bluuebunny/crossref_metadata_2025 huggingface dataset:
Invasive aspergillosis in lung transplant recipients: a retrospective clinical analysis in a single center
Authors: Zhao Li , Chen Wenhui , Guo Lijuan , Liang Chaoyang , Wang Chen
Published: April 2022

Invasive aspergillosis (IA) infection is common and remains a major cause of morbidity and mortality in lung transplant recipients (LTRs).In this observational cross-sectional study, we gathered clinical data of 157 adult LTRs from March 2017 to December 2018 in a lung transplant center in China. All recipients were followed until the end of March 2019. Forty-three of the 157 LTRs (27.4%) developed IA infection. The most common pathogens were Aspergillus flavus (n=16/37 strains, 43.2%), followed by Aspergillus fumigatus (n=11/37 strains, 29.7%) and Aspergillus niger (n=5/37 strains, 13.5%). Intravenous echinocandins and inhaled amphotericin B were universally used for antifungal prophylaxis. The vast majority of infected LTRs (83.7%, 36/43) were treated with voriconazole monotherapy, and the rest (16.3%) were voriconazole-based combination therapy. The all-cause mortality 1 month and 6 months postoperatively was 4.7% and 18.6% respectively, and 34.9% had died at the conclusion of this study. The mortality rate of patients with early-onset IA (within 3 months) reached 40.0%, which seemed to be higher than that of patients with late-onset IA (more than 3 months, 12.5%). The incidence of IA in LTRs is high. The most common form of infection was TBA, with Aspergillus flavus as the main pathogenic fungus. Due to poor prognosis, it is important to select appropriate antifungal prophylaxis strategy and initiate antifungal therapy as early as possible upon confirmation of the diagnosis of IA infection.
Co-composting of sawdust with food waste: effects of physical properties on composting process and products quality
Authors: BELLO HADI , AJAO Jamiu Olamilekan , SADIKU Nusirat Aderinsola
Published: April 2022

Sawdust and food waste have been part of solid organic waste causing great environmental pollution. Composting is a popular utilization method of converting waste like sawdust and food waste to sanitized and stabilized soil amendment. Unfortunately, many composting systems failed due to a dearth of information as a result of little or no scientific research focused on the effects of the physical properties of composting materials on the composting process. To fill this knowledge gap, three composting experiments of food wastes mixed with sawdust at ratio 20:80, 30:70, and 40:60 and compacted to different initial bulk densities of 15, 20, and 25 kg/m3 respectively was carried out. Physicochemical parameters monitored throughout the composting process include bulk density; porosity; particle density, temperature, moisture content; pH, and electrical conductivity (EC). The highest temperature (65.3 oC) was recorded by trial 3 while trial 1 recorded the lowest temperature (49.3 0C). A steady decrease in temperature after the thermophilic stage was observed throughout the composting process. Among trials 1, 2, and 3, the maximum pH (9.2) and EC (5.1 mS/cm) were observed in compost trial 3. Additionally, the lowest pH (5.3) and EC (1.4 mS/cm) was observed in trial 1. Moisture content ranged from 60–15%. Trial 3 had the highest percentage finest and lowest fibrosity content. A significant increase in bulk density, porosity, and particle density was observed in the three compost trials. The compost’s bulk density of (25 kg/m3) in trial 3 was observed to attained maturity and stability as compared with trials 1 and 2.
LCBDE, three ports, and primary continuous suture of common bile duct for the treatment of cholelithiasis and choledocholithiasis: a retrospective study in Eastern China
Authors: Zhao Chunlong , Hu Weidong , Ge Chen , He Songbing , Zhang Zhengwei , Zhao Wanwen , Dai Zhengxing , Tang Neng , Zhang Shuo , Wang Weiguo , Gu Jiayu , Xu Zipeng , Chen Chaobo
Published: April 2022

Background
Laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct exploration (LCBDE) in combination with choledocholithiasis is convenient in the treatment of cholelithiasis. It has the advantage of accelerated recovery. This retrospective study aimed to summarize the experience of cholelithiasis and choledocholithiasis treatment via LC plus LCBDE approach in Eastern China.
Methods
Patients diagnosed with cholelithiasis and choledocholithiasis between July 2019 and October 2021 at the Xishan People’s Hospital of Wuxi City were included in the study. During treatment, patients who received LC + LCBDE + primary suturing of the CBD were assigned to the LCBDE-P group, and those who received LC + LCBDE + T-tube drainage of CBD were assigned to the LCBDE-T group. The measurement data were compared between the two groups. P-values < 0.05 indicated statistical significance.
Results
A total number of 88 patients (48 females and 40 males) were divided into two groups: LCBDE-P (n = 50) and LCBDE-T (n = 38). Multiple linear regression analysis showed that LCBDE-P affected the risk-adjusted hospitalization stay (unstandardized coefficient, -5.352 days; 95% CI: -0.387 to -4.761; P < 0.001) and medical cost (unstandardized coefficient, -0.494 RMB; 95% CI: -0.712 to -0.277; P < 0.001) with significant differences. On the other hand, no significant differences were detected in the operation time, intraoperative hemorrhage, clearance rate of CBD stones, postoperative liver function, and postoperative complications (P > 0.05) between the two groups.
Conclusions
LCBDE is a safe and feasible strategy for the management of cholelithiasis and choledocholithiasis. Compared to LCBDE-T, LCBDE-P is an independent factor associated with the days and medical costs during hospitalization.
Hybrid recommender system with core users selection
Authors: Jin Chenxia , Mi Jusheng , Li Fachao , Zhang Jiahuan
Published: April 2022

