bluuebunny/crossref_metadata_2025 huggingface dataset:
STING-triggered CNS inflammation in human neurodegenerative diseases
Authors: Ferecskó Alex S. , Smallwood Miranda J. , Moore Adrian , Liddle Corin , Newcombe Jia , Holley Janet , Whatmore Jacqueline , Gutowski Nicholas J. , Eggleton Paul
Published: November 2022

Background
Some neurodegenerative diseases have an element of neuroinflammation that is triggered by viral nucleic acids, resulting in the generation of type I interferons. In the cGAS-STING pathway, microbial and host-derived DNA bind and activate the DNA sensor cGAS, the resulting cyclic dinucleotide, 2’3-cGAMP binds to a critical adaptor protein, stimulator of interferon genes (STING), which leads to activation of downstream pathway components. However, there is limited work demonstrating the activation of the cGAS- STING pathway in human neurodegenerative diseases.
Methods
Post-mortem CNS tissue from donors with multiple sclerosis (n = 4), Alzheimer's diseases (n = 6) and Parkinson's disease (n = 3), amyotrophic lateral sclerosis (n = 3) and non-neurodegenerative controls (n = 11) were screened by immunohistochemistry for STING and relevant protein aggregates (e.g., amyloid-β, α-synuclein, TDP-43). Human brain endothelial cells were cultured and stimulated with the STING agonist palmitic acid (1-400µM) and assessed for mitochondrial stress (release of mitochondrial DNA into cytosol, increased oxygen consumption), and downstream regulator factors, TBK-1/pIRF3 and inflammatory biomarkers interferon-β release and changes ICAM-1 integrin expression.
Results
In neurodegenerative brain, elevated STING protein was observed mainly in brain endothelial cells and neurons compared to non-neurodegenerative control tissues where STING protein staining was weaker in comparison. Interestingly, higher STING presence was associated with toxic protein aggregates. (e.g., in neurons). Similarly high STING protein levels were observed within acute demyelinating lesions in multiple sclerosis subjects. To understand non-microbial/metabolic stress activation of the cGAS-STING pathway, brain endothelial cells were treated with palmitic acid. This evoked mitochondrial respiratory stress up to a ~ 2.5-fold increase in cellular oxygen consumption. Palmitic acid induced a statistically significant increase in cytosolic DNA leakage from endothelial cell mitochondria (Mander’s coefficient; P < 0.05) and a significant increase in TBK-1, phosphorylated transcription factor IFN regulatory factor 3, cGAS, cell surface ICAM. In addition, a dose response in secretion of interferon-β was observed but failed to reach statistical significance.
Conclusions
The histological evidence show that the common cGAS-STING pathway appears to be activated in endothelial and neural cells in all four neurodegenerative diseases examined. Together with the in vitro data suggest that the STING pathway might be activated via perturbation of mitochondrial stress and DNA leakage resulting in downstream neuroinflammation hence this pathway may be a target for future STING therapeutics.
Bilateral Acute Anterior Uveitis Associated with MiraLAX Bowel Prep
Authors: Tur Komalpreet , Omari Amro , Tajran Jahan , Ali Dania , Hart John
Published: November 2022

Background: Drug-induced uveitis is vision threatening and has been associated with various bioactive molecules. In this case report, we discuss a potential unique association between MiraLAX and bilateral anterior uveitis.
Case Presentation: We present a case of a 52-year-old gentleman with no significant medical history and a past ocular history of dry eye syndrome who developed an anaphylactic reaction and acute but mild bilateral anterior uveitis after recent MiraLAX bowel preparation for a screening colonoscopy. Extensive review of systems and screening for medical problems was otherwise unremarkable. The patient responded well to a short course of topical steroids and there were no sequelae of disease.
Conclusions: We aim to raise awareness of the potential association between MiraLAX and uveitis in order to prevent vision loss from the sequalae of disease.
Divergent responses of microbial metabolic limitations to cropland revegetation at erosion and deposition topographies in the hilly-gully region of the northern Loess Plateau, China
Authors: Yao Yufei , Tang Fangwang , Wang Chengcheng , Wei Xiaorong , Song Jinxi
Published: November 2022

Aims
Cropland revegetation is an effective measure to curb soil erosion on eroding hillslopes and increase farmers’ income at depositional check dams. However, how soil microbial metabolic limitation responds to cropland revegetation in erosion and deposition landscapes remains poorly understood, which has substantial implications for carbon (C) retention and nutrient cycling in the eroding environment.
Methods
We sampled 0-2 m soils in cropland and revegetated forest and grassland at upslopes and check dams on the hilly-gully region of the Loess Plateau, China. The activities of soil C-, nitrogen (N)-, and phosphorus (P)-acquiring enzymes were analyzed, and the improved V-T model derived from the vector model with the balance point was used to quantify microbial metabolic limitations based on ecoenzymatic stoichiometry.
Results
Microorganisms suffered from no energy (C) limitation, but the relative microbial C limitation was greater in revegetated land than in cropland in both landscapes. At upslopes, microbial P limitation occurred in the revegetated forest in soils below 20 cm due to the assimilation of P by the root system, while microorganisms were mainly limited by N in cropland and revegetated grassland. At check dams, land-use change had no significant influence on microbial N/P limitations owing to abundant soil C and nutrients and a wet environment.
Conclusions
Concludingly, this study revealed a non-response phenomenon of cropland revegetation on microbial metabolic limitation at lower-lying depositional topography, which compensates for the current understanding of resource restrictions on microorganisms at slopes or flat areas.
Blocking catalytic metal ion binding sites to develop antiviral therapies: exemplified using SARS-CoV-2 and HIV
Authors:   Virendra 1 Pandey, Comollo Thomas
Published: November 2022

