bluuebunny/crossref_metadata_2025 huggingface dataset:
The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases
Authors: Wu Xue , Sun Meng , Yang Zhi , Lu Chenxi , Wang Qiang , Wang Haiying , Deng Chao , Liu Yonglin , Yang Yang
Published: August 2021

Chemokine is a structure-related protein with a relatively small molecular weight, which can target cells to chemotaxis and promote inflammatory response. Inflammation plays an important role in aging. C-C chemokine receptor 9 (CCR9) and its ligand C-C chemokine ligand 25 (CCL25) are involved in the regulating the occurrence and development of various diseases, which has become a research hotspot. Early research analysis of CCR9-deficient mouse models also confirmed various physiological functions of this chemokine in inflammatory responses. Moreover, CCR9/CCL25 has been shown to play an important role in a variety of inflammation-related diseases, such as cardiovascular disease (CVD), rheumatoid arthritis, hepatitis, inflammatory bowel disease, asthma, etc. Therefore, the purpose of this review gives an overview of the recent advances in understanding the roles of CCR9/CCL25 in inflammation and inflammation-associated diseases, which will contribute to the design of future experimental studies on the potential of CCR9/CCL25 and advance the research of CCR9/CCL25 as pharmacological inflammatory targets.
Inhibition of Postn Rescues Myogenesis Defects in Myotonic Dystrophy Type 1 Myoblast Model
Authors: Shen Xiaopeng , Liu Zhongxian , Wang Chunguang , Xu Feng , Zhang Jingyi , Li Meng , Lei Yang , Wang Ao , Bi Chao , Zhu Guoping
Published: August 2021

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease caused by expanded CTG repeats in the 3′ untranslated region (3′UTR) of the DMPK gene. The myogenesis process is defective in DM1, which is closely associated with progressive muscle weakness and wasting. Despite many proposed explanations for the myogenesis defects in DM1, the underlying mechanism and the involvement of the extracellular microenvironment remained unknown. Here, we constructed a DM1 myoblast cell model and reproduced the myogenesis defects. By RNA sequencing (RNA-seq), we discovered that periostin (Postn) was the most significantly upregulated gene in DM1 myogenesis compared with normal controls. This difference in Postn was confirmed by real-time quantitative PCR (RT-qPCR) and western blotting. Moreover, Postn was found to be significantly upregulated in skeletal muscle and myoblasts of DM1 patients. Next, we knocked down Postn using a short hairpin RNA (shRNA) in DM1 myoblast cells and found that the myogenesis defects in the DM1 group were successfully rescued, as evidenced by increases in the myotube area, the fusion index, and the expression of myogenesis regulatory genes. Similarly, Postn knockdown in normal myoblast cells enhanced myogenesis. As POSTN is a secreted protein, we treated the DM1 myoblast cells with a POSTN-neutralizing antibody and found that DM1 myogenesis defects were successfully rescued by POSTN neutralization. We also tested the myogenic ability of myoblasts in the skeletal muscle injury mouse model and found that Postn knockdown improved the myogenic ability of DM1 myoblasts. The activity of the TGF-β/Smad3 pathway was upregulated during DM1 myogenesis but repressed when inhibiting Postn with a Postn shRNA or a POSTN-neutralizing antibody, which suggested that the TGF-β/Smad3 pathway might mediate the function of Postn in DM1 myogenesis. These results suggest that Postn is a potential therapeutical target for the treatment of myogenesis defects in DM1.
EQCM Analysis of the Insertion Phenomena in a n-Doped Poly-Alkyl-Terthiophene With Regioregular Pattern of Substitution
Authors: Dini Danilo , Salatelli Elisabetta , Decker Franco
Published: August 2021

In the present work, we have undertaken the study of the n-doping process in poly-3,3″-didodecyl-2,2′:5′,2″-terthiophene (poly-33″-DDTT) employing the electrochemical quartz crystal microbalance (EQCM). The present study aims at understanding how cathodic charge in n-doped poly-33″-DDTT is compensated. For this purpose, the in situ analysis of the variations of the polymeric mass has been considered. Poly-33″-DDTT was obtained as a thin coating onto a metallic substrate via the anodic coupling of the corresponding monomer 3,3″-didodecyl-2,2′:5′,2″-terthiophene (33″-DDTT). When subjected to electrochemical n-doping in the polarization interval -2.5 ≤ Eappl ≤ 0 V vs. Ag/Ag+, the films of poly-33″-DDTT varied their mass according to a mechanism of cations insertion during n-doping and cations extraction during polymer neutralization. In fact, the electrochemical doping of polythiophenes requires the accompanying exchange of charged species to maintain the electroneutrality within the structure of the polymer in all states of polarization. At the end of a full electrochemical cycle (consisting of the n-doping and the successive neutralization of poly-33″-DDTT), the polymer retains a fraction of the mass acquired during n-doping, thus manifesting the phenomena of mass trapping. The combined analysis of electrochemical and microgravimetric data suggests that poly-33″-DDTT in the n-doped state undergoes (or electrocatalyzes) uncontrolled electrochemical reactions that are not accompanied by mass variations.
Graphene-Assisted Electrochemical Sensor for Detection of Pancreatic Cancer Markers
Authors: Xu Zhenglei , Peng Minsi , Zhang Zhuliang , Zeng Haotian , Shi Ruiyue , Ma Xiaoxin , Wang Lisheng , Liao Bihong
Published: August 2021

