bluuebunny/crossref_metadata_2025 huggingface dataset:
Silicon Nitride, a Bioceramic for Bone Tissue Engineering: A Reinforced Cryogel System With Antibiofilm and Osteogenic Effects
Authors: Lee Seunghun S. , Laganenka Leanid , Du Xiaoyu , Hardt Wolf-Dietrich , Ferguson Stephen J.
Published: December 2021

Silicon nitride (SiN [Si3N4]) is a promising bioceramic for use in a wide variety of orthopedic applications. Over the past decades, it has been mainly used in industrial applications, such as space shuttle engines, but not in the medical field due to scarce data on the biological effects of SiN. More recently, it has been increasingly identified as an emerging material for dental and orthopedic implant applications. Although a few reports about the antibacterial properties and osteoconductivity of SiN have been published to date, there have been limited studies of SiN-based scaffolds for bone tissue engineering. Here, we developed a silicon nitride reinforced gelatin/chitosan cryogel system (SiN-GC) by loading silicon nitride microparticles into a gelatin/chitosan cryogel (GC), with the aim of producing a biomimetic scaffold with antibiofilm and osteogenic properties. In this scaffold system, the GC component provides a hydrophilic and macroporous environment for cells, while the SiN component not only provides antibacterial properties and osteoconductivity but also increases the mechanical stiffness of the scaffold. This provides enhanced mechanical support for the defect area and a better osteogenic environment. First, we analyzed the scaffold characteristics of SiN-GC with different SiN concentrations, followed by evaluation of its apatite-forming capacity in simulated body fluid and protein adsorption capacity. We further confirmed an antibiofilm effect of SiN-GC against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as well as enhanced cell proliferation, mineralization, and osteogenic gene upregulation for MC3T3-E1 pre-osteoblast cells. Finally, we developed a bioreactor to culture cell-laden scaffolds under cyclic compressive loading to mimic physiological conditions and were able to demonstrate improved mineralization and osteogenesis from SiN-GC. Overall, we confirmed the antibiofilm and osteogenic effect of a silicon nitride reinforced cryogel system, and the results indicate that silicon nitride as a biomaterial system component has a promising potential to be developed further for bone tissue engineering applications.
Endovascular Thrombolysis in Hypothenar Hammer Syndrome: A Systematic Review
Authors: Jud Philipp , Pregartner Gudrun , Berghold Andrea , Rief Peter , Muster Viktoria , Gütl Katharina , Brodmann Marianne , Hafner Franz
Published: December 2021

Objectives: Hypothenar hammer syndrome (HHS) is a rare vascular disease caused by blunt trauma of the hypothenar region. The optimal therapeutic strategy remains debatably since no large comparative studies are available yet. We want to evaluate the effectiveness of intra-arterial thrombolysis on angiographic and clinical outcome parameters in patients with HHS by performing a systematic review of the existing literature.

Methods: A literature search of PUBMED/MEDLINE and SCIENCE DIRECT databases was performed up to May 2021.

Results: In total, 16 manuscripts with 43 patients were included in the systematic review. Intra-arterial thrombolysis led to angiographic improvement in 29 patients (67.4%) and to clinical improvement in 34 patients (79.1%). Deterioration of arterial perfusion or clinical symptoms after thrombolysis were absent. Post-interventional complications were reported in only one patient (2.3%) without any bleeding complication. Logistic regression analyses demonstrated that a combined administration of fibrinolytics and heparin was associated with a significantly improved arterial patency [OR 12.57 (95% CI 2.48–97.8), p = 0.005] without significant amelioration of clinical symptoms [OR 3.20 (95% CI 0.6–18.9), p = 0.172]. The use of rt-PA compared to other fibrinolytics and a prolonged thrombolysis duration of more than 24 h did not show statistically significant effects. Intra-arterial thrombolysis was significantly less effective in patients who had undergone thrombolysis with a delay of more than 30 days regarding clinical improvement [OR 0.07 (95% CI 0.00–0.54), p = 0.024].