Recommender system plays an increasingly important role in identifying the individual’s preference and accordingly makes a personalized recommendation. Matrix factorization is currently the most popular model-based collaborative filtering (CF) method that achieves high recommendation accuracy. However, similarity computation hinders the development of CF-based recommendation systems. Preference obtained only depends on the explicit rating without considering the implicit content feature, which is the root cause of preference bias. In this paper, the content feature of items described by fuzzy sets is integrated into the similarity computation, which helps to improve the accuracy of user preference modelling. The importance of a user is then defined according to preferences, which serves as a baseline standards of the core users selection. Furthermore, core users based matrix factorization model (CU-FHR) is established, then genetic algorithm is used to predict the missing rating on items. Finally, MovieLens is used to test the performance of our proposed method. Experiments show CU-FHR achieves better accuracy in prediction compared with the other recommendation methods.
Posterior Paramedian Approach—A Simple Technique to Obtain a Lateral Viewing Angle for Spinal Lesions
Authors: Chang Han Soo , Sano Fumiya , Sorimachi Takatoshi , Matsumae Mitsunori
Published: April 2022

A wide lateral viewing angle is often necessary for spinal surgery. However, the skin and paraspinal muscles limit this angle in the traditional posterior midline approach. This article describes a simple, less-invasive approach that provides good lateral viewing angles to spinal lesions. The approach consisted of (1) a horizontal skin incision, (2) unilateral dissection and exposure of the laminae, (3) a horizontal fascial incision, and (4) application of retractors in the longitudinal direction with a minimal incision on the multifidus muscle. We successfully used this approach on 24 patients with various spinal diseases. The pathology of the lesions included nine schwannomas, five meningiomas, four ossification of ligamentum flavum (OLF), three malignant tumors, and three others. There were nine cervical, twelve thoracic, two lumbar, and one sacral lesions. We could achieve gross total removal in most cases without significant complications. The approach provided an excellent surgical field for removing ventrally located tumors with minimal cord retraction. This simple technique will be a valuable addition to the armamentarium of spine surgeons.
Evaluation of a grid-based surveillance strategy to ensure elimination and prevent reintroduction of malaria in high-risk border communities in China
Authors: Wang Duo-quan , Lu Shen-ning , Ding Wei , Wang Jia-zhi , Zhou Xing-wu , Xu Qiu-li , Sun Xiao-dong , Cotter Chris , Hsiang Michelle S , Tatarsky Allison , Gosling Roly , Lv Shan
Published: April 2022

Grid management is a grassroots governance strategy widely implemented in China since 2004 to improve the government’s efficiency to actively find and solve problems among populated regions. A grid-based strategy surveillancing high-risk groups, including mobile and migrant populations (MMPs), in the China–Myanmar border region has played an indispensable role in promoting and sustaining malaria elimination efforts by tracking and timely identification of potential importation or reintroduction of malaria among MMPs. This paper distills the implementation mechanism of the grid-based strategy for malaria surveillance and highlights the role of the grid-based strategy in the elimination and prevention of reestablishment of malaria transmission.
Novel efficiently piscine orally nano-vaccine delivery system: modified halloysite nanotubes (HNTs) preventing streptococcosis disease in Tilapia (Oreochromis sp.)
Authors: Pumchan Ansaya , Sae-Ueng Udom , Prasittichai Chaiya , Sirisuay Soranuth , Areechon Nontawith , Unajak Sasimanas
Published: April 2022

Background
Generally, the injection method is recommended as the best efficient method for vaccine application in fish. However, labor-intensive and difficult injecting to certain fish sizes is always considered as a limitation to the aquatic animals. To demonstrate the effectiveness of a novel oral delivery system for the piscine vaccine, the nano-delivery made from nano clay, halloysite nanotube (HNTs), and their modified forms, were loaded with killed vaccines and determined the ability of the system in releasing vaccines in the mimic digestive system. The efficaciousness of orally piscine vaccine nano-delivery was evaluated as the level of antibody production and level of disease prevention in Nile tilapia (Oreochromis niloticus).
Results
Unmodified HNTs (H) and modified HNTs [HNT-Chitosan (HC), HNT-APTES (HA), and HNT-APTES-Chitosan (HAC)] were successfully harboring streptococcal bivalent vaccine; inactivated S. agalactiae, designated as HF, HAF, HCF, and HACF, respectively. The releasing of loading antigens in the mimic digestive tract demonstrated a diverse pattern of proteins releasing depending on the types of HNTs. Remarkedly, HCF could properly release loading antigens in relevance to the increasing pH buffer. The oral vaccines revealed the greatest elevation of specific antibodies to S. agalactiae serotype Ia in HCF orally administered fish and to some extent in serotype III. The efficacy of streptococcal disease protection was determined by continually feeding with HF, HAF, HCF, and HACF coated feed pellets for 7 days with a week after week program. HCF showed significant RPS (75.00 ± 10.83%) among other tested groups [HF (18.75 ± 10.83%), HAF (37.50 ± 10.83%) and HACF (18.75 ± 10.83%)]. Interestingly, the HCF-treated group exhibited noticeable efficacy similar to the bivalent vaccine injected group (RPS 81.25 ± 0.00%).
Conclusions
This novel nano-delivery system for the fish vaccine was successfully developed and exhibited appropriated immune stimulation and promised disease prevention through oral administration. This delivery system would greatly support animals’ immune stimulation which conquers the limitation in vaccine application in aquaculture systems. Moreover, this delivery system would apply to carry diverse types of biologics including DNA, RNA, and subunit protein vaccines.
Phase separation-mediated condensation of N protein-deaminase complex promotes SARS-CoV-2 mutagenesis
Authors: Huang Xingxu , Li Zhean , Luo Lingling , Ju Xiaohui , Huang Shisheng , Liu Jia , Zhang Pumin , Chi Tian , Ma Peixiang , Huang Cheng , Ding Qiang , Zhang Yu
Published: April 2022