Despite widely disseminated COVID19 vaccinations, infections continue. Treating COVID19 by inhibition of the RNA dependent-RNA polymerase of the causative virus, SARS-CoV2, is a helpful strategy. In this manuscript we describe a method of inhibiting SARS-CoV2 and other viral polymerases by blocking the binding of catalytic metal ions to the catalytic site in these polymerases. We performed an ~ 900,000 small molecule,in silico, virtual screening for small molecule compounds that would bind the metal ion site on nsp12; the SARS-CoV-2 replicase. We also tested seven of the best scoring “hit” compounds in anin vitroactivity assay for HIV reverse transcriptase. We found that even though thein silicoscreen for compounds had be targeted at nsp12, our compounds, at 10 µM, still had up to 24.4% inhibitory activity on HIV-RT in an enzymatic assay. Docking to a model of HIV-RT found that these seven molecules dock in overlapping pockets an near the catalytic metal ion binding site, occluding it. Presumably these molecules inhibit HIV-RT in the same fashion they were intended to inhibit SARS-CoV-2’s nsp12. Further development of compounds that target catalytic metal ion binding sites can generate antivirals for a variety of viruses or even broad-spectrum antiviral therapeutics.
Efficient Thermal-Energy-Storage Chiller Plant Facility Management with Digital Twin-assisted Augmented Reality Application
Authors: Sanzana Mirza Rayana , Abdulrazic Mostafa Osama Mostafa , Wong Jing Ying , Yip Chun-Chieh
Published: November 2022

This paper contributes to an interesting method of Digital Twin (DT)-assisted Augmented Reality (AR) application for the Thermal-Energy-Storage chiller plant facility management. AR with DT can greatly facilitate management and maintenance of complex Thermal-Energy-Storage Chiller Plants with better and remote accessibility, as well as improved communication among staff. This involves utilizing AR for viewing the chiller plant with related maintenance details. Besides, this application will be assisted by DT to allow a real-time update about when certain components are maintained. The manager can input information regarding maintenance tasks he wants to be completed using the AR application. A chiller plant is an unsuitable and noisy environment with various pieces of equipment for some individuals. Moreover, sometimes a chiller plant is situated in the basement and requires the manager to physically perform supervision visits. This paper provides an innovative framework that will allow facility managers to maintain and manage the chiller plants remotely. Furthermore, it also provides an opportunity for disabled people to pursue such management roles as they can simply view and manage from their smartphones.
Evaluation of the Main Regulators of Systemic Iron Homeostasis in Pyruvate Kinase Deficiency
Authors: Zaninoni Anna , Marra Roberta , Fermo Elisa , Consonni Dario , Andolfo Immacolata , Marcello Anna Paola , Rosato Barbara Eleni , Vercellati Cristina , Barcellini Wilma , Iolascon Achille , Bianchi Paola , Russo Roberta
Published: November 2022

Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied the main regulators of iron balance and erythropoiesis, as soluble transferrin receptor (sTfR), hepcidin, erythroferrone (ERFE), and erythropoietin (EPO), in a cohort of 41 PKD patients, compared with 42 affected by congenital hemolytic anemia type II (CDAII) and 50 with hereditary spherocytosis (HS). PKD patients showed intermediate values of hepcidin and ERFE between CDAII and HS, and clear negative correlations between log-transformed hepcidin and log-EPO (Person’s r correlation coefficient = -0.34), log-hepcidin and log-ERFE (r = -0.47), and log-hepcidin and sTfR (r = -0.44). sTfR was significantly higher in PKD; EPO levels were similar in PKD and CDAII, both higher than in HS. Finally, genotype-phenotype correlation in PKD showed that more severe patients, carrying non-missense/non-missense genotypes, had lower hepcidin and increased ERFE, EPO, and sTFR compared with the others (missense/missense and missense/non-missense), suggesting a higher rate of ineffective erythropoiesis. We herein investigated the main regulators of systemic iron homeostasis in the largest cohort of PKD patients described so far, opening new perspectives on the molecular basis and therapeutic approaches of this disease.
Agricultural practices in a high-altitude valley of the Southern Andes: new insights from organic residue analysis from La Ciénega valley, Argentina (ca. 200 BCE-900 CE)
Authors: Fiorani Agustina V. , Fundurulić Ana , Manhita Ana , Salvi Valeria Franco , Dias Cristina Barrocas
Published: November 2022

The consolidation of villager life in the Southern Andes implied profound transformations in human lifeways and groups’ relations with the landscape with the adoption of settled life and food production economies. Contributions from archaeological sciences can cast light into these research questions providing, for example, new information about patterns of susbsistence strategies. In this paper, we present the first organic residue analysis on ceramic containers of early villager societies of Northwestern Argentina (La Cienéga valley, ca. 200 BCE-900 CE) through two simultaneous lipid extraction methods (H2SO4/MeOH and CHCl3/MeOH). We aimed to put to test the existent characterization of the study area as a peripheric herding settlement evaluating the subsistence strategies and food economies of villager groups through the lens of absorbed organic residues in pottery. Preliminary evidence obtained in this article indicated a predominance of biomarkers associable to vegetable products in the vessels (i.e. maize) and a lower contribution of animal fats. Furthermore, a comparison and evaluation of the performance of each extraction method for specific compounds is given.
WNT2–SOX4 positive feedback loop promotes chemoresistance and tumorigenesis by inducing stem-cell like properties in gastric cancer
Authors: Fu Li , Tan Xiang-Yu , Li Yuting , Li Hua-Hui , Ma Li-Xiang , Zeng Chui-Mian , Zhang Tian-Tian , Huang Tu-Xiong
Published: November 2022

