bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection and Characterization of ssDNA Aptamers Targeting Largemouth Bass Virus Infected Cells With Antiviral Activities
Authors: Yu Qing , Li Mengmeng , Liu Mingzhu , Huang Shuaishuai , Wang Gaoxue , Wang Taixia , Li Pengfei
Published: December 2021

Largemouth bass virus (LMBV) is one of the most devastating viral pathogens in farmed Largemouth bass. Aptamers are novel molecule probes and have been widely applied in the field of efficient therapeutic and diagnostic agents development. LMBV-infected fathead minnow cells (LMBV-FHM) served as target cells in this study, and three DNA aptamers (LBVA1, LBVA2, and LBVA3) were generated against target cells by SELEX technology. The selected aptamers could specifically bind to LMBV-FHM cells, with rather high calculated dissociation constants (Kd) of 890.09, 517.22, and 249.31 nM for aptamers LBVA1, LBVA2, and LBVA3, respectively. Three aptamers displayed efficient antiviral activities in vitro. It indicates that the selected aptamers have great potentials in developing efficient anti-viruses treatments. The targets of aptamers LBVA1, LBVA2, and LBVA3 could be membrane proteins on host cells. The targets of aptamers (LBVA1, LBVA2, and LBVA3) come out on the cells surface at 8, 10, 8 h post-infection. As novel molecular probes for accurate recognition, aptamer LBVA3 could detect LMBV infection in vitro and in vivo, it indicates that the selected aptamers could be applied in the development of rapid detective technologies, which are characterized by high sensitivity, accuracy, and easy operation.
Activation and Evasion of RLR Signaling by DNA Virus Infection
Authors: Jia Junli , Fu Jiangan , Tang Huamin
Published: December 2021

Antiviral innate immune response triggered by nucleic acid recognition plays an extremely important role in controlling viral infections. The initiation of antiviral immune response against RNA viruses through ligand recognition of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) was extensively studied. RLR’s role in DNA virus infection, which is less known, is increasing attention. Here, we review the research progress of the ligand recognition of RLRs during the DNA virus infection process and the viral evasion mechanism from host immune responses.
GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19
Authors: Coric Vesna , Milosevic Ivana , Djukic Tatjana , Bukumiric Zoran , Savic-Radojevic Ana , Matic Marija , Jerotic Djurdja , Todorovic Nevena , Asanin Milika , Ercegovac Marko , Ranin Jovan , Stevanovic Goran , Pljesa-Ercegovac Marija , Simic Tatjana
Published: December 2021

Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferasesGSTA1,GSTM1,GSTM3,GSTP1(rs1695andrs1138272), andGSTT1were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity.GSTpolymorphisms were determined by appropriate PCR methods. Among sixGSTpolymorphisms analyzed in this study,GSTP1rs1695 andGSTM3were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variantGSTP1-Valallele exhibit lower odds of COVID-19 development (p = 0.002), contrary to carriers of variantGSTM3-CCgenotype which have higher odds for COVID-19 (p = 0.024). Moreover, combinedGSTP1(rs1138272andrs1695) andGSTM3genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (p = 0.001 andp = 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.
A Novel Hybrid Logic-ODE Modeling Approach to Overcome Knowledge Gaps
Authors: Selvaggio Gianluca , Cristellon Serena , Marchetti Luca
Published: December 2021

Mathematical modeling allows using different formalisms to describe, investigate, and understand biological processes. However, despite the advent of high-throughput experimental techniques, quantitative information is still a challenge when looking for data to calibrate model parameters. Furthermore, quantitative formalisms must cope with stiffness and tractability problems, more so if used to describe multicellular systems. On the other hand, qualitative models may lack the proper granularity to describe the underlying kinetic processes. We propose a hybrid modeling approach that integrates ordinary differential equations and logical formalism to describe distinct biological layers and their communication. We focused on a multicellular system as a case study by applying the hybrid formalism to the well-known Delta-Notch signaling pathway. We used a differential equation model to describe the intracellular pathways while the cell–cell interactions were defined by logic rules. The hybrid approach herein employed allows us to combine the pros of different modeling techniques by overcoming the lack of quantitative information with a qualitative description that discretizes activation and inhibition processes, thus avoiding complexity.
Exploring the Retinal Binding Cavity of Archaerhodopsin-3 by Replacing the Retinal Chromophore With a Dimethyl Phenylated Derivative
Authors: Tsuneishi Taichi , Takahashi Masataka , Tsujimura Masaki , Kojima Keiichi , Ishikita Hiroshi , Takeuchi Yasuo , Sudo Yuki
Published: December 2021

