bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy Efficiency and Pollution Control Through ICTs for Sustainable Development
Authors: Popkova Elena G. , Inshakova Agnessa O. , Bogoviz Aleksei V. , Lobova Svetlana V.
Published: November 2021

The goal of this paper is to prove the necessity for a more thorough consideration and more active use of the modern ICTs for the technological support for the practical implementation of the SDGs’ ecological block in the aspect of the increase of energy efficiency and environmental pollution control. The originality of this paper is as follows: it develops a proprietary methodology of evaluating the technical readiness (level of the development of ICTs) for implementing the ecological block of the SDGs, which envisage the increase of energy efficiency and the growth of environmental pollution control. The highest (but moderate) technological readiness to implement the ecological block of the SDGs among developed countries has been shown by Canada (14.42 points) and Denmark (11.03 points), among developing countries—China (7.72 points). As a result, it has been proved that UCTs are a perspective tool of the practical implementation of the ecological block of the SDGs, stimulating the increase of energy efficiency and improving the environment pollution control. For developed countries, it is recommended to increase the use of Big data and AI analytics by 90.36% and increase the use of ICTs in E-government by 89.74%. This will allow achieving the growth of energy efficiency by 8.28% and the decrease of environmental pollution by 28.41%. In developing countries, it is recommended to increase world robots distribution by 14.17% and increase the use of ICTs in E-government by 76.74%. This will allow increasing the energy efficiency by 16.77% and decreasing the level of environmental pollution by 15.54%. This paper’s contribution to literature (innovative aspect of research) consists in filling the gap of the uncertainty (underdevelopment) of the tools for practical implementation of the SDGs ecological block. This paper has demonstrated the substantial potential of ICTs in the stimulation of the growth of energy efficiency and reduction of environmental pollution in developed and developing countries.
Perturbation Observer Based Fractional-Order Control for SMES Systems Based on Jellyfish Search Algorithm
Authors: Luo Ke , Jiao Yingying , Zhu Jiawei
Published: November 2021

The electric energy storage system (EESS) is considered as an efficient and promising tool to alleviate the power imbalance of grid-connected microgrid with distributed generation (DG). This work develops a perturbation observer-based fractional-order control (POFOC) strategy for superconducting magnetic energy storage (SMES) system. Initially, a high-gain state and perturbation observer (HGSPO) is designed for reliable estimation of the combined impact of the nonlinearities, parameter uncertainties, unmodeled dynamics, and external disturbances of SMES. Then the storage function of an SMES system is designed, which takes favorable terms into serious consideration to sufficiently utilize the physical properties of the SMES system. Moreover, a fractional-order control framework is applied for complete compensation for the estimated perturbation and adopted as the attached input to boost its dynamical responses. Furthermore, a newly proposed jellyfish search algorithm (JSA) is utilized to realize optimization and tuning of control gains of the developed strategy, upon which high-quality global optimum can be obtained to ensure prominent controlling performance. Case studies, e.g., active power and reactive power supply and system restoration capability under power grid fault effectively validate the effectiveness and reliability of the POFOC strategy compared with traditional PID control and interconnection and damping assignment passivity-based controller (IDA-PBC). In particular, the overshoot of PID is 115.264% of the rated value, while POFOC has no overshoot.
Recommendations for Creating Codes of Conduct for Processing Personal Data in Biobanking Based on the GDPR art.40
Authors: Krekora-Zając Dorota , Marciniak Błażej , Pawlikowski Jakub
Published: November 2021

Personal data protection has become a fundamental normative challenge for biobankers and scientists researching human biological samples and associated data. The General Data Protection Regulation (GDPR) harmonises the law on protecting personal data throughout Europe and allows developing codes of conduct for processing personal data based on GDPR art. 40. Codes of conduct are a soft law measure to create protective standards for data processing adapted to the specific area, among others, to biobanking of human biological material. Challenges in this area were noticed by the European Data Protection Supervisor on data protection and Biobanking and BioMolecular Resources Research Infrastructure–European Research Infrastructure Consortium (BBMRI.ERIC). They concern mainly the specification of the definitions of the GDPR and the determination of the appropriate legal basis for data processing, particularly for transferring data to other European countries. Recommendations indicated in the article, which are based on the GDPR, guidelines published by the authority and expert bodies, and our experiences regarding the creation of the Polish code of conduct, should help develop how a code of conduct for processing personal data in biobanks should be developed.
A Novel Risk-Score Model With Eight MiRNA Signatures for Overall Survival of Patients With Lung Adenocarcinoma
Authors: Wu Jun , Lou Yuqing , Ma Yi-Min , Xu Jun , Shi Tieliu
Published: November 2021