Gastric cancer (GC) is characterized by its vigorous chemoresistance to current therapies, which is attributed to the highly heterogeneous and immature phenotype of cancer stem cells (CSCs) during tumor initiation and propagation. The secretory WNT2 ligand regulates multiple cancer pathways and has been demonstrated to be a potential therapeutic target for gastrointestinal tumors; however, its role involved in gastric CSCs (GCSCs) remains unclear. Here, we found that WNT2 was overexpressed in GCSCs and positively regulated by its transcription factor SOX4. SOX4 was in turn upregulated by the canonical WNT2/FZD8/β-catenin signaling pathway to form an auto-regulatory positive feedback loop, resulting in the maintenance of GCSC self-renewal and tumorigenicity. Furthermore, blocking WNT2 using a specific monoclonal antibody significantly disrupted the WNT2–SOX4 positive feedback loop in GCSCs and enhanced the chemotherapeutic efficacy when synergized with the chemo-drugs 5-fluorouracil and oxaliplatin in a GCSC-derived mouse xenograft model. Overall, this study identified a novel WNT2–SOX4 positive feedback loop as a mechanism for GCSC-induced chemo-drugs resistance and suggested that the WNT2–SOX4 axis may be a potential therapeutic target for gastric cancer treatment.
DNA sequence-specific ligands. XX. Synthesis, spectral properties, virological and biochemical studies of fluorescent dimeric trisbenzimidazoles DB3P(n)1
Authors: Arutyunyan Albert F. , Kostyukov Alexey , Lushpa Vladislav A. , Mineev Konstantin S. , Korolev Sergey P. , Gottikh Marina B. , Klimova Regina R. , Kushch Alla A. , Kalabina Kseniya V. , Susova Olga Yu. , Zhuze Alexei L.
Published: November 2022

A new series of AT-specific minor groove DNA ligands (DB3P(n); n = 1,2,3,4) were synthesized and their spectral, biological and virological properties were investigated in water media. The variable length of methylene spacer in middle of molecule structure allows to “recognize” sequences of blocks of three AT pairs located at different distances from each other. The biological trials have shown sufficient capability to suppress activity of HIV-1 integrase catalytic activity at sub micromolar concentrations (0.25 – 0.50 µМ). DB3P(n) were found as very effective inhibitor of simplex virus type I and DNA topoisomerase I. By confocal microscopy confirmed ability of compounds stain nuclei, that can be used as gene-expression regulator.
Estimating Active Cases of COVID-19
Authors: Alvarez Javier , Baquero Carlos , Cabana Elisa , Champati Jaya Prakash , Anta Antonio Fernandez , Frey Davide , Garcia-Agundez Augusto , Georgiou Chryssis , Goessens Mathieu , Hernandez Harold , Lillo Rosa , Menezes Raquel , Moreno Raul , Nicolaou Nicolas , Ojo Oluwasegun , Ortega Antonio , Rausell Estrella , Rufino Jesus , Stavrakis Efstathios , Jeevan Govind , Glorioso Christin
Published: November 2022

Introduction: Having accurate and timely data on active COVID-19 cases is challenging, since it depends on the availability of an appropriate infrastructure to perform tests and aggregate their results. In this work, we propose alternative methods to assess the number of active cases of COVID-19.
Methods: We consider a case to be active if it is infectious, and we propose three methods to estimate the number of active infectious cases of COVID-19 using (1) official publications based on PCR testing, (2) fatalities using the case fatality ratio, and (3) three public surveys from the Delphi Group at Carnegie Mellon University, the University of Maryland, and our self-developed survey entitled Coronasurveys.
Results: We show that public surveys are a viable option in countries with reduced testing capacity or infrastructures.
Effect of Sodium Fluorescein Strip Application on Cornea Parameters Commonly Used in Laser-assisted in-situ Keratomileusis
Authors: Han Dongmei , Xie Wenjuan , Yuan Muqu , Cui Jing , Wang Qifeng , Zhang Qingsong
Published: November 2022

Purpose
To assess the effects of sodium fluorescein (NaF) strips on corneal parameters commonly used in Laser-assisted in-situ keratomileusis (LASIK).
Method
Eighty-six subjects (172 eyes) scheduled for LASIK between January and March 2022 were recruited. Topographic measurements of corneal parameters, including central corneal thickness (CCT), anterior keratometric (K) readings (K1, flat keratometry; K2, steep keratometry), horizontal corneal diameter (white to white, WTW), and corneal asphericity (Q value), were obtained using a Scheimpflug device (Pentacam) before and 10 min after NaF strip treatment.
Results
The Pentacam recorded a small significant increase in CCT (mean 538.88 ± 28.78µm to 547.90 ± 29.94µm; p < .001, paired samples t-test), with no differences in K1 and K2 (mean 42.24 ± 1.35D to 42.24 ± 1.35D, and mean 43.34 ± 1.50D to 43.32 ± 1.51D; P > .05, Wilcoxon signed-rank test, for all), or WTW (mean 11.58 ± 0.32 mm to 11.58 ± 0.32 mm; P > .05, Wilcoxon signed-rank test) before and after treatment. Furthermore, there was no significant difference in the Q value (mean − 0.30 ± 0.13 to -0.30 ± 0.14; P > .05, paired samples t-test).
Conclusions
These results indicate that clinicians should avoid NaF strip application before obtaining precise topographic measurements of cornea parameters.
Effects of tannic acid on the immunity and intestinal health of broiler chickens with Clostridium perfringens-induced necrotic enteritis
Authors: Xu Huiping , Fu Jianyang , Luo Yimeng , Li Peng , Song Bochen , Lv Zengpeng , Guo Yuming
Published: November 2022

