bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical guidelines. Crohn’s disease (К50), adults
Authors: Shelygin Yury A. , Ivashkin Vladimir T. , Achkasov Sergey I. , Reshetov Igor V. , Maev Igor V. , Belousova Elena A. , Vardanyan Armen V. , Nanaeva Bella A. , Adamyan Leila V. , Drapkina Oksana M. , Namazova-Baranova Leila S. , Razumovsky Aleksandr Yu. , Revishvili Amiran Sh. , Khatkov Igor E. , Shabunin Aleksey V. , Livzan Maria A. , Sazhin Aleksandr V. , Timerbulatov Vil M. , Khlynova Olga V. , Abdulganieva Diana I. , Abdulkhakov Rustem A. , Aleksandrov Timofey L. , Alekseeva Olga P. , Alekseenko Sergey A. , Anosov Ivan S. , Bakulin Igor G. , Barysheva Olga Yu. , Bolikhov Kirill V. , Veselov Viktor V. , Golovenko Oleg V. , Gubonina Irina V. , Dolgushina Anastasia I. , Zhigalova Tatiana N. , Kagramanova Anna V. , Kashnikov Vladimir N. , Knyazev Oleg V. , Kostenko Nikolay V. , Likutov Aleksey A. , Lomakina Ekaterina Y. , Loranskaya Irina D. , Mingazov Airat F. , Moskalev Aleksey I. , Nazarov Ilya V. , Nikitina Natalia V. , Odintsova Alfia H. , Omelyanovsky Vitaly V. , Osipenko Marina F. , Оshchepkov Аndrey V. , Pavlenko Vladimir V. , Poluektova Elena A. , Rodoman Grigory V. , Segal Anastasia M. , Sitkin Stanislav I. , Skalinskaya Maria I. , Surkov Andrey N. , Sushkov Oleg I. , Tarasova Larisa V. , Uspenskaya Yulia B. , Frolov Sergey A. , Chashkova Elena Yu. , Shifrin Oleg S. , Shcherbakova Olga V. , Shchukina Oksana B. , Shkurko Tatiana V. , Makarchuk P. A.
Published: August 2023

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Vladislav E. Pak. 70 years
Authors: Editorial Article
Published: August 2023

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Changing Molecular Profiles of Human Cryptosporidiosis Cases in Scotland as a Result of the Coronavirus Disease, COVID-19 Pandemic
Authors: Bacchetti Ross , Connelly Lisa , Browning Lynda , Alexander Claire L.
Published: August 2023

Cryptosporidium, the most frequently reported parasite in Scotland, causes gastrointestinal illness resulting in diarrhoea, nausea and cramps. Two species are responsible for most cases: Cryptosporidium hominis (C. hominis) and Cryptosporidium parvum (C. parvum). Transmission occurs faecal-orally, through ingestion of contaminated food and water, or direct contact with faeces. In 2020, the COVID-19 pandemic led to global restrictions, including national lockdowns to limit viral transmission. Such interventions led to decreased social mixing, and reduced/no local and international travel, which are factors associated with transmission of multiple communicable diseases, including cryptosporidiosis. This report assessed the impact of the pandemic on Scottish cryptosporidiosis cases, and identified changes in circulating molecular variants of Cryptosporidium species. Molecular data generated using real time PCR and GP60 nested-PCR assays on laboratory-confirmed cryptosporidiosis cases reported during 2018–22 were analysed. The Scottish Microbiology Reference Laboratories (SMiRL), Glasgow, received 774 Cryptosporidium-positive faeces during 2018–22, of which 486 samples were successfully subtyped. During this time period, C. hominis (n = 155; 21%) and C. parvum (n = 572; 77%) were the most commonly detected species. The total number of cases during 2020, which was greatly affected by the pandemic, was markedly lower in comparison to case numbers in the 2 years before and after 2020. The most predominant C. hominis family detected prior to 2020 was the Ib family which shifted to the Ie family during 2022. The most common C. parvum variant during 2018–22 was the IIa family, however a rise in the IId family was observed (n = 6 in 2018 to n = 25 in 2022). The dominant C. hominis subtype IbA10G2, which accounted for 71% of C. hominis subtypes in 2018–19 was superseded by three rare subtypes: IeA11G3T3 (n = 15), IdA16 (n = 8) and IbA9G3 (n = 3) by 2022. Frequently reported C. parvum subtypes in 2018–19 were IIaA15G2R1 and IIaA17G1R1, accounting for 59% of total C. parvum subtypes. By 2022, IIaA15G2R1 remained the most common (n = 28), however three unusual subtypes in Scotland emerged: IIdA24G1 (n = 7), IIaA16G3R1 (n = 7) and IIaA15G1R2 (n = 7). Continuous monitoring of Cryptosporidium variants following the pandemic will be essential to explore further changes and emergence of strains with altered virulence.
Expression dynamics of metalloproteinases during mandibular bone formation: association with Myb transcription factor
Authors: Varadinkova S. , Oralova V. , Clarke M. , Frampton J. , Knopfova L. , Lesot H. , Bartos P. , Matalova E.
Published: August 2023

