bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated monitoring system for disaster-causing organisms in the water intake areas of coastal nuclear power plants
Authors: Li Chao , Huo Jian-ling , Song Yu-ze , Yang Lei , Liu Song-tang
Published: January 2023

Nowadays, nuclear power plays an important role in the energy structure of many countries. However, A bloom of a disaster-causing organism (DCO) in the cold-water intake area of a coastal nuclear power plant can block the water cooling system and seriously affect the operational safety of the nuclear power unit. Currently, the traditional method of protection is to estimate the DCO abundance by regular manual investigation and sampling, but that method cannot give continuous real-time data. Instead, proposed and implemented here is a seafloor in situ integrated monitoring system for DCOs (known as IMSDCO), which is equipped with an optical microscopic imager (OMI) and hydrometric sensors to monitor automatically the DCO abundance and hydrology. All the data are transmitted to a terminal in the shore station through a photoelectric composite cable for real-time display. When the DCO abundance reaches a preset threshold, software automatically raises an alarm. Since placing IMSDCO at the cold-water intake of the Changjiang nuclear power plant, a six-month field trial has been completed, during which large amounts of hydrology data and DCO images were obtained. IMSDCO successfully identified and estimated the abundances of various DCOs (e.g., Phaeocystis globosa, Acetes chinensis, and small fish) and predicted their movements based on hydrology data. Based on the analysis of the experimental data, we discussed the reasons for the error in the abundance estimation of DCO and the methods to reduce the error. The experimental results show that the OMI-based IMSDCO can monitor and give early warning of DCOs in the water intake areas of costal nuclear power plants and is worthy of long-term deployment.
Numerical investigation of fractional Maxwell nano-fluids between two coaxial cylinders via the finite difference approach
Authors: Asjad Muhammad Imran , Usman Muhammad , Assiri Taghreed A. , Ali Arfan , Tag-ElDin ElSayed M.
Published: January 2023

This study deals with numerical solution of momentum and heat transfer of fractional ordered Maxwell fluids within a coaxial cylinder. It is well known that the complex dynamics of flow regime can be well-described by the fractional approach. In this paper, a fractional differentiation operator Dtα of Caputo was applied for fractional modeling of magneto-hydro-dynamic (MHD) fluid. A set of appropriate transformations was applied to make the governing equations dimensionless. The finite differences were calculated by the discretization of momentum profile ur,t and heat profile Tr,t. The results obtained for ur,t and Tr,t were plotted against different physical parameters, such as Prandtl number Pr, the square of Hartmann number Ha, thermal Grashof number Gr, thermal radiation parameter Nr, and heat source/sink parameter Q0. The results were verified by comparing data from the proposed method with MAPLE built-in command results. Subjecting the system to a strong magnetic field led to increasing Tr,t and decreasing ur,t. It was found that increasing Gr and Pr increased the velocity and temperature profiles. Addition of Cu nanoparticles to a base fluid of H2O enhanced its heat transfer capability. Also, increasing the angular frequency of inner cylinder velocity resulted in a high velocity profile of fractional Maxell nano-fluids within a coaxial region (cylinder).
Measuring depression in Primary Health Care in Spain: Psychometric properties and diagnostic accuracy of HSCL-5 and HSCL-10
Authors: Rodríguez-Barragán María , Fernández-San-Martín María Isabel , Clavería Ana , Le Reste Jean Yves , Nabbe Patrice , Motrico Emma , Gómez-Gómez Irene , Peguero-Rodríguez Eva
Published: January 2023

Background

Depression has a high prevalence among European countries. Several instruments have been designed to assess its symptoms in different populations. The Hopkins Symptom Checklist 25 (HSCL-25) scale has been identified as valid, reproducible, effective, and easy to use. There are short versions of this scale that could be useful in Primary Care (PC) settings, but their psychometric properties are unknown.

Aim

To assess in PC patients the psychometric properties and diagnostic accuracy of the Spanish version of the HSCL-10 and the HSCL-5 consisting of 10 and 5 items, respectively.

Methods

A multicenter, cross-sectional study was carried out at six PC centers in Spain. The HSCL-25 was administered to outpatients aged 45–75 who also participated in the structured Composite International Diagnostic Interview (CIDI). HSCL-10 and HSCL-5 were assessed and compared to HSCL-25 regarding total score correlation, internal consistency, and criterion validity against the gold-standard CIDI. This is a methodological study from a secondary data analysis and the primary data has been previously published.

Results

Out of 790 patients, 767 completed the HSCL-25 and 736 the CIDI interview (96.0%). Cronbach’s Alpha was 0.84 for HSCL-10 and 0.77 for HSCL-5. The known-group method and confirmatory factor analysis were acceptable for the establishment of construct validity. Sensitivity was 79.7% (CI95%, 67.7–88.0%) for HSCL-10, and 78.0% (CI95%, 65.9–86.6%) for HSCL-5, whereas specificity was 83% (CI95%, 80.0–85.7%) for HSCL-10, and 72.8% (CI95%, 69.3–76.0%) for HSCL-5. Area under the curve against CIDI was 0.88 (CI95%, 0.84–0.92%) for HSCL-10, and 0.85 (CI95%, 0.81–0.89%) for HSCL-5. Optimum cutoff point calculated with Youden Index was 1.90 for the HSCL-10 and 1.80 for the HSCL-5.