Pancreatic cancer is a highly lethal gastrointestinal malignancy. Most patients are already in the middle to advanced stages of pancreatic cancer at the time of diagnosis and cannot be treated completely. As a single-atom planar two-dimensional crystal, graphene’s unusual electronic structure, specific electronic properties and excellent electron transport capacity make it uniquely advantageous in the field of electrochemical sensing. In this mini-review, we summarize the potential application of graphene in pancreatic cancer detection. K-Ras gene, CEA and MicroRNA are important in the early diagnosis of pancreatic cancer.
Molecular Detection of Insecticide Resistance Mutations in Anopheles gambiae from Sierra Leone Using Multiplex SNaPshot and Sequencing
Authors: Yin Jianhai , Yamba Frederick , Zheng Canjun , Zhou Shuisen , Smith Samuel Juana , Wang Lili , Li Hongmei , Xia Zhigui , Xiao Ning
Published: August 2021

Vector control interventions including long-lasting insecticidal nets and indoor residual spraying are important for malaria control and elimination. And effectiveness of these interventions depends entirely on the high level of susceptibility of malaria vectors to insecticides. However, the insecticide resistance in majority of mosquito vector species across African countries is a serious threat to the success of vector control efforts with the extensive use of insecticides, while no data on insecticide resistance was reported from Sierra Leone in the past decade. In the present study, the polymerase chain reaction was applied for the identification of species of 757 dry adult female Anopheles gambiae mosquitoes reared from larvae collected from four districts in Sierra Leone during May and June 2018. And the mutations of kdr, rdl, ace-1 genes in An. gambiae were detected using SNaPshot and sequencing. As a result, one sample from Western Area Rural district belonged to Anopheles melas, and 748 An. gambiae were identified. Furthermore, the rdl mutations, kdr west mutations and ace-1 mutation were found. The overall frequency was 35.7%, 0.3%, 97.6% and 4.5% in A296G rdl, A296S rdl, kdrW and ace-1, respectively. The frequencies of A296G rdl mutation (P < 0.001), kdrW mutation (P = 0.001) and ace-1 mutation (P < 0.001) were unevenly distributed in four districts, respectively, while no statistical significance was found in A296S rdl mutation (P = 0.868). In addition, multiple resistance patterns were also found. In conclusion, multiple mutations involved in insecticide resistance in An. gambiae populations in Sierra Leone were detected in the kdrW, A296G rdl and ace-1 alleles in the present study. It is necessary to monitor vector susceptibility levels to insecticides used in this country, and update the insecticide resistance monitoring and management strategy.
Exposure to COVID-19 Vaccine Hesitancy Is as Impactful as Vaccine Misinformation in Inducing a Decline in Vaccination Intentions in New Zealand: Results from Pre-Post Between-Groups Randomized Block Experiment
Authors: Thaker Jagadish , Subramanian Arun
Published: August 2021

While recent studies have investigated how health messages on vaccine characteristics shift public intentions to get a COVID-19 vaccine, a few studies investigate the impact of real-world, widely shared vaccine misinformation on COVID-19 vaccine acceptance. Moreover, there is currently no research that investigates how exposure to hesitancy, as compared to misinformation, is associated with COVID-19 vaccination intentions. Based on data from a nationally representative survey experiment conducted in March 2021 (N = 1,083), exposure to outright COVID-19 vaccine misinformation as well as exposure to vaccine hesitancy induces a decline in COVID-19 vaccination intentions to protect self and to get the vaccine to protect others in New Zealand, compared to factual information from government authorities. Moreover, there is no significant difference in exposure to misinformation or hesitancy in the self-reported change in COVID-19 vaccination intentions. However, respondents are more likely to believe in vaccine hesitancy information and share such information with family and followers compared to misinformation. Implications for research in health communication campaigns on COVID-19 are presented.
Modelling Fractional Behaviours Without Fractional Models
Authors: Sabatier Jocelyn
Published: August 2021

This paper first warns about the confusion or rather the implicit link that exists in the literature between fractional behaviours (of physical, biological, thermal, etc. origin) and fractional models. The need in the field of dynamic systems modelling is for tools that can capture fractional behaviours that are ubiquitous. Fractional models are only one class of models among others that can capture fractional behaviours, but with associated drawbacks. Several other modelling tools are proposed in this paper, thus showing that a distinction is needed between fractional behaviours and fractional models.
Determinants and Prediction Equations of Six-Minute Walk Test Distance Immediately After Cardiac Surgery
Authors: Radi Basuni , Ambari Ade Meidian , Dwiputra Bambang , Intan Ryan Enast , Triangto Kevin , Santoso Anwar , Setianto Budhi
Published: August 2021

Background: To date, there is no reference for a 6-min walk test distance (6-MWD) immediately after cardiac surgery. Therefore, this study aimed to identify the determinants and to generate equations for prediction reference for 6-MWD in patients immediately after cardiac surgery.

Methods: This is a cross-sectional study of the 6-min walk test (6-MWT) prior to participation in the cardiac rehabilitation (CR) program of patients after coronary artery bypass surgery (CABG) or valve surgery. The 6-MWT were carried out in a gymnasium prior to the CR program immediately after the cardiac surgery. Available demographic and clinical data of patients were analyzed to identify the clinical determinants of 6-MWD.