As the dentition forms and becomes functional, the alveolar bone is remodelled. Metalloproteinases are known to contribute to this process, but new regulators are emerging and their contextualization is challenging. This applies to Myb, a transcription factor recently reported to be involved in bone development and regeneration. The regulatory effect of Myb on Mmps expression has mostly been investigated in tumorigenesis, where Myb impacted the expression of Mmp1, Mmp2, Mmp7, and Mmp9. The aim of this investigation was to evaluate the regulatory influence of the Myb on Mmps gene expression, impacting osteogenesis and mandibular bone formation. For that purpose, knock-out mouse model was used. Gene expression of bone-related Mmps and the key osteoblastic transcription factors Runx2 and Sp7 was analysed in Myb knock-out mice mandibles at the survival limit. Out of the metalloproteinases under study, Mmp13 was significantly downregulated. The impact of Myb on the expression of Mmp13 was confirmed by the overexpression of Myb in calvarial-derived cells causing upregulation of Mmp13. Expression of Mmp13 in the context of other Mmps during mandibular/alveolar bone development was followed in vivo along with Myb, Sp7 and Runx2. The most significant changes were observed in the expression of Mmp9 and Mmp13. These MMPs and MYB were further localized in situ by immunohistochemistry and were identified in pre/osteoblastic cells as well as in pre/osteocytes. In conclusion, these results provide a comprehensive insight into the expression dynamics of bone related Mmps during mandibular/alveolar bone formation and point to Myb as another potential regulator of Mmp13.
Assessment of three triage systems by medical undergraduate students using simulated disaster patients: a comparative study
Authors: Zhang Jieqiong , Liu Kui , Chen Ruilin , Ren Jie , Wang Rui , Li Linyi , Jiang Jun , Hua Yan , Wan Yi
Published: August 2023

Background

Triage is an initial important step in emergency medical rescues for mass casualty incidents, and different triage systems are used in practice. However, quantitative analysis-based evidence comparing these triage systems in mass casualty incidents is limited.

Objective

To compare the performance of three triage systems, simple triage and rapid treatment (START), abbreviated scoring method for combat casualty (ASMcc), and sort assess lifesaving interventions treatment/transport (SALT) system, for simulated disaster patients, as assessed by medical undergraduate students.

Methods

Medical undergraduates were recruited and randomly divided into three groups to evaluate the performance of the three triage systems by using simulated disaster patient cards. The triage time, accuracy, and overtriage and undertriage rates were analyzed among groups. Furthermore, a questionnaire survey was used to investigate the responses of the participants regarding learning, practice, and satisfaction among the three triage systems.

Results

A total of 30 participants were included in the study. The participants were male medical undergraduate students with a mean age of 20.73 ± 0.45 years. ASMcc had the highest accuracy of 75% with the lowest over-triage rate of 20%, SALT had the lowest undertriage rate of 19%, and START had the shortest triage time of 12.68 ± 4.96 min (all P < 0.05). Furthermore, the results of the questionnaire survey showed that START was easy to learn and recall with high efficiency and, among the three systems, had the highest satisfaction ratings from the participants.

Conclusion

The results of the study showed that the three triage systems had their own characteristics and advantages, and they are all suitable for use in mass casualty incidents. Further studies involving more triage systems with data based on real conditions are recommended.
Identification and validation of key biomarkers based on RNA methylation genes in sepsis
Authors: Zhang Qianqian , Bao Xiaowei , Cui Mintian , Wang Chunxue , Ji Jinlu , Jing Jiongjie , Zhou Xiaohui , Chen Kun , Tang Lunxian
Published: August 2023

Background

RNA methylation is closely involved in immune regulation, but its role in sepsis remains unknown. Here, we aim to investigate the role of RNA methylation-associated genes (RMGs) in classifying and diagnosing of sepsis.

Methods

Five types of RMGs (m1A, m5C, m6Am, m7G and Ψ) were used to identify sepsis subgroups based on gene expression profile data obtained from the GEO database (GSE57065, GSE65682, and GSE95233). Unsupervised clustering analysis was used to identify distinct RNA modification subtypes. The CIBERSORT, WGCNA, GO and KEGG analysis were performed to explore immune infiltration pattern and biological function of each cluster. RF, SVM, XGB, and GLM algorithm were applied to identify the diagnostic RMGs in sepsis. Finally, the expression levels of the five key RMGs were verified by collecting PBMCs from septic patients using qRT-PCR, and their diagnostic efficacy for sepsis was verified in combination with clinical data using ROC analysis.

Results

Sepsis was divided into three subtypes (cluster 1 to 3). Cluster 1 highly expressed NSUN7 and TRMT6, with the characteristic of neutrophil activation and upregulation of MAPK signaling pathways. Cluster 2 highly expressed NSUN3, and was featured by the regulation of mRNA stability and amino acid metabolism. NSUN5 and NSUN6 were upregulated in cluster 3 which was involved in ribonucleoprotein complex biogenesis and carbohydrate metabolism pathways. In addition, we identified that five RMGs (NSUN7, NOP2, PUS1, PUS3 and FTO) could function as biomarkers for clinic diagnose of sepsis. For validation, we determined that the relative expressions of NSUN7, NOP2, PUS1 and PUS3 were upregulated, while FTO was downregulated in septic patients. The area under the ROC curve (AUC) of NSUN7, NOP2, PUS1, PUS3 and FTO was 0.828, 0.707, 0.846, 0.834 and 0.976, respectively.