The emergence of SARS-CoV-2 variants poses enormous challenges to the prevention and control of COVID-19 with alterations in antigenicity, transmissibility and pathogenicity. The rapid evolution of RNA viruses could be caused by high mutation frequencies during replication, arising by replication errors, intergenomic recombination or even host deaminases. We sought to understand whether host deaminases are involved in SARS-CoV-2 mutation, and how they orchestrate host deaminases to trigger this process. Herein, we provided the experimental evidence that APOBEC and ADAR deaminases act as the driving forces for SARS-CoV-2 mutagenesis. Mechanistically, SARS-CoV-2 nucleocapsid (N) protein, which is responsible for packaging viral genomic RNA, complexes with host deaminases to facilitate viral RNA mutation. Moreover, N protein employs deaminases-involved condensates to further promote viral RNA mutation. Mutant N protein with F17A substitution, defective in entry of deaminases-involved RNA granules, leads to the decreased mutation of viral RNA, confirming the function of N protein-deaminase condensates on RNA editing. Our study sheds light on the novel mechanism of SARS-CoV-2 mutation during host-virus arms race.
Role of exogenous elicitors in canola plant defense against cabbage aphid by regulating physiological balance and secondary metabolite biosynthesis
Authors: Shahrokhi Mahdieh , Yali Maryam Pahlavan , Bozorg-Amirkalaee Maryam
Published: April 2022

Induced resistance in plants can be manipulated by the application of elicitors. In this research, the effects of salicylic acid (SA), chitosan, γ-aminobutyric acid (GABA), Serenad Aso (Bacillus subtilis QST713), and integrated application of these elicitors were studied on the induced resistance of canola to the cabbage aphid, Brevicoryne brassicae L. (Hem: Aphididae). In the field experiments (during 2019 and 2020), the number of B. brassicae attracted to canola plants treated with different inducers was significantly lower compared to control plants. The lowest population density of this aphid was observed under treatments of SA + GABA and SA + chitosan. Moreover, the positive effect of the integrated application of SA and chitosan/GABA on canola growth parameters was significantly obvious in our study. The highest amounts of glucosinolates and total phenol were recorded in SA + GABA treatment. The contents of energy resources (sugar, lipid, and glycogen) of B. brassicae were lowest when fed on plants treated with SA integrated with GABA /chitosan. Furthermore, the activity of catalase, esterase, peroxidase, and glutathione S- transferase enzymes was the lowest on SA + GABA and SA + chitosan treatments. We concluded that these elicitors cause resistance induction of canola plants to the cabbage aphid. These findings especially suggested that SA integrated with GABA /chitosan on canola plants act successfully for reducing the B. brassicae population and can be considered in integrated management programs of this aphid.
A research on PM2.5 transmission mode based on motif analysis
Authors: Wang Dan , Wang Qian , Li Cuiping
Published: April 2022

PM2.5 has had a huge impact on human health and global climate. With accurate modeling ofthe transmission mode of PM2.5, the government can formulate and implement more preciseenvironmental policies to control PM2.5 emissions, thereby generating co-benefits in multiple fields.We select 93 cities including the three provinces of Northeast China, Shandong Province, HenanProvince, Shanxi Province and Jing-Jin-Ji region as examples. Higher-order organization of complexnetworks are applied to our study. The data we use contains meteorological conditions of wind speedand wind direction, social factor of region’s GDP (Gross Domestic Product), as well as geographicdistance and PM2.5 concentrations. To our knowledge,it is the first work to include GDP in the analysisof PM2.5 transmission. By the motif analysis method, the major potential PM2.5 pollution victims areidentified in each cluster. In the region including Shandong, Henan and Shanxi Province, Xingyang isvulnerable to pollution in PM2.5 transport. In the Jing-Jin-Ji region, Beijing and Tianjin are vulnerableto pollution. In addition, we also found that Shijiazhuang, Handan and Baoding, as the gathering placeof large-scale industries, are the main contributors of pollution transmission, which provides us witha strong guidance to control the pollution.
A Deep learning based patient care application for skin cancer detection
Authors: Dong Hanlin , Farid Farnaz
Published: April 2022