Results: This study obtained and analyzed the data of 1,509 patients after CABG and 632 patients after valve surgery. The 6-MWD of all patients was 321.5 ± 73.2 m (60–577). The distance was longer in the valve surgery group than that of patients in the CABG group (327.75 ± 70.5 vs. 313.59 ± 75.8 m, p < 0.001). The determinants which significantly influence the 6-MWD in the CABG group were age, gender, diabetes, atrial fibrillation, and body height, whereas in the valve surgery group these were age, gender, and atrial fibrillation. The multivariable regression models generated two formulas using the identified clinical determinants for patients after CABG: 6-MWD (meter) = 212.57 + 30.47 (if male gender) − 1.62 (age in year) + 1.09 (body height in cm) − 12.68 (if with diabetes) − 28.36 (if with atrial fibrillation), and for patients after valve surgery with the formula: 6-MWD (meter) = 371.05 + 37.98 (if male gender) − 1.36 (age in years) − 10.61 (if atrial with fibrillation).

Conclusion: This study identified several determinants for the 6-MWD and successively generated two reference equations for predicting 6-MWD in patients after CABG and valve surgery.
Blood Conservation and Hemostasis Management in Pediatric Cardiac Surgery
Authors: Sebastian Roby , Ahmed M. Iqbal
Published: August 2021

Pediatric cardiac surgery is associated with significant perioperative blood loss needing blood product transfusion. Transfusion carries serious risks and implications on clinical outcomes in this vulnerable population. The need for transfusion is higher in children and is attributed to several factors including immaturity of the hemostatic system, hemodilution from the CPB circuit, excessive activation of the hemostatic system, and preoperative anticoagulant drugs. Other patient characteristics such as smaller relative size of the patient, higher metabolic and oxygen requirements make successful blood transfusion management extremely challenging in this population and require meticulous planning and multidisciplinary teamwork. In this narrative review we aim to summarize risks and complications associated with blood transfusion in pediatric cardiac surgery and also to summarize perioperative coagulation management and blood conservation strategies.
The Effects of Vitamin D Supplementation on Metabolic and Oxidative Stress Markers in Patients With Type 2 Diabetes: A 6-Month Follow Up Randomized Controlled Study
Authors: Cojic Milena , Kocic Radivoj , Klisic Aleksandra , Kocic Gordana
Published: August 2021

Vitamin D deficiency could play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) as it may alter several crucial processes in the development of diabetes and its complications, such as pancreatic insulin secretion, peripheral insulin resistance, persistence of systemic „sterile” inflammation and immune activation. Vitamin D may also have an antioxidant effect through the inhibition of free radicals generation. The reported study was designed with eligible consecutively recruited patients with T2DM on standard metformin therapy (n=130), randomized in 1:1 ratio, considered to have undergone Vitamin D supplementation according to the guidelines proposed by the Endocrine Society, or to have continued with metformin only. The potential benefit was monitored through the influence on glycemia level, glycated haemoglobin (HbA1c), insulin resistance index (calculated as homeostatic model assessment; HOMA-IR), Castelli Risk Index I and Tryglicerides/Thiobarbituric acid-reactive substances (TG/TBARS) Index in a 6-month follow up period. Our study indicates that oral daily doses of vitamin D improve HbA1c levels over the 3-month and 6-month period, followed by a significant decrease in advanced oxidation protein products levels over the 3-month period when higher vitamin D doses are given. The effect of vitamin D on HOMA-IR index, malondialdehyde levels and TG/TBARS index was not statistically significant. Further investigation should consider defining the doses of vitamin D in patients with T2DM which may attenuate the oxidative stress risk, the risk of metabolic syndrome and the risk of related cardiovascular events.
Update on Targeted Therapy in Medullary Thyroid Cancer
Authors: Okafor Christian , Hogan Julie , Raygada Margarita , Thomas Barbara J. , Akshintala Srivandana , Glod John W. , Del Rivero Jaydira
Published: August 2021

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that accounts for 2-4% of all thyroid cancers. All inherited MTC and approximately 50% of sporadic cases are driven by mutations in the REarranged during Transfection (RET) proto-oncogene. The recent expansion of the armamentarium of RET-targeting tyrosine kinase inhibitors (TKIs) has provided effective options for systemic therapy for patients with metastatic and progressive disease. However, patients that develop resistant disease as well as those with other molecular drivers such as RAS have limited options. An improved understanding of mechanisms of resistance to TKIs as well as identification of novel therapeutic targets is needed to improve outcomes for patients with MTC.
First-in-Human Evaluation of Positron Emission Tomography/Computed Tomography With [18F]FB(ePEG12)12-Exendin-4: A Phase 1 Clinical Study Targeting GLP-1 Receptor Expression Cells in Pancreas
Authors: Fujimoto Hiroyuki , Fujita Naotaka , Hamamatsu Keita , Murakami Takaaki , Nakamoto Yuji , Saga Tsuneo , Ishimori Takayoshi , Shimizu Yoichi , Watanabe Hiroyuki , Sano Kohei , Harada Norio , Nakamura Hiroshi , Toyoda Kentaro , Kimura Hiroyuki , Nakagawa Shunsaku , Hirai Mitsuharu , Murakami Atsushi , Ono Masahiro , Togashi Kaori , Saji Hideo , Inagaki Nobuya
Published: August 2021