Conclusions

Our study uncovered that dysregulation of RNA methylation genes (m1A, m5C, m6Am, m7G and Ψ) was closely involved in the pathogenesis of sepsis, providing new insights into the classification of sepsis endotypes. We also revealed that five hub RMGs could function as novel diagnostic biomarkers and potential targets for treatment.
Membrane-bound Interleukin-1α mediates leukocyte adhesion during atherogenesis
Authors: Maeder Christina , Speer Thimoteus , Wirth Angela , Boeckel Jes-Niels , Fatima Sameen , Shahzad Khurrum , Freichel Marc , Laufs Ulrich , Gaul Susanne
Published: August 2023

Introduction

The interleukin-1 (IL-1) family and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome contribute to atherogenesis but the underlying mechanisms are incompletely understood. Unlike IL-1β, IL-1α is not dependent on the NLRP3 inflammasome to exert its pro-inflammatory effects. Here, a non-genetic model was applied to characterize the role of IL-1α, IL-1β, and NLRP3 for the pathogenesis of atherosclerosis.

Methods

Atherogenesis was induced by gain-of-function PCSK9-AAV8 mutant viruses and feeding of a high-fat western diet (WTD) for 12 weeks in C57Bl6/J wildtype mice (WT) and in Il1a-/-, Nlrp3-/-, and Il1b-/- mice.

Results

PCSK9-Il1a-/- mice showed reduced atherosclerotic plaque area in the aortic root with lower lipid accumulation, while no difference was observed between PCSK9-WT, PCSK9-Nlrp3-/- and PCSK9-Il1b-/- mice. Serum proteomic analysis showed a reduction of pro-inflammatory cytokines (e.g., IL-1β, IL-6) in PCSK9-Il1a-/- as well as in PCSK9-Nlrp3-/- and PCSK9-Il1b-/- mice. Bone marrow dendritic cells (BMDC) of PCSK9-WT, PCSK9-Nlrp3-/-, and PCSK9-Il1b-/- mice and primary human monocytes showed translocation of IL-1α to the plasma membrane (csIL-1α) upon stimulation with LPS. The translocation of IL-1α to the cell surface was regulated by myristoylation and increased in mice with hypercholesterolemia. CsIL-1α and IL1R1 protein-protein interaction on endothelial cells induced VCAM1 expression and monocyte adhesion, which was abrogated by the administration of neutralizing antibodies against IL-1α and IL1R1.

Conclusion

The results highlight the importance of IL-1α on the cell surface of circulating leucocytes for the development of atherosclerosis. PCSK9-Il1a-/- mice, but not PCSK9-Nlrp3-/- or PCSK9-Il1b-/- mice, are protected from atherosclerosis after induction of hypercholesterolemia independent of circulating cytokines. Myristoylation and translocation of IL-1α to the cell surface in myeloid cells facilitates leukocyte adhesion and contributes to the development of atherosclerosis.
Rule-based semi-automated tools for mapping seabed morphology from bathymetry data
Authors: Huang Zhi , Nanson Rachel , McNeil Mardi , Wenderlich Michal , Gafeira Joana , Post Alexandra , Nichol Scott
Published: August 2023

Seabed morphology maps and data are critical for knowledge-building and best practice management of marine environments. To facilitate objective and repeatable production of these maps, we have developed a number of semi-automated, rule-based GIS tools (Geoscience Australia’s Semi-automated Morphological Mapping Tools - GA-SaMMT) to operationalise the mapping of a common set of bathymetric high and bathymetric low seabed Morphological Features. The tools have a graphical user interface and were developed using Python scripts under the widely-adopted proprietary ArcGIS Pro platform. The utility of these tools was tested across nine case study areas that represent a diverse range of complex bathymetric and physiographic settings. Overall, the mapping results are found to be more consistent than manual mapping and allow for capture of greater detail across a range of spatial scales. The mapping results demonstrate a number of advantages of GA-SaMMT, including: 1) requirement of only a bathymetry grid as sole data input; 2) flexibility to apply domain knowledge to user-defined tool parameters, or to instead use the default parameter settings; 3) repeatability and consistency in the mapping outputs when using a consistent set of tool parameters (user defined or default); 4) high-degree of objectivity; and 5) efficiency in mapping a large number (thousands) of seabed morphology features in a single dataset. In addition, GA-SaMMT can comprehensively quantify the characteristics of individual seabed bathymetric high and low features, respectively generating 34 and 46 metrics for each type of feature. Our results indicate that attribute metrics are invaluable in the interpretation and modelling of mapped Morphology Features and provide insights into their formative processes and habitat potential for marine communities.
Effects of the harmful alga Margalefidinium (aka Cochlodinium) polykrikoides on clearance rates of the hard clam, Mercenaria mercenaria
Authors: de Silva Darren , Gobler Christopher J.
Published: August 2023