Conclusions: Intra-arterial thrombolysis with a combination of fibrinolytics and heparin is an effective and safe therapeutic option in patients with acute HHS.
Effects of Hot Balloon vs. Cryoballoon Ablation for Atrial Fibrillation: A Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Peng Xinyi , Liu Xiao , Tian Hongbo , Chen Yu , Li Xuexun
Published: December 2021

Background: Balloon-based catheter ablations, including hot balloon ablation (HBA) and cryoballoon ablation (CBA), have rapidly emerged as alternative modalities to conventional catheter atrial fibrillation (AF) ablation owing to their impressive procedural advantages and better clinical outcomes and safety. However, the differences in characteristics, effectiveness, safety, and efficacy between HBA and CBA remain undetermined. This study compares the characteristic and prognosis differences between HBA and CBA.

Methods: Electronic search was conducted in six databases (PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrial.gov, and medRxiv) with specific search strategies. Eligible studies were selected based on specific criteria; all records were identified up to June 1, 2021. The mean difference, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Heterogeneity and risk of bias were assessed using predefined criteria.

Results: Seven studies were included in the final meta-analysis. Compared with CBA, more patients in the HBA group had residual conduction and required a higher incidence of touch-up ablation (TUA) [OR (95% CI) = 2.76 (2.02–3.77), P = 0.000]. The most frequent sites of TUA were the left superior pulmonary veins (PVs) in the HBA group vs. the right inferior PVs in the CBA group. During HBA surgery, the left and right superior PVs were more likely to have a higher fluid injection volume. Furthermore, the procedure time was longer in the HBA group than in the CBA group [weighted mean difference (95% CI) = 14.24 (4.39–24.09), P = 0.005]. Patients in the CBA group could have an increased risk of AF occurrence, and accepted more antiarrhythmic drug therapy; however, the result was insignificant.

Conclusions: HBA and CBA are practical ablation approaches for AF treatment. Patients who received HBA had a higher incidence of TUA and longer procedure time. Clinical outcomes during the mid-term follow-up between HBA and CBA were comparable.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259487, identifier: CRD42021259487.
When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis
Authors: Hayes Kaleen N. , Baschant Ulrike , Hauser Barbara , Burden Andrea M. , Winter Elizabeth M.
Published: December 2021

Glucocorticoid-induced osteoporosis (GIOP) leads to fractures in up to 40% of patients with chronic glucocorticoid (GC) therapy when left untreated. GCs rapidly increase fracture risk, and thus many patients with anticipated chronic GC exposures should start anti-osteoporosis pharmacotherapy to prevent fractures. In addition to low awareness of the need for anti-osteoporosis therapy among clinicians treating patients with GCs, a major barrier to prevention of fractures from GIOP is a lack of clear guideline recommendations on when to start and stop anti-osteoporosis treatment in patients with GC use. The aim of this narrative review is to summarize current evidence and provide considerations for the duration of anti-osteoporosis treatment in patients taking GCs based on pre-clinical, clinical, epidemiologic, and pharmacologic evidence. We review the pathophysiology of GIOP, outline current guideline recommendations on initiating and stopping anti-osteoporosis therapy for GIOP, and present considerations for the duration of anti-osteoporosis treatment based on existing evidence. In each section, we illustrate major points through a patient case example. Finally, we conclude with proposed areas for future research and emerging areas of interest related to GIOP clinical management.
The Significance of Planned Fertility Preservation for Women With Endometrioma Before an Expected Ovarian Cystectomy
Authors: Hong Yeon Hee , Lee Hyun Kyoung , Kim Seul Ki , Lee Jung Ryeol , Suh Chang Suk
Published: December 2021

