bluuebunny/crossref_metadata_2025 huggingface dataset:
Inter-rater agreement between humans and computer in quantitative assessment of computed tomography after cardiac arrest
Authors: Kenda Martin , Cheng Zhuo , Guettler Christopher , Storm Christian , Ploner Christoph J. , Leithner Christoph , Scheel Michael
Published: October 2022

Background

Head computed tomography (CT) is used to predict neurological outcome after cardiac arrest (CA). The current reference standard includes quantitative image analysis by a neuroradiologist to determine the Gray-White-Matter Ratio (GWR) which is calculated via the manual measurement of radiodensity in different brain regions. Recently, automated analysis methods have been introduced. There is limited data on the Inter-rater agreement of both methods.

Methods

Three blinded human raters (neuroradiologist, neurologist, student) with different levels of clinical experience retrospectively assessed the Gray-White-Matter Ratio (GWR) in head CTs of 95 CA patients. GWR was also quantified by a recently published computer algorithm that uses coregistration with standardized brain spaces to identify regions of interest (ROIs). We calculated intraclass correlation (ICC) for inter-rater agreement between human and computer raters as well as area under the curve (AUC) and sensitivity/specificity for poor outcome prognostication.

Results

Inter-rater agreement on GWR was very good (ICC 0.82–0.84) between all three human raters across different levels of expertise and between the computer algorithm and neuroradiologist (ICC 0.83; 95% CI 0.78–0.88). Despite high overall agreement, we observed considerable, clinically relevant deviations of GWR measurements (up to 0.24) in individual patients. In our cohort, at a GWR threshold of 1.10, this did not lead to any false poor neurological outcome prediction.

Conclusion

Human and computer raters demonstrated high overall agreement in GWR determination in head CTs after CA. The clinically relevant deviations of GWR measurement in individual patients underscore the necessity of additional qualitative evaluation and integration of head CT findings into a multimodal approach to prognostication of neurological outcome after CA.
Effects of individualized brain anatomies and EEG electrode positions on inferred activity of the primary auditory cortex
Authors: Ignatiadis Karolina , Barumerli Roberto , Tóth Brigitta , Baumgartner Robert
Published: October 2022

Due to its high temporal resolution and non-invasive nature, electroencephalography (EEG) is considered a method of great value for the field of auditory cognitive neuroscience. In performing source space analyses, localization accuracy poses a bottleneck, which precise forward models based on individualized attributes such as subject anatomy or electrode locations aim to overcome. Yet acquiring anatomical images or localizing EEG electrodes requires significant additional funds and processing time, making it an oftentimes inaccessible asset. Neuroscientific software offers template solutions, on which analyses can be based. For localizing the source of auditory evoked responses, we here compared the results of employing such template anatomies and electrode positions versus the subject-specific ones, as well as combinations of the two. All considered cases represented approaches commonly used in electrophysiological studies. We considered differences between two commonly used inverse solutions (dSPM, sLORETA) and targeted the primary auditory cortex; a notoriously small cortical region that is located within the lateral sulcus, thus particularly prone to errors in localization. Through systematical comparison of early evoked component metrics and spatial leakage, we assessed how the individualization steps impacted the analyses outcomes. Both electrode locations as well as subject anatomies were found to have an effect, which though varied based on the configuration considered. When comparing the inverse solutions, we moreover found that dSPM more consistently benefited from individualization of subject morphologies compared to sLORETA, suggesting it to be the better choice for auditory cortex localization.
Theiler’s virus-induced demyelinating disease as an infectious model of progressive multiple sclerosis
Authors: Pike Steven C. , Welsh Nora , Linzey Michael , Gilli Francesca
Published: October 2022

Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease of unknown etiology. However, several studies suggest that infectious agents, e.g., Human Herpes Viruses (HHV), may be involved in triggering the disease. Molecular mimicry, bystander effect, and epitope spreading are three mechanisms that can initiate immunoreactivity leading to CNS autoimmunity in MS. Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) is a pre-clinical model of MS in which intracerebral inoculation of TMEV results in a CNS autoimmune disease that causes demyelination, neuroaxonal damage, and progressive clinical disability. Given the spectra of different murine models used to study MS, this review highlights why TMEV-IDD represents a valuable tool for testing the viral hypotheses of MS. We initially describe how the main mechanisms of CNS autoimmunity have been identified across both MS and TMEV-IDD etiology. Next, we discuss how adaptive, innate, and CNS resident immune cells contribute to TMEV-IDD immunopathology and how this relates to MS. Lastly, we highlight the sexual dimorphism observed in TMEV-IDD and MS and how this may be tied to sexually dimorphic responses to viral infections. In summary, TMEV-IDD is an underutilized murine model that recapitulates many unique aspects of MS; as we learn more about the nature of viral infections in MS, TMEV-IDD will be critical in testing the future therapeutics that aim to intervene with disease onset and progression.
Zebrafish as a model organism for neurodegenerative disease
Authors: Chia Kelda , Klingseisen Anna , Sieger Dirk , Priller Josef
Published: October 2022

