bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA interference cannot be operated in lepidopteran insect? A nanocarrier breaks bottlenecks at all developmental stages of Spodoptera frugiperda
Authors: Chao Zijian , Ma Zhongzheng , Zhang Yunhui , Yan Shuo , Shen Jie 
Published: October 2022

Abstract
RNA interference (RNAi) has become an essential technique in functional analysis of insect genes and pest management. However, insensitivity to RNAi is the main obstacle that limits the identification of functional genes in lepidopteran insects. Hereby we explored an efficient nanocarrier (star polycation, SPc)-mediated dsRNA delivery system to achieve efficient RNAi at all developmental stages of lepidopteran insect Spodoptera frugiperda. Double-stranded RNA (dsRNA) was synthesized targeting a consistently expressed gene V-type proton ATPase subunit d (ATP-d) as well as enhanced green fluorescent protein (eGFP) for various operation tests. At the egg and early larval stages, SPc-loaded dsRNA could penetrate the physical obstacles of eggshell and larval body wall. Thus, soaking and topical applications of SPc-loaded dsRNA were suitable for efficient RNAi at egg and 1st-2nd instar larval stages, respectively. The SPc could protect dsRNA from degradation by midgut fluid of mid-late instar larvae. Thereby oral feeding of SPc-loaded dsRNA silenced the target gene at mid-late larval stages more efficiently compared to dsRNA alone. Finally, for pupal and adult stages, injection of SPc-loaded dsRNA was enough to induce high RNAi effect. A key developmental gene, Chitin deacetylase 1 (CDA1), was taken as an example to test the pest control efficiency of SPc-based RNAi system. The constructed system could remarkably induce the knockdown of CDA1 and lead to growth retardation and mortality. Overall, the present study constructed an efficient nanocarrier-based RNAi system for whole developmental stages of lepidopteran insects, which would provide a powerful tool for identifying functional genes in lepidopteran insects.
Multi-layer 5G Network Slicing with UAVs: an optimization model
Authors: Colajanni Gabriella , Sciacca Daniele 
Published: October 2022

Abstract
In this paper, we present a network-based optimization model describing a closed-loop supply chain for the provision of 5G network slices on demand to users and devices on the ground. The three-tier supply chain network consists of a fleet of pre-existing UAVs, to which others can be added, managed by a fleet of UAV controllers, whose purpose is to perform services requested by users and devices on the ground. The aim of this paper is to provide a constrained optimization problem through which the providers’ profits are maximized, determining the global optimal distributions of request flows, the global optimal distributions of executed services and the optimal reliability level of pre-existing UAVs of the fleet. We also derive the associated Variational inequality formulation of the problem and, finally, a numerical simulation is performed to validate the effectiveness of the model.
Heterogeneity of weight gain after initiation of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis
Authors: Gramegna Andrea , Majo Fabio , Leonardi Gloria , Cristiani Luca , Amati Francesco , Contarini Martina , Aliberti Stefano , Fiocchi Alessandro Giovanni , Blasi Francesco 
Published: October 2022

Abstract
Background. The introduction of the novel therapy with Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been showed to be effective in weight gain in both clinical trials and real-world studies. However, this effect appears heterogeneous across patient subgroups and predictors of individual weight gain after treatment are still missing.
Methods. This was a multicenter, prospective cohort study enrolling 93 adults with CF at two major CF Centers in Italy. For the pourpose of this study, the cohort was divided into two groups according to median BMI change after 6 months of ETI treatment: ‘responders’ included patients with BMI increase ≥1 kg/m2 and ‘poor responders’ those with BMI increase <1 kg/m2.
Results. The median increase in BMI after six months of ETI was 1.0 kg/m2 (0.4-1.7), in line with previous studies. We identified a correlation between BMI increase and both BMI before ETI initiation (r -0.392, P <0.001) and the duration of ETI treatment (r 0.293, P =0.006). BMI responders were more likely to have Phe508del/MF genotype (71% VS. 37%, P = <0.001), younger age at diagnosis (1 [0-4] VS. 5 [0-14] years, P =0.018), pancreatic insufficiency (92% VS. 77%, P =0.042) and CF-related diabetes (49% VS. 21%, P =0.006). Low BMI before ETI initiation (OR 0.75; 95% CI 0.64-0.0.92; P =0.005), pancreatic insufficiency (OR 5.08; 95% CI 1.34-19.28; P =0.017) and the previous use of earlier CFTR modulators (OR 3.41; 95% CI 1.21-9.57; P =0.020) were predictive factors for the status of BMI responder.
Conclusions. Our results might help to identify a subset of patients that might deserve both a targeted clinical approach and a translational characterization.
Comparison of serum cytokine profiles of patients with pulmonary tuberculosis and aspergillus infections
Authors: Ren Weicong , Li Haoran , Guo Can , Shang Yuanyuan , Wang Wei , Zhang Xuxia , Li Shanshan , Pang Yu 
Published: October 2022