Background
In broiler chickens, necrotic enteritis (NE) infection can reduce production performance. Tannic acid, as a kind of plant extract, has received extensive attention. However, the appropriate dosage of tannic acid in NE of broilers and the improvement effect on intestinal health are not very clear. In this study, we aimed to investigate the effects of different doses of tannic acid on the production performance, immunity, and intestinal health of broilers by constructing an NE model with C. perfringens infection and determining the appropriate dosage of tannic acid with regard to NE.
Results
Challenged birds showed significant reduction in body weights, villus heights, and the ratio of villus height to crypt depth (V/C) (P < 0.05) and increase in the feed consumption gain ratio, intestinal lesion score, and crypt depth (P < 0.05). NE infection significantly reduced the relative Bacteroides and Ligilactobacillus abundance (P < 0.05) and increased the ratio of Firmicutes/Bacteroides and cecal content of C. perfringens (P < 0.05). Challenged birds fed diets supplemented with tannic acid showed significantly increased mRNA expression of nutrient transport carriers and intestinal barrier genes and growth performance and reduced serum zonulin and endotoxin levels (P < 0.05). Addition of tannic acid to the diet inhibited the inflammatory response by reducing the number of coccidia oocysts in feces and the content of C. perfringens in the cecum. Specifically, tannin acid reduced the serum levels of C reactive protein, myeloperoxidase, and specific IgY and ileal mucosal secretory immunoglobulin A (sIgA) levels in the ileal mucosa compared with those in the NE-infected birds. NE-infected birds fed diets supplemented with tannin acid also showed significantly increased relative Anaerocolumna, Thermoanaerobacterium, and Thermosinus abundance (P < 0.05); their microbial composition and functional predictions were similar to those of the NC group.
Conclusions
Tannic acid in the diet alleviated NE by enhancing the intestinal barrier and absorption function. The recommended dietary tannic acid additive level is 500–750 mg/kg. Our study findings would be useful in reducing related economic losses in the broiler industry.
The study of stereoselectivity and mesomeric effect of N-nitrosamins via 1H NMR spectroscopy
Authors: Yaghmaeiyan Nahid , Mirzaei Mahdi , Bamoniri Abdolhamid
Published: November 2022

Nano-kaolin-SO3H was prepared and used to synthesis of N-nitrosamines. The products were characterized by their spectral (IR and 1H NMR) data. N-nitrosamines can exist in two mesomeric forms but the reaction is quite regioselective and only one of mesomers is formed as main product which can exist in two E and Z stereoisomers. In this paper, we have studied the mesomeric effect of N-nitrosamines which explained the diastereotopic nature of corresponding protons in symmetric N-nitrosamines and formation of two isomers in asymmetric N-nitrosamines.
Application of biochar and sulfur-modified biochar in a saline-sodic and calcareous soil: Effects on soil water content, soil biochemical properties and millet (Panicum miliaceum) yield
Authors: Taheri Musa al-Reza , Astaraei Ali reza , Lakzian Amir , Emami Hojat
Published: November 2022

Aims
Soil microbial and enzymatic activity have important roles in soil health, nutrient cycle, and plant growth. Biochar is excellent biomass for increasing soil water content, but some of the biochar compounds due to high pH are harmful to the soil. This study aimed to investigate the effect of biochar and sulfur-modified biochar on improving, soil water content and biochemical properties of soil in a millet cropping system.
Methods
The field experiment was performed in a completely random design with three replications under field conditions. Experimental treatments included control, 15 t ha− 1 sunflower biochar (B), and 15 t ha− 1 sulfur-modified biochar (BS).
Results
Soil water content in B treatment was higher than that in BS treatment. B and BS treatments improved soil biological properties (MBC, BR, CAT, DHA, UA and ALP) compared to control. Application of B and BS treatments decreased soil EC and SAR compared to the control. The highest (8.26) and lowest (7.83) values of soil pH were related to B and BS treatments, respectively. Treatment of soil with B and BS enhanced soil DOC (90% and 33%), AN (74% and 48%), and AP (60% and 96%) compared to control. Application of B and BS treatments enhanced plant nutrients such as N, P and K and increased RWC (40% and 14%) and plant yield (58% and 115%) compared to the control.
Conclusions
The sulfur increased the efficiency of biochar on amending saline and calcareous soil and enhance plant yield through improving chemical properties (pH and CEC) of biochar.
Use of thoracoscopy for thoracic sympathetic nerve block in primary hyperhidrosis
Authors: Han Jung Wook , Ahn Seha , Jeong Jin Yong , Park Chan Beom , Eom Eunjin , Park Soo Seog
Published: November 2022