The zebrafish is increasingly recognized as a model organism for translational research into human neuropathology. The zebrafish brain exhibits fundamental resemblance with human neuroanatomical and neurochemical pathways, and hallmarks of human brain pathology such as protein aggregation, neuronal degeneration and activation of glial cells, for example, can be modeled and recapitulated in the fish central nervous system. Genetic manipulation, imaging, and drug screening are areas where zebrafish excel with the ease of introducing mutations and transgenes, the expression of fluorescent markers that can be detected in vivo in the transparent larval stages overtime, and simple treatment of large numbers of fish larvae at once followed by automated screening and imaging. In this review, we summarize how zebrafish have successfully been employed to model human neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. We discuss advantages and disadvantages of choosing zebrafish as a model for these neurodegenerative conditions.
Fortification of cocoa semi-skimmed milk formulations with native lactic acid bacteria: Cell viability, physicochemical and functional properties for developing novel foods
Authors: Tenea Gabriela N. , Ascanta Pamela
Published: October 2022

This study aimed to evaluate several cocoa semi-skimmed milk formulations (CSMFs) as potential carriers of native lactic acid bacteria (LAB) strains to obtain novel probiotic beverages (PBs) with improved technological and functional characteristics, and satisfactorily organoleptic acceptance. The viability of two native LAB (Lactiplantibacillus plantarum UTNGt2 and Lactiplantibacillus pentosus UTNGt5) was assessed in comparison with two references (Lactococcus lactis subsp. lactis ATCC11474 and Limosilactobacillus reuteri DSM17938) strains in supplemented CSMFs throughout storage with refrigeration. The optimum conditions to produce novel beverages supplemented with native LAB were pH 6.6, 42°C, and 1 h of fermentation. Moreover, the effect of LAB strains fortification on pH, titratable acidity, total solids (°Brix), total polyphenolic compounds (TPC), antioxidant capacity (AOX), and ascorbic acid content (AAC), total proteins and fat, at initial and final storage was evaluated. The addition of two native LAB strains did alter the physicochemical quality of CSMFs to a lesser extent, where the bioactive molecules improved significantly (p < 0.05) with the increase of cocoa concentration and depending on the supplied strain. Although a statistically significant (p < 0.05) decrease in cell counts was recorded during storage, the LAB cells were found to be viable up to 21 days of storage at 4°C (>6 logCFU/ml), which is sufficient in number to prove their stability in vitro. Overall organoleptic results suggested that LAB supplementation had a significant impact on sensory attributes with satisfactory acceptability (>78%) of PBs containing the native strains and 1–2% cocoa, while CSMFs counterparts were less appreciated (40%) as perceived off-flavor. It appears that supplying bacteria to CSMF preserves flavor in the final product. Furthermore, the final beverages were free of harmful bacteria; thus, they comply with consumer safety regulations. This study concludes that CSMF can be used as a carrier of native LAB strains, maintaining cell viability, unaltered physicochemical properties, and improved functional and sensory characteristics, for which final beverages can be regarded as functional food. From the application standpoint, these formulations are an alternative to delivering native LAB strains and could help the cocoa and dairy industry to develop more attractive products for the growing regional market.
Is there any putative mediatory role of inflammatory markers on the association between ultra-processed foods and resting metabolic rate?
Authors: Bahrampour Niki , Shiraseb Farideh , Noori Sahar , Clark Cain C. T. , Mirzaei Khadijeh
Published: October 2022

The resting metabolic rate (RMR) represents the largest component of total daily energy expenditure. The sale of ultra-processed foods (UPF) is increasing globally; however, UPF can have many adverse effects, including increasing inflammatory markers and altering RMRs. This cross-sectional study included 285 healthy overweight and obese women. Anthropometric measurements were evaluated using a bioelectrical impedance analyzer InBody 770 scanner. High-sensitivity C-reactive protein (hs-CRP), plasminogen activator-1 (PAI-1), monocyte chemoattractant protein (MCP-1), and interleukin-1 beta (IL-1β) blood levels were measured after a 12-h fasting. Indirect calorimetry was used to evaluate the RMR by using the Weir equation, and RMR deviation (RMR estimated - RMR actual), RMR per body mass index (BMI), and free fat mass (FFM) were estimated. A validated food frequency questionnaire (FFQ) was used, and seven groups of UPFs were extracted based on the NOVA method. A negative association between the RMR [β = −0.159, 95% confidence interval (CI): −0.471, −0.052, P = 0.044], RMR per BMI (β = −0.014, 95% CI: −0.025, −0.006, P = 0.036), and RMR per FFM (β = −0.241, 95% CI: −0.006, −0.000, P = 0.041) using the NOVA score was observed after adjusting for confounders. This association disappeared after inclusion of each inflammatory marker. All the markers may inversely mediate the relationship between the mentioned variables and the NOVA score. hs-CRP and MCP-1 also had a negative effect on the relationship between the NOVA score and RMR deviation. Finally, UPF intake is likely related with the RMR, mediated through changes in the production of hs-CRP, PAI-1, MCP-1, and IL-1β.
Metagenomic and metabolomic analyses show correlations between intestinal microbiome diversity and microbiome metabolites in ob/ob and ApoE−/− mice
Authors: Dong Sashuang , Wu Chengwei , He Wencan , Zhong Ruimin , Deng Jing , Tao Ye , Zha Furong , Liao Zhenlin , Fang Xiang , Wei Hong
Published: October 2022