Pancreatic β-cell mass (BCM) has a central importance in the pathophysiology of diabetes mellitus. Recently, pancreatic β-cell-specific imaging, especially positron emission tomography (PET) with exendin-based probes, has emerged for non-invasive evaluation of BCM. We developed a novel exendin-based probe labeled with fluorine-18, [18F]FB(ePEG12)12-exendin-4 (18F-Ex4) for PET imaging. We subsequently conducted a first-in-human phase 1 study of 18F-Ex4 PET/computed tomography (CT) and investigated the safety and utility for visualizing the pancreas. Six healthy male subjects were enrolled in this study. A low dose (37.0 MBq) of 18F-Ex4 PET/CT was administered (first cohort: n = 2), and subsequently a higher dose (74.0 MBq) was administered (second cohort: n = 4). In the first and second cohorts, 38.6 ± 4.8 and 71.1 ± 4.8 MBq of 18F-Ex4 were administered, respectively. No serious adverse events were observed in both groups. Only one participant in the first cohort showed transient hypoglycemia during the PET scans. 18F-Ex4 PET/CT successfully visualized the pancreas in all participants. The mean standardized uptake value of the pancreas was found to be higher than that in the surrounding organs, except for the bladder and kidney, during the observation. Dosimetry analyses revealed the effective systemic doses of 18F-Ex4 as 0.0164 ± 0.0019 mSv/MBq (first cohort) and 0.0173 ± 0.0020 mSv/MBq (second cohort). 18F-Ex4 PET/CT demonstrated the safety and utility for non-invasive visualization of the pancreas in healthy male subjects. 18F-Ex4 is promising for clinical PET imaging targeting pancreatic β cells.
Influencing Factors of New Energy Development in China: Based on ARDL Cointegration and Granger Causality Analysis
Authors: Xue Fuliang , Feng Xiaotong , Liu Jing
Published: August 2021

The development and competition of the new energy industry will become an important battlefield of a new round of technological and industrial competition. This study use the annual data from 1990 to 2019 to understand the factors affecting the development of new energy development in China by examining the long-run and causal relationship among the proportion of new energy consumption, energy prices, carbon emissions, industrial structure, economic growth, and new energy power generation in a multivariate model for China. The findings indicate that in the long run, new energy generation is positively linked with new energy consumption, whereas energy prices and carbon emissions have a negative and significant impact on new energy consumption. In the short run, economic growth can promote the growth of new energy consumption. However, this positive effect is gradually formed and is unlikely to happen soon. However, whether the impact of industrial structure optimization on new energy consumption is a long- or short-run estimate is not significant. Causality results suggest that a one-way Granger causality exists between each factor and new energy consumption in different lag orders, except for industrial structure. Re-examining the energy price mechanism and carbon emission mechanism policy, maintaining stable GDP growth, increasing the installed capacity of new energy power generation, and improving power generation conversion efficiency are vital for ensuring new energy development.
Low Benthic Oxygen and High Internal Phosphorus-Loading are Strongly Associated With the Invasive Macrophyte Nitellopsis obtusa (starry stonewort) in a Large, Polymictic Lake
Authors: Harrow-Lyle Tyler J. , Kirkwood Andrea E.
Published: August 2021

Lake Scugog is an important headwater to the Trent Severn-Waterway in Ontario, Canada. In recent years, notable ecosystem-level changes have occurred coinciding with the emergence of the non-native invasive charophyte Nitellopsis obtusa. Despite N. obtusa arriving in North America in the early 1970s, studies documenting the impact of N. obtusa on invaded ecosystems are scarce. Given the increasing dominance of N. obtusa in inland waters of the Great Lakes basin, we investigated the ecosystem-level impacts of N. obtusa in Lake Scugog over a 3-year period. We show for the first time a strong association between N. obtusa occurrence and biomass with benthic anoxia in this shallow, polymictic lake. Benthic dissolved oxygen concentrations were significantly lower (p-value < 0.001) at sites with N. obtusa compared to sites without N. obtusa. Additionally, N. obtusa biomass was a negative predictor of near-bed oxygen concentration (R2 = 0.59, p-value < 0.001). Knowing that anoxia can promote the internal loading of phosphorus, we measured soluble reactive phosphorus (SRP) in the pore-water of sediments at each site, and found N. obtusa biomass explained 90% of sediment pore-water SRP (R2 = 0.90, p-value < 0.001). These notable associations between N. obtusa and key lake elements indicates that N. obtusa may be acting as an ecosystem engineer in invaded lakes by altering the biogeochemical fate of oxygen and phosphorus.
Predicting LncRNA–Disease Association by a Random Walk With Restart on Multiplex and Heterogeneous Networks
Authors: Yao Yuhua , Ji Binbin , Lv Yaping , Li Ling , Xiang Ju , Liao Bo , Gao Wei
Published: August 2021