Rhodopsins act as photoreceptors with their chromophore retinal (vitamin-A aldehyde) and they regulate light-dependent biological functions. Archaerhodopsin-3 (AR3) is an outward proton pump that has been widely utilized as a tool for optogenetics, a method for controlling cellular activity by light. To characterize the retinal binding cavity of AR3, we synthesized a dimethyl phenylated retinal derivative, (2E,4E,6E,8E)-9-(2,6-Dimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenal (DMP-retinal). QM/MM calculations suggested that DMP-retinal can be incorporated into the opsin of AR3 (archaeopsin-3, AO3). Thus, we introduced DMP-retinal into AO3 to obtain the non-natural holoprotein (AO3-DMP) and compared some molecular properties with those of AO3 with the natural A1-retinal (AO3-A1) or AR3. Light-induced pH change measurements revealed that AO3-DMP maintained slow outward proton pumping. Noteworthy, AO3-DMP had several significant changes in its molecular properties compared with AO3-A1 as follows; 1) spectroscopic measurements revealed that the absorption maximum was shifted from 556 to 508 nm and QM/MM calculations showed that the blue-shift was due to the significant increase in the HOMO-LUMO energy gap of the chromophore with the contribution of some residues around the chromophore, 2) time-resolved spectroscopic measurements revealed the photocycling rate was significantly decreased, and 3) kinetical spectroscopic measurements revealed the sensitivity of the chromophore binding Schiff base to attack by hydroxylamine was significantly increased. The QM/MM calculations show that a cavity space is present at the aromatic ring moiety in the AO3-DMP structure whereas it is absent at the corresponding β-ionone ring moiety in the AO3-A1 structure. We discuss these alterations of the difference in interaction between the natural A1-retinal and the DMP-retinal with binding cavity residues.
Assessing the Effects of Vitamin D on Neural Network Function in Patients With Parkinson’s Disease by Measuring the Fraction Amplitude of Low-Frequency Fluctuation
Authors: Lv Lingling , Zhang Hainan , Tan Xuling , Qin Lixia , Peng Xinke , Bai Rongrong , Xiao Qile , Tan Changlian , Liao Haiyan , Yan Weiqian , Tan Jieqiong , Tang Beisha , Wang Chunyu
Published: December 2021

Background: Recently, many studies have shown that low vitamin D (VD) levels may be related to an increased risk of Parkinson’s disease (PD), but the underlying mechanisms remain unclear.

Objective: To explore the relationship between PD and VD levels, as well as to analyze the effects of VD on spontaneous brain activity and explore the possible mechanism of its involvement in PD risk.

Methods: In a cross-sectional study, we quantified the difference in VD levels between 330 PD patients and 209 healthy controls (HC) to explore the correlation between VD and PD risk. We also acquired resting-state Functional Magnetic Resonance Imaging (rs-fMRI) data from 46 PD patients and 21 HC. The PD patients were divided into three groups according to 25(OH)D levels: PD patients with VD deficiency (PD + VDD), PD patients with VD insufficiency (PD + VDI), and PD patients with normal VD (PD + NVD). The effect of VD status on spontaneous neuronal activity in the whole brain was analyzed by measuring the fraction amplitude of low-frequency fluctuation (fALFF).

Results: Compared with HC, the PD patients had lower serum 25(OH)D levels (23.60 ± 7.27 vs. 25.60 ± 5.78, P < 0.001). The 25(OH)D level may have a potential dose-dependent effect on the risk of PD (Ptrend = 0.007). A high risk of PD was associated with VD deficiency [25(OH)D < 20 ng/mL, OR = 2.319], and the lowest quartile of 25(OH)D concentration was associated with a high risk of PD (OR = 1.941). In the rs-fMRI study, PD + VDD patients had wider brain regions with altered fALFF than other PD groups when compared with the corresponding HC groups. Both PD + VDD and PD + VDI showed higher fALFF in the cuneus, left precuneus, calcarine cortex and right lingual, as well as lower fALFF in the left middle temporal gyrus. PD + VDD patients also showed higher fALFF in the left superior, middle and inferior frontal gyri, as well as the left precentral gyrus than HC. Among PD patients, there was only a statistically significant difference in fALFF between the PD + VDD and PD + NVD groups. Compared with the PD + NVD group, PD + VDD patients exhibited higher fALFF in the left precentral and left postcentral gyrus, as well as the left inferior parietal lobule.

Conclusion: These results demonstrate that PD patients had lower serum VD levels than HC, and VD may have a potential dose-dependent effect on PD risk. Lower serum VD levels can affect the spontaneous neuronal activity of default-mode network (DMN) and visual pathway neurons in PD patients, providing a possible mechanism for its effect on PD risk.
Low Toe–Brachial Index Is Associated With Stroke Outcome Despite Normal Ankle–Brachial Index
Authors: Han Minho , Kim Young Dae , Lee Ilhyung , Lee Hyungwoo , Heo Joonnyung , Lee Hye Sun , Nam Hyo Suk
Published: December 2021

Introduction:We investigated whether the toe–brachial index (TBI) is associated with stroke prognosis and evaluated this association in patients with normal ankle–brachial index (ABI).

Methods:Acute ischemic stroke patients who underwent TBI measurements were enrolled. Poor functional outcome was defined as modified Rankin Scale score ≥3. Major adverse cardiovascular event (MACE) was defined as stroke recurrence, myocardial infarction, or death. Normal ABI was defined as 0.9 ≤ ABI ≤ 1.4.

Results:A total of 1,697 patients were enrolled and followed up for a median 39.7 (interquartile range, 25.7–54.6) months. During the period, 305 patients suffered MACE (18.0%), including 171 (10.1%) stroke recurrences. TBI was associated with hypertension, diabetes, atrial fibrillation, aortic plaque score, ABI, and brachial–ankle pulse wave velocity (allp< 0.05). In multivariable logistic regression, TBI was inversely associated with poor functional outcome in all patients [odds ratio (OR) 0.294, 95% confidence interval (CI) 0.114–0.759], even in patients with normal ABI (OR 0.293, 95% CI 0.095–0.906). In multivariable Cox regression, TBI < 0.6 was associated with stroke recurrence [hazard ratio (HR) 1.651, 95% CI 1.135–2.400], all-cause mortality (HR 2.105, 95% CI 1.343–3.298), and MACE (HR 1.838, 95% CI 1.396–2.419) in all patients. TBI < 0.6 was also associated with stroke recurrence (HR 1.681, 95% CI 1.080–2.618), all-cause mortality (HR 2.075, 95% CI 1.180–3.651), and MACE (HR 1.619, 95% CI 1.149–2.281) in patients with normal ABI.