Obesity and atherosclerosis are the most prevalent metabolic diseases. ApoE−/− and ob/ob mice are widely used as models to study the pathogenesis of these diseases. However, how gut microbes, gut bacteriophages, and metabolites change in these two disease models is unclear. Here, we used wild-type C57BL/6J (Wt) mice as normal controls to analyze the intestinal archaea, bacteria, bacteriophages, and microbial metabolites of ob/ob and ApoE−/− mice through metagenomics and metabolomics. Analysis of the intestinal archaea showed that the abundances of Methanobrevibacter and Halolamina were significantly increased and decreased, respectively, in the ob/ob group compared with those in the Wt and ApoE−/− groups (p < 0.05). Compared with those of the Wt group, the relative abundances of the bacterial genera Enterorhabdus, Alistipes, Bacteroides, Prevotella, Rikenella, Barnesiella, Porphyromonas, Riemerella, and Bifidobacterium were significantly decreased (p < 0.05) in the ob/ob mice, and the relative abundance of Akkermansia was significantly decreased in the ApoE−/− group. The relative abundances of A. muciniphila and L. murinus were significantly decreased and increased, respectively, in the ob/ob and ApoE−/− groups compared with those of the Wt group (p < 0.05). Lactobacillus_ prophage_ Lj965 and Lactobacillus _ prophage _ Lj771 were significantly more abundant in the ob/ob mice than in the Wt mice. Analysis of the aminoacyl-tRNA biosynthesis metabolic pathway revealed that the enriched compounds of phenylalanine, glutamine, glycine, serine, methionine, valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, and tyrosine were downregulated in the ApoE−/− mice compared with those of the ob/ob mice. Aminoacyl-tRNA synthetases are considered manifestations of metabolic diseases and are closely associated with obesity, atherosclerosis, and type 2 diabetes. These data offer new insight regarding possible causes of these diseases and provide a foundation for studying the regulation of various food nutrients in metabolic disease models.
The visceral and liver fat are significantly associated with the prevalence of hyperuricemia among middle age and elderly people: A cross-sectional study in Chongqing, China
Authors: Bai Ruixue , Ying Xiuquan , Shen Jieqiang , Wu Tingting , Lai Xingyu , Wang Lingyun , Yu Meng , Qi Xiaoya , Mei Ying
Published: October 2022

Background

The prevalence of hyperuricemia (HUA) has been increasing in recent years. HUA is a crucial risk factor for gout and an independent risk factor for cardiovascular diseases (CVDs). Identifying potentially modifiable factors of HUA is vital for preventing gout and even CVDs. This study aimed to explore the associations of fat distribution with HUA among middle-aged and elderly people in Chongqing, China.

Materials and methods

A cross-sectional study was conducted between July 2020 and September 2021. People who underwent quantitative computed tomography (QCT) scans were invited to participate in the study. A total of 3,683 individuals whose clinical characteristics and QCT-based fat distribution measurements included visceral fat area (VFA), subcutaneous fat area (SFA), and liver fat content (LFC) were well-recorded were included. HUA was defined as having a serum uric acid level greater than 420.0 μmol/L. Multivariate logistic regression models were used to evaluate the association between these adipose variables and HUA prevalence.

Results

The HUA prevalence was 25.6% (943/3,683), which was 39.6% (817/2,063) in men and 7.8% (126/1,620) in women. In the fully adjusted model (model 4), the comparison of the highest one with the lowest quartiles of adipose variables showed that the multivariable OR (95% confidence intervals) of HUA were 2.08 (1.36–3.16; P for trend = 0.001) for VFA, 0.89 (0.63–1.25; P for trend = 0.651) for SFA, and 1.83 (1.42–2.34; P for trend < 0.0001) for LFC. For VFA, the association was more evident in men than in women.

Conclusion

Higher VFA and LFC were significantly associated with the increased prevalence of HUA in middle-aged and elderly Chinese individuals. VFA and LFC may have a predictive effect on HUA. Controlling visceral and liver fat accumulation may be beneficial for middle-aged and older people. HUA can be prevented with specific effective healthy physical activity and balanced diet guidelines.
Critical review of indicators, metrics, methods, and tools for monitoring and evaluation of biofortification programs at scale
Authors: Rodas-Moya Santiago , Giudici Francesca M. , Mudyahoto Bho , Birol Ekin , Kodish Stephen R. , Lachat Carl , Abreu Taymara C. , Melse-Boonstra Alida , van het Hof Karin H. , Brouwer Inge D. , Osendarp Saskia , Feskens Edith J. M.
Published: October 2022

Sound monitoring and evaluation (M&E) systems are needed to inform effective biofortification program management and implementation. Despite the existence of M&E frameworks for biofortification programs, the use of indicators, metrics, methods, and tools (IMMT) are currently not harmonized, rendering the tracking of biofortification programs difficult. We aimed to compile IMMT for M&E of existing biofortification programs and recommend a sub-set of high-level indicators (HLI) for a harmonized global M&E framework. We conducted (1) a mapping review to compile IMMT for M&E biofortification programs; (2) semi-structured interviews (SSIs) with biofortification programming experts (and other relevant stakeholders) to contextualize findings from step 1; and (3) compiled a generic biofortification program Theory of Change (ToC) to use it as an analytical framework for selecting the HLI. This study revealed diversity in seed systems and crop value chains across countries and crops, resulting in differences in M&E frameworks. Yet, sufficient commonalities between implementation pathways emerged. A set of 17 HLI for tracking critical results along the biofortification implementation pathway represented in the ToC is recommended for a harmonized global M&E framework. Further research is needed to test, revise, and develop mechanisms to harmonize the M&E framework across programs, institutions, and countries.
Altered mannose metabolism in chronic stress and depression is rapidly reversed by vitamin B12
Authors: Franzka Patricia , Turecki Gustavo , Cubillos Susana , Kentache Takfarinas , Steiner Johann , Walter Martin , Hübner Christian A. , Engmann Olivia
Published: October 2022