Endometrioma is known to reduce the ovarian reserve and the extent of the decrease is more severe when ovarian surgery is performed. Therefore, to prevent this decline in fertility, patients with endometrioma are considered candidates for preoperative fertility preservation (FP). In this study, we evaluate the efficacy of FP in women with endometrioma before planned ovarian surgery. A total of 95 cycles in 62 patients with endometrioma, undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin-releasing hormone (GnRH) antagonist protocol before an expected ovarian surgery, were enrolled retrospectively. COS outcomes were compared according to endometrioma laterality. Additionally, first COS cycle outcomes in patients with endometrioma were compared with those in infertile patients, or in patients with a benign ovarian cyst using propensity score matching. When multiple COS cycles were performed, the results of cumulative cycles were analyzed. Embryo quality was worse in the bilateral endometrioma group. Compared with the infertile patient group, the patients with endometrioma had significantly lower Anti-Müllerian Hormone (AMH) and fewer numbers of oocytes retrieved (median, 3.3 vs. 1.2, p<0.001; 7.0 vs. 4.0, p=0.009, respectively). Compared with mature oocytes in infertile patients or patients with a benign cyst, mature oocytes were fewer in patients with endometrioma, but this was not statistically significant (median, 4.0 vs. 3.0, p=0.085; 5.5 vs. 3.0, p=0.052, respectively). The median value of the cumulative number of cryopreserved oocytes or embryos was 14.5 up to the fourth cycle compared to 3 up to the first cycle, with cumulative effect. Women with endometrioma should be counseled for FP before planned ovarian cystectomy. The number of cryopreserved oocytes or embryos can be increased by repeated cycles.
Refinements of Pin-Based Pointwise Energy Slowing-Down Method for Resonance Self-Shielding Calculation-II: Verifications
Authors: Kim Wonkyeong , Choi Sooyoung , Lee Deokjung
Published: December 2021

The pin-based pointwise energy slowing-down method (PSM) has been refined through eliminating the approximation for using the pre-tabulated collision probability during the slowing-down calculation. A collision probability table is generated by assuming that material composition and temperature are constant in the fuel pellet using the collision probability method (CPM). Refined PSM (PSM-CPM), which calculates the collision probability in the isolated fuel pellet during the slowing-down calculation using CPM, can consider nonuniform material and temperature distribution. For the methods, the extensive comparative analysis is performed with problems representing various possible conditions in a light water reactor (LWR) design. Conditions are categorized with the geometry, material distribution, temperature profile in the fuel pellet, and burnup. With test problems, PSMs (PSM and PSM-CPM) have been compared with conventional methods based on the equivalence theory. With overall calculation results, PSMs show the accuracy in the eigenvalue with differences in the order of 100 pcm compared to the reference results. There was no noticeable difference in the multigroup cross sections, reaction rates, and pin power distributions. However, PSM-CPM maintains the accuracy in the calculation of the fuel temperature coefficient under the condition with 200% power and nonuniform temperature distribution in the fuel pellet. PSM shows the difference in the eigenvalue in the order of 2,000 pcm for the fictitious pin-cell problem with highly steep temperature profiles and material compositions, but PSM-CPM shows the difference in the eigenvalue within 100 pcm.
Two-Stage Energy Management for Energy Storage System by Using Stochastic Model Predictive Control Approach
Authors: Zhuang Huimin , Tang Zao , Zhang Jianglin
Published: December 2021

There is a growing tendency for industrial consumers to invest in both photovoltaic (PV) and energy storage systems (ESSs) to meet their electricity requirements. However, the uncertainty of load demand and PV output brings great challenges for ESS operation. In this paper, a stochastic model predictive control (MPC) approach-based energy management strategy for ESSs is proposed. A non-parametric probabilistic prediction method embedded in time series correlation is adopted to describe the uncertainty of load demand and PV output. Then, a two-stage energy management model is proposed aiming at minimizing the total operation cost. The upper stage can generate an hourly operation strategy for ESSs, while the lower stage focuses on a more detailed minute-level operation strategy. The hourly operation strategy is also used as a basis to guide the ESS operation in the lower stage. Besides, a chance constraint was introduced to achieve a win–win solution between PV power consumption and electricity tariff, while the terminal value constraint of the capacity of ESSs to better cope with the uncertainty beyond the prediction time window. Finally, the numerical results showed that the proposed method can achieve an effective ESS energy management strategy.
Small-Area Estimation for the USDA Forest Service, National Woodland Owner Survey: Creating a Fine-Scale Land Cover and Ownership Layer to Support County-Level Population Estimates
Authors: Harris Vance , Caputo Jesse , Finley Andrew , Butler Brett J. , Bowlick Forrest , Catanzaro Paul
Published: December 2021