Studies have found that long non-coding RNAs (lncRNAs) play important roles in many human biological processes, and it is critical to explore potential lncRNA–disease associations, especially cancer-associated lncRNAs. However, traditional biological experiments are costly and time-consuming, so it is of great significance to develop effective computational models. We developed a random walk algorithm with restart on multiplex and heterogeneous networks of lncRNAs and diseases to predict lncRNA–disease associations (MHRWRLDA). First, multiple disease similarity networks are constructed by using different approaches to calculate similarity scores between diseases, and multiple lncRNA similarity networks are also constructed by using different approaches to calculate similarity scores between lncRNAs. Then, a multiplex and heterogeneous network was constructed by integrating multiple disease similarity networks and multiple lncRNA similarity networks with the lncRNA–disease associations, and a random walk with restart on the multiplex and heterogeneous network was performed to predict lncRNA–disease associations. The results of Leave-One-Out cross-validation (LOOCV) showed that the value of Area under the curve (AUC) was 0.68736, which was improved compared with the classical algorithm in recent years. Finally, we confirmed a few novel predicted lncRNAs associated with specific diseases like colon cancer by literature mining. In summary, MHRWRLDA contributes to predict lncRNA–disease associations.
Genome-Wide SNP Discovery and Population Genetic Analysis of Mesocentrotus nudus in China Seas
Authors: Wang Quanchao , Liu Ying , Yan Lang , Chen Linlin , Li Baoquan
Published: August 2021

Mesocentrotus nudus is an important commercially aquatic species because of its high edible and medicinal values. However, wild stocks have dramatically decreased in recent decades. Understanding the population structure and genetic diversity can provide vital information for genetic conservation and improvement. In the present study, the genotyping-by-sequencing (GBS) approach was adopted to identify the genome-wide single-nucleotide polymorphisms (SNPs) from a collection of 80 individuals consisting of five geographical populations (16 individuals from each population), covering the natural habitats of M. nudus in China seas. An average of 0.96-Gb clean reads per sample were sequenced, and a total of 51,738 biallelic SNPs were identified. Based on these SNPs, diversity index analysis showed that all populations have a similar pattern with positive Fis (0.136) and low Ne (724.3). Low genetic differentiation and high genetic connectivity among five geographical populations were detected by pairwise Fst, principal component analysis (PCA), admixture, and phylogenetic analysis. Besides, two YWL individuals originating from an isolated ancestor may imply that there is a genetically differentiated population in the adjacent sea. Overall, the results showed that GBS is an effective method to detect genome-wide SNPs for M. nudus and suggested that the protective measures and the investigation with larger spatial scale and sample size for M. nudus should be carried out in the future.
Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders
Authors: Ouyang Xuejun , Zhang Yu , Zhang Lijuan , Luo Jixuan , Zhang Ting , Hu Hui , Liu Lin , Zhong Lieqiang , Zeng Shaoying , Xu Pingyi , Bai Zhenjiang , Wong Lee-Jun , Wang Jing , Wang Chunli , Wang Bin , Zhang Victor Wei
Published: August 2021

Genetic disorders are a frequent cause of hospitalization, morbidity and mortality in pediatric patients, especially in the neonatal or pediatric intensive care unit (NICU/PICU). In recent years, rapid genome-wide sequencing (exome or whole genome sequencing) has been applied in the NICU/PICU. However, mtDNA sequencing is not routinely available in rapid genetic diagnosis programs, which may fail to diagnose mtDNA mutation-associated diseases. Herein, we explored the clinical utility of rapid exome sequencing combined with mtDNA sequencing in critically ill pediatric patients with suspected genetic disorders. Rapid clinical exome sequencing (CES) was performed as a first-tier test in 40 critically ill pediatric patients (aged from 6 days to 15 years) with suspected genetic conditions. Blood samples were also collected from the parents for trio analysis. Twenty-six patients presented with neuromuscular abnormalities or other systemic abnormalities, suggestive of suspected mitochondrial diseases or the necessity for a differential diagnosis of other diseases, underwent rapid mtDNA sequencing concurrently. A diagnosis was made in 18 patients (45.0%, 18/40); three cases with de novo autosomal dominant variants, ten cases with homozygous or compound heterozygous variants, three cases with hemizygous variants inherited from mother, three cases with heterozygous variants inherited from either parent, and one case with a mtDNA mutation. The 18 patients were diagnosed with metabolic (n = 7), immunodeficiency (n = 4), cardiovascular (n = 2), neuromuscular (n = 2) disorders, and others. Genetic testing reports were generated with a median time of 5 days (range, 3–9 days). Thirteen patients that were diagnosed had an available medical treatment and resulted in a positive outcome. We propose that rapid exome sequencing combined with mitochondrial DNA sequencing should be available to patients with suspected mitochondrial diseases or undefined clinical features necessary for making a differential diagnosis of other diseases.
Serological Testing for COVID-19, Immunological Surveillance, and Exploration of Protective Antibodies
Authors: Peroni Luis A. , Toscaro Jessica M. , Canateli Camila , Tonoli Celisa C. C. , de Olivera Renata R. , Benedetti Celso E. , Coimbra Lais D. , Pereira Alexandre Borin , Marques Rafael E. , Proença-Modena José L. , Lima Gabriel C. , Viana Renata , Borges Jessica B. , Lin-Wang Hui Tzu , Abboud Cely S. , Gun Carlos , Franchini Kleber G. , Bajgelman Marcio C.
Published: August 2021