Harmful algal blooms (HABs) such as those formed by the ichthyotoxic dinoflagellate, Margalefidinium (aka Cochlodinium) polykrikoides can have adverse effects on bivalves. While M. polykrikoides has caused significant die offs of bivalves and other marine organisms, the Northern quahog or hard clam, Mercenaria mercenaria, is comparatively more resistant to this HAB. This study quantified clearance rates of juvenile hard clams (10-20 mm) exposed to three different North American populations of M. polykrikoides (bloom, strain CP1, strain CPSB-1G) as well as the nonharmful cryptophyte, Rhodomonas salina and the nonharmful dinoflagellate, Gymnodinium aureolum, in single and mixed algal exposures. Multiple biovolume exposures with M. polykrikoides bloom water and R. salina (1,000, 1,500, 3,000 cells mL-1M. polykrikoides biovolume equivalent) were completed to assess the effects of increasing biomass on hard clam clearance rates and selection. Hard clams opened and actively cleared algal mixtures at and below 1,000 M. polykrikoides cells mL-1. During single species exposures, strain CPSB-1G and R. salina were cleared significantly faster than wild M. polykrikoides populations and strain CP1. During mixed exposures, R. salina was cleared significantly faster than CPSB-1G but not other M. polykrikoides populations and there was no difference between hard clam clearance rates of G. aureolum and R. salina. Clearance rates of M. polykrikoides at ≥1,500 cells mL-1M. polykrikoides/R. salina mixtures were not significantly different than zero unlike clearance of those at <1,000 cells mL-1 indicating a density dependent effect of blooms. Collectively, the results demonstrate that hard clams can actively clear M. polykrikoides cells at moderate (≤1,000 cells mL-1) but not elevated (> 1,000 cells mL-1) bloom densities. Given this, and the documented survival of hard clams during blooms, M. mercenaria may be candidate for aquaculture and restoration in regions prone to HABs caused by M. polykrikoides.
Dynamic analysis and validation of a multi-body floating wind turbine using the moving frame method
Authors: Grindheim Ole-Martin , Xing Yihan , Impelluso Thomas
Published: August 2023

This research applies the moving frame method (MFM) to the multi-body dynamic analysis of an OC3 phase IV spar buoy with the NREL 5MW turbine. Further, it verifies previous results obtained through numerical comparisons with commercial software. The long-term goal is to lay the foundation for leveraging the MFM to create a self-contained software system for future analyses that can incorporate effects that are more sophisticated, when commercial codes fall short. In this first evidentiary phase, this project treats the floating turbine as a three-bodied system consisting of the platform (platform + tower), nacelle and rotor (hub + blades). Then the paper presents the MFM in a tutorial style—in the context of this problem’s resolution. The paper supplements the multi-body dynamic equations of motion obtained through the MFM with simplified and reduced hydrodynamic, aerodynamic and mooring loads to simulate the translational and rotational response of the floating turbine under various load conditions. The results closely approximate those found in previous work and, in the process, demonstrates MFM’s analytical advantage. Current results capture the coupled responses in all degrees of freedom and gyroscopic effects occurring when the platform pitches with the spinning rotor. The project thus provides an accurate model for the dynamics of the turbine and opens the door to inserting correct advanced hydrodynamics to validate the model further. The work presents simulations for the different load cases through a 3D web page using WebGL and the ThreeJS library. Users may download all software to verify the results. An undergraduate student conducted the work alone, demonstrating the ease of implementation of the MFM.
Relationship between paramacular thinning, cerebral vasculopathy, and hematological risk factors in sickle cell disease
Authors: Orssaud Christophe , Flamarion Edouard , Michon Adrien , Ranque Brigitte , Arlet Jean Benoit
Published: August 2023

Purpose

To identify risk factors for sickle cell maculopathy due to hematological parameters (especially anemia and hemolysis) or cerebral vasculopathy.

Methods

This retrospective study was conducted at a Referral Center. The follow-up included optical coherent tomography/optical coherent tomography angiography, neuro-radiological imaging, and a hematological assessment (hemoglobin, hemoglobin S level, reticulocytes, mean corpuscular volume, bilirubin, and lactate dehydrogenase).

Results

Hundred and thirty-two sickle cell patients were included. Maculopathy was observed in 127 eyes of SS patients and 10 eyes of SC patients (p < 0.001), unrelated to peripheral retinopathy. Cerebral vasculopathy was more frequent in SS patients (p < 0.001) and was also associated with the presence of maculopathy (p = 0.049), and it was related to peripheral retinopathy (p < 0.001). All biological parameters significantly differed according to the genotype (p < 0.001) but not according to the presence of cerebral vasculopathy or maculopathy. In the multivariate analysis, reticulocytes and bilirubin were associated with the presence of cerebral vasculopathy and maculopathy.

Conclusion

The data obtained were consistent with the role of anemia or hemolysis markers in cerebral vasculopathy and macular involvement. As a trend of hemolysis appears to be a risk factor for these complications, this validates the use of preventive plasmapheresis in these patients.
Effect of NaCl stress on exoproteome profiles of Bacillus amyloliquefaciens EB2003A and Lactobacillus helveticus EL2006H
Authors: Naamala Judith , Subramanian Sowmyalakshmi , Msimbira Levini A. , Smith Donald L.
Published: August 2023

Salt stress can affect survival, multiplication and ability of plant growth promoting microorganisms to enhance plant growth. Changes in a microbe’s proteome profile is one of the mechanisms employed by PGPM to enhance tolerance of salt stress. This study was focused on understanding changes in the exoproteome profile of Bacillus amyloliquefaciens EB2003A and Lactobacillus helveticus EL2006H when exposed to salt stress. The strains were cultured in 100 mL M13 (B. amyloliquefaciens) and 100 mL De man, Rogosa and Sharpe (MRS) (L. helveticus) media, supplemented with 200 and 0 mM NaCl (control), at pH 7.0. The strains were then incubated for 48 h (late exponential growth phase), at 120 rpm and 30 (B. amyloliquefaciens) and 37 (L. helveticus) °C. The microbial cultures were then centrifuged and filtered sterilized, to obtain cell free supernatants whose proteome profiles were studied using LC–MS/MS analysis and quantified using scaffold. Results of the study revealed that treatment with 200 mM NaCl negatively affected the quantity of identified proteins in comparison to the control, for both strains. There was upregulation and downregulation of some proteins, even up to 100%, which resulted in identification of proteins significantly unique between the control or 200 mM NaCl (p ≤ 0.05), for both microbial species. Proteins unique to 200 mM NaCl were mostly those involved in cell wall metabolism, substrate transport, oxidative stress tolerance, gene expression and DNA replication and repair. Some of the identified unique proteins have also been reported to enhance plant growth. In conclusion, based on the results of the work described here, PGPM alter their exoproteome profile when exposed to salt stress, potentially upregulating proteins that enhance their tolerance to this stress.
An extracellular polysaccharide is involved in the aluminum tolerance of Pullulanibacillus sp. CA42, a newly isolated strain from the Chinese water chestnut growing in an actual acid sulfate soil area in Vietnam
Authors: Aizawa Tomoko , Sato Junki , Saito Shimon , Yasuda Takanari , Maruyama Yutaro , Urai Makoto
Published: August 2023