Conclusions:Low TBI is independently associated with poor short- and long-term outcomes in acute ischemic stroke patients despite normal ABI.
Immune Checkpoint Inhibition in Non-Melanoma Skin Cancer: A Review of Current Evidence
Authors: Stonesifer Connor J. , Djavid A. Reza , Grimes Joseph M. , Khaleel Alexandra E. , Soliman Yssra S. , Maisel-Campbell Amanda , Garcia-Saleem Tiffany J. , Geskin Larisa J. , Carvajal Richard D.
Published: December 2021

Immuno-oncology is a rapidly evolving field with growing relevance in the treatment of numerous malignancies. The prior study of immunotherapy in dermatologic oncology has largely focused on cutaneous melanoma. However, recent focus has shifted to the use of immunotherapy to treat non-melanoma skin cancers (NMSCs), such as basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC). NMSCs represent the most ubiquitous cancers globally and, while they have a lower propensity to develop into advanced disease than cutaneous melanoma, their absolute mortality burden has recently surpassed that of melanoma. Patients with advanced NMSC are now benefiting from the successes of immunotherapy, including checkpoint inhibition with anti-CTLA-4 and anti-PD-1 monoclonal antibodies. In this review, we discuss the existing clinical evidence for immunotherapy in the treatment of NMSCs, with an emphasis on checkpoint inhibitor therapies. We highlight key studies in the field and provide up-to-date clinical evidence regarding ongoing clinical trials, as well as future study directions. Our review demonstrates that checkpoint inhibitors are positioned to provide unparalleled results in the previously challenging landscape of advanced NMSC treatment.
Can a Computer-Aided Mass Diagnosis Model Based on Perceptive Features Learned From Quantitative Mammography Radiology Reports Improve Junior Radiologists’ Diagnosis Performance? An Observer Study
Authors: He Zilong , Li Yue , Zeng Weixiong , Xu Weimin , Liu Jialing , Ma Xiangyuan , Wei Jun , Zeng Hui , Xu Zeyuan , Wang Sina , Wen Chanjuan , Wu Jiefang , Feng Chenya , Ma Mengwei , Qin Genggeng , Lu Yao , Chen Weiguo
Published: December 2021

Radiologists’ diagnostic capabilities for breast mass lesions depend on their experience. Junior radiologists may underestimate or overestimate Breast Imaging Reporting and Data System (BI-RADS) categories of mass lesions owing to a lack of diagnostic experience. The computer-aided diagnosis (CAD) method assists in improving diagnostic performance by providing a breast mass classification reference to radiologists. This study aims to evaluate the impact of a CAD method based on perceptive features learned from quantitative BI-RADS descriptions on breast mass diagnosis performance. We conducted a retrospective multi-reader multi-case (MRMC) study to assess the perceptive feature-based CAD method. A total of 416 digital mammograms of patients with breast masses were obtained from 2014 through 2017, including 231 benign and 185 malignant masses, from which we randomly selected 214 cases (109 benign, 105 malignant) to train the CAD model for perceptive feature extraction and classification. The remaining 202 cases were enrolled as the test set for evaluation, of which 51 patients (29 benign and 22 malignant) participated in the MRMC study. In the MRMC study, we categorized six radiologists into three groups: junior, middle-senior, and senior. They diagnosed 51 patients with and without support from the CAD model. The BI-RADS category, benign or malignant diagnosis, malignancy probability, and diagnosis time during the two evaluation sessions were recorded. In the MRMC evaluation, the average area under the curve (AUC) of the six radiologists with CAD support was slightly higher than that without support (0.896 vs. 0.850, p = 0.0209). Both average sensitivity and specificity increased (p = 0.0253). Under CAD assistance, junior and middle-senior radiologists adjusted the assessment categories of more BI-RADS 4 cases. The diagnosis time with and without CAD support was comparable for five radiologists. The CAD model improved the radiologists’ diagnostic performance for breast masses without prolonging the diagnosis time and assisted in a better BI-RADS assessment, especially for junior radiologists.
Molecular Imaging of Ulex Europaeus Agglutinin in Colorectal Cancer Using Confocal Laser Endomicroscopy (With Video)
Authors: Wang Weijun , Tian Shuxin , Jiang Xin , Pang Suya , Shi Huiying , Fan Mengke , Wang Zeyu , Jiang Weiwei , Hu Weiqian , Xiao Xueyan , Lin Rong
Published: December 2021

Background and Study Aims

Previous studies have identified that colorectal cancer has different fucosylation levels compared to the normal colon. Ulex europaeus agglutinin-I (UEA-I), which specifically combines with α1-2 fucose glycan, is usually used to detect fucosylation levels. Therefore, we used confocal laser endomicroscopy (CLE) to investigate fluorescently labeled UEA-Fluorescein isothiocyanate (FITC) for detecting colonic cancer.