Conclusion

HSCL-10 and HSCL-5 are reliable and valid tools to detect depression symptoms and can be used in PC settings.
A novel optical imaging probe for targeted visualization of NLRP3 inflammasomes in a mouse model of age-related macular degeneration
Authors: Paguaga Marcell E. , Penn John S. , Uddin MD Imam
Published: January 2023

Purpose

Wet form of age-related macular degeneration (wet AMD) is a progressive vascular disease that mainly affects older adults and causes severe and irreversible vision loss. A key complication of wet AMD is choroidal neovascularization (CNV), which may be driven in part by NLRP3 inflammasomes that are associated with macrophages migration to CNV lesions. Since activated NLRP3 is correlated with CNV, visualizing NLRP3 inflammasomes and their associated macrophages is of great interest to monitor wet AMD progression and develop effective therapies against it. However, to the best of our knowledge, current ophthalmic imaging systems do not permit such targeted imaging. Therefore, in this study, we developed InflammaProbe-1, an optical imaging probe for targeted visualization of NLRP3 inflammasomes in CNV lesions.

Methods

InflammaProbe-1 was synthesized by conjugating a clinically relevant fluorophore, Oregon Green® 488, to the selective NLRP3 inhibitor, CY-09. The ability of InflammaProbe-1 to target NLRP3 was assessed with an enzyme-linked immunosorbent assay by comparing its ability to inhibit NLRP3-mediated secretion of IL-1β to that of CY-09 in LPS-primed and nigericin-stimulated BMDMs. In vitro confocal imaging of NLRP3 was performed on InflammaProbe-1-stained BMDMs that had been induced to express NLRP3 with LPS. In vivo imaging of NLRP3 was conducted on mouse laser induced choroidal neovascularization (LCNV), a model of AMD, 6 h after an intraperitoneal injection of InflammaProbe-1 at 10 mg/kg on day 4 post-LCNV.

Results

InflammaProbe-1 was just as effective as CY-09 at inhibiting IL-1β secretion (p < 0.01 at 10 μM for both the InflammaProbe-1 and CY-09 groups relative to the control). InflammaProbe-1-stained BMDMs that had been induced to express NLRP3 showed significantly brighter fluorescence than untreated cells (p < 0.0001 for LPS treatment group and p < 0.001 for LPS and nigericin treatment group). Furthermore, in vivo molecular imaging of NLRP3 was achieved in mouse LCNV.

Conclusion

We propose that InflammaProbe-1 may be a useful molecular imaging probe to monitor the onset, progression, and therapeutic response of AMD and other NLRP3-mediated diseases.
Treatment of striae albae with 1,550 nm Er: Glass vs. CO2 fractional laser: A self-controlled study
Authors: Luo Yanfei , Lin Yan , Wang Meiling , Gao Xiaoyuan , Liu Xiaodong , Liu Huaxu
Published: January 2023

Objective

The objective of this study was to compare the efficacy and safety of fractional CO2 laser and 1,550 nm Er: glass laser in the treatment for the patients with striae albae.

Methods

The female adults with striae albae in the abdomen for at least 12 months were recruited. After informed consent obtained, the patient received three treatments at 2-month intervals. The lesions on the left abdomen were treated with 10,600 nm CO2 fractional laser and right side treated with 1,550 nm Er: glass fractional laser. The pictures were taken before each visit and 3 months after the final treatment. The criteria for the evaluations using a quartile grading scale were excellent (76–100%), good (51–75%), fair (26–50%), poor (1-25%), and no improvement (0%). The safety and efficacy of the two lasers were independently evaluated using before and after photographs by two dermatologists. In addition, the self-reports to investigate the pain and satisfaction from patients were also recorded.

Results

Totally, 27 cases were recruited, and 25 patients completed the treatments and follow-up. The excellent and good results (improvement of 51–100%) were achieved on the right abdomen in 84% of the patients, while 48% on the left site (p < 0.05). Hyper-pigmentation was seen in 20% of the patients assessed on the left abdomen and only in 8% on the right abdomen. During the treatments, average score of the pain on the right abdomen was 5.41 ± 2.13, which was higher than that on the left (4.19 ± 2.12) (p < 0.001). No permanent hyper-pigmentation was found on the both sides. Considering the whole treatments, the patients favored the modality used on the right side (80 vs. 68%, p < 0.05).

Conclusion

Compared with CO2 fractional laser, 1,550 nm Er: glass fractional laser therapy provides the significantly better clinical outcomes and fewer side effects in the treatment of striae albae.

Limitations

The sample size and follow-up time were limited.
Improvement of Long COVID symptoms over one year
Authors: Oliveira Carlos R. , Jason Leonard A. , Unutmaz Derya , Bateman Lucinda , Vernon Suzanne D.
Published: January 2023

Importance

Early and accurate diagnosis and treatment of Long COVID, clinically known as post-acute sequelae of COVID-19 (PASC), may mitigate progression to chronic diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our objective was to determine the utility of the DePaul Symptom Questionnaire (DSQ) to assess the frequency and severity of common symptoms of ME/CFS, to diagnose and monitor symptoms in patients with PASC.