A novel aluminum-tolerant bacterial strain CA42 was isolated from the aquatic plant Eleocharis dulcis, which grows in a highly acidic swamp in Vietnam. Inoculation with CA42 allowed Oryza sativa to grow in the presence of 300 μM AlCl3 at pH 3.5, and biofilms were observed around the roots. Using 16S rRNA gene sequencing analysis, the strain was identified as Pullulanibacillus sp. CA42. This strain secreted large amounts of an extracellular polysaccharide (CA42 EPS). Results from structural analyses on CA42 EPS, namely methylation analysis and nuclear magnetic resonance (NMR), indicated that the chemical structure of CA42 EPS was a glycogen-like α-glucan. Purified CA42 EPS and the commercially available oyster glycogen adsorbed aluminum ions up to 15–30 μmol/g dry weight. Digestion treatments with α-amylase and pullulanase completely attenuated the aluminum ion-adsorbing activity of purified CA42 EPS and oyster glycogen, suggesting that the glycogen-like structure adsorbed aluminum ions and that its branching structure played an important role in its aluminum adsorbing activity. Furthermore, the aluminum tolerance of CA42 cells was attenuated by pullulanase treatment directly on the live CA42 cells. These results suggest that CA42 EPS adsorbs aluminum ions and is involved in the aluminum tolerance mechanism of Pullulanibacillus sp. CA42. Thus, this strain may be a potential plant growth-promoting bacterium in acidic soils. In addition, this study is the first to report a glycogen-like polysaccharide that adsorbs aluminum ions.
Uric acid regulates α-synuclein transmission in Parkinsonian models
Authors: Shin Yu Jin , Kim Yeon Ju , Lee Ji Eun , Kim Yi Seul , Lee Jung Wook , Kim HyeonJeong , Shin Jin Young , Lee Phil Hyu
Published: August 2023

Ample evidence demonstrates that α-synuclein (α-syn) has a critical role in the pathogenesis of Parkinson’s disease (PD) with evidence indicating that its propagation from one area of the brain to others may be the primary mechanism for disease progression. Uric acid (UA), a natural antioxidant, has been proposed as a potential disease modifying candidate in PD. In the present study, we investigated whether UA treatment modulates cell-to-cell transmission of extracellular α-syn and protects dopaminergic neurons in the α-syn-enriched model. In a cellular model, UA treatment decreased internalized cytosolic α-syn levels and neuron-to-neuron transmission of α-syn in donor-acceptor cell models by modulating dynamin-mediated and clathrin-mediated endocytosis. Moreover, UA elevation in α-syn-inoculated mice inhibited propagation of extracellular α-syn which decreased expression of phosphorylated α-syn in the dopaminergic neurons of the substantia nigra leading to their increased survival. UA treatment did not lead to change in markers related with autophagolysosomal and microglial activity under the same experimental conditions. These findings suggest UA may control the pathological conditions of PD via additive mechanisms which modulate the propagation of α-syn.
Association between choline supplementation and Alzheimer’s disease risk: a systematic review protocol
Authors: Aguree Sixtus , Zolnoori Maryam , Atwood Thea Patricia , Owora Arthur
Published: August 2023

Background and aims

There is growing evidence suggesting choline intake might have beneficial effects on cognitive function in the elderly. However, some studies report no relationship between choline intake and cognitive function or improvement in Alzheimer’s disease patients. This protocol is for a systematic review of choline intake and Alzheimer’s disease that aims to assess the comparative clinical effectiveness of choline supplementation on Alzheimer’s disease risk.

Methods and analysis

literature search will be performed in PubMed, MEDLINE, EMBASE, CINAHL, Scopus, Cochrane, and the Web of Science electronic databases from inception until October 2023. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies will be included if they compared two different time points of choline biomarkers measures in men or women (65+) with Alzheimer’s Disease. The risk of bias in the included studies will be assessed within the Covidence data-management software.

Results

This review will summarize the clinical trial and quasi-experimental evidence of choline intake on Alzheimer’s disease risk for adults aged 65+. The results from all eligible studies included in the analysis will be presented in tables, text, and figures. A descriptive synthesis will present the characteristics of included studies (e.g., age, sex of participants, type, length of intervention and comparator, and outcome measures), critical appraisal results, and descriptions of the main findings.

Discussion

This systematic review will summarize the existing evidence on the association between Choline intake and AD and to make recommendations if appropriate. The results of this review will be considered with respect to whether there is enough evidence of benefit to merit a more definitive randomized controlled trial. The results will be disseminated through peer-reviewed journals population.