Patients and Methods

We stained frozen mouse colon tissue sections of normal, adenoma, and adenocarcinoma species with UEA-FITC to detect fucosylation levels in different groups. White light endoscopy and endocytoscopy were first used to detect the lesions. The UEA-FITC was then stained in the mice and human colon tissues in vitro. The CLE was used to detect the UEA-FITC levels of the corresponding lesions, and videos were recorded for quantitation analysis. The diagnostic accuracy of UEA-FITC using CLE was evaluated in terms of sensitivity and specificity.

Results

The UEA expression level in colorectal cancer was lower than that in normal intestinal epithelium. The fluorescence intensity ratio of UEA-FITC in colorectal cancer was significantly lower than that in normal tissue detected by CLE in both mice and humans. The combination of UEA-FITC and CLE presented a good diagnostic accuracy with a sensitivity of 95.6% and a specificity of 97.7% for detecting colorectal cancer. The positive and negative predictive values were 91.6% and 95.6%, respectively. Overall, 95.6% of the sites were correctly classified by CLE.

Conclusions

We developed a new imaging strategy to improve the diagnostic efficacy of CLE by using UEA-FITC.
Postoperative Outcomes of Distal Pancreatectomy for Retroperitoneal Sarcoma Abutting the Pancreas in the Left Upper Quadrant
Authors: Kim Kyeong Deok , Lee Kyo Won , Lee Ji Eun , Hwang Jeong Ah , Jo Sung Jun , Kim Jinseob , Lim So Hee , Park Jae Berm
Published: December 2021

Background

En bloc resection of the tumor with adjacent organs is recommended for localized retroperitoneal sarcoma (RPS). However, resection of the pancreas is controversial because it may cause serious complications, such as pancreatic fistula or bleeding. Thus, we evaluated the outcomes of distal pancreatectomy (DP) in pancreas-abutting RPS of the left upper quadrant (LUQ).

Methods

We retrospectively reviewed all consecutive patients who underwent surgery for RPS between September 2001 and April 2020. We selected 150 patients with all or part of their tumor located in the LUQ on preoperative computed tomography. Eighty-six patients who had tumors abutting the pancreas were finally enrolled in our study.

Results

Fifty-three patients (53/86; 61.6%) were included in the non-DP group, and 33 patients (33/86; 38.4%) were included in the DP group. Total postoperative complications and complication rates for those Clavien–Dindo grade 3 or higher were similar between the non-DP group and DP group (p = 0.290 and p = 0.550). In the DP group, grade B pancreatic fistulae occurred in 18.2% (6/33) of patients, but grade C pancreatic fistulae were absent, and microscopic pancreatic invasion was noted in 42.4% (14/33) of patients. During multivariate analysis, microscopic pancreatic invasion was deemed a risk factor for local recurrence (p = 0.029). However, there were no significant differences on preoperative computed tomography findings between the pancreatic invasion and non-invasion groups.

Conclusion

DP is a reasonable procedure for pancreas-abutting RPS located at the LUQ when both complications and complete resection are considered.
Comparison of Necrotizing Enterocolitis in Pre-mature Infants vs. Term-Born Infants With Congenital Heart Disease
Authors: Frid Gabriela , Reppucci Marina , Lum Tony , Paul Megan , Seiden Howard , Coakley Brian A.
Published: December 2021

Purpose: Necrotizing enterocolitis (NEC) is a serious illness that occurs among premature infants and term-born infants with congenital heart disease (CHD). Prior studies have suggested these two groups may experience different disease entities. We sought to evaluate if there are differences in disease characteristics between these two populations.

Materials and Methods: A retrospective chart review of infants treated for Bells stage 2-3 NEC from 2011 to 2020 was performed. Demographic information, CHD diagnoses and clinical data were recorded. Prior to data analysis, patients were divided into two groups: term-born patients with CHD (TC) and premature patients without CHD (PT).

Results: 99 patients were analyzed−23 TC patients and 76 PT patients. Platelet counts (222.7 ± 176.1 vs. 310.2 ± 174.5 cells/uL, P = 0.03) and C-reactive protein (CRP) levels (53.6 ± 81.7 vs. 117.6 ± 90.4 mg/L, P < 0.001) were significantly higher among the PT group. In addition, PT patients were more likely to develop pneumatosis (30.4 vs. 68.4%, P = 0.002) than TC patients. NEC-specific mortality was similar between both groups of patients.

Conclusions: When compared to TC patients, PT patients had higher CRP levels, higher platelet counts and more commonly developed pneumatosis. These factors may point toward a difference in disease pathophysiology regarding NEC development in premature patients vs. term-born patients with CHD.
Genetic Ablation of the Mitochondrial Calcium Uniporter (MCU) Does not Impair T Cell-Mediated Immunity In Vivo
Authors: Wu Hao , Brand Benjamin , Eckstein Miriam , Hochrein Sophia M. , Shumanska Magdalena , Dudek Jan , Nickel Alexander , Maack Christoph , Bogeski Ivan , Vaeth Martin
Published: December 2021