Abstract
Objectives: aspergillus fumigatus induced chronic pulmonary aspergillosis (CPA) is the most common sequelae of pulmonary tuberculosis (TB), which caused by intracellular infection pathogen Mycobacterium tuberculosis (Mtb). Timely and accurate detection of the potential infection of A. fumigatus in TB patients will undoubtedly greatly improve the prognosis of TB patients. At present, galactomannan (GM) antigen test is commonly used to detect A. fumigatusinfection, but its poor sensitivity is not adequate for clinical practice.
Design or methods: given the different host immune responses induced by CPA and TB, we aimed to evaluate the serum cytokine profiles of TB, CPA-TB, and CPA patients without TB using multiple cytokine analyses.
Results: the results showed that the expression of a large number of proinflammatory cytokines such as IL-1β, IL-6, IL-8, IL-12p70, IFN-α, IFN-γ and TNF-α in peripheral blood of patients with CPA was significantly higher than that of patients with TB. Cytokine IL-8 alone has the best performance to diagnose TB patients from CPA-TB (AUC=0.949) or CPA (AUC=0.964) patients. Moreover, IL-8 and TNF-α combination (AUC=0.996) could distinguish patients with TB or CPA. Likewise, the combination of IL-8, TNF-α and IL-6 can help distinguish all CPA patients with TB or not from TB-alone patients.
Conclusions: our study provided multiple cytokines as potential markers to accurately diagnosis TB and CPA, and contribute to the prognosis of TB patients with CPA.Furthermore, the results help better understand the immune function disorder during Mtb and/or A. fumigatus infections.
Effect of vacuum impregnation and high hydrostatic pressure treatments on shelf-life, physicochemical, and sensory properties of seabream fillets
Authors: Bou Ricard , Guerrero Luis , López Mariló , Claret Anna , López-Mas Laura , Castellari Massimo 
Published: October 2022

Abstract
Marination is commonly used to preserve fish, which, in combination with other non-thermal technologies, such as vacuum impregnation and high hydrostatic pressures, may help to preserve freshness and extend shelf life. In addition, marination may mask changes on the physicochemical properties and sensory attributes of fish resulting from intense pressurization treatments. In this study, the effect of vacuum impregnation (50 mbar for 5 min) alone or in combination with a moderate pressurization treatment (250 MPa for 6 min) on the physicochemical properties, microbiological and oxidative stability, and sensory properties of refrigerated seabream fillets was investigated. The results showed that compared to conventional marination, vacuum impregnation had no effect on the aforementioned properties, except for a higher perception of lemon aroma. Pressurization resulted in total viable counts below 4 log CFU/g after 16 d of storage at ≤2°C. In addition, lipid oxidation was maintained at low and similar levels as those of the non-pressurized treatments. Compared to the control, in pressurized fish, lightness increased from 52 to 78, which was the instrumental color and texture parameter most affected. Despite this, pressurization at moderate pressures allows for the extension of shelf life with minimal negative effects, given that only minor changes were observed in texture and sensory properties, which may in turn be minimized by marinades.
Rabies Virus Infection is Associated with Variations in Calbindin D-28K and Calretinin mRNA Expression Levels in Mouse Brain Tissue.
Authors: Korie George Chibuike , Sallau Abdullahi Balarabe , Kanu Brenda , Kia Grace Sabo Nok , Kwaga Jacob K.P 
Published: October 2022