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer with heterogeneous outcomes and diverse therapeutic responses. To classify patients into different groups and facilitate the suitable therapeutic strategy, we first selected eight microRNA (miRNA) signatures in The Cancer Genome Atlas (TCGA)-LUAD cohort based on multi-strategy combination, including differential expression analysis, regulatory relationship, univariate survival analysis, importance clustering, and multivariate combinations analysis. Using the eight miRNA signatures, we further built novel risk scores based on the predefined cutoff and beta coefficients and divided the patients into high-risk and low-risk groups with significantly different overall survival time (p-value < 2 e−16). The risk-score model was confirmed with an independent dataset (p-value = 4.71 e−4). We also observed that the risk scores of early-stage patients were significantly lower than those of late-stage patients. Moreover, our model can also provide new insights into the current clinical staging system and can be regarded as an alternative system for patient stratification. This model unified the variable value as the beta coefficient facilitating the integration of biomarkers obtained from different omics data.
A Combined Nomogram Model to Predict Disease-free Survival in Triple-Negative Breast Cancer Patients With Neoadjuvant Chemotherapy
Authors: Xia Bingqing , Wang He , Wang Zhe , Qian Zhaoxia , Xiao Qin , Liu Yin , Shao Zhimin , Zhou Shuling , Chai Weimin , You Chao , Gu Yajia
Published: November 2021

Background: To investigate whether the radiomics signature (Rad-score) of DCE-MRI images obtained in triple-negative breast cancer (TNBC) patients before neoadjuvant chemotherapy (NAC) is associated with disease-free survival (DFS). Develop and validate an intuitive nomogram based on radiomics signatures, MRI findings, and clinicopathological variables to predict DFS.

Methods: Patients (n = 150) from two hospitals who received NAC from August 2011 to May 2017 were diagnosed with TNBC by pathological biopsy, and follow-up through May 2020 was retrospectively analysed. Patients from one hospital (n = 109) were used as the training group, and patients from the other hospital (n = 41) were used as the validation group. ROIs were drawn on 1.5 T MRI T1W enhancement images of the whole volume of the tumour obtained with a 3D slicer. Radiomics signatures predicting DFS were identified, optimal cut-off value for Rad-score was determined, and the associations between DFS and radiomics signatures, MRI findings, and clinicopathological variables were analysed. A nomogram was developed and validated for individualized DFS estimation.

Results: The median follow-up time was 53.5 months, and 45 of 150 (30.0%) patients experienced recurrence and metastasis. The optimum cut-off value of the Rad-score was 0.2528, which stratified patients into high- and low-risk groups for DFS in the training group (p<0.001) and was validated in the external validation group. Multivariate analysis identified three independent indicators: multifocal/centric disease status, pCR status, and Rad-score. A nomogram based on these factors showed discriminatory ability, the C-index of the model was 0.834 (95% CI, 0.761–0.907) and 0.868 (95% CI, 0.787–949) in the training and the validation groups, respectively, which is better than clinicoradiological nomogram(training group: C-index = 0.726, 95% CI = 0.709–0.743; validation group: C-index = 0.774,95% CI = 0.743–0.805).

Conclusion: The Rad-score derived from preoperative MRI features is an independent biomarker for DFS prediction in patients with TNBC to NAC, and the combined radiomics nomogram improved individualized DFS estimation.
Adhesion Molecules Involved in Stem Cell Niche Retention During Normal Haematopoiesis and in Acute Myeloid Leukaemia
Authors: Grenier Julien M. P. , Testut Céline , Fauriat Cyril , Mancini Stéphane J. C. , Aurrand-Lions Michel
Published: November 2021

In the bone marrow (BM) of adult mammals, haematopoietic stem cells (HSCs) are retained in micro-anatomical structures by adhesion molecules that regulate HSC quiescence, proliferation and commitment. During decades, researchers have used engraftment to study the function of adhesion molecules in HSC’s homeostasis regulation. Since the 90’s, progress in genetically engineered mouse models has allowed a better understanding of adhesion molecules involved in HSCs regulation by BM niches and raised questions about the role of adhesion mechanisms in conferring drug resistance to cancer cells nested in the BM. This has been especially studied in acute myeloid leukaemia (AML) which was the first disease in which the concept of cancer stem cell (CSC) or leukemic stem cells (LSCs) was demonstrated. In AML, it has been proposed that LSCs propagate the disease and are able to replenish the leukemic bulk after complete remission suggesting that LSC may be endowed with drug resistance properties. However, whether such properties are due to extrinsic or intrinsic molecular mechanisms, fully or partially supported by molecular crosstalk between LSCs and surrounding BM micro-environment is still matter of debate. In this review, we focus on adhesion molecules that have been involved in HSCs or LSCs anchoring to BM niches and discuss if inhibition of such mechanism may represent new therapeutic avenues to eradicate LSCs.
CXCL13 Neutralization Attenuates Neuropsychiatric Manifestations in Lupus-Prone Mice
Authors: Huang Michelle W. , Stock Ariel D. , Putterman Chaim
Published: November 2021

