9%) with age more than 50 years (106: 74.1%). We found 22 ACE2 SNPs rs2285666 SNP most prevalent with 49.2% CC, 45.2% TT, 4.8% CT heterozygosity, and 0.8% AA genotypes. Variants with multiple genotypes were also insignificantly associated with the severity of COVID-19 in the analysis of the dominant model. Only rs2285666 had a significant statistical link with gender (p-value 0.034, OR; 1.438, CI; 1.028-2.011) while rs768883316 with age groups (p-value 0.026, OR; 1.953, CI; 1.085-3.514). Haplotypes ATC of three polymorphisms (rs560997634, rs201159862, and rs751170930) commonly found in 120 (69.77%) and TTTGTAGTTAGTA haplotype consisting of 13 polymorphisms (rs756737634, rs146991645, rs1601703288, rs1927830489, rs1927831624, rs764947941, rs752242172, rs73195521, rs781378335, rs756597390, rs780478736, rs148006212, rs768583671) in 112 (90.32%) had statistically significant association with the severity having p=value 0.029 and 0.001 respectively. Males of old age and diabetics are found to have more severe COVID-19 infection in the current study. We also found that common ACE2 polymorphism rs2285666 influences the susceptibility of acquiring the severe SARS-CoV-2 infection.
Cerebrospinal fluid leakage prevention using the anterior transpetrosal approach with versus without postoperative spinal drainage: an institutional cohort study
Authors: Adachi Kazuhide , Hasegawa Mitsuhiro , Hirose Yuichi 
Published: March 2023

Abstract
The efficacy of spinal drain (SD) placement for cerebrospinal fluid (CSF) leakage prevention after anterior transpetrosal approach (ATPA) remains unclear. Thus, we aimed to assess whether postoperative SD placement improved postoperative CSF leakage after a skull base reconstruction procedure using a small abdominal fat and pericranial flap and clarify whether bed rest with postoperative SD placement increased the length of hospital stay. This retrospective cohort study included 48 patients who underwent primary surgery using ATPA between November 2011 and February 2022. First, we evaluated the necessity of SD placement for CSF leakage prevention by comparing the routine SD placement period to a period in which the SD was removed immediately after surgery. Second, the effects of different SD placement durations were evaluated to understand the adverse effects of SD placement requiring bed rest. No patient with or without SD placement developed CSF leakage. The median postoperative time to first ambulation was 3 days shorter (P < 0.05) and the length of hospital stay was 7 days shorter (P < 0.05) for patients who underwent SD removal immediately after surgery (2 and 12 days, respectively) than for those who underwent SD removal on postoperative day 1 (5 and 19 days, respectively). This skull base reconstruction technique was effective in preventing CSF leakage in patients undergoing ATPA, and postoperative SD placement was not necessary. Removing the SD immediately after surgery can lead to earlier postoperative ambulation and shorter hospital stay by reducing medical complications and improving functional capacity.
Investigating the Correlation between Genetic and Biochemical Markers in Multiple Sclerosis
Authors: Borisovs Vitalijs , Trapina Ilva , Paramonova Natalia , Sjakste Nikolajs 
Published: March 2023

Abstract
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with a complex etiology involving genetic and environmental factors. Genome-wide association studies have identified several genetic variants associated with MS susceptibility, including the XRCC1 gene involved in DNA base excision repair. Environmental factors such as exposure to nitric oxide have also been linked to MS development and progression. This study aims to investigate the potential association between these factors, including patient demographic descriptors and biochemical markers, to better understand the mechanisms underlying MS. This scientific article discusses the results of statistical analysis of biomarkers in relation to multiple sclerosis (MS). Our findings reveal significant associations between various factors, such as levels of nitric oxide (NO) and serum nitrite levels, NO and plasma malondialdehyde (MDA) levels, nitrite and nitrate levels in serum, and nitrite and MDA levels in plasma. It also suggests a potential association between XRCC1 rs25487 T > C locus deviation from Hardy-Weinberg equilibrium and MS in the population of Latvia. Furthermore, XRCC1 rs25487 T > C is found to be statistically significantly associated with DNA damage in peripheral blood mononuclear cells (PBMNC) and potentially associated with levels of NO. Additionally, PARP1 rs1136410 A > G is linked to plasma levels of MS patients. Finally, the study finds that XRCC1 rs25487 T > C is associated with both plasma nitrite levels and serum malondialdehyde (MDA) levels of MS patients, with the rare allele T specifically correlated with the latter.
Another non-anthropic leporid accumulation in Southwestern Iberia? The case of a leporid sample from Morgado superior (Tomar, Portugal)
Authors: Almeida Nelson J. , Saladié Palmira , Cerrillo-Cuenca Enrique , Oosterbeek Luiz 
Published: March 2023