Thoracic sympathetic nerve block (TSNB) has been widely used in the treatment of neuropathic pain. To reduce block failure rates, TSNB is assisted with several modalities including fluoroscopy, computed tomography, and ultrasonography. The present study describes our experience assessing the usefulness of thoracoscopy in TSNB for predicting compensatory hyperhidrosis before sympathectomy in primary hyperhidrosis. From September 2013 to October 2021, TSNB was performed under local anesthesia using a 2-mm thoracoscope in 302 patients with severe primary hyperhidrosis. Among the 302 patients, 294 were included for analysis. The target level of TSNB was T3 in almost all patients. The mean procedure time was 21 minutes. Following TSNB, the mean temperature of the left and right palms significantly changed from 31.5°C to 35.3°C and from 31.5°C to 34.8°C, respectively. With TSNB, primary hyperhidrosis was relieved in all patients. Pneumothorax occurred in six patients, in which no chest tube insertion was required. One patient developed hemothorax and was discharged the next day after small-bore catheter drainage. Transient ptosis developed in 10 patients and improved within a day in all patients. Our experiences showed that thoracoscopic TSNB is accurate, safe, and feasible to block the thoracic sympathetic nerve in patients with severe primary hyperhidrosis.
Ventral striatal islands of Calleja neurons bidirectionally mediate depression-like behaviors in mice
Authors: Zhang Yun-Feng , Wang Yingqi , Johnson Natalie , Bhattarai Janardhan , Espitia Camilo Guevara , Shoenhard Hannah , Fuccillo Marc , Wesson Daniel , Ma Minghong
Published: November 2022

The ventral striatum, composed of the nucleus accumbens (NAc) and olfactory tubercle (OT), is a key reward center implicated in the pathophysiology of depression. Although the OT is known to regulate motivational and reward-related behaviors, its involvement in depression remains unexplored. We recently report that islands of Calleja, clusters of dopamine D3 receptor-expressing granule cells that are predominately situated in the OT, regulate self-grooming, a repetitive behavior manifested in mood disorders including depression. Here we show that chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depressive phenotypes. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model to explain how OT D3 neurons may influence dopamine release into the NAc via synaptic connections with OT spiny projection neurons (SPNs) that project to midbrain dopamine neurons. Our study reveals a novel role of OT D3 neurons in bidirectionally mediating depressive phenotypes, suggesting an attractive therapeutic target.
Revisiting self-interference in Young’s double-slit experiments
Authors: Kim Sangbae , Ham Byoung S.
Published: November 2022

Quantum superposition is the heart of quantum mechanics as mentioned by Dirac and Feynman. In an interferometric system, single photon self-interference has been intensively studied over the last several decades in both quantum and classical regimes. In Born rule tests, the Sorkin parameter indicates the maximum number of possible quantum superposition allowed to the input photons entering an interferometer, where multi-photon interference fringe is equivalent to that of a classical version by a laser. Here, an attenuated laser light in a quantum regime is investigated for self-interference in a Mach-Zehnder interferometer, and the results are compared with its classical version. The resulting equivalent results support the Born rule tests, where the classical interference originates in the superposition of individual single-photon self-interferences. This understanding sheds light on the fundamental physics of quantum features between bipartite systems.
Variability of column ozone dependence on ODSs and GHGs: 500-member ensemble simulations
Authors: Akiyoshi Hideharu , Kadowaki Masanao , Yamashita Yousuke , Nagatomo Toshiharu
Published: November 2022

State-of-the-art chemistry–climate models (CCMs) have indicated that a future decrease in ozone-depleting substances (ODSs) combined with an increase in greenhouse gases (GHGs) would increase the column ozone amount in most regions except the tropics and Antarctic. However, large Arctic ozone losses have occurred at a frequency of approximately once per decade since the 1990s (1997, 2011 and 2020), despite the ODS concentration peaking in the mid-1990s. To investigate this contradiction, CCMs were used to conduct 24 simulations using 500-member ensembles, with ODS and GHG concentrations set based on predicted values for future years. The 50 ensemble members with the lowest column ozone in the mid- and high latitudes of the Northern Hemisphere showed a clear ODS dependence associated with low temperatures and a strong westerly zonal mean zonal wind. Even with high GHG concentrations, several ensemble members showed extremely low spring column ozone in the Arctic when ODS concentration remained above the 1980–1985 level. Hence, ODS concentrations should be reduced to avoid large ozone losses not only in the Antarctic, but also in the presence of a stable Arctic polar vortex in the mid- and high latitudes of the Northern Hemisphere.
Evaluation of three scoring systems for predicting renal prognosis in antineutrophil cytoplasmic antibody-associated glomerulonephritis
Authors: Wang Xinfang , Zhang Xiaofeng , Chen Lin , Ma Qiuling , Su Yajing , Liu Jingwen , Shi Huihui , Wang Ruiqiang
Published: November 2022