Methods

This prospective, observational cohort study enrolled 185 people that included 34 patients with PASC that had positive COVID-19 test and persistent symptoms of >3 months and 151 patients diagnosed with ME/CFS. PASC patients were followed over 1 year and responded to the DSQ at baseline and 12 months. ME/CFS patients responded to the DSQ at baseline and 1 year later. Changes in symptoms over time were analyzed using a fixed-effects model to compute difference-in-differences estimates between baseline and 1-year follow-up assessments.

Participants

Patients were defined as having PASC if they had a previous positive COVID-19 test, were experiencing symptoms of fatigue, post-exertional malaise, or other unwellness for at least 3 months, were not hospitalized for COVID-19, had no documented major medical or psychiatric diseases prior to COVID-19, and had no other active and untreated disease processes that could explain their symptoms. PASC patients were recruited in 2021. ME/CFS patients were recruited in 2017.

Results

At baseline, patients with PASC had similar symptom severity and frequency as patients with ME/CFS and satisfied ME/CFS diagnostic criteria. ME/CFS patients experienced significantly more severe unrefreshing sleep and flu-like symptoms. Five symptoms improved significantly over the course of 1 year for PASC patients including fatigue, post-exertional malaise, brain fog, irritable bowel symptoms and feeling unsteady. In contrast, there were no significant symptom improvements for ME/CFS patients.

Conclusion and relevance

There were considerable similarities between patients with PASC and ME/CFS at baseline. However, symptoms improved for PASC patients over the course of a year but not for ME/CFS patients. PASC patients with significant symptom improvement no longer met ME/CFS clinical diagnostic criteria. These findings indicate that the DSQ can be used to reliably assess and monitor PASC symptoms.
Luteolin-rich fraction from Perilla frutescens seed meal inhibits spike glycoprotein S1 of SARS-CoV-2-induced NLRP3 inflammasome lung cell inflammation via regulation of JAK1/STAT3 pathway: A potential anti-inflammatory compound against inflammation-induced long-COVID
Authors: Dissook Sivamoke , Umsumarng Sonthaya , Mapoung Sariya , Semmarath Warathit , Arjsri Punnida , Srisawad Kamonwan , Dejkriengkraikul Pornngarm
Published: January 2023

Objective

The multi-systemic inflammation as a result of COVID-19 can persevere long after the initial symptoms of the illness have subsided. These effects are referred to as Long-COVID. Our research focused on the contribution of the Spike protein S1 subunit of SARS-CoV-2 (Spike S1) on the lung inflammation mediated by NLRP3 inflammasome machinery and the cytokine releases, interleukin 6 (IL-6), IL-1beta, and IL-18, in lung epithelial cells. This study has attempted to identify the naturally- occurring agents that act against inflammation-related long-COVID. The seed meal of Perilla frutescens (P. frutescens), which contains two major dietary polyphenols (rosmarinic acid and luteolin), has been reported to exhibit anti-inflammation activities. Therefore, we have established the ethyl acetate fraction of P. frutescens seed meal (PFEA) and determined its anti-inflammatory effects on Spike S1 exposure in A549 lung cells.

Methods

PFEA was established using solvent-partitioned extraction. Rosmarinic acid (Ra) and luteolin (Lu) in PFEA were identified using the HPLC technique. The inhibitory effects of PFEA and its active compounds against Spike S1-induced inflammatory response in A549 cells were determined by RT-PCR and ELISA. The mechanistic study of anti-inflammatory properties of PFEA and Lu were determined using western blot technique.

Results

PFEA was found to contain Ra (388.70 ± 11.12 mg/g extract) and Lu (248.82 ± 12.34 mg/g extract) as its major polyphenols. Accordingly, A549 lung cells were pre-treated with PFEA (12.5-100 μg/mL) and its two major compounds (2.5-20 μg/mL) prior to the Spike S1 exposure at 100 ng/mL. PFEA dose-dependently exhibited anti-inflammatory properties upon Spike S1-exposed A549 cells through IL-6, IL-1β, IL-18, and NLRP3 gene suppressions, as well as IL-6, IL-1β, and IL-18 cytokine releases with statistical significance (p < 0.05). Importantly, Lu possesses superior anti-inflammatory properties when compared with Ra (p < 0.01). Mechanistically, PFEA and Lu effectively attenuated a Spike S1-induced inflammatory response through downregulation of the JAK1/STAT3-inflammasome-dependent inflammatory pathway as evidenced by the downregulation of NLRP3, ASC, and cleaved-caspase-1 of the NLRP3 inflammasome components and by modulating the phosphorylation of JAK1 and STAT3 proteins (p < 0.05).