Neuropsychiatric lupus (NPSLE), the nervous system presentation of systemic lupus erythematosus (SLE), remains challenging to treat due to its unclear pathogenesis and lack of available targeted therapies. A potential contributor to disease progression is brain tertiary lymphoid structures (TLS); these ectopic lymphoid follicles that can develop tissue-targeted antibodies have recently been described in the MRL/lpr lupus mouse strain, a classic model for studying NPSLE. The brains of MRL/lpr mice show a significant increase of CXCL13, an important chemokine in lymphoid follicle formation and retention that may also play a role in the disease progression of NPSLE. The aim of the present study was to inhibit CXCL13 and examine the effect of this intervention on lymphoid formation and the development of neurobehavioral manifestations in lupus mice. Female MRL/lpr mice were injected with an anti-CXCL13 antibody, an IgG1 isotype-matched antibody, or PBS either three times a week for 12 weeks intraperitoneally (IP) starting at 6-8 weeks of age, or continuously intracerebroventricularly (ICV) with an osmotic pump over a two-week period starting at 15 weeks of age. Cognitive dysfunction and depression-like behavior were assessed at the end of treatment. When treatment was delivered IP, anti-CXCL13 treated mice showed significant improvement in cognitive function when compared to control treated mice. Depression-like behavior was attenuated as well. Furthermore, mice that received anti-CXCL13 by the ICV route showed similar beneficial effects. However, the extent of lymphocyte infiltration into the brain and the general composition of the aggregates were not substantively changed by anti-CXCL13 irrespective of the mode of administration. Nevertheless, analysis of brain gene expression in anti-CXCL13 treated mice showed significant differences in key immunological and neuro-inflammatory pathways that most likely explained the improvement in the behavioral phenotype. Our results indicate that CXCL13 affects the behavioral manifestations in the MRL/lpr strain and is important to the pathogenesis of murine NPSLE, suggesting it as a potential therapeutic target.
Occurrence and Phylogenetic Analysis of DWV in Stingless Bee (Apidae sp.) in China: A Case Report
Authors: Zhang Lina , Deng Yanchun , Zhao Hongxia , Zhang Ming , Hou Chunsheng
Published: November 2021

Honey bees play a vital role in providing pollination services for agricultural crops and wild flowering plants. However, the spillover risk of their pathogens to other pollinators or wild insects is becoming a cause for concern. There is some evidence that stingless bees can carry honey bee viruses, but little is known about the presence of honey bee viruses in stingless bees in China. Here, we investigate the occurrence of major honey bee pathogens including bacteria, fungi, and viruses in stingless bees (Apidae: sp.). Our results show that the stingless bees (Apidae: sp.) were mainly infected with DWV-A, but no DWV-B and DWV-C. Phylogenetic analysis on fragments of lp, RdRp, and VP3 of DWV-A indicated that genetic variation in VP3 might an important indicator for host-specific viruses, but it requires further study. Our results indicated that DWV-A is not only the major strain of virus currently circulating in managed bee colonies in China and globally, but in stingless bee species as a whole.
Mesoscale Eddy-Induced Ocean Dynamic and Thermodynamic Anomalies in the North Pacific
Authors: Zhou Jiang , Zhou Guidi , Liu Hailong , Li Zhuhua , Cheng Xuhua
Published: November 2021

Oceanic mesoscale eddies are associated with large thermodynamic anomalies, yet so far they are most commonly studied in terms of surface temperature and in the sense of composite mean. Here we employ an objective eddy identification and tracking algorithm together with a novel matching and filling procedure to more thoroughly examine eddy-induced thermodynamic anomalies in the North Pacific, their relationship with eddy amplitude (SSH), and the percentage of variability they explain on various timescales from submonthly to interannual. The thermodynamic anomalies are investigated in terms of sea surface temperature (SST), isothermal layer depth (ITD), and upper ocean heat content (HCT). Most eddies are weak in amplitude and are associated with small thermodynamic anomalies. In the sense of composite mean, anticyclonic eddies are generally warm eddies with deeper isothermal layer and larger heat content, and the reverse is true for cyclonic eddies. A small fraction of eddies, most probably subsurface eddies, exhibits the opposite polarities. Linear relationships with eddy amplitude are found for each of the thermodynamic parameters but with different level of scatter and seasonality. HCT-amplitude relation scatters the least and has the smallest seasonal difference, ITD-amplitude relation has the largest scatter and seasonality, while SST-amplitude relation is in between. For the Kuroshio and Oyashio Extension region, the most eddy-rich region in the North Pacific, eddies are responsible for over 50% of the total SSH variability up to the intra-seasonal scale, and ITD and HCT variability up to interannual. Eddy-induced SST variability is the highest along the Oyashio Extension Front on the order of 40–60% on submonthly scales. These results highlight the role of mesoscale eddies in ocean thermodynamic variability and in air-sea interaction.
Identification of Novel Conopeptides and Distinct Gene Superfamilies in the Marine Cone Snail Conus quercinus
Authors: Zhang Han , Wang Lei , Yang Xiang , Lian Zhiwei , Qiu Yinbin , Dong Zhanying , Wu Xuedong , Pan Xinghua
Published: November 2021

Conopeptides from the marine cone snails are a mixture of cysteine-rich active peptides, representing a unique and fertile resource for neuroscience research and drug discovery. The ConoServer database includes 8,134 conopeptides from 122 Conus species, yet many more natural conopeptides remain to be discovered. Here, we identified 517 distinct conopeptide precursors in Conus quercinus using de novo deep transcriptome sequencing. Ten of these precursors were verified at the protein level using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The combined gene and protein analyses revealed two novel gene superfamilies (Que-MNCLQ and Que-MAMNV), and three other gene superfamilies (N, P, and I1) were reported for the first time in C. quercinus. From the Que-MAMNV superfamily, a novel conotoxin, Que-0.1, was obtained via cloning and prokaryotic expression. We also documented a new purification process that can be used to induce the expression of conopeptides containing multiple pairs of disulfide bonds. The animal experiments showed that Que-0.1 strongly inhibited neuroconduction; the effects of Que-1.0 were 6.25 times stronger than those of pethidine hydrochloride. In addition, a new cysteine framework (CC-C-C-C-C-C-CC-C-C-C-C-C) was found in C. quercinus. These discoveries accelerate our understanding of conopeptide diversity in the genus, Conus and supply promising materials for medical research.
Coupled Strengthening Effects by Lattice Distortion, Local Chemical Ordering, and Nanoprecipitates in Medium-Entropy Alloys
Authors: Cheng Wenqiang , Yuan Fuping , Wu Xiaolei
Published: November 2021