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) is characterized by rapidly progressive glomerulonephritis, and timely initiation of treatment and evaluation is critical to prevent progression of renal disease to end-stage renal disease (ESRD). This study aimed to evaluate the predictive value of the renal risk score (RRS), Birmingham vasculitis activity score (BVAS), and renal vascular lesions (RVLs) score for renal prognosis in AAGN.
Methods: A retrospective analysis of ninety-three patients diagnosed with AAGN after renal biopsy was performed. The RRS, BVAS, and RVLs score were evaluated in relation to clinicopathologic features and renal prognosis. A receiver operating characteristic (ROC) curve was used to evaluate their prognostic value for the kidneys.
Results: The median follow-up time was 36 months. Thirty-eight patients progressed to ESRD. Survival analysis showed that renal prognosis worsened within the RRS group in the order of low, medium, and high RRS (P＜0.05). Within the RVLs group, the renal prognosis of the groups with severe and moderate RVLs was worse than that of the group without RVLs (P = 0.017, P< 0.001), and the group with mild RVLs was close to that of the group without RVLs. ROC analysis showed that the AUC of RRS, BVAS, RVLs score, RVLs score combined with RRS (RVLs score & RRS, RR), RVLs score and RRS combined with BVAS (RVLs score & RRS & BVAS, RRB) were 0.862, 0.759, 0.618, 0.908, and 0.914, respectively. The predictive power of RRB and RR was comparable and significantly better than the RRS, BVAS, and RVLs score. On the basis of simplicity and validity, RR was selected as the best predictor, and the relationship between RRS, RVLs score, and RR was calculated using a linear fit, resulting in the linear equation RR = -0.4766 + 0.1231 × RVLs score + 0.395 × RRS (P < 0.001).
Conclusions:In AAGN, the predictive power of RR for renal prognosis was superior to that of RRS, BVAS, and RVLs score. RR may serve as a new predictor of renal prognosis in AAGN.
Experimental study on triaxial unloading mechanical properties and acoustic emission response of shale with different water contents
Authors: Li Bingyang , Yang Fengwei , Li Haofei , Du Pengzhao , Liu Zhenhong
Published: November 2022

Water is one of the most significant factors influencing the mechanical properties of rocks. Triaxial unloading acoustic emission (AE) tests were performed to study the unloading mechanical characteristics and damage evolution mechanism of shale with various water contents. The damage evolution characteristics of shale under triaxial unloading conditions were analyzed using AE time series parameters. The results show that when the water saturation coefficient rises, the number of AE rings and the energy value of shale decrease. Based on the results of the AE test, the ratios of the crack initiation stress and damage stress to the peak stress are 0.4 ~ 0.6 and 0.9, respectively. The closure stress, crack initiation stress, damage stress, and other characteristic stresses determined by the stress axial strain method and the AE method all decrease with the increase of the water saturation coefficient, demonstrating that water has a significant impact on the mechanical characteristics of the shale during the unloading damage and damage process. Based on the test results, a statistical damage constitutive model is established, and it uses the AE cumulative ringing count to represent the damage variable. The calculated results of the model are in good agreement with the experimental data, indicating that the established model can more accurately depict the evolution process of shale unloading damage and failure under different water contents. The study's findings can be used as a reference for determining the extent of rock damage caused by water-rock interaction.
Characterization of Exosomes Isolated from Non-Small Lung Cancer Cell (NC1975) using Improved Morphological and Surface Protein Biomarkers methods
Authors: Mahgoub Ilham , Abdella Galal M.
Published: November 2022

Lung cancer is considered one of the leading causes of death worldwide. Usually, disease detection is difficult in the early stages; new methods for diagnosis using non-invasive ways are developed using Nano-molecules called exosomes. Exosomes are cell-derived vesicles carrying different molecules (proteins, DNA, RNA, microRNA) and displaying many proteins on their membrane surfaces. In this study, NCI 1975 Cells line has been used as a source of exosomes. First, the isolation processes were carried out using different ultra-centrifugation devices. Then isolated exosomes were characterized using surface protein biomarkers. Finally, the Exosome isolated products were screened under Transmission Electron Microscopy (TEM) and compared with Scanning Electron Microscopy (SEM). The results showed that the size distributions of apoptotic vesicles (APV) 450nm and necrotic bodies (NCB) 280 nm (extracellular vesicles )were significantly different from exosomes(P < 0.001). This study confirmed the accessible use of exosomes in the diagnosis and prognosis of Non-Small Cell Lung Cancer (NSCLC).
Differential influence of temperature on the toxicity of three insecticides against the codling moth Cydia pomonella (L.) and two natural enemies
Authors: Perrin Marie , Borowiec Nicolas , Thaon Marcel , Siegwart Myriam , Delattre Thomas , Moiroux Joffrey
Published: November 2022

Insecticide toxicity may strongly vary with temperature, and interspecific differences have been commonly reported for this relationship. A differential influence of temperature on insecticide toxicity between pests and their natural enemies may have important consequences on biological control in a global warming context. This study aimed to investigate cross effects between temperature and three insecticides - i.e., chlorantraniliprole, emamectin and spinosad - on the mortality of a major pest in orchards, Cydia pomonella L., and two of its natural enemies in southern France, the predatory earwig Forficula auricularia L. and the introduced parasitoid Mastrus ridens Horstmann. We observed a decreased efficiency of emamectin and spinosad with increasing temperature on mortality of codling moth, while no influence of temperature on chlorantraniliprole efficacy was observed. Increasing temperatures increased the toxicity of all insecticides against M. ridens and only for emamectin on F. auricularia. This study provides essential insight to make recommendations for using these insecticides in combination with two natural enemies to control the codling moth in a warming world. Our results suggest that the use of spinosad may become sub-optimal under higher temperatures. In contrast, chlorantraniliprole should remain suitable under warmer climatic conditions to control C. pomonella, conserve F. auricularia and facilitate the establishment of M. ridens. For conservation biological control relying on F. auricularia, alternating use of emamectin during early spring, when its toxicity is the lowest on this natural enemy, and chlorantraniliprole during summer could limit resistance risks in codling moth populations and reduce the insecticides' impact on the populations of natural enemies.
Remediation of Pb-contaminated soil using Biochar-Based Slow- Release P Fertilizer and biomonitoring employing bioindicators
Authors: Luque María Paula Acosta , López Julián E. , Henao Nancy , Saldarriaga Juan F.
Published: November 2022