Abstract
The Morgado superior rock shelter is located near the city of Tomar, in Central Portugal. This site presents important funerary contexts that according to published information encompass the Neolithic, Chalcolithic, and Bronze Age. Other non-funerary uses are not yet characterized but were briefly suggested. A faunal sample of the 1988 and 2012 interventions is analysed from a zooarchaeological and taphonomical perspective, focusing on the leporid remains that largely dominate the assemblage. Clear indicators of a human origin are absent, while a configurational approach allows the description of exogenous and intrusive origins. The characteristics of the registered consumption taphonomical indicators are suggestive of scat and non-ingested accumulation by foxes. Furthermore, this study allows us to discuss some aspects of the formation of the stratigraphy of this important cave necropolis, while also serving as an example of the expected results of foxes’ action on leporid remains in an archaeological site.
Navigating the Maze of Global Debt: An Analysis of International Debt Statistics with PostgreSQL
Authors: Nasir Muhammad Taha , Tulkinov Shavkatjon 
Published: March 2023

Abstract
Countries often take on debt as a means of financing their economic development, such as funding infrastructure projects, investing in education or healthcare, or stimulating economic growth. This paper aims to analyze international debt statistics using the PostgreSQL database management system, specifically focusing on the external debt of countries as presented in the World Bank's International Debt Statistics (IDS) database. The analysis examines the most prevalent debt indicators and investigates the amount of debt owed by countries to identify potential economic issues and findings show that long-term external debt is the most common form of external debt for low- and middle-income countries. The IDS dataset displays that the most prevalent debt indicators are DT.INT.OFFT.CD, DT.INT.MLAT.CD, DT.INT.DLXF.CD, DT.AMT.OFFT.CD, DT.AMT.MLAT.CD, and DT.AMT.DLXF.CD. The study also finds that among the top five countries with the highest maximum debt, four are from emerging market economies, suggesting that they may be facing economic challenges. However, the study emphasizes that the findings should be interpreted with caution and that other economic indicators, such as the debt-to-GDP ratio and debt sustainability, should be considered when analyzing a country's overall economic health.
SNV/indel hypermutator phenotype in biallelic RAD51C variant - Fanconi anemia
Authors: Zemet Roni , Du Haowei , Gambin Tomasz , Liu Pengfei , Lupski James R , Stankiewicz Paweł 
Published: March 2023

Abstract
We previously reported a fetus with Fanconi anemia (FA), complementation group O due to compound heterozygous variants involving RAD51C. Interestingly, the trio exome sequencing analysis also detected eight apparent de novo mosaic variants with variant allele fraction (VAF) ranging between 11.5%-37%. Here, using whole genome sequencing and a 'home-brew' variant filtering pipeline and DeepMosaic module, we investigated the number and signature of de novo heterozygous and mosaic variants and the rare phenomenon of hypermutation. Eight-hundred-thirty apparent dnSNVs and 21 de novo indels had VAFs below 37.41% and were considered postzygotic somatic mosaic variants. The VAFs showed a bimodal distribution, with one component with an average VAF of 25% (range: 18.7-37.41%) (n=446), representing potential postzygotic first mitotic events, and the other component with an average VAF of 12.5% (range: 9.55-18.69%) (n=384), describing potential second mitotic events. No increased rate of CNV formation was observed. The mutational pattern analysis for somatic single base substitution showed SBS40, SBS5, and SBS3 as the top recognized signatures. SBS3 is a known signature associated with homologous recombination-based DNA damage repair error. Our data demonstrate that biallelic RAD51C variants show evidence for defective genomic DNA damage repair and thereby result in a hypermutator phenotype with the accumulation of postzygotic de novo mutations, at least in the prenatal period. This 'genome hypermutator phenomenon' might contribute to the observed hematological manifestations and the predisposition to tumors in patients with FA, and pregnancy loss in general. We propose that other FA groups should be investigated for genome-wide de novo variants.
Clinical features of thyroid cancer in paediatric age. Experience of a tertiary centre in the 2000-2020 period
Authors: Tuli Gerdi , Munarin Jessica , Matarazzo Patrizia , Marino Antonio , Corrias Andrea , Palestini Nicola , Quaglino Francesco , De Sanctis Luisa 
Published: March 2023