Small area estimation is a powerful modeling technique in which ancillary data can be utilized to “borrow” additional information, effectively increasing sample sizes in small spatial, temporal, or categorical domains. Though more commonly applied to biophysical variables within the study of forest inventory analyses, small area estimation can also be implemented in the context of understanding social values, behaviors, and trends among types of forest landowners within small domains. Here, we demonstrate a method for deriving a continuous fine-scale land cover and ownership layer for the state of Delaware, United States, and an application of that ancillary layer to facilitate small-area estimation of several variables from the USDA Forest Service’s National Woodland Owner Survey. Utilizing a proprietary parcel layer alongside the National Land Cover Database, we constructed a continuous layer with 10-meter resolution depicting land cover and land ownership classes. We found that the National Woodland Owner Survey state-level estimations of total acreage and total ownerships by ownership class were generally within one standard error of the population values calculated from the raster layer, which supported the direct calculation of several population-level summary variables at the county levels. Subsequently, we compare design-based and model-based methods of predicting commercial harvesting by family forest ownerships in Delaware in which forest ownership acreage, taken from the parcel map, was utilized to inform the model-based approach. Results show general agreement between the two modes, indicating that a small area estimation approach can be utilized successfully in this context and shows promise for other variables, especially if additional variables, e.g., United States Census Bureau data, are also incorporated.
The Physical, Psychological, and Social Day-to-Day Experience of Women Living With Endometriosis Compared to Healthy Age-Matched Controls—A Mixed-Methods Study
Authors: Olliges Elisabeth , Bobinger Alina , Weber Annemarie , Hoffmann Verena , Schmitz Timo , Popovici Roxana M. , Meissner Karin
Published: December 2021

Background: Endometriosis is characterized by lesions of endometrial tissue outside the uterus. Chronic pain is considered as main symptom, but challenges can relate to various physical, mental, and social aspects of the women's lives. The aim of our study was to gain a holistic understanding of the everyday reality of women with endometriosis compared to healthy controls.

Methods: The total sample comprised 12 hormone-free endometriosis patients (EP) and 11 age-matched healthy women (HC). A mixed-methods design was used comprising semi-structured interviews, standardized questionnaires and a comprehensive diary to assess pain ratings and various mental and physical symptoms over the course of a menstrual cycle. Interviews were recorded, transcribed, and evaluated according to phenomenological analysis using the MAXQDA software.

Results: Interviews showed that living with endometriosis was associated with an impairment in everyday life. Physical strains, especially pain, high levels of psychological distress, and social limitations have been reported. Living with endometriosis affected the patients' personality and they “no longer felt like themselves.” Physical and psychological symptoms were reported to interfere with social interaction and participation. Evaluation of the standardized questionnaires revealed significant impairments in EP compared to HC in regard to anxiety and depression scores (both p < 0.001; Hospital Anxiety and Depression Scale), mental and physical quality of life (both p < 0.001; Short-Form Health Survey-12), stress ratings (p < 0.001; Patient Health Questionnaire-15) and functional well-being (p < 0.001; Functional Well-being-7). The highest levels of mean pelvic pain and dyschezia were observed in EP during menstruation, but mean pain ratings and dyschezia were increased in EPs compared to HP during the whole cycle. EP reported mental symptoms (e.g., depressed mood or anxiety) mainly during menstruation, while HC did not show any mental symptoms during the cycle. In addition, physical symptoms were elevated during the entire cycle in EPs (all p < 0.01).