Conclusion

This protocol outlines the methodology for a systematic review of choline intake and AD. The resulting systematic review from this protocol will form an evidence-based foundation to advance nutrition care for individuals with AD or poor cognitive function.

Systematic review registration

http://www.crd.york.ac.uk/PROSPERO, identifier CRD42023395004.
Lumbar V3 interneurons provide direct excitatory synaptic input onto thoracic sympathetic preganglionic neurons, linking locomotor, and autonomic spinal systems
Authors: Chacon Camila , Nwachukwu Chioma V. , Shahsavani Narjes , Cowley Kristine C. , Chopek Jeremy W.
Published: August 2023

Although sympathetic autonomic systems are activated in parallel with locomotion, the neural mechanisms mediating this coordination are incompletely understood. Sympathetic preganglionic neurons (SPNs), primarily located in the intermediate laminae of thoracic and upper lumbar segments (T1-L2), increase activation of tissues and organs that provide homeostatic and metabolic support during movement and exercise. Recent evidence suggests integration between locomotor and autonomic nuclei occurs within the brainstem, initiating both descending locomotor and sympathetic activation commands. However, both locomotor and sympathetic autonomic spinal systems can be activated independent of supraspinal input, in part due to a distributed network involving propriospinal neurons. Whether an intraspinal mechanism exists to coordinate activation of these systems is unknown. We hypothesized that ascending spinal neurons located in the lumbar region provide synaptic input to thoracic SPNs. Here, we demonstrate that synaptic contacts from locomotor-related V3 interneurons (INs) are present in all thoracic laminae. Injection of an anterograde tracer into lumbar segments demonstrated that 8–20% of glutamatergic input onto SPNs originated from lumbar V3 INs and displayed a somatotopographical organization of synaptic input. Whole cell patch clamp recording in SPNs demonstrated prolonged depolarizations or action potentials in response to optical activation of either lumbar V3 INs in spinal cord preparations or in response to optical activation of V3 terminals in thoracic slice preparations. This work demonstrates a direct intraspinal connection between lumbar locomotor and thoracic sympathetic networks and suggests communication between motor and autonomic systems may be a general function of the spinal cord.
Perceived antidepressant efficacy associated with reduced negative and enhanced neutral mnemonic discrimination
Authors: Phillips Taylor O. , Castro Madelyn , Vas Rishi K. , Ferguson Lorena A. , Harikumar Amritha , Leal Stephanie L.
Published: August 2023

Introduction

While antidepressants are one of the first-line treatments for depression, the mechanisms underlying antidepressant action are unclear. Furthermore, the extent to which antidepressants impact emotional and cognitive dysfunction in depression requires more fine-grained approaches toward measuring these impacts in humans. Depression is associated with emotion and mood dysregulation in addition to cognitive deficits. Depressed individuals experience general memory impairment as well as a negativity bias in episodic memory, where negative events are better remembered than positive or neutral events. One potential mechanism hypothesized to underlie the negativity bias in memory is dysfunctional hippocampal pattern separation, in which depressed individuals tend to show impaired general pattern separation but enhanced negative pattern separation. Mnemonic discrimination tasks have been designed to tax hippocampal pattern separation in humans and provide a powerful approach to develop a mechanistic account for cognitive dysfunction in depression. While antidepressants have been examined primarily in rodent models in the context of hippocampal pattern separation, this has yet to be examined in humans.

Methods

Here, we investigated how antidepressant usage and their perceived efficacy was associated with emotional mnemonic discrimination, given our prior work indicating a negativity bias for mnemonic discrimination in individuals with greater depressive symptoms.

Results

We found that individuals who reported a greater improvement in their depressive symptoms after taking antidepressants (responders) showed reduced negative and enhanced neutral mnemonic discrimination compared to those with little to no improvement (non-responders). Perceived antidepressant efficacy was the strongest predictor of a reduction in the negativity bias for mnemonic discrimination, even when controlling for current depressive symptoms, antidepressant type, and other relevant factors.

Discussion

These results suggest that antidepressants, when effective, can shift memory dynamics toward healthy function.
Generation of a whole-brain hemodynamic response function and sex-specific differences in cerebral processing of mechano-sensation in mice detected by BOLD fMRI
Authors: Chen Hui-Fen , Lambers Henriette , Nagelmann Nina , Sandbrink Martin , Segelcke Daniel , Pogatzki-Zahn Esther , Faber Cornelius , Pradier Bruno
Published: August 2023

BOLD fMRI has become a prevalent method to study cerebral sensory processing in rodent disease models, including pain and mechanical hypersensitivity. fMRI data analysis is frequently combined with a general-linear-model (GLM) -based analysis, which uses the convolution of a hemodynamic response function (HRF) with the stimulus paradigm. However, several studies indicated that the HRF differs across species, sexes, brain structures, and experimental factors, including stimulation modalities or anesthesia, and hence might strongly affect the outcome of BOLD analyzes. While considerable work has been done in humans and rats to understand the HRF, much less is known in mice. As a prerequisite to investigate mechano-sensory processing and BOLD fMRI data in male and female mice, we (1) designed a rotating stimulator that allows application of two different mechanical modalities, including innocuous von Frey and noxious pinprick stimuli and (2) determined and statistically compared HRFs across 30 brain structures and experimental conditions, including sex and, stimulus modalities. We found that mechanical stimulation lead to brain-wide BOLD signal changes thereby allowing extraction of HRFs from multiple brain structures. However, we did not find differences in HRFs across all brain structures and experimental conditions. Hence, we computed a whole-brain mouse HRF, which is based on 88 functional scans from 30 mice. A comparison of this mouse-specific HRF with our previously reported rat-derived HRF showed significantly slower kinetics in mice. Finally, we detected pronounced differences in cerebral BOLD activation between male and female mice with mechanical stimulation, thereby exposing divergent processing of noxious and innocuous stimuli in both sexes.
Potential targets of natural medicines: preventing lung cancer pre-metastatic niche formation by regulating exosomes
Authors: Zhu Xiao-yu , Li Jie
Published: August 2023