Extraordinary mechanical properties can be achieved in high-entropy alloys (HEAs) or medium-entropy alloys (MEAs) with nanoprecipitates. In the present study, the extra coupled strengthening effects by lattice distortion, local chemical ordering, and nanoprecipitates in the HEAs and MEAs with nanoprecipitates have been systematically investigated by large-scale molecular dynamics simulations. The moving of the dislocation can be slowed down, and the dislocation line shows a wavy configuration due to lattice distortion and local chemical ordering, resulting in strengthening. The degree of the wavy configuration increases and the sliding velocity of the dislocation decreases with increasing degrees of local chemical ordering. It is clearly indicated that the dislocation moves via nanoscale segment detrapping mechanism due to the effects of lattice distortion and local chemical ordering, resulting in roughened dislocation pathways for strengthening. The activated nanoscale segments are observed to be easier to detrap from the regions with stronger Co-Cr local chemical ordering and then propagate into the regions without such chemical ordering. These moving characteristics of the dislocation can delay the unpinning process from nanoprecipitates; thus, extra coupled strengthening effect has been revealed in the HEAs and MEAs with nanoprecipitates compared to pure Orowan’s strengthening.
Raman Imaging of Pathogenic Candida auris: Visualization of Structural Characteristics and Machine-Learning Identification
Authors: Pezzotti Giuseppe , Kobara Miyuki , Asai Tenma , Nakaya Tamaki , Miyamoto Nao , Adachi Tetsuya , Yamamoto Toshiro , Kanamura Narisato , Ohgitani Eriko , Marin Elia , Zhu Wenliang , Nishimura Ichiro , Mazda Osam , Nakata Tetsuo , Makimura Koichi
Published: November 2021

Invasive fungal infections caused by yeasts of the genus Candida carry high morbidity and cause systemic infections with high mortality rate in both immunocompetent and immunosuppressed patients. Resistance rates against antifungal drugs vary among Candida species, the most concerning specie being Candida auris, which exhibits resistance to all major classes of available antifungal drugs. The presently available identification methods for Candida species face a severe trade-off between testing speed and accuracy. Here, we propose and validate a machine-learning approach adapted to Raman spectroscopy as a rapid, precise, and labor-efficient method of clinical microbiology for C. auris identification and drug efficacy assessments. This paper demonstrates that the combination of Raman spectroscopy and machine learning analyses can provide an insightful and flexible mycology diagnostic tool, easily applicable on-site in the clinical environment.
Hypolipidemic Effects of Fermented Seaweed Extracts by Saccharomyces cerevisiae and Lactiplantibacillus plantarum
Authors: Yue Qiulin , Wang Zhongjian , Tang Xueyang , Zhao Chen , Li Kunlun , Su Le , Zhang Song , Sun Xin , Liu Xinli , Zhao Lin
Published: November 2021

The fermentation of food materials with suitable probiotic strains is an effective way to improve biological activities. In this study, seaweed extracts were fermented by Saccharomyces cerevisiae and Lactiplantibacillus plantarum, and the hypolipidemic effects of the fermentation products were investigated. In vitro experiments suggested that fermented seaweed extracts have a high capacity for bile acid-binding. Additionally, a significant inhibitory effect against pancreatic lipase was observed. Furthermore, effects in hyperlipidemic mice were determined. Fermented seaweed extracts can alleviate lipid metabolism disorder. The administration of fermented seaweed extracts to mice showed decreased total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels and increased high-density lipoprotein cholesterol (HDL-C) levels. Combined, these results suggest that fermented seaweed extracts perform a potent hypolipidemic action, thus providing an effective method for the preparation of functional foods to combat cardiovascular diseases.
NLRP3 Inflammasome Activation Enhanced by TRIM25 is Targeted by the NS1 Protein of 2009 Pandemic Influenza A Virus
Authors: Park Hong-Su , Lu Yao , Pandey Kannupriya , Liu GuanQun , Zhou Yan
Published: November 2021

Nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome-mediated interleukin-1 beta (IL-1β) production is one of the crucial responses in innate immunity upon infection with viruses including influenza A virus (IAV) and is modulated by both viral and host cellular proteins. Among host proteins involved, we identified tripartite motif-containing protein 25 (TRIM25) as a positive regulator of porcine NLRP3 inflammasome-mediated IL-1β production. TRIM25 achieved this function by enhancing the pro-caspase-1 interaction with apoptosis-associated speck-like protein containing caspase recruitment domain (ASC). The N-terminal RING domain, particularly residues predicted to be critical for the E3 ligase activity of TRIM25, was responsible for this enhancement. However, non-structural protein 1 (NS1) C-terminus of 2009 pandemic IAV interfered with this action by interacting with TRIM25, leading to diminished association between pro-caspase-1 and ASC. These findings demonstrate that TRIM25 promotes the IL-1β signaling, while it is repressed by IAV NS1 protein, revealing additional antagonism of the NS1 against host pro-inflammatory responses.
Reproduction in Animal Models of Lysosomal Storage Diseases: A Scoping Review
Authors: Vuolo Daniela , Do Nascimento Cinthia Castro , D’Almeida Vânia
Published: November 2021

Background:Lysosomal storage diseases (LSDs) are caused by a mutation in a specific gene. Enzymatic dysfunction results in a progressive storage of substrates that gradually affects lysosomal, cellular and tissue physiology. Their pathophysiological consequences vary according to the nature of the stored substrate, making LSDs complex and multisystemic diseases. Some LSDs result in near normal life expectancies, and advances in treatments mean that more people reach the age to have children, so considering the effects of LSDs on fertility and the risks associated with having children is of growing importance.

Objectives:As there is a lack of clinical studies describing the effect of LSDs on the physiology of reproductivity, we undertook a scoping review of studies using animal models of LSDs focusing on reproductive parameters.

Methods:We searched six databases: MEDLINE, LILACS, Scopus, Web of Science, Embase and SciELO, and identified 49 articles that met our inclusion criteria.

Results:The majority of the studies used male animal models, and a number reported severe morphological and physiological damage in gametes and gonads in models of sphingolipidoses. Models of other LSDs, such as mucopolysaccharidoses, presented important morphological damage.

Conclusion:Many of the models found alterations in reproductive systems. Any signs of subfertility or morphological damage in animal models are important, particularly in rodents which are extremely fertile, and may have implications for individuals with LSDs. We suggest the use of more female animal models to better understand the physiopathology of the diseases, and the use of clinical case studies to further explore the risks of individuals with LSDs having children.
Explore Protein Conformational Space With Variational Autoencoder
Authors: Tian Hao , Jiang Xi , Trozzi Francesco , Xiao Sian , Larson Eric C. , Tao Peng
Published: November 2021

Molecular dynamics (MD) simulations have been actively used in the study of protein structure and function. However, extensive sampling in the protein conformational space requires large computational resources and takes a prohibitive amount of time. In this study, we demonstrated that variational autoencoders (VAEs), a type of deep learning model, can be employed to explore the conformational space of a protein through MD simulations. VAEs are shown to be superior to autoencoders (AEs) through a benchmark study, with low deviation between the training and decoded conformations. Moreover, we show that the learned latent space in the VAE can be used to generate unsampled protein conformations. Additional simulations starting from these generated conformations accelerated the sampling process and explored hidden spaces in the conformational landscape.
Regional Brain Volume, Brain Reserve and MMSE Performance in Healthy Aging From the NEUROAGE Cohort: Contributions of Sex, Education, and Depression Symptoms
Authors: Pettemeridou Eva , Kallousia Eleni , Constantinidou Fofi
Published: November 2021

Objective: The aim of this study was twofold. First, to investigate the relationship between age, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes, brain reserve (BR), and specific regions of interest (ROIs) with global cognitive function in healthy older adults participating in a longitudinal study on aging in the island country of Cyprus. Second, to assess the contribution of important demographic and psychosocial factors on brain volume. Specifically, the effects of sex and years of education and the association between depression symptoms on brain volume were also explored in this Mediterranean cohort.

Methods: Eighty-seven healthy older adults (males = 37, females = 50) scoring ≥24 on the Mini-Mental State Examination (MMSE) were included, with a mean age of 72.75 years and a mean educational level of 10.48 years. The Geriatric Depression Scale was used to assess depression. T1-weighted magnetic resonance images were used to calculate global and regional volumes.

Results: Age was negatively correlated with GM, WM, BR, MMSE scores, and ROIs, including the hippocampus, amygdala, entorhinal cortex, prefrontal cortex, anterior cingulate gyrus, and positively with CSF. Higher MMSE scores positively correlated with GM volume. Women exhibited greater levels of depression than men. Depression was also negatively correlated with GM volume and MMSE scores. Men had greater ventricular size than women and participants with higher education had greater ventricular expansion than those with fewer years in education.

Conclusions: The reported structural changes provide evidence on the overlap between age-related brain changes and healthy cognitive aging and suggest that these age changes affect certain regions. Furthermore, sex, depressive symptomatology, and education are significant predictors of the aging brain. Brain reserve and higher education accommodate these changes and works against the development of clinical symptoms.
Microemulsions: Unique Properties, Pharmacological Applications, and Targeted Drug Delivery
Authors: Suhail Nida , Alzahrani A. Khuzaim , Basha W. Jamith , Kizilbash Nadeem , Zaidi Arsalan , Ambreen Jaweria , Khachfe Hassan M.
Published: November 2021