Discussion: The mixed-methods approach enabled to interpret the interviews, the standardized questionnaires, and the symptom diary in a broader context of everyday life. The symptoms do not appear to act independently, but rather influence each other. This leads to a complex interplay of physical, mental, and social impairments, with pain often being the starting point.
Understanding Gene Expression and Transcriptome Profiling of COVID-19: An Initiative Towards the Mapping of Protective Immunity Genes Against SARS-CoV-2 Infection
Authors: Chakraborty Chiranjib , Sharma Ashish Ranjan , Bhattacharya Manojit , Zayed Hatem , Lee Sang-Soo
Published: December 2021

The COVID-19 pandemic has created an urgent situation throughout the globe. Therefore, it is necessary to identify the differentially expressed genes (DEGs) in COVID-19 patients to understand disease pathogenesis and the genetic factor(s) responsible for inter-individual variability. The DEGs will help understand the disease’s potential underlying molecular mechanisms and genetic characteristics, including the regulatory genes associated with immune response elements and protective immunity. This study aimed to determine the DEGs in mild and severe COVID-19 patients versus healthy controls. The Agilent-085982 Arraystar human lncRNA V5 microarray GEO dataset (GSE164805 dataset) was used for this study. We used statistical tools to identify the DEGs. Our 15 human samples dataset was divided into three groups: mild, severe COVID-19 patients and healthy control volunteers. We compared our result with three other published gene expression studies of COVID-19 patients. Along with significant DEGs, we developed an interactome map, a protein-protein interaction (PPI) pattern, a cluster analysis of the PPI network, and pathway enrichment analysis. We also performed the same analyses with the top-ranked genes from the three other COVID-19 gene expression studies. We also identified differentially expressed lncRNA genes and constructed protein-coding DEG-lncRNA co-expression networks. We attempted to identify the regulatory genes related to immune response elements and protective immunity. We prioritized the most significant 29 protein-coding DEGs. Our analyses showed that several DEGs were involved in forming interactome maps, PPI networks, and cluster formation, similar to the results obtained using data from the protein-coding genes from other investigations. Interestingly we found six lncRNAs (TALAM1, DLEU2, and UICLM CASC18, SNHG20, and GNAS) involved in the protein-coding DEG-lncRNA network; which might be served as potential biomarkers for COVID-19 patients. We also identified three regulatory genes from our study and 44 regulatory genes from the other investigations related to immune response elements and protective immunity. We were able to map the regulatory genes associated with immune elements and identify the virogenomic responses involved in protective immunity against SARS-CoV-2 infection during COVID-19 development.
Titanium Nanoparticles Enhance Production and Suppress Stabilin-1-Mediated Clearance of GDF-15 in Human Primary Macrophages
Authors: Silva-Bermudez Lina S. , Sevastyanova Tatyana N. , Schmuttermaier Christina , De La Torre Carolina , Schumacher Leonie , Klüter Harald , Kzhyshkowska Julia
Published: December 2021