GDP-Mannose Pyrophosphorylase B (GMPPB) is a key enzyme for glycosylation. Previous studies suggested a dysregulation of GMPBB and mannose in depression. Evidence, however, was sporadic and interventions to reverse these changes are unknown. Here, we show that GMPPB protein, but not RNA abundance is increased in the postmortem prefrontal cortex (PFC) of depressed patients and the chronic variable stress (CVS) mouse-model. This is accompanied by higher plasma mannose levels. Importantly, a single dose of intraperitoneally administered vitamin B12, which has previously been shown to rapidly reverse behavioral symptoms and molecular signatures of chronic stress in mice, normalized GMPPB plasma mannose levels and elevated GDP-mannose abundance. In summary, these data underline metabolic dysregulation in chronic stress and depression and provide further support for rapid effects of vitamin B12 on chronic stress.
Impact of fibre and red/processed meat intake on treatment outcomes among patients with chronic inflammatory diseases initiating biological therapy: A prospective cohort study
Authors: Overgaard Silja H. , Sørensen Signe B. , Munk Heidi L. , Nexøe Anders B. , Glerup Henning , Henriksen Rikke H. , Guldmann Tanja , Pedersen Natalia , Saboori Sanaz , Hvid Lone , Dahlerup Jens F. , Hvas Christian L. , Jawhara Mohamad , Andersen Karina W. , Pedersen Andreas K. , Nielsen Ole H. , Bergenheim Fredrik , Brodersen Jacob B. , Heitmann Berit L. , Halldorsson Thorhallur I. , Holmskov Uffe , Bygum Anette , Christensen Robin , Kjeldsen Jens , Ellingsen Torkell , Andersen Vibeke
Published: October 2022

Background

Biologic disease-modifying drugs have revolutionised the treatment of a number of chronic inflammatory diseases (CID). However, up to 60% of the patients do not have a sufficient response to treatment and there is a need for optimization of treatment strategies.

Objective

To investigate if the treatment outcome of biological therapy is associated with the habitual dietary intake of fibre and red/processed meat in patients with a CID.

Methods

In this multicentre prospective cohort study, we consecutively enrolled 233 adult patients with a diagnosis of Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis (RA), Axial Spondyloarthritis, Psoriatic Arthritis and Psoriasis, for whom biologic therapy was planned, over a 3 year period. Patients with completed baseline food frequency questionnaires were stratified into a high fibre/low red and processed meat exposed group (HFLM) and an unexposed group (low fibre/high red and processed meat intake = LFHM). The primary outcome was the proportion of patients with a clinical response to biologic therapy after 14–16 weeks of treatment.

Results

Of the 193 patients included in our primary analysis, 114 (59%) had a clinical response to biologic therapy. In the HFLM group (N = 64), 41 (64%) patients responded to treatment compared to 73 (56%) in the LFHM group (N = 129), but the difference was not statistically significant (OR: 1.48, 0.72–3.05). For RA patients however, HFLM diet was associated with a more likely clinical response (82% vs. 35%; OR: 9.84, 1.35–71.56).

Conclusion

Habitual HFLM intake did not affect the clinical response to biological treatment across CIDs. HFLM diet in RA patients might be associated with better odds for responding to biological treatment, but this would need confirmation in a randomised trial.

Trial registration

(clinicaltrials.gov), identifier [NCT03173144].
Music improves the therapeutic effects of bevacizumab in rats with glioblastoma: Modulation of drug distribution to the brain
Authors: Semyachkina-Glushkovskaya Oxana , Diduk Sergey , Anna Eroshova , Elina Dosadina , Artem Kruglov , Khorovodov Alexander , Shirokov Alexander , Fedosov Ivan , Dubrovsky Alexander , Blokhina Inna , Terskov Andrey , Navolokin Nikita , Evsukova Arina , Elovenko Daria , Adushkina Viktoria , Kurths Jürgen
Published: October 2022

Background

The development of new methods for modulation of drug distribution across to the brain is a crucial step in the effective therapies for glioblastoma (GBM). In our previous work, we discovered the phenomenon of music-induced opening of the blood-brain barrier (OBBB) in healthy rodents. In this pilot study on rats, we clearly demonstrate that music-induced BBB opening improves the therapeutic effects of bevacizumab (BZM) in rats with GBM via increasing BZM distribution to the brain along the cerebral vessels.

Methods

The experiments were performed on Wistar male rats (200–250 g, n=161) using transfected C6-TagRFP cell line and the loud rock music for OBBB. The OBBB was assessed by spectrofluorometric assay of Evans Blue (EB) extravasation and confocal imaging of fluorescent BZM (fBZM) delivery into the brain. Additionally, distribution of fBZM and Omniscan in the brain was studied using fluorescent and magnetic resonance imaging (MRI), respectively. To analyze the therapeutic effects of BZM on the GBM growth in rats without and with OBBB, the GBM volume (MRI scans), as well as immunohistochemistry assay of proliferation (Ki67 marker) and apoptosis (Bax marker) in the GBM cells were studied. The Mann–Whitney–Wilcoxon test was used for all analysis, the significance level was p < 0.05, n=7 in each group.