Conclusion

The findings suggested that luteolin and PFEA can modulate the signaling cascades that regulate Spike S1-induced lung inflammation during the incidence of Long-COVID. Consequently, luteolin and P. frutescens may be introduced as potential candidates in the preventive therapeutic strategy for inflammation-related post-acute sequelae of COVID-19.
Rise of the planet of rare anemias: An update on emerging treatment strategies
Authors: Fattizzo Bruno , Motta Irene
Published: January 2023

Therapeutic options for rare congenital (hemoglobinopathies, membrane and enzyme defects, congenital dyserythropoietic anemia) and acquired anemias [warm autoimmune hemolytic anemia (wAIHA), cold agglutinin disease CAD, paroxysmal nocturnal hemoglobinuria (PNH), and aplastic anemia (AA)] are rapidly expanding. The use of luspatercept, mitapivat and etavopivat in beta-thalassemia and pyruvate kinase deficiency (PKD) improves transfusion dependence, alleviating iron overload and long-term complications. Voxelotor, mitapivat, and etavopivat reduce vaso-occlusive crises in sickle cell disease (SCD). Gene therapy represents a fascinating approach, although patient selection, the toxicity of the conditioning regimens, and the possible long-term safety are still open issues. For acquired forms, wAIHA and CAD will soon benefit from targeted therapies beyond rituximab, including B-cell/plasma cell targeting agents (parsaclisib, rilzabrutinib, and isatuximab for wAIHA), complement inhibitors (pegcetacoplan and sutimlimab for CAD, ANX005 for wAIHA with complement activation), and inhibitors of extravascular hemolysis in the reticuloendothelial system (fostamatinib and FcRn inhibitors in wAIHA). PNH treatment is moving from the intravenous anti-C5 eculizumab to its long-term analog ravulizumab, and to subcutaneous and oral proximal inhibitors (anti-C3 pegcetacoplan, factor D and factor B inhibitors danicopan and iptacopan). These drugs have the potential to improve patient convenience and ameliorate residual anemia, although patient compliance becomes pivotal, and long-term safety requires further investigation. Finally, the addition of eltrombopag significantly ameliorated AA outcomes, and data regarding the alternative agent romiplostim are emerging. The accelerated evolution of treatment strategies will need further effort to identify the best candidate for each treatment in the precision medicine era.
Effects of nitrogen input on soil bacterial community structure and soil nitrogen cycling in the rhizosphere soil of Lycium barbarum L.
Authors: Li Yuekun , Zou Nan , Liang Xiaojie , Zhou Xuan , Guo Shuhan , Wang Yajun , Qin Xiaoya , Tian Yehan , Lin Jin
Published: January 2023

Lycium barbarum L., goji berry, is a precious traditional Chinese medicine and it is homology of medicine and food. Its growth is heavily dependent on nitrogen. The use of chemical fertilizers has significantly promoted the yield of goji berry and the development of the L. barbarum L. industry. However, crop plants are inefficient in the acquisition and utilization of applied nitrogen, it often leads to excessive application of nitrogen fertilizers by producers, which cause negatively impact to the environment ultimately. The exploration of an interaction model which deals with crops, chemical fertilizers, and rhizosphere microbes to improve nitrogen use efficiency, is, therefore, an important research objective to achieve sustainable development of agriculture greatly. In our study, we explored the effects of nitrogen input on soil microbial community structure, soil nitrogen cycling, and the contents of nutrients in L. barbarum fruits. The structure and composition of the bacterial community in the rhizosphere soil of L. barbarum were significantly different under different nitrogen supply conditions, and high nitrogen addition inhibited the diversity and stability of bacterial communities. Low nitrogen input stimulated the relative abundance of ammonia-oxidizing bacteria (AOB), such as Nitrosospira, catalyzing the first step of the ammonia oxidation process. The results of the GLMM model showed that the level of nitrogen fertilizer (urea) input, the relative abundance of AOB, the relative abundance of Bradyrhizobium, and their combinations had significant effects on the soil nitrogen cycling and contents of nutrients in L. barbarum fruits. Therefore, we believe that moderately reducing the use of urea and other nitrogen fertilizers is more conducive to improving soil nitrogen use efficiency and Goji berry fruit quality by increasing the nitrogen cycling potential of soil microorganisms.
Lactobacillus helveticus EL2006H cell-free supernatant enhances growth variables in Zea mays (maize), Glycine max L. Merill (soybean) and Solanum tuberosum (potato) exposed to NaCl stress
Authors: Naamala Judith , Msimbira Levini A. , Subramanian Sowmyalakshmi , Smith Donald L.
Published: January 2023

Plant growth promoting microorganisms and their derived compounds, such as cell-free supernatant (CFS), enhance plant growth under stressed and non stressed conditions. Such technology is sustainable and environmentally friendly, which is desirable amidst the climate change threat. The current study evaluated the effect of CFS obtained from Lactobacillus helveticus EL2006H on its ability to enhance mean percentage germination and mean radicle length of corn and soybean, as well as growth parameters of potato, using treatment formulations that consisted of 0.2 and 1.0% [v/v] L. helveticus EL2006H CFS concentrations and 100 mM NaCl and 150 mM NaCl levels. Results show that treatment with 100 mM NaCl lowered percentage germination of corn by 52.63%, at 72 h, and soybean by 50%, at 48 h. Treatment with 100 NaCl +0.2% EL2006H enhanced percentage germination of soybean by 44.37%, at 48 h, in comparison to that of the 100 mM NaCl control. One hundred mM NaCl lowered radicle length of corn and soybean by 38.58 and 36.43%, respectively. Treatment with 100 Mm NaCl +1.0% EL2006H significantly increased radicle length of corn by 23.04%. Treatment with 100 mM NaCl +0.2% EL2006H significantly increased photosynthetic rate, leaf greenness and fresh weight of potato. Increasing NaCl concentration to 150 NaCl lowered the effectiveness of the 0.2% EL2006H CFS on the same growth variables of potato. In general, the lower CFS concentration of 0.2% was more efficient at enhancing germination in soybean while the higher concentration of 1.0% was more efficient at enhancing radicle length of corn. There was an observed variation in the effectiveness of L. helveticus EL2006H CFS across the different CFS concentrations, NaCl levels and crop species studied. In conclusion, based on findings of this study, CFS obtained from L. helveticus can be used as a bio stimulant to enhance growth of corn, soybean and potato. However, further studies need to be conducted, for validation, especially under field conditions, for commercial application.
Defining the altered glycoproteomic space of the early secretory pathway by class I mannosidase pharmacological inhibition
Authors: Munteanu Cristian V. A. , Chirițoiu Gabriela N. , Petrescu Andrei-Jose , Petrescu Ștefana M.
Published: January 2023