Microemulsions, comprising oil, water and a surfactant, in association with some co-surfactant, are thermodynamically stable systems. They have found applications in a large number of chemical and pharmacological processes due to their unique properties such as large interfacial area, low interfacial tension, and most importantly, the ability to solubilize and deliver hydrophobic drugs. In addition to the oral and intravenous route, they are suitable for drug delivery through the ophthalmic, vaginal, pulmonary, dental, and topical routes. This review highlights the properties and several recent developments in the use of microemulsions for medical treatment purposes including targeted drug delivery.
Cerebrovascular Risk Profiles in a Saudi Arabian Cohort of Young Stroke Patients
Authors: Eltemamy Marwa Ahmed , Tamayo Arturo , Altarsha Eyad , Sedghi Annahita , Pallesen Lars-Peder , Barlinn Jessica , Puetz Volker , Illigens Ben Min-Woo , Barlinn Kristian , Siepmann Timo
Published: November 2021

Background: The constantly increasing incidence of stroke in younger individuals substantiates an urgent need for research to elucidate underlying risk factors and etiologies. Heretofore, the vast majority of studies on stroke in the young have been carried out in European and North American regions. We aimed to characterize cerebrovascular risk profiles in a Saudi Arabic cohort of consecutive young stroke patients.

Methods: We retrospectively analyzed data from consecutive ischemic stroke patients aged 15 to 49 years who underwent detailed cardiocerebrovascular evaluation at a tertiary stroke care center in Makkah, Saudi Arabia. Distributions of risk factors and stroke etiologies were assessed in the entire cohort and in two strata of very young (15–40 years) and young to middle-aged patients (41–49) to account for variability in suggested age cutoffs.

Results: In the entire cohort [n = 63, ages 44 (34–47) median, interquartile range], dyslipidemia (71.4%) and small vessel occlusion (31.7%) displayed highest prevalence followed by diabetes (52.4%) and cardioembolism (19%). In very young patients, cardioembolism was the most prevalent etiology (27.3%). Risk profiles were similar between both age strata except for a higher prevalence of diabetes among the older cohort (31.8 vs. 63.4%, p = 0.01). Logistic regression identified diabetes as strongest predictor for association to the older strata (odds ratio = 4.2, 95% confidence interval = 1.2–14.1, p = 0.02).

Conclusion: Cerebrovascular risk profiles and stroke etiologies in our cohort of young stroke patients differ from those of previous cohorts, suggesting the need for tailored prevention strategies that take into account local epidemiological data on cerebrovascular health.
Health Concerns of Adolescents and Adults With Spina Bifida
Authors: Starowicz Jessica , Cassidy Caitlin , Brunton Laura
Published: November 2021

Due to advancements in medical care, people with spina bifida (SB) are surviving well into adulthood, resulting in a growing number of patients transitioning to an adult sector unequipped to care for people with chronic rehabilitative and medical needs. The Transitional and Lifelong Care (TLC) program is a multidisciplinary clinical service that compensates for this gap, providing comprehensive, coordinated care to adolescents, and adults with SB. As a relatively new clinical service, objective data about the patients using the service and their needs is scant. This study sought to identify the most common health concerns among TLC patients with SB at initial clinical consultation. A retrospective chart review of 94 patient charts was performed. Following data extraction, descriptive analyses were completed. The mean age of the sample was 29.04 ± 13.8 years. One hundred individual concerns and 18 concern categories were identified. On average, patients or care providers identified nine health concerns across various spheres of care, with care coordination being the most prevalent concern identified (86%). Patients also commonly had concerns regarding neurogenic bladder (70%), medications (66%), assistive devices (48%), and neurogenic bowel (42%). The numerous and wide-ranging health concerns identified support the need for individualised, coordinated care and a “medical home” for all adolescents and adults with SB during and following the transition to adult care. Health care providers caring for this population should continue to address well-documented health concerns and also consider raising discussion around topics such as sexual health, mental health, and bone health. Further research is required to understand how best to address the complex medical issues faced by adults with SB to maximise health and quality of life and improve access to healthcare.
Imaging Markers of Subcortical Vascular Dementia in Patients With Multiple-Lobar Cerebral Microbleeds
Authors: Lin Chia-Yen , Jhan Song-Ru , Lee Wei-Ju , Chen Po-Lin , Chen Jun-Peng , Chen Hung-Chieh , Chen Ting-Bin
Published: November 2021

Background and Purpose: Small vessel disease (SVD) imaging markers are related to ischemic and hemorrhage stroke and to cognitive dysfunction. This study aimed to clarify the relationship between SVD imaging markers and subcortical vascular dementia in severe SVD burden.

Methods: A total of 57 subjects with multiple lobar cerebral microbleeds (CMBs) and four established SVD imaging markers were enrolled from the dementia and stroke registries of a single center. Visual rating scales that are used to semi-quantify SVD imaging changes were analyzed individually and compositely to make correlations with cognitive domains and subcortical vascular dementia.

Results: Dementia group had higher subcortical and total white matter hyperintensities (WMHs) and SVD composite scores than non-dementia group. Individual imaging markers correlated differently with one another and had distinct cognitive correlations. After adjusting for demographic factors, multivariate logistic regression indicated associations of subcortical WMHs (odds ratio [OR] 2.03, CI 1.24–3.32), total WMHs (OR 1.43, CI 1.09–1.89), lacunes (OR 1.18, CI 1.02–1.35), cerebral amyloid angiopathy-SVD scores (OR 2.33, CI 1.01–5.40), C1 scores (imaging composite scores of CMB and WMH) (OR 1.41, CI 1.09–1.83), and C2 scores (imaging composite scores of CMB, WMH, perivascular space, and lacune) (OR 1.38, CI 1.08–1.76) with dementia.