Melanoma is one of the deadliest skin cancer. It can, however, be cured with a high success rate if found in the early stage. With the recent development in Artificial Intelligence (AI), there has been an increase in the research of Machine Learning (ML) and Deep Learning (DL) models for melanoma detection. However, such deployments are primarily trial-based and still waiting to gain wider acceptance from the practitioners. One of the primary reasons for such lower acceptance lies in the inherent approach and ethical concerns. To this end, our study designs a Deep Learning based recommendation application for the patients to advise whether they need to see a dermatologist based on provided skin lesion image. The traditional AI-based melanoma classifiers tend to be developed based on bulk image training and hence would classify images on an individual level. However, they neglect that a single skin lesion is merely a part of the patient. Thereby this research considers the contextual information between different lesions on the same patient. It produces a personalized patient classification rather than focusing on lesion level prediction. Several models are developed using ML and DL techniques, such as transfer learning and deep neural networks. These models are then tested on a real melanoma dataset with the true label provided. External benchmark is also established from recent similar studies using the same dataset. The best classifier achieves an 81.6% Area Under the Receiver Operating Characteristic Curve (AUROC) score using the patient's unique biological features.
Ontology-based rumor identification system using social network data
Authors: Sarfraz Amber , Ahmad Adnan , Zeshan Furkh , Ahmed Sohaib
Published: April 2022

With the tremendous expansion of online social networks (OSNs) such as Twitter and Facebook, have become not only one of the utmost effective modes for viral advertising. But also, the main source of news among people nowadays. Besides these encouraging features, however, comes the risk of rumor dissemination. Due to the enormous users of OSN, there is a considerable challenge to proficiently contain the viral spread of rumors. In addition, because of a huge number of news on OSN, the manual detection of rumors is not possible. So, we need an auto-detection and authentic knowledge sharing method in a machine-readable as well as the human-readable format for OSN. In this regard, several researchers, doing research in this domain. But no method deals with uniform, authentic, and machine-readable as well as human-readable knowledge sharing among OSN users. To address this issue, ontology-based systems can be used because ontology-based systems deal with all such kinds of issues very effectively. However, for effective categorization of OSN posts, ontology-based systems should consider roles, rating, confidence level, location, and post categorization while decision making about OSN posts. Whereas, several ontology-based methods presented for rumors verification, consider only a few requirements resulting in low accuracy of authenticated posts. Experimental results verify that the proposed ontology-based approach can produce accurate results according to human understanding.
Clinical Features of and Risk Factors for Infection in Patients with Rheumatoid Arthritis
Authors: Xie Yan , Lin Yiping
Published: April 2022

Background
To explore the infection characteristics of patients with rheumatoid arthritis(RA) and related risk factors for infection.
Methods
This was a retrospective analysis of the clinical data of 648 hospitalized patients with RA, related risk factors for infection and infection sites, pathogens, and drug resistance patterns. The chi-square test 、Mann-Whitney U test and binary logistic-regression analysis were used to identify risk factors.
Results
A total of 648 patients with RA had 182 cases of infection, and the infection rate was 28.09%. Common infections were pneumonia(19.60%), urinary tract infections(5.25%), and upper respiratory tract infections(5.09%). Gram-negative bacteria ranked first in terms of pathogen composition (67.57%), and the main pathogenic bacteria were Pseudomonas aeruginosa and Escherichia coli; Staphylococcus aureus was the main pathogenic bacteria species among the gram-positive bacteria. The proportion of resistant isolates was relatively high, and the gram-negative bacteria had a relatively high sensitivity to penicillins/cephalosporins + β-lactamase inhibitors, aminoglycosides, and carbapenems. The risk factors included older age (P = 0.020), a long disease duration (P = 0.004), smoking (P = 0.016), hypoproteinaemia (P = 0.010),and the use of corticosteroids (P < 0.01).The use of nonbiologic disease-modifying antirheumaic drugs(DMARDs) was negatively associated with infection(P = 0.006).
Conclusions
Our results indicate that the most common infection sites in patients with RA were the respiratory and urinary tracts. Gram-negative bacteria were the common pathogens. RA patients with older age, a long disease duration, smoking, hypoproteinaemia, and long-term use of corticosteroids were prone to infection. Nonbiologic DMARDs use was significantly associated with a decreased risk for infection. The proportion of drug-resistant infections in patients with RA was relatively high.
Poly (ADP-Ribose) polymerase inhibitors have efficacy in a fraction of platinum-resistant ovarian cancer patients
Authors: Zhang Mingjun , Lee Siyu , Fei Xichang , Wang Tao , Zheng Yuting , Dai Haiming
Published: April 2022