N-glycosylation is a key process for various biological functions like protein folding, maturation and sorting for the conventional secretory compartment, cell-cell communication and immune response. This is usually accomplished by a complex system of mannosidases in which those from class I have an outstanding role, commonly involved in the early protein sorting associated to the Endoplasmic Reticulum (ER) in the N-glycan dependent quality control (ERQC) and ER-associated degradation (ERAD). Although these are vital processes in maintaining cellular homeostasis, large-scale analysis studies for this pool of molecules, further denoted as proteins from the early secretory pathway (ESP), were limited addressed. Here, using a custom workflow employing a combination of glycomics and deglycoproteomics analyses, using lectin affinity and selective Endoglycosidase H (Endo H) digestion, we scrutinize the steady-state oligomannosidic glycoprotein load and delineate ESP fraction in melanoma cells. All of these were assessed by applying our workflow for glycosite relative quantification of both the peptide chain and carbohydrate structure in cells with inhibited activity of class I mannosidases after kifunensine treatment. We found that most of the ESP are transient clients involved in cell communication via extracellular matrix, particularly integrin-mediated communication which adopt Man9 N-glycans in kifunensine-treated cells. Moreover, our results reveal that core-fucosylation is decreased subsequent inhibition of class I mannosidases and this could be explained by a general lower protein level of FUT8, the enzyme responsible for fucosylation. By comparing our data with results obtained following downregulation of a key mannosidase in misfolded protein degradation, we mapped both novel and previously suggested endogenous substrate candidates like PCDH2, HLA-B, LAMB2 or members of the integrin family of proteins such as ITGA1 and ITGA4, thus validating the findings obtained using our workflow regarding accumulation and characterization of ESP transitory members following mannosidase class I inhibition. This workflow and the associated dataset not only allowed us to investigate the oligomannosidic glycoprotein fraction but also to delineate differences mediated at glycosite-level upon kifunensine treatment and outline the potential associated cellular responses.
Inflammatory status in pediatric sickle cell disease: Unravelling the role of immune cell subsets
Authors: Marchesani Silvio , Bertaina Valentina , Marini Olivia , Cossutta Matilde , Di Mauro Margherita , Rotulo Gioacchino Andrea , Palma Paolo , Sabatini Letizia , Petrone Maria Isabella , Frati Giacomo , Monteleone Giulia , Palumbo Giuseppe , Ceglie Giulia
Published: January 2023

Introduction: The mutation of the beta-globin gene that causes sickle cell disease (SCD) results in pleiotropic effects, such as hemolysis and vaso-occlusive crisis that can induce inflammatory mechanisms with deleterious consequences on the organism. Moreover, SCD patients display an increased susceptibility to infections. Few studies are currently available that evaluate a wide immunological profile in a pediatric population. This study proposes an evaluation of the immune profile in subjects with SCD in a pediatric population through a detailed analysis by flow cytometry.

Methods and Materials: Peripheral blood samples from 53 pediatric patients with SCD (mean age 9.8 years, interquartile range 9 years) were obtained and then analyzed by flow cytometry, in order to evaluate changes in the immune populations compared to 40 healthy donors (mean age 7.3 years, interquartile range 9.5 years).

Results: Our data showed an increase in neutrophils (with a reduction in the CD62L + subpopulation) and monocytes (with a decrease in HLA-DRlow monocytes) with normal values of lymphocytes in SCD patients. In the lymphocyte subpopulations analysis we observed lower values of CD4+ T cells (with higher number of memory and central memory T lymphocytes) with increased frequency of CD8+ T cells (with a predominant naive pattern). Moreover, we observed higher values of CD39+ Tregs and lower HLA-DR+ and CD39− T cells with an increased Th17, Th1-17 and Th2 response.

Conclusion: We observed immunological alterations typical of an inflammatory status (increase in activated neutrophils and monocytes) associated with a peculiar Treg pattern (probably linked to a body attempt to minimize inflammation intrinsic to SCD). Furthermore, we highlighted a T helper pathway associated with inflammation in line with other studies. Our data showed that immunological markers may have an important role in the understanding the pathophysiology of SCD and in optimizing targeted therapeutic strategies for each patient.
Relationship between lower limb muscle activity and cortical activation among elderly people during walking: Effects of fast speed and cognitive dual task
Authors: Kim Jinuk , Lee Jungsoo , Lee Gihyoun , Chang Won Hyuk , Ko Myoung-Hwan , Yoo Woo-Kyoung , Ryu Gyu-Ha , Kim Yun-Hee
Published: January 2023

Objective

Gait is a complex behavior that involves not only the musculoskeletal system, but also higher-order brain functions, including cognition. This study was performed to investigate the correlation between lower limb muscle activity and cortical activation during treadmill walking in two groups of elderly people: the young-old (aged 65–74 years) and the old-old (aged 75–84 years).