Serological testing is a powerful tool in epidemiological studies for understanding viral circulation and assessing the effectiveness of virus control measures, as is the case of SARS-CoV-2, the pathogenic agent of COVID-19. Immunoassays can quantitatively reveal the concentration of antiviral antibodies. The assessment of antiviral antibody titers may provide information on virus exposure, and changes in IgG levels are also indicative of a reduction in viral circulation. In this work, we describe a serological study for the evaluation of antiviral IgG and IgM antibodies and their correlation with antiviral activity. The serological assay for IgG detection used two SARS-CoV-2 proteins as antigens, the nucleocapsid N protein and the 3CL protease. Cross-reactivity tests in animals have shown high selectivity for detection of antiviral antibodies, using both the N and 3CL antigens. Using samples of human serum from individuals previously diagnosed by PCR for COVID-19, we observed high sensitivity of the ELISA assay. Serological results with human samples also suggest that the combination of higher titers of antiviral IgG antibodies to different antigen targets may be associated with greater neutralization activity, which can be enhanced in the presence of antiviral IgM antibodies
Predictive Values of PET/CT in Combination With Regulatory B Cells for Therapeutic Response and Survival in Contemporary Patients With Newly Diagnosed Multiple Myeloma
Authors: Cui Jian , Zou Zhongqing , Duan Jiayu , Tang Wenjiao , Li Yan , Zhang Li , Pan Ling , Niu Ting
Published: August 2021

To assess patients with multiple myeloma (MM), the whole-body positron-emission tomography/computed tomography (PET/CT) occupies a pivotal position for diagnostic stratification, response evaluation, and survival prediction, while important limitations are recognized as incapable of representing tumor microenvironment. Regulatory B cells (Bregs) have been reported to have an inhibitory immune function, contributing to bone marrow (BM)-immunosuppressive microenvironment for MM. Therefore, to investigate the role of PET/CT in combination with Bregs’ ratios to predict therapeutic response and survival, we sequentially enrolled 120 patients with newly diagnosed MM (NDMM) who were treated with novel agents in our center, while conventional PET/CT parameters including maximum standard uptake value (SUVmax), ratios of BM-derived Bregs within CD19+ B cells, and patients’ clinical characteristics were collected. After a median follow-up of 28.20 months (range 7.00–46.93 months), SUVmax > 4.2 at onset, accounting for 53.2% of NDMM, was uncovered to predict inferior progression-free survival (PFS) as well as overall survival (OS). With regard to the ratios of BM-derived Bregs within CD19+ B cells, the cohort with the Bregs’ proportions lower than 10%, accounting for 46.2%, exerted poorer OS. Additionally, the patients with both SUVmax > 4.2 and Bregs’ ratios < 10%, accounting for 31.7%, yielded compromised therapeutic response and long-term survival. Collectively, this study may draw attention on the prognostic value of combination of PET/CT and Bregs’ ratios when clinical decisions are made for MM in the era of novel agents.
Serum Anti-PDLIM1 Autoantibody as Diagnostic Marker in Ovarian Cancer
Authors: Qiu Cuipeng , Duan Yaru , Wang Bofei , Shi Jianxiang , Wang Peng , Ye Hua , Dai Liping , Zhang Jianying , Wang Xiao
Published: August 2021

Background

Serum autoantibodies (AAbs) against tumor-associated antigens (TAAs) could be useful biomarkers for cancer detection. This study aims to evaluate the diagnostic value of autoantibody against PDLIM1 for improving the detection of ovarian cancer (OC).

Methods

Immunohistochemistry (IHC) test in tissue array containing 280 OC tissues, 20 adjacent tissues, and 8 normal ovarian tissues was performed to analyze the expression of PDLIM1 in tissues. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the autoantibody to PDLIM1 in 545 sera samples from 182 patients with OC, 181 patients with ovarian benign diseases, and 182 healthy controls.

Results

The results of IHC indicated that 84.3% (236/280) OC tissues were positively stained with PDLIM1, while no positive staining was found in adjacent or normal ovarian tissues. The frequency of anti-PDLIM1 autoantibody was significantly higher in OC patients than that in healthy and ovarian benign controls in both training (n=122) and validation (n=423) sets. The area under the curves (AUCs) of anti-PDLIM1 autoantibody for discriminating OC from healthy controls were 0.765 in training set and 0.740 in validation set, and the AUC of anti-PDLIM1 autoantibody for discriminating OC from ovarian benign controls was 0.757 in validation set. Overall, it was able to distinguish 35.7% of OC, 40.6% of patients with early-stage, and 39.5% of patients with late-stage. When combined with CA125, the AUC increased to 0.846, and 79.2% of OC were detected, which is statistically higher than CA125 (61.7%) or anti-PDLIM1(35.7%) alone (p<0.001). Also, anti-PDLIM1 autoantibody could identify 15% (18/120) of patients that were negative with CA125 (CA125 <35 U/ml).