Lung cancer is one of the most devastating diseases worldwide with high incidence and mortality, and the incidence continues to rise. Metastasis is the leading cause of death in lung cancer patients, yet the molecular effectors underlying tumor dissemination remain poorly defined. Research findings in recent years confirmed primed microenvironment of future metastatic sites, called the pre‐metastatic niche, is a prerequisite for overt metastasis. Exosomes have recently emerged as important players in pre‐metastatic niche formation. Natural medicines have traditionally been rich sources of drug discovery. Some of them exhibit favorable anti-lung cancer activity. The review focused on the latest advances in the regulation of the pre‐metastatic niche formation in lung cancer by the contents of exosomes of representative natural medicines. Additionally, the mechanism of natural medicines was summarized in detail, which would provide new insights for anti-cancer new drug development.
Development and validation of a nomogram to predict the recurrence of hepatocellular carcinoma patients with dynamic changes in AFP undergoing locoregional treatments
Authors: Sun Yu , Xiong Yiqi , Wang Qi , Qiao Wenying , Zhang Honghai , Zhang Yonghong
Published: August 2023

Background

Serum alpha-fetoprotein (AFP) is an important clinical indicator for screening, diagnosis, and prognosis of primary hepatocellular carcinoma (HCC). Our team’s previous study showed that patients with negative AFP at baseline and positive AFP at relapse had a worse prognosis (N-P). Therefore, the aim of our study was to develop and validate a nomogram for this group of patients.

Methods

A total of 513 patients with HCC who received locoregional treatments at Beijing You’an Hospital, Capital Medical University, from January 2012 to December 2019 were prospectively enrolled. Patients admitted from 2012 to 2015 were assigned to the training cohort (n = 335), while 2016 to 2019 were in the validation cohort (n =183). The clinical and pathological features of patients were collected, and independent risk factors were identified using univariate and multivariate Cox regression analysis as a basis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts.

Results

The content of the nomogram includes gender, tumor number, tumor size, lymphocyte, direct bilirubin (DBIL), gamma-glutamyl transferase (GGT), and prealbumin. The C-index (0.717 and 0.752) and 1-, 3-, and 5-year AUCs (0.721, 0.825, 0.845, and 0.740, 0.868, 0.837) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classify of patients with dynamic changes in AFP into three groups according to the risk of recurrence: low risk, intermediate risk, and high risk. There was a statistically significant difference in RFS between the three groups in the training and validation cohorts (P<0.001).

Conclusion

The nomogram developed and validated in this study had good predictive power for patients with dynamic changes in AFP.
Micro-simulation insights into the functional and mechanistic understanding of glycyrrhizin against asthma
Authors: Qi Jian-Hong , Xu Dong-Chuan , Wang Xiao-Long , Cai Ding-Yuan , Wang Yi , Zhou Wei
Published: August 2023

Asthma is a common chronic respiratory disease, which causes inflammation and airway stenosis, leading to dyspnea, wheezing and chest tightness. Using transgelin-2 as a target, we virtually screened the lead compound glycyrrhizin from the self-built database of anti-asthma compounds by molecular docking technology, and found that it had anti-inflammatory, anti-oxidative and anti-asthma pharmacological effects. Then, molecular dynamics simulations were used to confirm the stability of the glycyrrhizin-transgelin-2 complex from a dynamic perspective, and the hydrophilic domains of glycyrrhizin was found to have the effect of targeting transgelin-2. Due to the self-assembly properties of glycyrrhizin, we explored the formation process and mechanism of the self-assembly system using self-assembly simulations, and found that hydrogen bonding and hydrophobic interactions were the main driving forces. Because of the synergistic effect of glycyrrhizin and salbutamol in improving asthma, we revealed the mechanism through simulation, and believed that salbutamol adhered to the surface of the glycyrrhizin nano-drug delivery system through hydrogen bonding and hydrophobic interactions, using the targeting effect of the hydrophilic domains of glycyrrhizin to reach the pathological parts and play a synergistic anti-asthmatic role. Finally, we used network pharmacology to predict the molecular mechanisms of glycyrrhizin against asthma, which indicated the direction for its clinical transformation.
Effects of a multi-professional intervention on body composition, physical fitness and biochemical markers in overweight COVID-19 survivors: a clinical trial
Authors: Sordi Ana Flávia , Lemos Maurício Medeiros , de Souza Marques Déborah Cristina , Ryal Joed Jacinto , Priscila de Paula Silva Lalucci Marielle , Marques Marilene Guiraldi , Amaro Camilo Maria Luiza , De Paula Ramos Solange , Franzói De Moraes Solange Marta , Valdés-Badilla Pablo , Mota Jorge , Magnani Branco Braulio Henrique
Published: August 2023

Introduction: The sequelae post-COVID can affect different systems. In this sense, considering the multi-factorial etiology of COVID-19, multi-professional interventions could be a relevant strategy for recovery health indicators.