Results

Our finding clearly demonstrates that music-induced OBBB increases the delivery of EB into the brain tissues and the extravasation of BZM into the brain around the cerebral vessels of rats with GBM. Music significantly increases distribution of tracers (fBZM and Omniscan) in the rat brain through the pathways of brain drainage system (perivascular and lymphatic), which are an important route of drug delivery into the brain. The music-induced OBBB improves the suppressive effects of BZM on the GBM volume and the cellular mechanisms of tumor progression that was accompanied by higher survival among rats in the GBM+BZM+Music group vs. other groups.

Conclusion

We hypothesized that music improves the therapeutic effects of BZM via OBBB in the normal cerebral vessels and lymphatic drainage of the brain tissues. This contributes better distribution of BZM in the brain fluids and among the normal cerebral vessels, which are used by GBM for invasion and co-opt existing vessels as a satellite tumor form. These results open the new perspectives for an improvement of therapeutic effects of BZM via the music-induced OBBB for BZM in the normal cerebral vessels, which are used by GBM for migration and progression.
Current insights into the regulation of programmed cell death by TP53 mutation in cancer
Authors: Su Yali , Sai Yingying , Zhou Linfeng , Liu Zeliang , Du Panyan , Wu Jinghua , Zhang Jinghua
Published: October 2022

Gene mutation is a complicated process that influences the onset and progression of cancer, and the most prevalent mutation involves the TP53 gene. One of the ways in which the body maintains homeostasis is programmed cell death, which includes apoptosis, autophagic cell death, pyroptosis, ferroptosis, NETosis, and the more recently identified process of cuprotosis. Evasion of these cell deaths is a hallmark of cancer cells, and our elucidation of the way these cells die helps us better understands the mechanisms by which cancer arises and provides us with more ways to treat it.Studies have shown that programmed cell death requires wild-type p53 protein and that mutations of TP53 can affect these modes of programmed cell death. For example, mutant p53 promotes iron-dependent cell death in ferroptosis and inhibits apoptotic and autophagic cell death. It is clear that TP53 mutations act on more than one pathway to death, and these pathways to death do not operate in isolation. They interact with each other and together determine cell death. This review focuses on the mechanisms via which TP53 mutation affects programmed cell death. Clinical investigations of TP53 mutation and the potential for targeted pharmacological agents that can be used to treat cancer are discussed.
In silico characterization of competing endogenous RNA network in glioblastoma multiforme with a systems biology approach
Authors: Ghafouri-Fard Soudeh , Safarzadeh Arash , Mahmud Hussen Bashdar , Akhavan-Bahabadi Mehdi , Taheri Mohammad , Sharifi Guive
Published: October 2022

Glioblastoma multiforme (GBM) is the most frequent malignant type of primary brain cancers and is a malignancy with poor prognosis. Thus, it is necessary to find novel therapeutic modalities based on molecular events occur at different stages of tumor progression. We used expression profiles of GBM tissues that contained long non-coding RNA (lncRNA), microRNA (miRNA) and mRNA signatures to make putative ceRNA networks. Our strategy led to identification of 1080 DEmRNAs, including 777 downregulated DEmRNAs (such as GJB6 and SLC12A5) and 303 upregulated DEmRNAs (such as TOP2A and RRM2), 19 DElncRNAs, including 16 downregulated DElncRNAs (such as MIR7-3HG and MIR124-2HG) and 3 upregulated DElncRNAs (such as CRNDE and XIST) and 49 DEmiRNAs, including 10 downregulated DEmiRNAs (such as hsa-miR-10b-5p and hsa-miR-1290) and 39 upregulated DEmiRNAs (such as hsa-miR-219a-2-3p and hsa-miR-338-5p). We also identified DGCR5, MIAT, hsa-miR-129-5p, XIST, hsa-miR-128-3p, PART1, hsa-miR-10b-5p, LY86-AS1, CRNDE, and DLX6-AS1 as 10 hub genes in the ceRNA network. The current study provides novel insight into molecular events during GBM pathogenesis. The identified molecules can be used as therapeutic targets for GBM.
Metastasis patterns and prognosis in young breast cancer patients: A SEER database analysis
Authors: Zhang Weifang , Wu Shang , Liu Jinzhao , Zhang Xiangmei , Ma Xindi , Yang Chao , Cao Miao , Zhang Shuo , Liu Yunjiang
Published: October 2022

Background

There are few studies on young patients with metastatic breast cancer (MBC). This study aims to explore the metastasis pattern and prognosis of young patients with MBC.

Methods

A total of 6,336 MBC patients diagnosed in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were selected. They were divided into two age groups: the younger group (≤40 years old) and the older group (>40 years old). χ2 test was used to compare clinicopathological characteristics. Survival differences were compared by Kaplan–Meier analysis. Cox regression models were used to determine the prognostic factors affecting survival. Propensity score matching (PSM) was performed to balance the effects of baseline clinicopathological differences.

Results

Finally, 494 patients (7.8%) who are ≤40 years old and 5,842 patients (92.2%) who are >40 years old were included. In the younger group, the proportion of liver metastasis was significantly higher than that in the older group; the proportion of lung metastasis was significantly lower than that of the older group. Kaplan–Meier analysis showed that the younger group had the best prognosis and the older group had the worst. Youth is an independent protective factor for overall survival (OS). In the younger group, liver metastasis had the best prognosis among all metastatic sites, and the HER2-enriched subtype had the best prognosis among all subtypes.