Abstract

Rabies virus (RABV) infection leads to a fatal neurological outcome in humans and animals and is associated with major alterations in cellular gene expression. In this study, we describe the effects of RABV infection on the mRNA expression levels of two genes encoding the Ca2+ binding proteins (Ca-BPs) Calbindin D-28K (Calb1) and Calretinin (Calb2) in the brains of BALB/c mice. Sixty, 4-week-old mice were divided into two test and one control group. Mice were inoculated intra-muscularly with either a street rabies virus (SRV) or Challenge virus standard (CVS-11) strain and sacrificed at 3-day intervals up to day 18 post infection. Direct fluorescent antibody test (DFAT) verified RABV antigen in the brain tissues and real time quantitative PCR (RT-PCR) was used to assess the gene expressions. Infection with both RABV strains resulted in relatively significant (p<0.05) increases in Calb1 and Calb2 expression in the test animals, when compared with the controls at various time points in the study. Correlation analysis indicated very weak insignificant (p>0.05) negative and positive relationships respectively between Calb1 expression (r = -0.04) and Calb2 expression (r = 0.08) with viral load (CVS-11 strain). Insignificant (p>0.05) relationships were also obtained between Calb1 expression (r= -0.28) and Calb2 expression (r = 0.06) with viral load for the SRV strain.
The observed alterations in Calb1 and Calb2 expression in this study indicate possible impairments in neuronal Ca2+ buffering and Ca2+ homeostasis as a result of RABV infection and consequently, an implication of Calbindin-D28K and Calretinin in the neuro-pathogenesis of rabies.
Characteristic analysis of epileptic brain network based on attention mechanism
Authors: Yu Hong-Shi , Meng Xiang-Fu 
Published: October 2022

Abstract
Constructing an efficient and accurate epilepsy detection system is an urgent research task. In this paper, we developed an EEG-based multi-frequency multilayer brain network (MMBN) and an attentional mechanism based convolutional neural network (AM-CNN) model to study epilepsy detection. Specifically, based on the multi-frequency characteristics and correlation analysis of the brain, we first construct MMBN, where each layer corresponds to a specific frequency band. The time, frequency and channel related information of EEG signals are mapped into the multilayer network topology. On this basis, a multi branch AM-CNN model is designed, which completely matches the multilayer structure of the proposed brain network. The experimental results on public CHB-MIT dataset show that the accuracy of brain state detection is positively correlated with the fineness of frequency band division. When the raw EEG signal is divided into eight frequency bands, this method can accurately detect epilepsy, with an average accuracy of 99.75%, sensitivity of 99.43%, and specificity of 99.83%. All of these provide a reliable technical solution for epilepsy detection.
Adaptive immunity is required for durable responses to alectinib in murine models of EML4-ALK lung cancer
Authors: Nemenoff Raphael , Kleczko Emily , Hinz Trista , Navarro Andre , Le Anh , Nguyen Teresa , Gurule Natalia , Johnson Amber , Kwak Jeff , Polhac Diana , Clambey Eric , Weiser-Evans Mary , Merrick Daniel , Yang Michael , Patil Tejas , Schenk Erin , Heasley Lynn 
Published: October 2022

Abstract
Lung cancers bearing oncogenic EML4-ALK fusions respond to targeted tyrosine kinase inhibitors (TKIs; e.g. alectinib), with variation in the degree of shrinkage and duration of treatment (DOT). However, factors that control this response are not well understood. While the contribution of the immune system in mediating the response to immunotherapy has been extensively investigated, less is known regarding the contribution of immunity to TKI therapeutic responses. We previously demonstrated a positive association of a TKI-induced interferon gamma (IFNγ) transcriptional response with DOT in EGFR-mutant lung cancers. Herein, we used three murine models of EML4-ALK lung cancer to test the role for host immunity in the alectinib therapeutic response. The cell lines (EA1, EA2, EA3) were propagated orthotopically in the lungs of immunocompetent and immunodeficient mice and treated with alectinib. Tumor volumes were serially measured by μCT and immune cell content was measured by flow cytometry and multispectral immunofluorescence. Transcriptional responses to alectinib were assessed by RNAseq and secreted chemokines were measured by ELISA. All cell lines were similarly sensitive to alectinib in vitro and as orthotopic tumors in immunocompetent mice, exhibited durable shrinkage. However, in immunodeficient mice, all tumor models rapidly progressed on TKI therapy. In immunocompetent mice, EA2 tumors exhibited a complete response, whereas EA1 and EA3 tumors retained residual disease that rapidly progressed upon termination of TKI treatment. Prior to treatment, EA2 tumors had greater numbers of CD8+ T cells and fewer neutrophils compared to EA1 tumors. In addition, RNAseq of cancer cells recovered from untreated tumors revealed elevated levels of CXCL9 and 10 in EA2 tumors, and higher levels of CXCL1 and 2 in EA1 tumors. Analysis of pretreatment patient biopsies from ALK+ tumors revealed an association of neutrophil content with shorter time to progression. Combined, these data support a role for adaptive immunity in durability of TKI responses and demonstrate that the immune cell composition of the tumor microenvironment is predictive of response to alectinib therapy.
Single use plastic usage in the Maldives: Knowledge, practice and attitude
Authors: Naila Aishath , Raheem Raheema Abdul , Hassan Rifaath , Nazeer Abdullah , Samha Mariyam 
Published: October 2022