Conclusions

The anti-PDLIM1 autoantibody response in OC patients was positively correlated with PDLIM1 high expression in OC tissues, suggesting that the autoantibody against PDLIM1 might have the potential to be a novel serological biomarker of OC, serving as a complementary measure of CA125, which could improve the power of OC detection.
Coastal Ecosystems as Sources of Biofertilizers in Agriculture: From Genomics to Application in an Urban Orchard
Authors: Pajuelo Eloísa , Arjona Sandra , Rodríguez-Llorente Ignacio D. , Mateos-Naranjo Enrique , Redondo-Gómez Susana , Merchán Francisco , Navarro-Torre Salvadora
Published: August 2021

Pantoea agglomerans RSO7, a rhizobacterium previously isolated from Spartina maritima grown on metal polluted saltmarshes, had demonstrated good plant growth promoting activity for its host halophyte, but was never tested in crops. The aims of this study were: (1) testing PGP activity on a model plant (alfalfa) in vitro; (2) testing a bacterial consortium including RSO7 as biofertilizer in a pilot experiment in urban orchard; and (3) identifying the traits related to PGP activities. RSO7 was able to enhance alfalfa growth in vitro, particularly the root system, besides improving plant survival and protecting plants against fungal contamination. In addition, in a pilot experiment in urban orchard, a consortium of three bacteria including RSO7 was able to foster the growth and yield of several winter crops between 1.5 and 10 fold, depending on species. Moreover, the analysis of chlorophyll fluorescence revealed that photosynthesis was highly ameliorated. Genome analysis of RSO7 depicted the robustness of this bacterial strain which showed resilience to multiple stresses (heat, cold, UV radiation, several xenobiotics). Together with wide metabolic versatility, genes conferring resistance to oxidative stress were identified. Many genes involved in metal resistance (As, Cu, Ni, Co, Zn, Se, Te) and in tolerance toward high osmolality (production of a battery of osmoprotectans) were also found. Regarding plant growth promoting properties, traits for phosphate solubilization, synthesis of a battery of siderophores and production of IAA were detected. In addition, the bacterium has genes related to key processes in the rhizosphere including flagellar motility, chemotaxis, quorum sensing, biofilm formation, plant-bacteria dialog, and high competitiveness in the rhizosphere. Our results suggest the high potential of this bacterium as bioinoculant for an array of crops. However, the classification in biosecurity group 2 prevents its use according to current European regulation. Alternative formulations for the application of the bioinoculant are discussed.
Polycentric Regional Ocean Governance Opportunity in the Benguela Current Convention
Authors: Naidoo Ashley , Hamukuaya Hashali , Hara Mafaniso , Mngxe Yamkela , Raakjær Jesper
Published: August 2021

The Benguela Current Convention (BCC) has been operational for a decade and has emerged from the precursor natural and fisheries science large marine ecosystem programs. This regional ocean governance institution emerged indigenously as an intergovernmental working arrangement across the Republics of Angola, Namibia, and South Africa. The Convention has been described as a Centralized Authority mode of regional ocean governance. This paper explores this description with reference to the ecosystem-based approach to marine management. The study is focused on the level of working arrangements within the Convention and its Commission across the national and regional scales. It finds that the BCC does meet the theoretical criteria of a polycentric governance mechanism at the resolution of its operations. Polycentric ocean governance mechanisms are valued in regional ocean governance as they potentially offer greater impact through higher levels of coordination, codesign, and integration. Polycentric governance systems incorporate multiple centers of authority that operate at different scales. Existing instances and further opportunities for polycentric governance mechanisms within the working arrangements of the Convention are identified for the Southeast Atlantic.
Multi-Year ENSO Forecasts Using Parallel Convolutional Neural Networks With Heterogeneous Architecture
Authors: Ye Min , Nie Jie , Liu Anan , Wang Zhigang , Huang Lei , Tian Hao , Song Dehai , Wei Zhiqiang
Published: August 2021

The El Niño-Southern Oscillation (ENSO) is one of the main drivers of the interannual climate variability of Earth and can cause a wide range of climate anomalies, so multi year ENSO forecasts are a paramount scientific issue. However, most existing works rely on the conventional iterative mechanism and, thus, fail to provide reliable long-term predictions due to error accumulation. Although methods based on deep learning (DL) apply the parallel modeling scheme for different lead times instead of a single iteration model, they leverage the same DL model for prediction, which can not fully mine the variability of different lead times, resulting in a decrease of prediction accuracy. To solve this problem, we propose a novel parallel deep convolutional neural network (CNN) with a heterogeneous architecture. In this study, by adaptively selecting network architectures for different lead times, we realize variability modeling of different tasks (lead times) and thereby improve the reliability of long-term predictions. Furthermore, we propose a relationship between different prediction lead times and neural network architecture from a unique perspective, namely, the receptive field originally proposed in computer vision. According to the spatio-temporal correlated area and sampling scale of lead times, the size of the convolution kernel and the mesh size of sampling are adjusted as the lead time increases. The Coupled Model Intercomparison Project phase 5 (CMIP5) from 1861 to 2004 and the Simple Ocean Data Assimilation (SODA) from 1871 to 1973 were used for model training, and the GODAS from 1982 to 2017 were used for testing the forecast skill of the model. Experimental results demonstrate that the proposed method outperforms the other well-known methods, especially for long-term predictions.
Dependence of Biofuel Ignition Chemistry on OH-Initiated Branching Fractions
Authors: Hartness Samuel W. , Rotavera Brandon
Published: August 2021