Objective: This study aimed to investigate the effects of multi-professional intervention on body composition, physical fitness, and biomarkers in overweight COVID-19 survivors with different symptomatology.

Methodology: A non-randomized parallel group intervention included 69 volunteers (BMI ≥25 kg/m2), divided into three groups according to SARS CoV-2 symptomatology, but only 35 finished the longitudinal protocol [control group (n = 11); moderate group (n = 17) and severe group (n = 7)]. The groups were submitted to a multi-professional program (nutritional intervention, psychoeducation, and physical exercise intervention) for 8 weeks, and the volunteers underwent body composition assessments (primary outcome) and physical and biochemical tests (secondary outcome) in pre- and post-intervention. This study was registered on the Clinical Trials Registration Platform number: RBR-4mxg57b and with the local research ethics committee protocol under number: 4,546,726/2021.

Results: After the 8-week multi-professional intervention, the following results were observed for the moderate COVID-19 group: improved dynamic strength of lower- and (p = 0.003), upper-limbs (p = 0.008), maximal isometric lumbar-traction strength (p = 0.04), flexibility (p = 0.0006), and albumin (p = 0.0005), as well as a reduction in the C reactive protein (CRP) (p = 0.003) and fasting glucose (p = 0.001); for the severe COVID-19 group: an improvement in dynamic lower-body strength (p = 0.001), higher values of albumin (p = 0.005) and HDL-c (p = 0.002), and lower values of CRP (p = 0.05), and for the control group: an improvement in sit-up repetitions (p = 0.008), and a reduction of CRP (p = 0.01), fasting glucose (p = 0.001) and total cholesterol (p = 0.04) were identified. All experimental groups reduced triglycerides after intervention (p < 0.05).

Conclusion: Finally, 8 weeks of multiprofessional intervention can be an efficient tool for reversing the inflammatory process and promoting improvements in daily activities and quality of life, although it is believed that the severe COVID-19 group needs longer interventions to improve different health indicators.

Clinical Trial Registration:https://ensaiosclinicos.gov.br/, identifier: RBR-4mxg57b.
Uncovering the mechanisms of salicylic acid-mediated abiotic stress tolerance in horticultural crops
Authors: Yang Hua , Fang Rui , Luo Ling , Yang Wei , Huang Qiong , Yang Chunlin , Hui Wenkai , Gong Wei , Wang Jingyan
Published: August 2023

Salicylic acid (SA) has been recognized as a promising molecule for improving abiotic stress tolerance in plants due to its ability to enhance antioxidant defense system, and promote root architecture system. Recent research has focused on uncovering the mechanisms by which SA confers abiotic stress tolerance in horticultural crops. SA has been shown to act as a signaling molecule that triggers various physiological and morphological responses in plants. SA regulates the production of reactive oxygen species (ROS). Moreover, it can also act as signaling molecule that regulate the expression of stress-responsive genes. SA can directly interact with various hormones, proteins and enzymes involved in abiotic stress tolerance. SA regulates the antioxidant enzymes activities that scavenge toxic ROS, thereby reducing oxidative damage in plants. SA can also activate protein kinases that phosphorylate and activate transcription factors involved in stress responses. Understanding these mechanisms is essential for developing effective strategies to improve crop resilience in the face of changing environmental conditions. Current information provides valuable insights for farmers and plant researchers, offering new strategies to enhance crop resilience and productivity in the face of environmental challenges. By harnessing the power of SA and its signaling pathways, farmers can develop more effective stress management techniques and optimize crop performance. Plant researchers can also explore innovative approaches to breed or engineer crops with enhanced stress tolerance, thereby contributing to sustainable agriculture and food security.
Interventions to improve equational reasoning: replication and extension of the Cuisenaire-Gattegno curriculum effect
Authors: Benson Ian , Marriott Nigel , McCandliss Bruce D.
Published: August 2023

Introduction

The ability to reason about equations in a robust and fluent way requires both instrumental knowledge of symbolic forms, syntax, and operations, as well as relational knowledge of how such formalisms map to meaningful relationships captured within mental models. A recent systematic review of studies contrasting the Cuisenaire-Gattegno (Cui) curriculum approach vs. traditional rote schooling on equational reasoning has demonstrated the positive efficacy of pedagogies that focus on integrating these two forms of knowledge.

Methods

Here we seek to replicate and extend the most efficacious of these studies (Brownell) by implementing the curriculum to a high degree of fidelity, as well as capturing longitudinal changes within learners via a novel tablet-based assessment of accuracy and fluency with equational reasoning. We examined arithmetic fluency as a function of relational reasoning to equate initial performance across diverse groups and to track changes over four growth assessment points.

Results

Results showed that the intervention condition that stressed relational reasoning leads to advances in fluency for addition and subtraction with small numbers. We also showed that this intervention leads to changes in problem solving dispositions toward complex challenges, wherein students in the CUI intervention were more inclined to solve challenging problems relative to those in the control who gave up significantly earlier on multi-step problems. This shift in disposition was associated with higher accuracy on complex equational reasoning problems. A treatment by aptitude interaction emerged for both arithmetic equation reasoning and complex multi-step equational reasoning problems, both of which showed that the intervention had greatest impact for children with lower initial mathematical aptitude. Two years of intervention contrast revealed a large effect (d = 1) for improvements in equational reasoning for the experimental (CUI) group relative to control.

Discussion

The strong replication and extension findings substantiate the importance of embedding these teaching aides within the theory grounded curricula that gave rise to them.