Methods

Thirty-one young-old and 31 old-old people participated in this study. All participants were sequentially subjected to three gait conditions on a treadmill: (1) comfortable walking, (2) fast walking, and (3) cognitive dual-task walking. During treadmill walking, the activity of the lower limb muscles was measured using a surface electromyography system, and cortical activation was measured using a functional near-infrared spectroscopy system. The correlation between muscle activity and cortical activation during treadmill walking was analyzed and compared between the two groups.

Results

During comfortable walking, lower extremity muscle activity had a strong correlation with cortical activation, especially in the swing phase; this was significantly stronger in the young-old than the old-old. During fast walking, the correlations between lower limb muscle activity and cortical activation were stronger than those during comfortable walking in both groups. In cognitive dual-task walking, cortical activation in the frontal region and motor area was increased, although the correlation between muscle activity and cortical activation was weaker than that during comfortable walking in both groups.

Conclusion

The corticomotor correlation differed significantly between the old-old and the young-old. These results suggest that gait function is compensated by regulating corticomotor correlation as well as brain activity during walking in the elderly. These results could serve as a basis for developing gait training and fall prevention programs for the elderly.
The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway
Authors: Ortiz-Leal Irene , Torres Mateo V. , Vargas-Barroso Víctor , Fidalgo Luis Eusebio , López-Beceiro Ana María , Larriva-Sahd Jorge A. , Sánchez-Quinteiro Pablo
Published: January 2023

Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents.

Methods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques.

Results: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity.

Discussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues.
A multi-scale robotic tool grasping method for robot state segmentation masks
Authors: Xue Tao , Zheng Deshuai , Yan Jin , Liu Yong
Published: January 2023

As robots begin to collaborate with humans in their daily work spaces, they need to have a deeper understanding of the tasks of using tools. In response to the problem of using tools in collaboration between humans and robots, we propose a modular system based on collaborative tasks. The first part of the system is designed to find task-related operating areas, and a multi-layer instance segmentation network is used to find the tools needed for the task, and classify the object itself based on the state of the robot in the collaborative task. Thus, we generate the state semantic region with the “leader-assistant” state. In the second part, in order to predict the optimal grasp and handover configuration, a multi-scale grasping network (MGR-Net) based on the mask of state semantic area is proposed, it can better adapt to the change of the receptive field caused by the state semantic region. Compared with the traditional method, our method has higher accuracy. The whole system also achieves good results on untrained real-world tool dataset we constructed. To further verify the effectiveness of our generated grasp representations, A robot platform based on Sawyer is used to prove the high performance of our system.
The role of the endolysosomal pathway in α-synuclein pathogenesis in Parkinson’s disease
Authors: Smith Jessica K. , Mellick George D. , Sykes Alex M.
Published: January 2023

Parkinson’s disease (PD) is a chronic neurodegenerative disease that is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain (SNpc). Extensive studies into genetic and cellular models of PD implicate protein trafficking as a prominent contributor to the death of these dopaminergic neurons. Considerable evidence also suggests the involvement of α-synuclein as a central component of the characteristic cell death in PD and it is a major structural constituent of proteinaceous inclusion bodies (Lewy bodies; LB). α-synuclein research has been a vital part of PD research in recent years, with newly discovered evidence suggesting that α-synuclein can propagate through the brain via prion-like mechanisms. Healthy cells can internalize toxic α-synuclein species and seed endogenous α-synuclein to form large, pathogenic aggregates and form LBs. A better understanding of how α-synuclein can propagate, enter and be cleared from the cell is vital for therapeutic strategies.
Rescue stenting after the failure of mechanical thrombectomy to treat acute intracranial atherosclerotic occlusion
Authors: Guo Shunyuan , Jin Tianyu , Xu Chao , Huang Wei , Shi Zongjie , Geng Yu
Published: January 2023

Background

Acute ischemic stroke (AIS) with intracranial large vessel occlusion (LVO) is refractory to reperfusion because of the underlying intracranial atherosclerosis (ICAS), and this condition often requires salvage methods such as balloon angioplasty and rescue stenting (RS). In this study, we investigated the short-term outcomes of RS after failed mechanical thrombectomy (MT) for the treatment of acute intracranial atherosclerotic occlusion.

Methods

We retrospectively evaluated the clinical data of 127 patients who underwent MT for acute intracranial atherosclerotic occlusion in our hospital between August 2018 and January 2022. The degree of recanalization was evaluated immediately after the treatment by Modified Thrombolysis in Cerebral Infarction (mTICI). The modified Rankin Scale (mRS) was used 90 days after treatment to evaluate the neurological functions. In addition, the incidence of symptomatic intracranial hemorrhage (sICH) and postoperative mortality within 90 days of treatment were calculated.