BACKGROUD：Platinum-based chemotherapies are widely used as first line treatments for ovarian cancer after debulking surgery. Poly (ADP-ribose) polymerase inhibitors (PARPis) have also been approved for the treatment of some types of ovarian cancer, such as ovarian cancer with BRCA1 and BRCA2 mutations or deletions. Both platinum and PARPi treatments have been shown to relate to homologous recombination deficiency. However, whether PARPis are efficient in platinum-resistant patients is still unclear. METHODS：In this study, we enrolled 36 ovarian cancer patients who received treatments of both platinum and PARPis and analyzed the demographic, clinical, and pathological data. RESULTS：The results indicated that the patients who are sensitive to platinum had better responses to PARPis (P=0.004**, 99%CI: 0.002-0.005). PARPis show efficacy in a fraction of platinum resistant patients. Moreover, the earlier usage of PARPis was associated with a lower risk of death (P=0.006**, 95%CI: 0.66-0.630). CONCLUSIONS：Platinum-resistant patients were less responsive to PARPis. PARPis are also options for platinum-resistant patients.
Bioinformatics analysis and vivo experiment of Artemisia argyi essential oil for the treatment of pressure ulcer by modulating Wnt/β-catenin pathway
Authors: Lu shuting , Xie xiangyu , Ou weiwei , Huang ling , Tang lulu
Published: April 2022

Background
Pressure ulcer (PU) is a complex inflammatory disease caused by a variety of factors, which seriously affect the quality of life of patients and are an urgent challenge for clinical medical and nursing care. Artemisia argyi essential oil (AAEO) possesses a wide range of pharmacological properties in antibacterial, antioxidation, and anti-inflammation. To observe the effect of AAEO via modulating Wnt/β-catenin signaling pathway in accelerating the PU wound healing in rats.
Materials and methods
Bioinformatics methods were used for differential analysis of pressure ulcer genes. Differentially expressed genes (DEGs), Gene Ontology (GO) enrichment analysis, and protein-protein interaction networks were established to find the potential mechanism of PU. Sprague-Dawley rats (n = 10) were randomly divided into Control group, Model group, and AAEO group. Rats in the AAEO groups with PU were treated with AAEO topical daily for 10 days. To investigate how AAEO treats pressure ulcers, researchers used HE staining, Masson's staining, quantitative real-time PCR, and Western blotting analysis.
Results
A total of 26 upregulated and 69 downregulated genes were identified through intersected genes of Wnt/β-catenin pathway with GSE137897. GO analysis revealed that main items involved in inflammation response with the differentially expressed genes. Six hub genes with high degrees of connectivity were picked out, namely WNT3A, GSK3B, FZD1, BMP4, AXIN2, and SOX9 in the PPI network. In addition, rats experiment found that AAEO promotes wound healing by inhibiting apoptosis and Wnt/β-catenin signaling pathway. The INOS and IL-16 levels showed that AAEO significantly reduces inflammation in PU tissues. The Bax, Bcl-2, and Caspase-9 levels showed that AAEO inhibits apoptosis. We also observed that AAEO increase the expression of gsk3b, a downstream protein of the pathway, leading to the inhibition of β-catenin expression levels in vivo.
Conclusions
The study indicated that AAEO accelerates PU wound healing via mediating Wnt/β-catenin pathway.
VEGF to CITED2 Ratio Predicts the Collateral Circulation of Acute Ischemic Stroke
Authors: Lu Minyi , Liu Yuben , Xian Zhiqiang , Yu Xiaoyao , Chen Jian , Tan Sheng , Zhang Peidong , Guo Yang
Published: April 2022

Background: Evaluating the collateral circulation of acute ischemic stroke (AIS) mainly depends on the imaging examination. At present, there is no effective and sensitive biomarker for collateral circulation. Thus, the research objective was to evaluate the predicting role of the vascular endothelial growth factor to CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 Ratio (VEGF/CITED2) from peripheral blood mononuclear cells in the collateral circulation of AIS.Methods: A total of 67 patients with AIS were included in the study. We classified patients into two groups (the good collateral group and the poor collateral group) by DWI-ASPECTS score. The western blot was applied to test the protein expression of vascular endothelial growth factor (VEGF) and CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 (CITED2). Then, we calculated the VEGF/CITED2 and collected other clinical data. Binary logistic regression analysis between collateral circulation and clinical data was performed. Finally, Receiver operating characteristic (ROC) curve analysis was used to explore the predictive value of VEGF/CITED2.Results: There was a statistically significant difference in the white blood cell (WBC) count (P=0.036), neutrophil count (P=0.035), fibrinogen (Fib, P=0.038), homocysteine (Hcy, P=0.047), and VEGF/CITED2 (P=0.017) between the good collateral group and the poor collateral group. Moreover, WBC count (OR 0.77, 95%CI 0.63-0.95, P=0.016), neutrophil count (OR 0.78, 95%CI 0.63-0.95, P=0.016), NLR (OR 0.83, 95%CI 0.68-1.02, P=0.075), Hcy (OR 0.87, 95%CI 0.75-1.00, P=0.054), and Fib (OR 0.59, 95%CI 0.34-1.02, P=0.059) were the risk factors, and VEGF/CITED2 (OR 165.79, 95%CI 7.25-3791.54, P=0.001) was an independent protective factor. The ROC analyses showed an area under the ROC curve (AUC) of the VEGF/CITED2 was 0.861 (95%CI 0.761-0.961). The optimal cutoff value of 1.013 for VEGF/CITED2 had a sensitivity of 89.1% and a specificity of 85.7%.Conclusions: In patients with AIS, the VEGF/CITED2 was related to the establishment of collateral circulation. The VEGF/CITED2 is a potentially valuable biomarker for predicting collateral circulation.Trial registration: Clinical Trials. gov, NCT05345366, Registered on April 19, 2022, retrospectively registered.
Advanced simulations and screening to design a 3C protease inhibitor against the drug resistant human norovirus-induced gastroenteritis
Authors: Behmard Esmaeil , Barzegari Ebrahim , Farjadfar Akbar , Kouhpayeh Amin , Najafipour Sohrab
Published: April 2022