Soil contamination by Pb can result from different anthropogenic sources such as lead-based paints, gasoline, pesticides, coal burning, mining, among others. This work aimed to evaluate the potential of P-loaded biochar to remediate a Pb-contaminated soil and to apply a biomonitoring alternative after soil remediation. First, rice husk-derived biochar was obtained at different temperatures (450, 500, 550, and 600 ºC). Then, part of the resulting material was activated. Later, the raw biochars and activated biochars were immersed in a saturated KH2PO4 solution to produce P-loaded biochars. The ability of materials to immobilize Pb and increase the bioavailability of P in the soil was evaluated by an incubation test. The materials were incorporated into doses of 0.5, 1.0, and 2.0%. After 45 days, soil samples were taken to biomonitor the remediation process using two bioindicators: a phytotoxicity test and enzyme soil activity. Activated P-loaded biochar produced at 500 ºC has been found to present the best conditions for soil Pb remediation. This material significantly reduced the bioavailability of Pb and increased the bioavailability of P. The phytotoxicity test and the soil enzymatic activity were significantly correlated with the decrease in bioavailable Pb but not with the increase in bioavailable P. Biomonitoring using the phytotoxicity test is a promising alternative for the evaluation of soils after remediation processes.
Optimization of the air-conditioning energy performance and daylight performance of a residential building according to the bioclimatic design principles: An application to the Moroccan Mediterranean climate
Authors: Ameur Mohamed , Kharbouch Yassine , Taoukil Driss , Mimet Abdelaziz
Published: November 2022

The bioclimatic architecture concept refers to an approach that takes into account the various characteristics of a building environment to make it more comfortable for its occupants. This work aims to improve the passive design parameters of an air-conditioned residential building located in the north of Morocco, in accordance with bioclimatic principles. The bioclimatic chart diagram is used to select the passive design measures that are the most appropriate for the north Morocco climate characteristics. Then, a set of design parameters are selected for more delimitation in the optimization study. The optimization problem is multi-objective and aims to find the design solution that simultaneously includes the best air-conditioning energy performance and daylight performance. The obtained results showed that the multi-objective optimum design solution is characterized by massive walls and roof, exterior insulation, double window glazing type, and a high summer ventilation rate. Also, a small glazing area with a large sun-shading covering is needed for the east facade. Ultimately, the building performance analysis revealed that the optimum bioclimatic design solution fully meets the requirements established by the Moroccan Building Thermal Regulation (MBTR), leading to an energy performance improvement of about 52%.
A novel TPD52L2-ROS1 gene fusion expanding the molecular alterations in inflammatory myofibroblastic tumor: case report and literature review
Authors: Liu Xuguang , Duan Yaqi , Wang Guoping , Zhu Pengcheng
Published: November 2022

Background: Inflammatory myofibroblastic tumor (IMT) is a distinctive tumor composed of spindle cells accompanied by mixed inflammatory cells, and immunohistochemical positivity for ALK (anaplastic lymphoma kinase protein) can be detected in half of IMTs. The diagnosis of ALK-negative IMT could be a challenge. Recently, the fusions of some kinase genes, such as RET, NTRK1, ROS1, etc., are revealed in ALK-negative IMT.
Case presentation: A 19-year-old woman presented with swelling of the left upper arm. Magnetic resonance imaging (MRI) scan revealed a tumor in the left postbrachium extended to the left axillary, serratus anterior muscle, and latissimus dorsi muscle. Histopathologically, the irregular-circumscribed tumor was composed of dense spindle-shaped cells with eosinophilic abundant cytoplasm and hyalinized mesenchyme in an inflammatory background. Immunohistochemically (IHC), tumor cells were positive for SMA, MDM2, and p16; the cells were negative for desmin, MyoD1, Myogenin, pan-cytokeratin, S100, SOX10, HMB45, Malen-A, CD34, CD31, CD99, and ALK. By RNA-based NGS, a novel fusion between TPD52L2 3’ end of exon 1-4 and ROS1 5’ end of exon 36-43 was revealed. ROS1 IHC staining was negative. The final diagnosis of IMT with TPD52L2-ROS1fusion was made.Subsequently, the patient experienced a good clinical response to Crizotinib, and clinical follow-up showed stable disease after 9 months.
Conclusion: This report expands the spectrum of ROS1 gene rearrangements in the IMT and highlights the importance of molecular analysis of IMT for getting a diagnostic clue and determining potential therapeutic strategies.
Longitudinal weight status, and academic achievement
in elementary schoolchildren in the United States
Authors: Elish Paul , Boedeker Peter , Lash Timothy , Gazmararian Julie
Published: November 2022