T cell activation and differentiation is associated with metabolic reprogramming to cope with the increased bioenergetic demand and to provide metabolic intermediates for the biosynthesis of building blocks. Antigen receptor stimulation not only promotes the metabolic switch of lymphocytes but also triggers the uptake of calcium (Ca2+) from the cytosol into the mitochondrial matrix. Whether mitochondrial Ca2+ influx through the mitochondrial Ca2+ uniporter (MCU) controls T cell metabolism and effector function remained, however, enigmatic. Using mice with T cell-specific deletion of MCU, we here show that genetic inactivation of mitochondrial Ca2+ uptake increased cytosolic Ca2+ levels following antigen receptor stimulation and store-operated Ca2+ entry (SOCE). However, ablation of MCU and the elevation of cytosolic Ca2+ did not affect mitochondrial respiration, differentiation and effector function of inflammatory and regulatory T cell subsets in vitro and in animal models of T cell-mediated autoimmunity and viral infection. These data suggest that MCU-mediated mitochondrial Ca2+ uptake is largely dispensable for murine T cell function. Our study has also important technical implications. Previous studies relied mostly on pharmacological inhibition or transient knockdown of mitochondrial Ca2+ uptake, but our results using mice with genetic deletion of MCU did not recapitulate these findings. The discrepancy of our study to previous reports hint at compensatory mechanisms in MCU-deficient mice and/or off-target effects of current MCU inhibitors.
Investigating Factors of False-Positive Results of Aspergillus Galactomannan Assay: A Case–Control Study in Intensive Care Units
Authors: Hung Yu-Hsuan , Lai Hui-Hsiung , Lin Hui-Chuan , Sun Kuo-Shao , Chen Chung-Yu
Published: December 2021

Background: Studies on false-positive galactomannan (GM) enzyme immunoassay (EIA) results and treatment for critically ill patients are scarce.

Objectives: The study aimed to determine the false-positive rate of GM-EIA and to probe the risk factors of false positivity among patients in the intensive care units (ICUs).

Methods: A case–control approach was conducted to review adult patients who had at least one GM-EIA result and were admitted to the ICU. Those who had no fungal culture were excluded. The clinical characteristics and critical care between patients with false-positive and true-negative GM index (GMI) were compared.

Results: Of 206 patients enrolled and with GM-EIA results, 20 (9.7%) were considered to have false-positive antigenemia, including 9 in bronchoalveolar lavages (BAL) and 11 in serum. A total of 148 (71.8%) were true-negatives. After paired grouping of 1:4, factors researched in the previous studies showed no significant difference. However, compared with the true-negatives, patients with positive GM test results but were incompatible with the diagnosis of invasive aspergillosis were more prone to the risk of false positivity due to the use of colistin inhalation. It seemed to be the only factor that significantly increased the risk of false positivity after multivariate analysis (adjusted odds ratio, 35.68; 95% CI, 3.77–337.51, p = 0.002).

Conclusions: Colistin inhalation treatment may contribute to false-positive GM-EIA results. The positive GMI among patients receiving colistin nebulization should be interpreted with caution.
Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network
Authors: Umetsu Ryogo , Tanaka Mizuki , Nakayama Yoko , Kato Yamato , Ueda Natsumi , Nishibata Yuri , Hasegawa Shiori , Matsumoto Kiyoka , Takeyama Noriaki , Iguchi Kazuhiro , Tanaka Hiroyuki , Hinoi Eiichi , Inagaki Naoki , Inden Masatoshi , Muto Yoshinori , Nakamura Mitsuhiro
Published: December 2021

Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food and Drug Administration Adverse Event Reporting System (FAERS). Furthermore, we elucidated the potential toxicological mechanisms of montelukast-associated neuropsychiatric AEs through functional enrichment analysis of human genes interacting with montelukast. The reporting odds ratios of suicidal ideation and depression in the system organ class of psychiatric disorders were 21.5 (95% confidence interval (CI): 20.3–22.9) and 8.2 (95% CI: 7.8–8.7), respectively. We explored 1,144 human genes that directly or indirectly interact with montelukast. The molecular complex detection (MCODE) plug-in of Cytoscape detected 14 clusters. Functional analysis indicated that several genes were significantly enriched in the biological processes of “neuroactive ligand–receptor interaction.” “Mood disorders” and “major depressive disorder” were significant disease terms related to montelukast. Our retrospective analysis based on the FAERS demonstrated a significant association between montelukast and neuropsychiatric AEs. Functional enrichment analysis of montelukast-associated genes related to neuropsychiatric symptoms warrant further research on the underlying pharmacological mechanisms.
Resolvin D1 attenuates CCl4 Induced Liver Fibrosis by Inhibiting Autophagy-Mediated HSC activation via AKT/mTOR Pathway
Authors: Li Jiahuan , Deng Xiaoling , Wang Shuhan , Jiang Qianqian , Xu Keshu
Published: December 2021