Abstract
Solid waste management in the Maldives is under extreme stress due to the unique nature of its geography and economic structure. Plastic pollution has been a growing concern for the Maldives. The purpose of this research study was to identify the current consumption patterns of the plastic items particularly single use plastics (SUP) as well as identifying the level of knowledge among the consumers about the SUP and consumer behavior to change and the public confidence level in drinking tap water. A questionnaire was used as the key instrument for primary data collection in this study. It enabled researchers to collect data in a standardized way so that the data were internally consistent for analysis. A total 817 out of 1095 responded to the survey from across the Maldives. The overall finding suggested that the majority of the consumers in the Maldives are still using single-use plastic in their everyday life. However, large percentage of consumers know the benefits of reducing plastic on human health and environment. With regard to the challenges or barriers in implementing the single-use plastic, consumers identified lack of available alternatives, higher costs, inconvenient transport, lack of hygiene, and time requirement. In addition, majority of the participants do not trust the quality of tap water in the country for various reasons, therefore, they prefer to consume bottle water. It seems there is an immense and urgent need to explore ways to increase consumers awareness and subsequent efforts to reduce the consumption of plastic in the country.
The association between patterns of early respiratory disease and diastolic dysfunction in preterm infants
Authors: de Waal Koert , Crendal Edward , Poon Amy , Latheef Mariyam , Sachawars Elias , MacDougall Thomas , Phad Nilkant 
Published: October 2022

Abstract
Background
Distinct patterns of early respiratory dysfunction are described in very preterm infants. Although mostly attributed to pulmonary parenchymal disease, cardiac pathophysiology might play an important role in the development of these clinical signs and symptoms. Methods
Preterm infants < 29 weeks’ gestation underwent cardiac ultrasounds around day 7 and day 14-21. Respiratory dysfunction patterns were classified as stable (ST), respiratory deterioration (RD) or early persistent respiratory dysfunction (EPRD) according to oxygen need. Diastolic dysfunction was diagnosed using a multi-parameter approach.
Results
98 infants (mean 27 weeks) were included. The prevalence of ST, RD and EPRD was 53%, 21% and 26% respectively. Diastolic dysfunction was significantly more prevalent in the RD and EPRD groups. Risk factors for developing diastolic dysfunction were a patent ductus arteriosus and significant growth restriction. Not all infants with a PDA developed diastolic dysfunction.
Conclusion
Respiratory dysfunction patterns are associated with cardiac pathophysiology
Influence of the manufacturing process of traditional dry-cured tuna on biogenic amine and free fatty acid profiles.
Authors: Sánchez-Parra Mónica , Lopez Annalaura , Ordóñez-Díaz José Luis , Rodríguez-Solana Raquel , Montenegro-Gómez José Carlos , Aparicio Jesús Pérez , Rojas José Manuel Moreno 
Published: October 2022

Abstract

The aim of this study was to investigate the changes in the formation of biogenic amines and free fatty acids occurring during the manufacturing process of a traditional salt-dried product based on yellowfin tuna, Thunnus albacares. (Protected Geographical Indication – Mojama). Histamine levels found in all stages of the manufacturing process did not exceed the maximum limits established in the European Commission (100–200 mg/kg) and US Food and Drug Administration (50 mg/kg) regulations. Yellowfin tuna fillets could be classified as lean fish flesh, presenting 1.18% fat on average. An increment in the free fatty acid fraction was evidenced along the manufacturing process, ranging from 10.37% of the total lipids in fresh loins to 16.88% in the dry-cured fillet product. High levels of unsaturated free fatty acids were observed, arising from phospholipids' degradation in the muscle. The results indicated that the traditional processing method of this salt-dried tuna product inhibits and minimizes most undesirable effects and maintains food safety, ensuring the quality of this high added-value product highly appreciated as gourmet food.
Key molecules in bladder cancer affect patient prognosis and immunotherapy efficacy: further exploration for CNTN1 and EMP1
Authors: Chen Hengxin , Zhou Tailai , Wang Yinzhao , Wen Sijie , Dao Pinghong , Chen Minfeng 
Published: October 2022