Abstraction of hydrogen by ȮH is the dominant initiation step in low-temperature oxidation of biofuels. Theoretical chemical kinetics calculations for such reactions provide a direct means of quantifying rates of abstraction, which are critical to modeling biofuel combustion. However, in several cases and despite agreement on total rate coefficients, branching fractions (i.e. the distribution of initial radicals) can vary depending on the level of theory, which leads to variations in ignition delay time predictions. To examine the connection between branching fractions and ignition delay time predictions, simulations were conducted for 1-butanol, cyclopentanone, and methyl propanoate at 10 atm and from 500–1000 K. For each case, the simulations utilized recent combustion mechanisms to produce an initial set of ignition delay time trends. H-abstraction rates were then replaced using rates from the literature to examine the effects of ȮH-initiated branching fractions on ignition chemistry. Branching fractions were found to significantly influence ignition chemistry, specifically in the case of 1-butanol, even when total rate coefficients were relatively consistent. From comparison of site-specific rates in the literature, branching fractions for initiation of 1-butanol and methyl propanoate are not consistent, which resulted in ignition delay times differing by factors of up to 6.3 and 1.2 respectively. Conversely, in the case of cyclopentanone, for which both the total and the site-specific rate coefficients agree, ignition delay times were unaffected. From the observed dependence of ignition delay times on ȮH-initiated branching fractions, an intermediate step in the development of combustion mechanisms is necessary to validate site-specific rate coefficients and ensure accurate model predictions. Speciation measurements are one example that can provide a critical link to radical-specific, fundamental chemical pathways and determine accurate branching fractions.
Impact of Human Umbilical Cord Blood Mononuclear Cells on Gentamicin-Induced Renal Injury and Genotoxicity in Rats
Authors: Abu Almaaty Ali H. , Elmasry Reham A. , Farrag Mayada S. , Althobaiti Fayez , Aldhahrani Adil , Fayad Eman , Hussain Mona A.
Published: August 2021

Background: Acute kidney injury (AKI), also known as acute renal failure (ARF), has received considerable critical attention in recent years. Gentamicin (GM) is an antibiotic whose prolonged use results in AKI with a high mortality rate.

Methods: Fifty adult female albino rats weighing 150–200 g were used. The animals were divided into five groups: the first group was the normal healthy control one, the second group received only 1 × 106 HUCB mononuclear cells (MNCs)/rat by intravenous (iv) injection, the third diseased group was given GM 100 mg/kg for 10 consecutive days by intraperitoneal injections, the fourth preventive group received 1 × 106 HUCB MNCs/rat by iv injection 24 h before gentamicin treatment, and the fifth treated group received 1 × 106 HUCB MNCs/rat by iv injection 24 h after gentamicin treatment. After 1 week of treatment, blood samples were collected, and kidneys were removed for histopathological examination.

Results: Rats treated with HUCB MNCs in the treated group had a significant decrease in renal damage, low levels of biomarkers for nephrotoxicities such as serum creatinine and blood urea nitrogen, and low chromosomal aberrations compared to the diseased third group. The gene expression of KIM-1 and NGAL was decreased in response to HUCB treatment.

Conclusions: HUCB MNCs have a curative effect against AKI and gentamicin-induced genotoxicity owing to their regenerative property.
Frailty Predicts Poor Prognosis of Patients After Percutaneous Coronary Intervention: A Meta-Analysis of Cohort Studies
Authors: Wang Peng , Zhang Shutang , Zhang Ke , Tian Jie
Published: August 2021

Background: Frailty has been related to a higher risk of cardiovascular events, while the association between frailty and outcomes for patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI) remains unclear. We performed a meta-analysis of cohort studies to evaluate the above association.

Methods: Cohort studies aiming to determine the potential independent association between frailty and clinical outcomes after PCI were identified by search of PubMed, Embase, and Web of Science databases from inception to February 22, 2021. A random-effects model that incorporates the possible heterogeneity among the included studies was used to combine the results.

Results: Ten cohort studies with 7,449,001 patients were included. Pooled results showed that frailty was independently associated with higher incidence of all-cause mortality [adjusted risk ratio (RR) = 2.94, 95% confidence intervals (CI): 1.90–4.56, I2 = 56%, P < 0.001] and major adverse cardiovascular events [(MACEs), adjusted RR = 2.11, 95% CI: 1.32–3.66, I2 = 0%, P = 0.002]. Sensitivity analyses limited to studies including elderly patients showed consistent results (mortality: RR = 2.27, 95% CI: 1.51–3.41, I2 = 23%, P < 0.001; MACEs: RR = 2.44, 95% CI: 1.44–4.31, I2 = 0%, P = 0.001). Subgroup analyses showed that characteristics of study design, follow-up duration, or type of PCI did not seem to significantly affect the associations (P-values for subgroup analyses all >0.05).

Conclusions: Frailty may be an independent risk factor of poor prognosis for patients with CAD after PCI.
Giant Hepatic Hemangioma Regressed Significantly Without Surgical Management: A Case Report and Literature Review
Authors: Zhang Jingcong , Ye Zuyang , Tan Lei , Luo Jinmei
Published: August 2021

Hepatic hemangioma (HH) is a congenital vascular anomaly comprising networks of abnormal blood and/or lymphatic vessels with endothelial cell proliferation. Their pathophysiology is not fully understood, and no specific drug is available to treat them. Conservative management, which limits observation, is preferred for most patients. A HH larger than 4 cm is considered a giant HH that may be treated using surgery ranging from embolization to hepatic resection or liver transplantation. Here, we describe a case with multiple and giant HHs that regressed significantly after treatment with azithromycin (AZM). A systematic literature review of HH and the effects of AZM on angiogenesis was then conducted.