Results

Among the 127 patients, 86 patients (67.7%) had revascularization (mTICI 2b-3) immediately after MT (non-RS group), and RS was performed in 41 patients (32.3%) after MT failure (RS group). No difference in the sICH rate was observed between the two groups (17.1 vs. 16.3%, p = 0.91). There was a slightly higher mortality rate in the RS group (14.6 vs. 12.8%, p = 0.71); however, the difference was not significant. There was no difference in the proportion of patients in the RS and non-RS groups who had a 90-day mRS score of 0–2 (48.8 vs. 52.3%, p = 0.76).

Conclusions

Rescue stenting after MT failure might be a feasible rescue modality for treating acute intracranial atherosclerotic occlusion.
ADAMTS-13 activity in stroke of known and unknown cause: Relation to vascular risk factor burden
Authors: Grosse Gerrit M. , Leotescu Andrei , Sieweke Jan-Thorben , Schneppenheim Sonja , Budde Ulrich , Ziegler Nora L. , Biber Saskia , Gabriel Maria M. , Ernst Johanna , Schuppner Ramona , Lichtinghagen Ralf , Bavendiek Udo , Widder Julian , Weissenborn Karin
Published: January 2023

Background

The identification of the underlying mechanism in ischemic stroke has important implications for secondary prevention. A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS-13) has antithrombotic properties and was repeatedly implicated in the pathophysiology of stroke. In this study, we, therefore, aimed to investigate whether ADAMTS-13 is associated with stroke etiology and the burden of vascular risk factors.

Methods

We determined ADAMTS-13 activity in two prospectively recruited stroke cohorts in the long-term course after the event. Cohort 1 (n = 88) consisted of patients who suffered a stroke due to embolic stroke of undetermined source (ESUS), cardioembolic stroke due to atrial fibrillation (AF), large-artery atherosclerosis, or small vessel disease. In cohort 2, patients with cryptogenic stroke and patent foramen ovale (PFO) scheduled for PFO closure (n = 38) were enrolled. As measures of vascular risk factor burden, the CHA2DS2VASC score, the Essen Stroke Risk Score (ESRS), and the Risk of Paradoxical Embolism (RoPE) score were calculated, as appropriate.

Results

ADAMTS-13 activity was lower in patients with AF-related stroke compared to patients with ESUS (p = 0.0227), which was, however, due to confounding by vascular risk factors. ADAMTS-13 activity inversely correlated with the ESRS (r = −0.452, p < 0.001) and CHA2DS2VASC (r = −0.375, p < 0.001) in cohort 1. In accordance with these findings, we found a positive correlation between ADAMTS-13 activity and the RoPE score in cohort 2 (r = 0.413, p = 0.010).

Conclusion

ADAMTS-13 activity is inversely correlated with the number of vascular risk factors across different stroke etiologies. Further study is warranted to establish ADAMTS-13 as a mediator of cerebrovascular risk.
Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring
Authors: Bonaventura Eleonora , Alberti Luisella , Lucchi Simona , Cappelletti Laura , Fazzone Salvatore , Cattaneo Elisa , Bellini Matteo , Izzo Giana , Parazzini Cecilia , Bosetti Alessandra , Di Profio Elisabetta , Fiore Giulia , Ferrario Matilde , Mameli Chiara , Sangiorgio Arianna , Masnada Silvia , Zuccotti Gian Vincenzo , Veggiotti Pierangelo , Spaccini Luigina , Iascone Maria , Verduci Elvira , Cereda Cristina , Tonduti Davide ,   XALD-NBS Study Group
Published: January 2023

Introduction

X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the ABCD1 gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated. Hematopoietic stem cell transplantation is the standard treatment for cALD as it stabilizes WM degeneration when performed early in the disease. For this reason, early diagnosis is crucial, and several countries have already implemented their newborn screening programs (NBS) with the assessment of C26:0-lysophosphatidylcholine (C26:0-LPC) values as screening for X-ALD.

Methods

In June 2021, an Italian group in Lombardy launched a pilot study for the implementation of X-ALD in the Italian NBS program. A three-tiered approach was adopted, and it involved quantifying the values of C26:0-LPC and other metabolites in dried blood spots with FIA-MS/MS first, followed by the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique and, finally, the genetic confirmation via focused NGS.

Discussion

Genetically confirmed patients are set to undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if and when the first signs of brain damage appear, as suggested by international guidelines. A specific disease monitoring protocol has been created based on literature data and personal direct experience.

Conclusion

The primary aim of this study was to develop a model able to improve the early diagnosis and subsequent follow-up and timely treatment of X-ALD.

Ethics

The study was approved by the local ethics committee. The research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.
Novel heterozygous mutation in alpha-2-macroglobulin (A2M) suppressing the binding of amyloid-β (Aβ)
Authors: Qiu Guozhen , Cao Liming , Chen Yong-Jun
Published: January 2023

Introduction

Many studies have suggested that the alpha-2-macroglobulin (A2M) gene may be involved in the pathogenesis of Alzheimer's disease (AD). A2M encoded by the A2M gene can specifically bind to the β-amyloid peptide and prevent fiber formation.