Background/Objectives. Childhood overweight and obesity have a well-established negative impact on children’s health. Overweight and obesity might also negatively impact children’s academic performance, but existing literature on this association is inconclusive. This study uses a longitudinal design in a large, diverse elementary school sample to rigorously test the association between longitudinal weight status and academic achievement. Analyses also investigate modification by sex, race/ethnicity, and cardiorespiratory fitness (CRF).
Subjects/Methods. In a large suburban school district in the United States, 4 936 Grade 4 students were recruited. Demographic, course grade, and standardized test data were collected from school records for Grades 3 to 5, and body mass index (BMI) and CRF were assessed each year. Students wore accelerometers during the school day for up to 15 days across three semesters (Grade 4 Fall and Spring, Grade 5 Fall) to objectively measure physical activity. Multiple imputation addressed missing data and multilevel analyses controlled for student demographics and clustering within schools.
Results. Unadjusted multilevel models found small negative associations for students who were persistently obese with course grades and standardized test scores, but these associations largely disappeared when controlling for demographic characteristics. Residual associations for math and writing course grades were attenuated when controlling for CRF, though some marginal negative associations for math and writing remained for students who became obese during follow up. There was no evidence of modification by sex or race/ethnicity.
Conclusions Results suggest very small associations between obesity status and academic achievement that were largely explained by CRF. These findings support growing evidence that increasing CRF is more important than losing weight for improving children’s cognition and academic achievement.
Robotic total knee arthroplasty in clinical practice: protocol for a randomised controlled trial
Authors: Migliorini Filippo , Maffulli Nicola , Schäfer Luise , Schneider Jens , Nobili Andrea Maria , Kämmer Daniel , Michalak Milosch , Bell Andreas
Published: November 2022

Around 2–20% of patients who undergo total knee arthroplasty (TKA) reported restricted motion and anterior knee pain. Non-optimal implant components alignment represents a common cause for complain. In this context, the introduction of robotic assisted TKA is supposed to improve the accuracy of component positioning and to adapt more precisely to patient anatomy and biomechanics. Robotic TKA using has been introduced to improve component alignment, stability and proprioception. However, the advantages of robotic surgery over the conventional freehand TKA are still unclear and evidence are missing.
The present study is a protocol for a single-blind parallel-group randomized controlled trial in which each group of participants is exposed to only one of the study interventions. Patients will be randomly allocated to robotic TKA or standard TKA. The primary outcome of interest is to evaluate the learning curve. The secondary outcome of interest is to compare robotic TKA using CORI versus freehand arthroplasty in patients reported outcome measures (PROMs), length of the hospitalisation, blood values, implant positioning, blood transfusion units, range of motion. The third outcome of interest is to evaluate accuracy of component positioning of robotic TKA compared to the conventional TKA with respect to the pre-operative planning.
Level of evidence: Level I, randomised controlled trial
Registration: German Registry of Clinical Trials (ID: DRKS00030614)
Evaluation of the interaction between potent small molecules against the Nipah virus Glycoprotein in Malaysia and Bangladesh strains, accompanied by the human Ephrin-B2 and Ephrin-B3 receptors; a simulation approach
Authors: Ebrahimi Maryam , Alijanianzadeh Mahdi
Published: November 2022

In late September 1998 the first human case of Nipah virus (NiV) having been manifested in Malaysia with severe encephalitis and respiratory symptoms. Then, based on the viral genomic mutations two main strains (NiV-Malaysia and NiV-Bangladesh) have spread across the world. In the face of this biosafety level 4 pathogen with highly pandemic potential, no licensed molecular therapeutics have been approved. Considering the role of NiV attachment Glycoprotein in viral transmission, identifying small molecules that can be repurposed for inhibiting the Glycoprotein attachment, and also the viral receptors in human cells (Ephrin-B2 and Ephrin-B3) as the significant anti-NiV treatment were discussed. Thus, to prospect seven potential anti-COVID-19 drugs with clinical effectiveness (Pemirolast, Nitrofurantoin, Isoniazid Pyruvate, Eriodictyol, Cepharanthine, Ergoloid, and Hypericin) against NiV-G, Ephrin-B2, and Ephrin-B3 receptors, an annealing simulation, ligand-based pharmacophore modeling, and molecular docking simulations were implemented. Based on the annealing analysis, Pemirolast (pem) against efnb2 protein also Isoniazid Pyruvate (iso) against efnb3 receptor were repurposed as the best small molecule candidates. Moreover, Cepharanthine (ceph), and Hypericin (hyp) with noteworthy interaction values are the top Glycoprotein inhibitors in Malaysia and Bangladesh strains. Additionally, molecular docking calculation showed their binding affinity scores which are related to efnb2-pem (-7.1 kcal/mol), efnb3-iso (-5.8 kcal/mol), gm-hyp (-9.6 kcal/mol), gm-ceph (-10.1 kcal/mol), gb-ceph (-9.2 kcal/mol). Our computational research not only minimizes the challenge of time-consuming but also meets our precautionary demand for options to handle any new variants of the Nipah virus that might emerge in the future.
Automation of legal precedents retrieval: findings from a rapid literature review
Authors: Mentzingen Hugo , Bacao Fernando , António Nuno
Published: November 2022

Judges frequently rely their reasoning on precedents. In every circumstance, courts must preserve uniformity in case law and, depending on the legal system, previous cases compel rulings. The search for methods to accurately identify similar previous cases is not new and has been a vital input, for example, to case-based reasoning (CBR) methodologies. Innovations in language processing and machine learning (ML) brought momentum to identifying precedents while providing tools for automating this task. This rapid literature review investigated how research on the identification of legal precedents has evolved. It also examined the most promising automation strategies for this task and confirmed the growing interest in using artificial intelligence for legal precedents retrieval. The findings demonstrate that no artificial intelligence solution currently stands out as the most effective at finding past similar cases. Also, existing results require validation with statistically significant samples and ground truth provided by specialists. In addition, this work employed text mining (TM) to automate part of the literature review while still delivering an accurate picture of research in the field. Ultimately, this review suggests directions for future work, as more experimentation is required.