Conclusions

The disease in young MBC patients is more aggressive but has a better prognosis, especially in liver metastases and the HER2-enriched subtypes.
High rate of epidermal growth factor receptor-mutated primary lung cancer in patients with primary breast cancer
Authors: Zeng Tianyu , Xu Hai , Liu Yincheng , Sun Chunxiao , Yang Fan , Liang Yan , Huang Xiang , Fu Ziyi , Li Wei , Yin Yongmei
Published: October 2022

Background

With increased survival in breast cancer, resulting from advances in treatment, patients incur the possibility of subsequent primary malignancies, especially lung cancer. The aim of this study was to assess the frequency of CT-detected pulmonary ground-glass nodules and lung cancer following breast cancer diagnosis, the associations between breast cancer and lung cancer, the pathological features of double primary cancer, and the status of epidermal growth factor receptor (EGFR) mutations in second primary lung cancer.

Methods

Clinical data from more than 9000 individuals who were diagnosed with primary breast cancer at Jiangsu Province Hospital (Jiangsu, China) between January 2008 and December 2021 were retrospectively analyzed.

Results

Of the 9179 patients, 6512 underwent diagnostic CT, 55 (0.8%) were diagnosed with a second primary lung cancer, which accounted for approximately 18.4% of the pulmonary ground-glass nodules (GGNs) detected. The incidence was higher than in the general female population (standardized incidence ratio 1.4 [95% confidence interval (CI): 1.25-1.55]). Patients who experienced a second primary lung cancer exhibited a significantly higher rate of EGFR mutation (78.5%) than those with lung adenocarcinoma alone, with most exhibiting low-grade malignancy, older age, estrogen receptor negativity, low Ki67, and no lymph node metastasis.

Conclusions

Breast cancer patients, especially those with low-grade malignancy, were at high risk for developing primary lung cancer. For isolated GGN in patients with high-risk factors, clinicians should insist on close follow-up. Furthermore, EGFR may play an important role in primary lung adenocarcinomas and breast cancer.
Direct oral anticoagulants in pediatric venous thromboembolism: Review of approved products rivaroxaban and dabigatran
Authors: Al-Ghafry Maha , Sharathkumar Anjali
Published: October 2022

Venous thromboembolism is a major hospital acquired complication in the pediatric population over the last two-decades, with a 130% increase in the past decade. Direct oral anticoagulants (DOACs) are a newer class of anticoagulant medication for the treatment and prophylaxis of VTEs that provide the primary advantages of an oral route of administration without a requirement to adjust dosing to achieve a therapeutic level. It is anticipated that these medications will quickly replace parenteral anticoagulants and clinicians should familiarize themselves with DOACs. In this article, we provide an overview of the pharmacological properties of DOACs, with a specific focus on rivaroxaban and dabigatran, which have been approved for use in pediatric patients. Each drug's characteristics are discussed along with data from their respective clinical trials.
Comparison of outcomes of monochorionic twin pregnancies conceived by assisted reproductive technology vs. spontaneous conceptions: A systematic review and meta-analysis
Authors: Wang Minmin , Chai Jingjing
Published: October 2022

Background

This review aimed to assess if monochorionic twin pregnancies conceived by assisted conception have worse maternal and neonatal outcomes as compared to those conceived naturally.

Methods

Datasets of PubMed, ScienceDirect, CENTRAL, Embase, and Google Scholar were searched for studies comparing maternal and neonatal outcomes of monochorionic twin pregnancies conceived by assisted vs. spontaneous methods.

Results

Eight studies comparing 337 assisted with 2,711 spontaneously conceived monochorionic twin pregnancies were included. Meta-analysis revealed that the mode of conception of monochorionic twin pregnancies had no impact on the risk of hypertensive disorders of pregnancy (HDP) (OR: 1.36 95% CI, 0.73, 2.54 I2 = 9% p = 0.03), twin-twin transfusion syndrome (TTTS) (OR: 0.83 95% CI, 0.52, 1.31 I2 = 0% p = 0.42), and very preterm delivery (OR: 1.18 95% CI, 0.74, 1.88 I2 = 41% p = 0.49). We noted no statistically significant difference in the mean birth weights (MD: −17.66 95% CI, −157.23, 121.91 I2 = 82% p = 0.80), risk of intra-uterine death (OR: 0.90 95% CI, 0.51, 1.60 I2 = 36% p = 0.73) and small for gestational age between the two groups (OR: 0.92 95% CI, 0.67, 1.26 I2 = 0% p = 0.59). There was an increased risk of caesarean sections (OR: 1.34 95% CI, 1.00, 1.80 I2 = 0% p = 0.05) and neonatal death with assisted conceptions as compared to spontaneous conceptions (OR: 2.35 95% CI, 1.11, 5.01 I2 = 37% p = 0.03).

Conclusion

Monochorionic twin pregnancies conceived via assisted reproductive technology have a heightened risk of cesarean section and neonatal deaths. However, there is a need for further studies to supplement current evidence.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=325133, identifier: CRD42022325133.
Promoting positive physical activity behaviors for children and adolescents undergoing acute cancer treatment: Development of the CanMOVE intervention using the Behavior Change Wheel
Authors: Grimshaw Sarah L. , Taylor Nicholas F. , Conyers Rachel , Shields Nora
Published: October 2022

Background

Increasing participation in physical activity has the potential to improve outcomes for children and adolescents with cancer during treatment and into survivorship. The aim of this study is to outline the theoretical process behind development of CanMOVE, a behavior change intervention designed to increase physical activity for children and adolescents with cancer.