Abstract
Purpose. To describe the clinical features of a paediatric cohort affected by differentiated thyroid cancer (DTC) followed in a tertiary Department of Paediatric Endocrinology.
Methods. Clinical data of 41 patients affected by DTC in the 2000-2020 period were reviewed.
Results. The main risk factor was autoimmune thyroiditis (39%). Cytological categories were TIR3b in 39%, TIR4 in 9.8%, TIR5 in 51.2%. After total thyroidectomy, radioiodine treatment was performed in 38 subjects (92.7%). ATA low-risk category was assigned in 11 (30.5%), intermediate-risk category in 15 (41.7%), and high-risk category in 10 patients (27.8%). Age at diagnosis was 15.1 ± 0.92 years in low-risk category, 14.7 ± 0.59 in intermediate-risk category, 11.7 ± 0.89 years in high-risk category (p=0.01). TIR3b was manly observed in low-risk class (63.6%), while TIR5 was mainly reported in intermediate and high-risk class (60% and 80% respectively) (p= 0.04). Post-surgery stimulated thyroglobulin was increased in high-risk class (407.8±307.1 ng/ml) [p=0.04]. Tumour size was larger in high-risk category (42.6 ± 2.6 mm), than in low and intermediate-risk categories (19.4 ± 3.5 mm and 28.5 ± 3.9 mm, respectively) (p=0.008). Patients in intermediate and high-risk categories displayed more tumour multifocality (60% and 90% respectively) (p < 0.005). Disease relapse was mainly observed in high risk category (40%, p=0.04).
Conclusion. DTC in childhood is more aggressive than in adults, but the overall survival rate is excellent. The therapeutic approach is still heterogeneous, especially in low-risk category. Further studies are needed to standardize management and reduce disease persistence in childhood.
Surgical experience of extracorporeal membrane oxygenation for neonates with severe respiratory failure
Authors: Zhang Qi-Liang , Chen Xiu-Hua , Zhou Si-Jia , Cao Hua , Chen Qiang 
Published: March 2023

Abstract
Objective
Extracorporeal membrane oxygenation (ECMO) has been increasingly used for severe neonatal respiratory failure refractory to conventional treatments. This paper summarized our operation experience of neonatal ECMO via cannulation of the internal jugular vein and carotid artery.
Methods
The clinical data of 12 neonates with severe respiratory failure who underwent ECMO via internal jugular vein and carotid artery in our hospital from January 2021 to October 2022 were collected.
Results
All the neonates were successfully operation. The size of arterial intubation was 8 F, the size of venous intubation was 10 F. The operation time was 29 (22–40) minutes. ECMO was successfully removed in 8 neonates. They were successfully reconstructed the internal jugular vein and carotid artery. Arterial blood flow was unobstructed in 5 patients, mild stenosis in 2 patient, moderate stenosis in 1 patient. Venous blood flow was unobstructed in 6 patients, mild stenosis in 1 patient, and moderate stenosis in 1 patient. The complications were as follows: 1 case had poor neck incision healing after ECMO removing. No complications such as incisional bleeding, incisional infection, catheter-related blood infection, cannulation accidentally pulling away, vascular laceration, thrombosis, cerebral hemorrhage, cerebral infarction, and hemolysis occurred in all the patients.
Conclusion
Cannulation of the internal jugular vein and carotid artery can quickly establish an effective ECMO access for neonates with severe respiratory failure. Careful, skilled and delicate operation was essential. In addition, during the cannulation process, we should pay special attention to the position of cannulation, firm fixation and strict aseptic operation.