Methods

The patient in this study had progressive memory loss at the age of 60 years and underwent a series of neuropsychological tests, cranial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) biomarker analysis, and whole-exome sequencing (WES) to evaluate possible mutations. We used in silico tools and three-dimensional (3D) protein structure prediction to analyze the pathogenicity of the mutation and used a co-immunoprecipitation experiment to study the effect of mutations on amyloid-β (Aβ) binding.

Results

Based on neuropsychological tests, cranial MRI, and CSF biomarker analysis, the patient was diagnosed with AD. WES showed that there was a missense mutation in A2M (c.1229A>C, p.N410T). Bioinformatics analysis showed that this mutation was pathogenic. Moreover, 3D protein structure analysis showed that the A2M Asn410 residue was an N-glycosylation site, which was necessary for A2M activation to bind to Aβ. Missense mutations led to the loss of glycosylation at this site, which suppressed the binding of Aβ. The functional experiment also confirmed the prediction: the interaction between A2M and Aβ from the patient's plasma was weakened.

Conclusions

Our results demonstrate that this novel A2M p.N410T mutation may have a pathogenic role in AD, by altering the binding interactions between A2M and Aβ.
Outcomes in acute ischemic stroke patients undergoing endovascular thrombectomy: Cervical internal carotid artery pseudo-occlusion vs. true occlusion
Authors: Ni Heng , Yang Tao , Jia Zhenyu , Shi Haibin , Liu Sheng , Zhao Linbo
Published: January 2023

Background and purpose

Pseudo-occlusion of the cervical internal carotid artery (cICA) refers to an absence of intraluminal contrast on computed tomography angiography (CTA), while the artery is patent on digital subtraction angiography during endovascular thrombectomy. We aimed to compare the outcomes between the cICA pseudo-occlusion and true occlusion after thrombectomy.

Methods

We retrospectively analyzed patients with apparent cICA occlusion on CTA who underwent thrombectomy between January 2016 and August 2021, and divided them into the pseudo-occlusion and true occlusion groups based on angiographic exploration. Recanalization failure was defined as a modified Thrombolysis in Cerebral Infarction score of 0–2a. Poor outcome was defined as a 90-day modified Rankin Scale score of 3–6. Propensity score matching was performed to compare the outcomes. Sensitivity analysis using multivariate-adjusted regression in the original cohort was conducted to test the robustness of the findings.

Results

Of the 146 patients included, 79 patients (54.1%) had cICA pseudo-occlusion and 67 patients (45.9%) had true occlusion. Following 1:1 propensity score-matched analysis, patients with pseudo-occlusion had an increased likelihood of recanalization failure (OR, 3.18; 95% CI, 1.06–9.59; P = 0.040) and poor outcome (OR, 2.80; 95% CI, 1.07–7.30; P = 0.035) compared with patients with true occlusion. Sensitivity analysis showed that cICA pseudo-occlusion remained independently associated with recanalization failure (OR, 2.55; 95% CI, 1.07–6.09; P = 0.036) and poor outcome (OR, 2.48; 95% CI, 1.08–5.67; P = 0.032).

Conclusions

Patients with cICA pseudo-occlusion on CTA treated with thrombectomy had an increased risk of reperfusion failure and poor outcome compared with true occlusion patients.
Daily blood pressure variability in relation to neurological functional outcomes after acute ischemic stroke
Authors: Zhu Yuan , Wu Minghua , Wang Huihui , Zheng Yawei , Zhang Siqi , Wang Xintong , Wang Shana , Fang Zhuyuan
Published: January 2023

Background

Prior research has shown inconclusive findings regarding the relationship between blood pressure variability (BPV) in acute ischemic stroke (AIS) and functional outcomes. Most research has examined the connection between short-term BPV during the early 24–72 h after the occurrence of ischemic stroke and functional prognosis. We sought to determine the relationship between daily BPV at 7 days of commencement and functional outcomes during the 3 months following AIS.

Methods

Altogether, 633 patients with AIS admitted within 72 h of commencement were enrolled. AIS was defined as the time from the onset of symptoms to 7 days. Throughout this period, blood pressure (BP) was recorded twice daily (casual BP cuffs). The daily BPV, with standard deviation (SD) and coefficient of variation (CV), was calculated and matched to the functional results. The adverse outcome was characterized as a modified Rankin scale (mRS)≥3, which comprised the recurrence of stroke, clinical intracranial bleeding, and death.

Results

In total, 633 participants were included, and the incidence of adverse outcomes was 14.06% (89/633). There was a significant positive correlation between daily BPV and adverse outcomes but not between mean BP and risk. Smooth curve fitting revealed a U-shaped connection between the mean BP and adverse clinical outcomes. Multivariable logistic regression analysis showed an independent correlation between daily BPV and an adverse outcome in the top vs. bottom quartile of systolic BPV (odds ratio [OR] = 2.4, 95% confidence interval [CI]: 1.17–4.96, P = 0.018 for SD; OR = 2.4, 95% CI: 1.17–4.93, P = 0.017 for CV) during a 3-month follow-up period. Identical results have been reported for diastolic BPV.

Conclusion

Irrespective of BP level, elevated daily systolic BPV and diastolic BPV in AIS were associated with an increased risk of adverse outcomes within 3 months. We also discovered a U-shaped association between the mean BP and adverse clinical outcomes. These findings suggested that BPV should be a risk factor for adverse outcomes after ischemic stroke, which provided new insight into BP management strategy.