Resolvin D1 (RvD1) was previously reported to relieve inflammation and liver damage in several liver diseases, but its potential role in liver fibrosis remains elusive. The aim of our study was to investigate the effects and underlying mechanisms of RvD1 in hepatic autophagy in liver fibrosis. In vivo, male C57BL/6 mice were intraperitoneally injected with 20% carbon tetrachloride (CCl4, 5 ml/kg) twice weekly for 6 weeks to establish liver fibrosis model. RvD1 (100 ng or 300 ng/mouse) was added daily in the last 2 weeks of the modeling period. In vitro, lipopolysaccharide (LPS)-activated LX-2 cells were co-treated with increasing concentrations (2.5–10 nM) of RvD1. The degree of liver injury was measured by detecting serum AST and ALT contents and H&E staining. Hepatic fibrosis was assessed by masson's trichrome staining and metavir scoring. The qRT-PCR, western blot, immunohistochemistry, and immunofluorescence were applied to liver tissues or LPS-activated LX-2 cells to explore the protective effects of RvD1 in liver fibrosis. Our findings reported that RvD1 significantly attenuated CCl4 induced liver injury and fibrosis by decreasing plasma AST and ALT levels, reducing collagen I and α-SMA accumulation and other pro-fibrotic genes (CTGF, TIMP-1 and Vimentin) expressions in mouse liver, restoring damaged histological architecture and improving hepatic fibrosis scores. In vitro, RvD1 also repressed the LPS induced LX-2 cells activation and proliferation. These significant improvements mainly attributed to the inhibiting effect of RvD1 on autophagy in the process of hepatic stellate cell (HSC) activation, as demonstrated by decreased ratio of LC3-II/I and elevated p62 after RvD1 treatment. In addition, using AZD5363 (an AKT inhibitor that activates autophagy) and AZD8055 (an mTOR inhibitor, another autophagy activator), we further verified that RvD1 suppressed autophagy-mediated HSC activation and alleviated CCl4 induced liver fibrosis partly through AKT/mTOR pathway. Overall, these results demonstrate that RvD1 treatment is expected to become a novel therapeutic strategy against liver fibrosis.
Delivery of siRNA Using Functionalized Gold Nanorods Enhances Anti-Osteosarcoma Efficacy
Authors: Zhang Man , Lin Jinti , Jin Jiakang , Yu Wei , Qi Yiying , Tao Huimin
Published: December 2021

Gold nanorods (GNRs) are intensively explored for the application in cancer therapy, which has motivated the development of photothermal therapy (PTT) multifunctional nanoplatforms based on GNRs to cure osteosarcoma (OS). However, the major limitations include the toxicity of surface protectants of GNRs, unsatisfactory targeting therapy, and the resistant effects of photothermal-induced autophagy, so the risk of relapse and metastasis of OS increase. In the present study, the GNR multifunctional nanoplatforms were designed and synthesized to deliver transcription factor EB (TFEB)-siRNA–targeting autophagy; then, the resistance of autophagy to PTT and the pH-sensitive cell-penetrating membrane peptide (CPP) was weakened, which could improve the tumor-targeting ability of the GNR nanoplatforms and realize an efficient synergistic effect for tumor treatment. Meanwhile, it is worth noting that the GNR nanoplatform groups have anti-lung metastasis of OS. This study provides a new reference to improve the efficacy of OS clinically.
Quantum Walk-Based Vehicle Routing Optimisation
Authors: Bennett T. , Matwiejew E. , Marsh S. , Wang J. B.
Published: December 2021

This paper demonstrates the applicability of the Quantum Walk-based Optimisation Algorithm (QWOA) to the Capacitated Vehicle Routing Problem (CVRP). Efficient algorithms are developed for the indexing and unindexing of the solution space and for implementing the required alternating phase-walk unitaries, which are the core components of QWOA. Results of numerical simulation demonstrate that the QWOA is capable of producing convergence to near-optimal solutions for a randomly generated eight location CVRP. Preparation of the amplified quantum state in this example problem is demonstrated to produce higher-quality solutions than expected from classical random sampling of equivalent computational effort.
Phenotyping of Different Italian Durum Wheat Varieties in Early Growth Stage With the Addition of Pure or Digestate-Activated Biochars
Authors: Latini Arianna , Fiorani Fabio , Galeffi Patrizia , Cantale Cristina , Bevivino Annamaria , Jablonowski Nicolai David
Published: December 2021

This study aims to highlight the major effects of biochar incorporation into potting soil substrate on plant growth and performance in early growth stages of five elite Italian varieties of durum wheat (Triticum durum). The biochars used were obtained from two contrasting feedstocks, namely wood chips and wheat straw, by gasification under high temperature conditions, and were applied in a greenhouse experiment either as pure or as nutrient-activated biochar obtained by incubation with digestate. The results of the experiment showed that specific genotypes as well as different treatments with biochar have significant effects on plant response when looking at shoot traits related to growth. The evaluated genotypes could be clustered in two main distinct groups presenting, respectively, significantly increasing (Duilio, Iride, and Saragolla varieties) and decreasing (Marco Aurelio and Grecale varieties) values of projected shoot system area (PSSA), fresh weight (FW), dry weight (DW), and plant water loss by evapotranspiration (ET). All these traits were correlated with Pearson correlation coefficients ranging from 0.74 to 0.98. Concerning the treatment effect, a significant alteration of the mentioned plant traits was observed when applying biochar from wheat straw, characterized by very high electrical conductivity (EC), resulting in a reduction of 34.6% PSSA, 43.2% FW, 66.9% DW, and 36.0% ET, when compared to the control. Interestingly, the application of the same biochar after nutrient spiking with digestate determined about a 15–30% relief from the abovementioned reduction induced by the application of the sole pure wheat straw biochar. Our results reinforce the current basic knowledge available on biological soil amendments as biochar and digestate.
Crop Agnostic Monitoring Driven by Deep Learning
Authors: Halstead Michael , Ahmadi Alireza , Smitt Claus , Schmittmann Oliver , McCool Chris
Published: December 2021