Conclusions: SVD imaging markers might have differing associations with cognitive domains and dementia. They may provide valuable complementary information in support of personalized treatment planning against cognitive impairment, particularly in patients with a heavy SVD load.
Cardiopulmonary Sleep Spectrograms Open a Novel Window Into Sleep Biology—Implications for Health and Disease
Authors: Al Ashry Haitham S. , Ni Yuenan , Thomas Robert J.
Published: November 2021

The interactions of heart rate variability and respiratory rate and tidal volume fluctuations provide key information about normal and abnormal sleep. A set of metrics can be computed by analysis of coupling and coherence of these signals, cardiopulmonary coupling (CPC). There are several forms of CPC, which may provide information about normal sleep physiology, and pathological sleep states ranging from insomnia to sleep apnea and hypertension. As CPC may be computed from reduced or limited signals such as the electrocardiogram or photoplethysmogram (PPG) vs. full polysomnography, wide application including in wearable and non-contact devices is possible. When computed from PPG, which may be acquired from oximetry alone, an automated apnea hypopnea index derived from CPC-oximetry can be calculated. Sleep profiling using CPC demonstrates the impact of stable and unstable sleep on insomnia (exaggerated variability), hypertension (unstable sleep as risk factor), improved glucose handling (associated with stable sleep), drug effects (benzodiazepines increase sleep stability), sleep apnea phenotypes (obstructive vs. central sleep apnea), sleep fragmentations due to psychiatric disorders (increased unstable sleep in depression).
Weight Stigma and Social Media: Evidence and Public Health Solutions
Authors: Clark Olivia , Lee Matthew M. , Jingree Muksha Luxmi , O'Dwyer Erin , Yue Yiyang , Marrero Abrania , Tamez Martha , Bhupathiraju Shilpa N. , Mattei Josiemer
Published: November 2021

Weight stigma is a pressing issue that affects individuals across the weight distribution. The role of social media in both alleviating and exacerbating weight bias has received growing attention. On one hand, biased algorithms on social media platforms may filter out posts from individuals in stigmatized groups and concentrate exposure to content that perpetuates problematic norms about weight. Individuals may also be more likely to engage in attacks due to increased anonymity and lack of substantive consequences online. The critical influence of social media in shaping beliefs may also lead to the internalization of weight stigma. However, social media could also be used as a positive agent of change. Movements such as Body Positivity, the Fatosphere, and Health at Every Size have helped counter negative stereotypes and provide more inclusive spaces. To support these efforts, governments should continue to explore legislative solutions to enact anti-weight discrimination policies, and platforms should invest in diverse content moderation teams with dedicated weight bias training while interrogating bias in existing algorithms. Public health practitioners and clinicians should leverage social media as a tool in weight management interventions and increase awareness of stigmatizing online content among their patients. Finally, researchers must explore how experiences of stigma differ across in-person and virtual settings and critically evaluate existing research methodologies and terminology. Addressing weight stigma on social media will take a concerted effort across an expansive set of stakeholders, but the benefits to population health are consequential and well-worth our collective attention.
Prescription of Kampo Formulations for Pre-natal and Post-partum Women in Japan: Data From an Administrative Health Database
Authors: Suzuki Satoko , Obara Taku , Ishikawa Tomofumi , Noda Aoi , Matsuzaki Fumiko , Arita Ryutaro , Ohsawa Minoru , Mano Nariyasu , Kikuchi Akiko , Takayama Shin , Ishii Tadashi
Published: November 2021

Introduction: Traditional Japanese (Kampo) medicines are often prescribed for women in Japan before, during, and after pregnancy. However, detailed information on the actual frequency of use and safety of Kampo preparations during pregnancy is lacking.

Aim: To investigate the frequency of prescription of Kampo medicines for pregnant women in Japan.

Methods: Information on Kampo medicines prescribed during outpatient care and hospitalization of selected mothers from January 2005 to August 2016 were extracted from the Japan Medical Data Center (Tokyo, Japan), which is a large claims database.

Results: Of the 33,941 subscribers identified from the database, 16,294 (48%) received at least one prescription of a Kampo medicine. Kakkonto was the formula most prescribed during the study period, followed by shoseiryuto and tokishakuyakusan. In the 180 days before pregnancy, the most prescribed medicine was tokishakuyakusan, followed by kakkonto and shoseiryuto. Shoseiryuto, tokishakuyakusan, and kakkonnto were the formulae most prescribed during pregnancy. The most prescribed medicines during the 180 days postpartum were kakkonto, shoseiryuto, and saireito.