Human norovirus (HuNoV) causes acute viral gastroenteritis in all age groups, and dehydration and severe diarrhea in the elderly. The World Health Organization reports ~ 1.45 million deaths from acute gastroenteritis annually in the world. Rupintrivir, an inhibitory medicine against the human rhinovirus C3 protease, has been reported to inhibit HuNoV 3C protease. However, several HuNoV 3C protease mutations have been revealed to reduce the susceptibility of HuNoV to rupintrivir. The structural details behind rupintrivir-resistance of these single-point mutations (A105V and I109V) are not still clear. Hence, in this study, a combination of computational techniques were used to determine the rupintrivir-resistance mechanism and to propose an inhibitor against wild-type and mutant HuNoV 3C protease through structure-based virtual screening. Dynamic structural results indicated the unstable binding of rupintrivir at the cleft binding site of the wild-type and mutant 3C proteases, leading to its detachment. Our findings presented that the domain II of the HuNoV 3C protease had a critical role in binding of inhibitory molecules. Binding energy computations, steered molecular dynamics and umbrella sampling simulations confirmed that amentoflavone, the novel suggested inhibitor, strongly binds to the cleft site of all protease models and has a good structural stability in the complex system along the molecular dynamic simulations. Our in silico study proposed the selected compound as a potential inhibitor against the HuNoV 3C protease. However, additional experimental and clinical studies are required to corroborate the therapeutic efficacy of the compound.
Induction of Multiple Alternative Mitogenic Signaling Pathways Accompanies Emergence of Slowly Growing Drug-Tolerant Cancer Cells
Authors: Celeste Frank , Powers Scott
Published: April 2022

Drug resistance continues to be a major obstacle to curing cancer. Resistance can evolve from a subpopulation of cancer cells that initially survive drug treatment and then gradually form a pool of slowly growing drug-tolerant cells. Several studies have pinpointed activation of a specific bypass pathway that appears to provide the critical therapeutic target for preventing drug tolerance. Here we take a systems-biology approach using proteomics and genomics to examine the development of drug tolerance to EGFR inhibitors in EGFR-mutant lung adenocarcinoma cells and BRAF inhibitors in BRAF-mutant melanoma cells. We found that there are numerous alternative mitogenic pathways that become activated in both cases, including YAP, STAT3, IGFR1, and phospholipase C (PLC)/protein kinase C (PKC) pathways. Our results suggest that an effective therapeutic strategy to prevent drug tolerance will need to take multiple alternative mitogenic pathways into account rather than focusing on one specific pathway.
Odor Identification Quantitatively by Odorant Receptor Vectors
Authors: Kawai Kosei , Morishita Shin
Published: April 2022

Background: Odors are perceived by individuals through sensation, memory, experience, etc., and mainly subjective and qualitative evaluation has been performed until now. On the other hand, since Buck et al. succeeded in cloning the odorant receptor in 1991, researchers have shown interest in olfaction system, and molecular biology researches on olfaction system have begun actively. However, no objective evaluation has been made on the identification or similarity of odors. As for the odorant sensors, an odor is identified by using quartz oscillators or semiconductors and measuring a change in characteristics caused by odor molecules adhering to the sensor. In this study, we attempted to quantitatively express the direct association between odorant receptors and odor molecules at each concentration. The degree of similarity evaluated by taking inner product of the odorant receptor vectors was verified by comparing with the results by sensory evaluation tests published in past literatures in the form of correlation coefficient. A multi-layered artificial neural network whose input was the elements of prescribed odorant receptor vector was also introduced to identify odorant molecules in the output layer.Results: The inner product of proposed odorant receptor vector might evaluate the degree of similarity quantitatively among various odorants. Further, it might be possible to identify odorant molecules by the artificial neural network using EC50 of receptors to various odorants.Conclusions: In this paper, we proposed a vector consisting of the EC50 of odorant receptors and compared the inner product of the vector with the results of sensory evaluation tests based on the responses of odorant receptors to odorant substances at various concentrations. It was shown that not only the correlation between each odorant substance but also the correlation between the inner product of the odorant substance receptor vector and the results of the sensory evaluation test can be quantitatively evaluated. It was also shown that the EC50 of each odorant receptor can be placed in the input layer of an artificial neural network, and that an artificial neural network with odor molecules as the output layer can discriminate odors.
Guidance and counselling services in secondary schools in eastern Gojjam Administrative Zone: a mixed design evaluation of priority needs, service barriers and facilitators
Authors: Bitew Tesera , Adam Temesgen
Published: April 2022