Farmers require diverse and complex information to make agronomical decisions about crop management including intervention tasks. Generally, this information is gathered by farmers traversing their fields or glasshouses which is often a time consuming and potentially expensive process. In recent years, robotic platforms have gained significant traction due to advances in artificial intelligence. However, these platforms are usually tied to one setting (such as arable farmland), or algorithms are designed for a single platform. This creates a significant gap between available technology and farmer requirements. We propose a novel field agnostic monitoring technique that is able to operate on two different robots, in arable farmland or a glasshouse (horticultural setting). Instance segmentation forms the backbone of this approach from which object location and class, object area, and yield information can be obtained. In arable farmland, our segmentation network is able to estimate crop and weed at a species level and in a glasshouse we are able to estimate the sweet pepper and their ripeness. For yield information, we introduce a novel matching criterion that removes the pixel-wise constraints of previous versions. This approach is able to accurately estimate the number of fruit (sweet pepper) in a glasshouse with a normalized absolute error of 4.7% and anR2of 0.901 with the visual ground truth. When applied to cluttered arable farmland scenes it improves on the prior approach by 50%. Finally, a qualitative analysis shows the validity of this agnostic monitoring algorithm by supplying decision enabling information to the farmer such as the impact of a low level weeding intervention scheme.
Trajectories of Idea Emergence in Dialogic Collaborative Problem Solving: Toward a Complex Dynamic Systems Perspective
Authors: Hu Liru , Chen Gaowei
Published: December 2021

According to the complex dynamic systems (CDS) perspective, learning emerges at various system levels. This study built a coherent theoretical framework based on CDS and Bakhtinian dialogic theory and further employed the concept of attractor (i.e., certain stable states that recur over time) in CDS theory to investigate the trajectories of idea emergence and how they diversified group outcomes in dialogic collaborative problem solving (D-CPS). Two contrasting groups were compared using visual and qualitative analysis approaches. The analysis based on idea tree diagrams showed that new ideas emergent in group discussion tended to attract local utterances and performed features of attractors in CDS in both high-performing and low-performing groups. The analysis based on idea hierarchy diagrams revealed how ideas emerged at various system levels. It was also found that status problems were likely to affect the functioning of regulative feedback loops, which might give rise to different structures of idea evolution. This study proposed CDS theory as an alternative perspective, augmented by the ethical considerations of Bakhtinian dialogism, for examining the dynamics of D-CPS.
Mild Cognitive Decline Is a Risk Factor for Scam Vulnerability in Older Adults
Authors: Ueno Daisuke , Daiku Yasuhiro , Eguchi Yoko , Iwata Minako , Amano Shoka , Ayani Nobutaka , Nakamura Kaeko , Kato Yuka , Matsuoka Teruyuki , Narumoto Jin
Published: December 2021

Research on elderly financial exploitation has mostly focused on financial abuse that occurs in families and other types of trusted relationships. As such, little is known about financial frauds and scams perpetrated by strangers. Financial fraud and scam prevention activities for older adults must be promoted, for which the correlation between the psychological, social, and cognitive characteristics of their vulnerability needs to be determined. The present study aimed to determine whether cognitive decline is a risk factor for scam vulnerability in older adults. Thus, we created a scam vulnerability scale for older adults with cognitive decline and analyzed the data to reveal the correlation between them, including inhibition and executive function. We conducted an interview survey with 50 older adults with cognitive decline (average age: 79.42 years, SD: 5.44) and 51 older adults without cognitive decline (average age: 76.12 years, SD: 5.82). The interview survey included the scam vulnerability scale, psychosocial questionnaires, and neuropsychological tests. The scale included six items with a four-point Likert scale based on a previous study. Hierarchical multiple regression analysis revealed that lower scores on the Japanese version of the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Jcog; indicating higher general cognitive function) correlated with higher scam vulnerability in the cognitive decline group (β = −0.46, p < 0.001). In addition, men were found to be more vulnerable in both groups (cognitive decline group: β = −0.29, p = 0.015, cognitive non-decline group; β = −0.32, p = 0.018). Inhibition and executive function were found not to correlate significantly with scam vulnerability. These results suggest that mild cognitive decline correlates with higher scam vulnerability, whereas moderate to severe cognitive decline correlates with lower vulnerability, possibly because it makes understanding the scam attempt itself difficult. Older adults with mild cognitive decline and their families, particularly those visiting elderly care or outpatient facilities, should be notified of the scam vulnerability of older clients using the ADAS-Jcog score as an index to help them avoid victimization.
Decreased Immune Response in Alexithymic Women: A One-Year Longitudinal Study
Authors: Guilbaud Olivier , Perrin Claire , Curt Florence , Chaouat Gérard , Dugré-Le Bigre Corinne , Strebler Martine , Touitou Catherine , Corcos Maurice
Published: December 2021

Although previous cross-sectional studies suggested significantly dysregulated immune response in alexithymia, there is a lack of longitudinal studies. We sought to determine the reliability of the reported relationship between alexithymia and decreased immune response in a longitudinal study. Thirty-eight healthy women who had participated in a cross-sectional study were recontacted 1-year later. Of this sample, 26 were finally included: 13 females who had been found to be alexithymic, and 13 females who were classified as non-alexithymic under the 20-item Toronto Alexithymia Scale during the first phase of the study. A year later, they were still healthy women without any psychiatric disorders, their ages now ranging from 19 to 28 years old. Lymphocyte subset counts (CD4, CD8),in vitroproduction of interleukin 1β (IL-1β), IL-2, IL-4, and IL-10 by phytohemagglutinin stimulated peripheral blood lymphocytes, as well as serum cortisol levels, were compared between women with and without alexithymia. One-year later, alexithymic women still had significantly loweredin vitroproduction of IL-2 and IL-4, with lowered IL-2/IL-10 ratio and a reduced percentage of CD4. This is the first ever published study assessing cytokine production during a follow-upof alexithymics. Although our results should be interpreted with caution due the small sample size, they suggest a sustained reduction in both major type 1 and type 2 cytokines while the former seems to be more affected. The potential long-term health impact, if any, is still to be determined.
Negative Impact of Amphetamine-Type Stimulant Use on Opioid Agonist Treatment Retention in Ontario, Canada
Authors: Morin Kristen A. , Vojtesek Frank , Acharya Shreedhar , Marsh David C.
Published: December 2021