Abstract
Bladder cancer (BCa) is the most common male neoplastic disease, and its pathogenesis has not been fully explained. In this study, 5 key molecules, including CNTN1, MAP1A, EMP1, MFAP5, and PTGIS, were identified as key genes in the progression of BCa, and their riskScore was constructed. We found these five key genes to be significantly correlated with patient prognosis and immune checkpoint molecules, and the riskScore had a surprisingly accurate ability to predict patient prognosis and immunotherapy efficacy. Among the high-risk groups identified by the riskScore, patient prognosis and immunotherapy effect were significantly worse than the others. In summary, we proved that 5 key genes were able to impact the prognosis of BCa, TME immune infiltration, and the efficacy of immunotherapy, and the riskScore tool we constructed will contribute to the development of individualized treatment for BCa.
MYL2 is a potential diagnostic, prognostic, and immune biomarker for HNSC
Authors: Ding Shun , Duan Tingting , Yu Yaping , Wu Haolin , Xu Zhengyang , Yan Dongming , Meng Qingwen , Liu Qibing , Mu Zhonglin 
Published: October 2022

Abstract
The significance of MYL2 as a possible HNSC treatment gene is unknown, the purpose of this study was to determine the exact involvement of MYL2 in HNSC.The Tumor Immune Estimate Resource (TIMER), UALCAN, The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases were used to assess MYL2 mRNA and protein expression levels in HNSC. Experimental tests, including immunohistochemistry, were used to corroborate the findings using HNSC tumor tissues and normal controls. Next, the prognostic effect of MYL2 on HNSC was analyzed using TCGA and GEPIA. Understanding MYL2 mutations in HNSC through the cBioPortal database. The metascape and CAMOIP datasets were also used to further understand MYL2's functional role. Finally, the effect of MYL2 on the immune microenvironment was examined by immune infiltration and monomolecular analysis.A poor prognosis often accompanies high MYL2 expression in HNSC. MYL2 can serve as an effective predictive biomarker for distinguishing HNSC from normal tissue, according to ROC studies. In addition, in HNSC, MYL2 is mainly affected by amplifying mutations. MYL2 may have a role in HNSC tumorigenesis and development via the calcium signaling route, the cGMP-PKG signaling pathway, and the interaction of ECM and receptors. Ultimately, we found that MYL2 influences the development of HNSC through the regulation of multiple immune cells. The findings show that MYL2 plays a crucial role in HNSC development and that it might be a potential independent prognostic biomarker and therapy target for HNSC.
Tumor preventive and antioxidant efficacy of chlorogenic acid loaded chitosan nanoparticles in experimental skin carcinogenesis
Authors: Neelakandan M. , Manoharan S. , Muralinaidu R. , Monsi@Thara J. 
Published: October 2022

Abstract
Oxidative stress, a pathological condition, contributes to the pathophysiology of a number of diseases including carcinogenesis. Numerous studies pointed out the disturbed antioxidants status and accumulation of oxidative stress markers in the carcinogenesis. The present study analysed the anticancer efficacy of chlorogenic acid loaded chitosan nanoparticles by utilizing the oxidative stress biomarkers as an endpoint in mice with skin cancer developed by 7,12-dimethylbenz(a)anthracene (DMBA). Oxidative stress markers (lipid peroxidation by-products and antioxidants) levels or activities were measured using colorimetric assays. While mice exposed with DMBA alone showed a 100 percent tumour incidence, 0 and 50 percent tumor formation was seen in mice treated with DMBA+topical application of the nanoparticles and DMBA+orally administrated nanoparticles respectively. Also, the study noticed 33 percent and 67 percent tumor incidence was noticed in mice treated with DMBA+topical application of free chlorogenic acid and DMBA+orally administrated free chlorogenic acid respectively. The present study noticed that topical application of chlorogenic acid loaded chitosan nanoparticles to DMBA painted mice completely suppressed the tumour growth and restored the levels or activities of oxidative stress markers as compared to mice received DMBA+oral administration of chlorogenic acid loaded chitosan nanoparticles. The study observed chlorogenic acid loaded chitosan nanoparticles are more potent than free chlorogenic acid in preventing skin cancer in mice caused by DMBA. Thus, the present investigation explores the tumor inhibiting efficacy of chlorogenic acid loaded chitosan nanoparticles in experimental skin cancer and the tumor preventive efficiency could be attributed to their antilipid peroxitative and antioxidants effects.