Background: Problem areas that need urgent guidance and counselling intervention were not prioritized and barriers to fulfil these priority needs were not investigated in secondary schools of Ethiopia. Objective: This study aims to investigate students’ priority guidance and counselling needs and barriers and opportunities of meeting such guidance and counselling needs. Methods: A mixed methods design was used. A cross-sectional quantitative survey was used to investigate: (1) priority areas of guidance and counselling needs of the students and, (2) associates of these priority areas of counselling needs using linear regression. We conducted in-depth interview and FGD with school counsellors and school principals to investigate: (1) barriers and opportunities of providing guidance and counselling services. Thematic analysis was used to analyse the qualitative data. Results: Student participants were most worried about their education and vocation than their emotional, behavioural and social problems. Increment in depressive symptoms (β=0.266, p<001) and anxiety (β=0.154, p<001) scores were positively associated with increased score in guidance and counselling needs. Themes were identified as challenges related to meet prioritized student guidance and counselling needs were: (1) administrative challenges (2) counsellor competencies and motivation (3) resource constraints (4) beliefs (staff perceptions, cultural beliefs). Conclusion : Priority areas of guidance and counselling have been identified and barriers to meet such needs have been explored.
Collective Adaptability in a Replication Network of Minimal Nucleobase Sequences
Authors: Vela-Gallego Sonia , Pardo-Botero Zulay , Moya Cristian , Escosura Andrés de la
Published: April 2022

A major challenge for understanding the origins of life is to explore how replication networks can engage in an evolutionary process. Herein, we shed light on this problem by implementing a network constituted by two different types of extremely simple biological components: the amino acid cysteine and the canonical nucleobases adenine and thymine, connected through amide bonds to the cysteine amino group and oxidation of its thiol into three possible disulfides. Supramolecular and kinetic analyses revealed that both self- and mutual interactions between such dinucleobase compounds drive their assembly and replication pathways. Those pathways involving sequence complementarity led to enhanced replication rates, suggesting a potential bias for selection. The interplay of synergistic dynamics and competition between replicators was then simulated, under conditions that are not easily accessible with experiments, in an open reactor parametrized and constrained with the unprecedentedly complete experimental kinetic data obtained for our replicative network. Interestingly, the simulations show bistability, as a selective amplification of different species depending on the initial mixture composition. Overall, this network configuration can favor a collective adaptability to changes in the availability of feedstock molecules, with disulfide exchange reactions serving as 'wires' that connect the different individual auto- and cross-catalytic pathways.
Hydrogen occupation and hydrogen-induced volume expansion in Fe0.9Ni0.1Dxat highP-Tconditions
Authors: Shito Chikara , Kagi Hiroyuki , Kakizawa Sho , Aoki Katsutoshi , Komatsu Kazuki , Iizuka-Oku Riko , Abe Jun , Saitoh Hirioyuki , Sano-Furukawa Asami , Hattori Takanori
Published: April 2022

The density of the Earth’s core is several percent lower than that of iron-nickel alloy under conditions of pressure and temperature equivalent to the Earth’s core. Hydrogen is one of the most promising constituents accounting for the density deficit, but hydrogen occupation sites and density decrease of iron-nickel alloy caused by hydrogenation have never been investigated. In this study, the phase relation and crystal structure of Fe0.9Ni0.1Hx(Dx) at high pressures and temperatures up to 12 GPa and 1000 K were clarified by in situ X-ray diffraction and neutron diffraction measurements. Under the P-T conditions of the present study, no deuterium atoms occupied tetragonal (T) sites of face-centered cubic (fcc) Fe0.9Ni0.1Dx, although the T-site occupation was previously reported for fcc FeHx(Dx). The deuterium-induced volume expansion per deuterium vD was determined to be 2.45(4) and 3.31(6) Å3 for fcc and hcp Fe0.9Ni0.1Dx, respectively. These vD values are significantly larger than the corresponding values for FeDx. The vD value for fcc Fe0.9Ni0.1Dx slightly increases with increasing temperature. This study suggests that only 10% of nickel in iron drastically changes the behaviors of hydrogen in metal. Assuming that vD is constant regardless of pressure, the maximum hydrogen content in the Earth’s inner core is estimated to be one to two times the amount of hydrogen in the oceans.
Always Liminal, Always in Transition: Hong Kong as Staircase City
Authors: Lo Louis
Published: April 2022

This article analyses the ‘stair culture’ of Hong Kong Island, a place that is constrained by its topography, economic, and social-historical conditions. Staircases are interwoven into an infrastructure of vertical and horizontal pathways. Instead of just being a means of access, staircases play a key role in shaping the urban island. Through a critical examination of these structures and relevant literary and filmic texts (Leung Ping-Kwan’s poems, Wong Kar-wai’s films, and Tsai Ming-liang’s Walker series [2012]), the article provides a way of understanding the extent to which the perception of Hong Kong Island is re-imagined by way of an urbanscape punctuated by staircases. Staircases have the ability to mix up people in different classes in such places as the Central to Mid-Levels area and Sai Ying Pun Centre Street. Both districts are initially connected by staircases and later escalators. By examining the impact of escalators (such as high-speed gentrification, closing down of local stores, and the loss of real public spaces) and the effects of staircases on cultural activities in different areas, this article argues that staircases expose the nature of a classed society in Hong Kong Island – and, by extension, Hong Kong as a whole – and represent a nostalgia that is potentially productive.
“A Swamp Becomes the Capital”: Urban ecologies of empire in Suva (Fiji)
Authors: Vandertop Caitlin
Published: April 2022