Objective: The objective of this study was to evaluate epidemiological trends of co-use patterns of amphetamine-type stimulants and opioids and the impact of co-use patterns on Opioid Agonist Treatment (OAT) retention in Ontario, Canada. The secondary objective was to assess geographical variation in amphetamine-type stimulant use in Northern Rural, Northern Urban, Southern Rural and Southern Urban Areas of Ontario.

Methods: A retrospective cohort study on 32,674 adults receiving OAT from ~70 clinics was conducted between January 1, 2014, and December 31, 2020, in Ontario, Canada. Patients were divided into four groups base on the proportion of positive urine drug screening results for amphetamine-type stimulants during treatment: group 1 (0–25%), group 2 (25–50%), group 3 (50–75%), and groups 4 (75–100%). A Fractional logistic regression model was used to evaluate differences over time in amphetamine-type stimulant use with urine drug screening results. A Cox Proportional Hazard Ratio model was used to calculate the impact of amphetamine-type stimulant use on retention in OAT and adjusted for sociodemographic characteristics, drug use and clinical factors. Lastly, a logistic regression model was used on a subgroup of patients to assess the impact of geography on amphetamine-type stimulant use in Northern Rural, Northern Urban, Southern Rural and Southern Urban Areas of Ontario.

Results: There were significant differences in amphetamine-type stimulant positive urine drug screening results year-over-year from 2015 to 2020. Significant differences were observed between amphetamine-type stimulant groups with regards to sociodemographic, clinical and drug use factors. Compared to those with no amphetamine-type stimulant use, the number of days retained in OAT treatment for amphetamine-type stimulant users was reduced (hazard ratio 1.19; 95% confidence interval = 1.07–1.17; p < 0.001). Lastly, an adjusted logistic regression model showed a significant increase in the likelihood of amphetamine-type stimulant use in Northern Rural regions compared to Southern Urban areas.

Conclusion: There was a significant increase in amphetamine-type stimulant use among individuals in OAT from 2014 to 2020, associated with decreased OAT retention. Research is required to determine if tailored strategies specific to individuals in OAT who use amphetamine-type stimulants can improve OAT outcomes.
Observing Sucrose Accumulation With Sentinel-1 Backscatter
Authors: den Besten Nadja , Steele-Dunne Susan , Aouizerats Benjamin , Zajdband Ariel , de Jeu Richard , van der Zaag Pieter
Published: December 2021

In this study the impact of sucrose accumulation in Sentinel-1 backscatter observations is presented and compared to Planet optical observations. Sugarcane yield data from a sugarcane plantation in Xinavane, Mozambique are used for this study. The database contains sugarcane yield of 387 fields over two seasons (2018-2019 and 2019-2020). The relation between sugarcane yield and Sentinel-1 VV and VH backscatter observation is analyzed by using the Normalized Difference Vegetation Index (NDVI) data as derived from Planet Scope optical imagery as a benchmark. The different satellite observations were compared over time to sugarcane yield to understand how the relation between the observations and yield evolves during the growing season. A negative correlation between yield and Cross Ratio (CR) from Sentinel-1 backscatter was found while a positive correlation between yield and Planet NDVI was observed. An additional modeling study on the dielectric properties of the crop revealed how the CR could be affected by sucrose accumulation during the growing season and supported the opposite correlations. The results shows CR contains information on sucrose content in the sugarcane plant. This sets a basis for further development of sucrose monitoring and prediction using a combination of radar and optical imagery.
Global MHD Simulation of the Weak Southward IMF Condition for Different Time Resolutions
Authors: Park Kyung Sun
Published: December 2021

We performed high-resolution three-dimensional global MHD simulations to determine the impact of weak southward interplanetary magnetic field (IMF) (Bz = −2 nT) and slow solar wind to the Earth’s magnetosphere and ionosphere. We considered two cases of differing, uniform time resolution with the same grid spacing simulation to find any possible differences in the simulation results. The simulation results show that dayside magnetic reconnection and tail reconnection continuously occur even during the weak and steady southward IMF conditions. A plasmoid is generated on closed plasma sheet field lines. Vortices are formed in the inner side of the magnetopause due to the viscous-like interaction, which is strengthened by dayside magnetic reconnection. We estimated the dayside magnetic reconnection which occurred in relation to the electric field at the magnetopause and confirmed that the enhanced electric field is caused by the reconnection and the twisted structure of the electric field is due to the vortex. The simulation results of the magnetic field and the plasma properties show quasi-periodic variations with a period of 9–11 min between the appearances of vortices. Also the peak values of the cross-polar cap potential are both approximately 50 kV, the occurrence time of dayside reconnections are the same, and the polar cap potential patterns are the same in both cases. Thus, there are no significant differences in outcome between the two cases.