Study design

This study followed a theoretical design process consistent with the Behavior Change Wheel to inform the design of a complex intervention.

Materials and methods

The three stages of the Behavior Change Wheel intervention design process include: (1) understanding physical activity behavior within the pediatric cancer setting, (2) identifying potential intervention functions, and (3) identifying appropriate behavior change and implementation strategies. Qualitative and behavior change literature relevant to the pediatric cancer treatment setting were used to inform each stage.

Results

An individualized and flexible approach to physical activity promotion that considers intrinsic factors specific to the child/adolescent and their environment is required. Fifteen behavioral change strategies were identified to form the intervention components of CanMOVE. Implementation strategies were identified to build motivation, opportunity and capacity toward increasing physical activity behaviors. Key intervention components of CanMOVE include standardized assessment and monitoring (physical activity, physical function, and health-related quality of life), provision of an activity monitor to both child/adolescent and parent, and one-on-one capacity building sessions with a healthcare professional. Capacity building sessions include education, goal setting, an active supervised physical activity session, barrier identification and problem solving, and action planning.

Conclusion

CanMOVE is a novel approach to physical activity promotion in the pediatric cancer treatment setting. The use of a theoretical intervention design process will aid evaluation and replication of CanMOVE when it is assessed for feasibility in a clinical setting. The design process utilized here can be used as a guide for future intervention development.
Analysis of the network pharmacology and the structure-activity relationship of glycyrrhizic acid and glycyrrhetinic acid
Authors: Ni Qingqiang , Gao Yuxuan , Yang Xiuzhen , Zhang Qingmeng , Guo Baojian , Han Jinxiang , Chen Shaoru
Published: October 2022

Licorice, a herbal product derived from the root of Glycyrrhiza species, has been used as a sweetening agent and traditional herbal medicine for hundreds of years. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Both GL and GA have pharmacological effects against tumors, inflammation, viral infection, liver diseases, neurological diseases, and metabolic diseases. However, they also exhibit differences. KEGG analysis indicated that licorice is involved in neuroactive ligand‒receptor interactions, while 18β-GA is mostly involved in arrhythmogenic right ventricular cardiomyopathy. In this article, we comprehensively review the therapeutic potential of GL and GA by focusing on their pharmacological effects and working mechanisms. We systemically examine the structure-activity relationship of GL, GA and their isomers. Based on the various pharmacological activities of GL, GA and their isomers, we propose further development of structural derivatives of GA after chemical structure modification, with less cytotoxicity but higher targeting specificity. More research is needed on the clinical applications of licorice and its active ingredients.
Traditional Chinese medicine for the treatment of diabetic kidney disease: A study-level pooled analysis of 44 randomized controlled trials
Authors: Liu Xuele , Ge Minyao , Zhai Xinyu , Xiao Yang , Zhang Yaheng , Xu Ziling , Zhou Zhiguang , Mei Zubing , Yang Xuejun
Published: October 2022

Background: Accumulating evidence suggests that traditional Chinese medicine (TCM) has significant effects on reducing 24-h urinary protein (24-h UPRO) and improves renal function indices. The current level of evidence-based medicine is still not enough due to the limitation of clinical center size and sample size.

Objective: We aimed to update the current evidence on the efficacy of TCM in the treatment of diabetic kidney disease (DKD).

Methods: PubMed, Embase, the Cochrane Library, and SinoMed were searched to identify randomized controlled trials (RCTs) comparing the clinical efficacy of TCM combined with Western medicine with that of Western medicine alone for the treatment of DKD. The main outcome measure was 24-h UPRO. The secondary outcomes were serum creatinine (Scr), blood urea nitrogen (BUN), glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG). Meta-analyses were performed using random-effects models. The revised Cochrane risk-of-bias tool was used to assess the risk of bias.

Results: A total of 44 RCTs with 3,730 participants were included. The summary estimates showed that compared with Western medicine alone, TCM combined with Western medicine significantly improved 24-h UPRO [standardized mean difference (SMD) −1.10, 95% confidence interval (CI) −1.45 to −0.74]. Moreover, TCM combined with Western medicine significantly reduced the levels of other renal function indices, including Scr (SMD −1.25, 95% CI: −1.69 to −0.81) and BUN (SMD −0.75, 95% CI: −1.10 to −0.40). TCM combined with Western medicine also showed greater benefits in reducing the levels of FBG (SMD −0.31, 95% CI: −0.47 to −0.15) and HbA1c (SMD −0.62, 95% CI: −0.89 to −0.36) in patients with DKD. In addition, superior effects on the lipid profile were noted in the TCM combined with Western medicine group in terms of TG (SMD −1.17, 95% CI: −1.76 to −0.59) and TC (SMD −0.95, 95% CI: −1.43 to −0.47). The risk of bias could have resulted from selective reports, unclear randomization methods, unblinded assignments, and some missing data.