The nineteenth-century expansion of colonial port cities onto land reclaimed from the ocean generated both material and conceptual shifts in the relations between land and water. Focusing on the history of Suva, which was established as the British capital of Fiji in 1882, this article shows how, despite colonial accounts of successful efforts to ‘drain the swamp’, the city’s history has been narrativised as a series of urban disasters. From local critiques of the original unsuitability of ‘malarious swampland’ to indigenous oral accounts of the catastrophic consequences of abandoning hill forts, through to post- independence literary narratives of urban flooding, the reclaimed city has been imagined by its inhabitants as a shifting and precarious space whose terraqueous qualities undermine colonial narratives of a progressive ‘swamp to city’ trajectory. Showing how local accounts anticipate environmental concerns across coastal zones, this article proposes a ‘reclaimed’ urban method that connects colonial pasts to ecological futures, tracing the oceanic connections leading out from the Pacific city to other postcolonial sites.
Acute kidney injury and neurological toxicity caused by intravenous acyclovir
Authors: KARACA Cebrail , FİDAN Sena , GUL Yalcın , OZDEDE Ayse , SEYAHİ Nurhan , SEYAHİ Emire
Published: April 2022

Acyclovir is an effective antiviral agent in herpes simplex and varicella-zoster infections treatments. However, it may cause serious side effects. This case study reports a patient who developed both acute tubular necrosis and neurotoxicity induced by intravenous acyclovir and recovered promptly after hemodialysis. Caution is needed in monitoring patients receiving acyclovir. Eliminating acyclovir with early diagnosis and immediate daily hemodialysis is necessary for successful treatment.
visão da psicologia e da psiquiatria no fechamento do diagnóstico do Transtorno Dissociativo de Identidade:
Authors: Dias Forte Tammy Joy , Lima Coelho Thalyta , Gomes Miranda Alan , Dos Santos-Silva Marco Aurélio
Published: April 2022

A psiquiatria e a psicologia são ciências cujo alvo é a saúde mental, entretanto apresentam pontos de vista divergentes na conclusão de diagnósticos de algumas doenças com múltiplas causas e sintomas como o transtorno dissociativo de identidade (TDI). O presente estudo revisou as diferenças apresentadas pela psiquiatria e a psicologia em torno do diagnóstico do TDI. Ainda que sejam utilizados testes similares entre psiquiatras e psicólogos, os diagnósticos permanecem divergentes. Possivelmetne, a origem de tamannha heterogeneidade entre os diagnósticos psiquiátricos e psicológicos, pode estar associada a diversidade de testes aplicados e a falta de comunicação entre estes dois profissionais.
THE ACTIVE SITE OF BOVINE PANCREATIC RIBONUCLEASE: AN EXAMPLE OF	SOLVENT MODULATED SPECIFICITY
Authors: Gilliland Gary L. , Dill Jonathan , Pechik Igor , Svensson L. Anders , Sjolin Lennart
Published: April 2022

A dynamic role for conserved water molecules in modulating the substrate specificity of ribonuclease is proposed based upon X-ray and neutron crystallographic studies. The structures of ribonuclease complexed with a transition state and substrate analogs are compared with the high resolution structure of the unliganded enzyme. Two conserved water molecules change their donor-acceptor roles in hydrogen bonds for accommodation of either uracil or cytosine in the B1 pocket.
Model Building Predicts an Additional Conformational Switch when GTP Binds to the CDC42HS Protein
Authors: Sutcliffe Michael  J. , Feltham Joanna , Cerione Richard A. , Oswald Robert E.
Published: April 2022

The human Cdc42Hs protein is homologous to but contains a thirteen residue insertion with respect to the ras subfamily of GTP-binding proteins. The possible role of this region of structure has been investigated by model building. These studies suggest that this region could act as a conformational switch - in the ·on" conformation, it both covers the nucleotide binding site and forms an extension to the likely effector binding site; in the "off' conformation it is no longer able to bind effector.
Stability and Biological Activity of Native and Recombinant Ricin Toxin B-Chain
Authors: Tonevitsky Alexander  G. , Agapov Igor  I. , Bushueva Tatiana L. , Toptjgin Andrei  Yu. , Shamshiev Abdizhapar T. , Sweeney Edel C. , Palmer Rex A. , Frankel A.
Published: April 2022

Non-glycosylated recombinant ricin B-chain (rRTB) expressed in E. coli was compared with native RTB for stability and lectin activity. The heterodimer comprising native A-chain (RTA) and rRTB was further tested for cytotoxicity. These studies indicate that the asialofetuin binding activity, absorption spectra and binding with 8-anilino-1-naphthalene sulphonic acid (ANS) of rRTB are unchanged, whereas the fluorescence spectra are slightly modified compared to native RTB. Tryptic digestion showed that rRTB is more sensitive to degradation than native RTB. Cytotoxicity of native ricin is ten times greater than that of the heterodimer of native ricin A-chain with rRTB. These results suggest that glycosylation is not necessary for protein stability but prolongs resistance to proteolytic degradation in cells.