Conclusions: Information in the Japanese insurance system shows that Kampo medicines are often prescribed during pregnancy. Most of these prescriptions are generally used for the treatment of common cold. Tokishakuyakusan in particular is usually used in the treatment of various symptoms of pregnancy. Further research is needed to clarify the relationship between the use of Kampo medicines during pregnancy and adverse events in infants in Japan.
Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors
Authors: Opalińska Marta , Sowa-Staszczak Anna , Grochowska Anna , Olearska Helena , Hubalewska-Dydejczyk Alicja
Published: November 2021

Introduction

Neuroendocrine neoplasms including neuroendocrine tumors (NETs) are often diagnosed as primary disseminated or inoperable. In those cases, systemic extensive therapy is necessary, but radical treatment is unlikely. As described in the literature, in some selected cases, peptide receptor radionuclide therapy (PRRT) may be used as a first-line/neoadjuvant therapy that allows further successful surgery. Such treatment may enable a reduction of total tumor burden or allow a radical treatment which improves the final outcomes.

Aim

This study aims to assess whether neoadjuvant PRRT could be a treatment option for patients with initially unresectable NETs.

Methods

Among the group of 114 patients treated with PRRT between the years 2005 and 2020, in 32 cases, it was the first-line therapy, mainly due to massive disease burden at the time of diagnosis. Among them, nine patients received PRRT as the first-line treatment due to the primary inoperable tumors with the intention of preoperative reduction of the tumor size in order to allow for a surgical treatment.

Results

Neoadjuvant PRRT enabled surgery in four out of nine (45%) patients. Finally, in two out of four cases, the goal (radical surgery) has been achieved.

Conclusion

PRRT may be considered not only as a palliative but also as a neoadjuvant therapy in advanced, somatostatin-positive NETs that were initially inoperable.
Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy
Authors: Lin Po-Han , Wang Ming-Yang , Lo Chiao , Tsai Li-Wei , Yen Tzu-Chun , Huang Thomas Yoyan , Huang Wei-Chih , Yang Karen , Chen Chih-Kai , Fan Sheng-Chih , Kuo Sung-Hsin , Huang Chiun-Sheng
Published: November 2021

Background

Patients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer. We aimed to evaluate the prognostic value of ctDNA in the setting of neoadjuvant therapy (NAT).

Methods

Plasma was sampled at the initial diagnosis (defined as before NAT) and after breast surgery and neoadjuvant therapy(defined as after NAT). We extracted ctDNA from the plasma and performed deep sequencing of a target gene panel. ctDNA positivity was marked by the detection of alterations, such as mutations and copy number variations.

Results

A total of 95 patients were enrolled in this study; 60 patients exhibited ctDNA positivity before NAT, and 31 patients exhibited ctDNA positivity after NAT. A pathologic complete response (pCR) was observed in 13 patients, including one ER(+)Her2(-) patient, six Her2(+) patients and six triple-negative breast cancer (TNBC) patients. Among the entire cohort, multivariate analysis showed that N3 classification and ctDNA positivity after NAT were independent risk factors that predicted recurrence (N3, hazard ratio (HR) 3.34, 95% confidence interval (CI) 1.26 – 8.87, p = 0.016; ctDNA, HR 4.29, 95% CI 2.06 – 8.92, p < 0.0001). The presence of ctDNA before NAT did not affect the rate of recurrence-free survival. For patients with Her2(+) or TNBC, patients who did not achieve pCR were associated with a trend of higher recurrence (p = 0.105). Advanced nodal status and ctDNA positivity after NAT were significant risk factors for recurrence (N2 – 3, HR 3.753, 95% CI 1.146 – 12.297, p = 0.029; ctDNA, HR 3.123, 95% CI 1.139 – 8.564, p = 0.027). Two patients who achieved pCR had ctDNA positivity after NAT; one TNBC patient had hepatic metastases six months after surgery, and one Her2(+) breast cancer patient had brain metastasis 13 months after surgery.

Conclusions

This study suggested that the presence of ctDNA after NAT is a robust marker for predicting relapse in stage II to III breast cancer patients.
Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α
Authors: Liu Juan , Yang Chao , Huang Xiao-Mei , Lv Pan-Pan , Yang Ya-Kun , Zhao Jin-Na , Zhao Si-Yuan , Sun Wan-Jun
Published: November 2021

The transcription suppressor factor FBI-1 (the factor that binds to inducer of short transcripts-1) is an important regulator of hepatocellular carcinoma (HCC). In this work, the results showed that FBI-1 promoted the Warburg effect and enhances the resistance of hepatocellular carcinoma cells to molecular targeted agents. Knockdown of FBI-1 via its small-interfering RNA (siRNA) inhibited the ATP level, lactate productions, glucose uptake or lactate dehydrogenase (LDH) activation of HCC cells. Transfection of siFBI-1 also decreased the expression of the Warburg-effect-related factors: hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A (LDHA), or GLUT1, and the epithelial–mesenchymal transition-related factors, Vimentin or N-cadherin. The positive correlation between the expression of FBI-1 with HIF-1α, LDHA, or GLUT1 was confirmed in HCC tissues. Mechanistically, the miR-30c repressed the expression of HIF-1α by binding to the 3′-untranslated region (3′-UTR) of HIF-1α in a sequence-specific manner, and FBI-1 enhanced the expression of HIF-1α and HIF-1α pathway’s activation by repressing the expression of miR. By modulating the miR-30c/HIF-1α, FBI-1 promoted the Warburg effect or the epithelial–mesenchymal transition of HCC cells and promoted the resistance of HCC cells to molecular targeted agents.