Conclusion: The results of this meta-analysis suggest that TCM combined with Western medicine has significant effects on reducing 24-h UPRO and improves renal function indices and lipid profiles compared with Western medicine alone for DKD. However, the results should be interpreted with caution due to the risk of bias of the included trials.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=213199], identifier [CRD: 42020213199].
Population pharmacokinetic analysis, renal safety, and dosing optimization of polymyxin B in lung transplant recipients with pneumonia: A prospective study
Authors: Cai Xiao-Jun , Chen Yan , Zhang Xiao-Shan , Wang Yu-Zhen , Zhou Wen-Bo , Zhang Chun-Hong , Wu Bo , Song Hui-Zhu , Yang Hang , Yu Xu-Ben
Published: October 2022

Objectives: This study aims to characterize the population pharmacokinetics of polymyxin B in lung transplant recipients and optimize its dosage regimens.

Patients and methods: This prospective study involved carbapenem-resistant organisms-infected patients treated with polymyxin B. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological efficacy, nephrotoxicity, and hyperpigmentation were assessed. Monte Carlo simulation was performed to calculate the probability of target attainment in patients with normal or decreased renal function.

Results: A total of 34 hospitalized adult patients were included. 29 (85.29%) patients were considered of clinical cure or improvement; 14 (41.18%) patients had successful bacteria elimination at the end of the treatment. Meanwhile, 5 (14.71%) patients developed polymyxin B-induced nephrotoxicity; 19 (55.88%) patients developed skin hyperpigmentation. A total of 164 concentrations with a range of 0.56–11.66 mg/L were obtained for pharmacokinetic modeling. The pharmacokinetic characteristic of polymyxin B was well described by a 1-compartment model with linear elimination, and only creatinine clearance was identified as a covariate on the clearance of polymyxin B. Monte Carlo simulations indicated an adjusted dosage regimen might be needed in patients with renal insufficiency and the currently recommended dose regimens by the label sheet of polymyxin B may likely generate a subtherapeutic exposure for MIC = 2 mg/L.

Conclusion: Renal function has a significant effect on the clearance of polymyxin B in lung transplant recipients, and an adjustment of dosage was needed in patients with renal impairments.
Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling
Authors: Yang Fang , Chen Ze-Ran , Yang Xu-Hong , Xu Yue , Ran Ning-Jing , Liu Mei-Jun , Jin Shuo-Guo , Jia Hua-Nan , Zhang Yang
Published: October 2022

Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natural products play important roles in improving neurological disorders. Furthermore, our previous results also suggested that Shenxiong Tongmai granule, a clinically used herbal medicines’ prescription, has a good ameliorating effect on IS. In the present study, we found that Monomethyl lithospermate (MOL), a constituent of Shenxiong Tongmai granule, significantly improved the neurological damage in middle cerebral artery occlusion (MCAO) rats. MOL can significantly improve the neurological deficit score of MCAO rats, and improve the damage of hippocampal neurons caused by ischemia-reperfusion (IR). At the same time, we also found that MOL could reduce the level of oxidative stress in the brain tissues of MCAO rats. Furthermore, the oxygen and glucose deprivation/Reoxygenation (OGD/R)-induced SHSY-5Y cell model was established in vitro to investigate the pharmacological activity and molecular mechanisms of MOL in improving the nerve injury of IS rats. The results showed that MOL could increase the cell viability of SHSY-5Y cells, inhibit the mitochondrial membrane potential (MMOP) collapse and suppress apoptosis. In addition, MOL also ameliorated the elevated oxidative stress level caused by OGR/R treatment in SHSY-5Y cells. Further mechanistic studies showed that MOL could activate the PI3K/AKT pathway via promoting the phosphorylation of PI3K and AKT in MCAO rats and OGR/R-induced SHSY-5Y cells, which could be partially blocked by addition of PI3K/AKT pathway inhibitor of LY294002. Taken together, our current study suggested that MOL exerts a protective effect against neural damage caused by IS in vivo and in vitro by activating the PI3K/AKT pathway.
Bergenin ameliorates airway inflammation and remodeling in asthma by activating SIRT1 in macrophages to regulate the NF-κB pathway
Authors: Huang Dan , Sun Chaoqun , Chen Min , Bai Shuyou , Zhao Xuanna , Wang Weiming , Geng Kang , Huang Wenbo , Zhao Tingting , Wu Bin , Zhang Guilin , Wu Dong , Xu Youhua
Published: October 2022

Airway inflammation and remodeling are critical pathological changes in asthma, and macrophage activation plays a vital role in this process. Sirtuin 1 (SIRT1) reduces airway inflammation by affecting macrophages in asthma. This study aimed to investigate the potential benefit and underlying mechanism of the SIRT1 agonist bergenin as a treatment for asthma. We performed in vivo and in vitro experiments by establishing a Sirt1fl/fl-LysMcre mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that Sirt1fl/fl-LysMcre asthmatic mice exhibited more severe airway inflammation and airway remodeling than wild-type mice. As an activator of SIRT1, bergenin attenuated asthmatic airway pathology and reduced production of interleukins 1β, IL-5, IL-6, and matrix metalloproteinase 9 (MMP-9) in wild-type asthmatic mice. However, the therapeutic effects of bergenin were significantly attenuated in Sirt1fl/fl-LysMcre asthmatic mice or following coadministration with the SIRT1 inhibitor EX-527. Further experiments showed that activation of SIRT1 by bergenin deacetylates nuclear factor κB and hinders its nuclear translocation, thereby affecting IL-1β, IL-5, IL-6, and MMP-9 production by regulating transcriptional activity. Our study suggests that bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 in macrophages.