Macrophages are key innate immune cells that mediate implant acceptance or rejection. Titanium implants degrade over time inside the body, which results in the release of implant wear-off particles. Titanium nanoparticles (TiNPs) favor pro-inflammatory macrophage polarization (M1) and lower tolerogenic activation (M2). GDF-15 regulates immune tolerance and fibrosis and is endocytosed by stabilin-1. How TiNPs affect the healing activities of macrophages and their release of circulating cytokines is an open question in regenerative medicine. In this study for the first time, we identified the transcriptional program induced and suppressed by TiNPs in human pro-inflammatory and healing macrophages. Microarray analysis revealed that TiNPs altered the expression of 5098 genes in M1 (IFN-γ-stimulated) and 4380 genes in M2 (IL-4–stimulated) macrophages. 1980 genes were differentially regulated in both M1 and M2. Affymetrix analysis, confirmed by RT-PCR, demonstrated that TiNPs upregulate expression of GDF-15 and suppress stabilin-1, scavenger receptor of GDF-15. TiNPs also significantly stimulated GDF-15 protein secretion in inflammatory and healing macrophages. Flow cytometry demonstrated, that scavenging activity of stabilin-1 was significantly suppressed by TiNPs. Confocal microscopy analysis showed that TiNPs impair internalization of stabilin-1 ligand acLDL and its transport to the endocytic pathway. Our data demonstrate that TiNPs have a dual effect on the GDF-15/stabilin-1 interaction in macrophage system, by increasing the production of GDF-15 and suppressing stabilin-1-mediated clearance function. In summary, this process can result in a significant increase of GDF-15 in the extracellular space and in circulation leading to unbalanced pro-fibrotic reactions and implant complications.
Foam Cell Macrophages in Tuberculosis
Authors: Agarwal Pooja , Gordon Siamon , Martinez Fernando O.
Published: December 2021

Mycobacterium tuberculosis infects primarily macrophages in the lungs. Infected macrophages are surrounded by other immune cells in well organised structures called granulomata. As part of the response to TB, a type of macrophage loaded with lipid droplets arises which we call Foam cell macrophages. They are macrophages filled with lipid laden droplets, which are synthesised in response to increased uptake of extracellular lipids, metabolic changes and infection itself. They share the appearance with atherosclerosis foam cells, but their lipid contents and roles are different. In fact, lipid droplets are immune and metabolic organelles with emerging roles in Tuberculosis. Here we discuss lipid droplet and foam cell formation, evidence regarding the inflammatory and immune properties of foam cells in TB, and address gaps in our knowledge to guide further research.
A Support Vector Machine Based on Liquid Immune Profiling Predicts Major Pathological Response to Chemotherapy Plus Anti-PD-1/PD-L1 as a Neoadjuvant Treatment for Patients With Resectable Non-Small Cell Lung Cancer
Authors: Peng Jie , Zou Dan , Han Lijie , Yin Zuomin , Hu Xiao
Published: December 2021

The biomarkers for the pathological response of neoadjuvant chemotherapy plus anti-programmed cell death protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) (CAPD) are unclear in non-small cell lung cancer (NSCLC). Two hundred and eleven patients with stage Ib-IIIa NSCLC undergoing CAPD prior to surgical resection were enrolled, and 11 immune cell subsets in peripheral blood were prospectively analyzed using multicolor flow cytometry. Immune cell subtypes were selected by recursive feature elimination and least absolute shrinkage and selection operator methods. The support vector machine (SVM) was used to build a model. Multivariate analysis for major pathological response (MPR) was also performed. Finally, five immune cell subtypes were identified and an SVM based on liquid immune profiling (LIP-SVM) was developed. The LIP-SVM model achieved high accuracies in discovery and validation sets (AUC = 0.886, 95% CI: 0.823–0.949, P < 0.001; AUC = 0.874, 95% CI: 0.791–0.958, P < 0.001, respectively). Multivariate analysis revealed that age, radiological response, and LIP-SVM were independent factors for MPR in the two sets (each P < 0.05). The integration of LIP-SVM, clinical factors, and radiological response showed significantly high accuracies for predicting MPR in discovery and validation sets (AUC = 0.951, 95% CI: 0.916–0.986, P < 0.001; AUC = 0.943, 95% CI: 0.912–0.993, P < 0.001, respectively). Based on immune cell profiling of peripheral blood, our study developed a predictive model for the MPR of patients with NSCLC undergoing CAPD treatment that can potentially guide clinical therapy.
Strategies to Circumvent the Side-Effects of Immunotherapy Using Allogeneic CAR-T Cells and Boost Its Efficacy: Results of Recent Clinical Trials
Authors: Smirnov Sergei , Petukhov Alexey , Levchuk Ksenia , Kulemzin Sergey , Staliarova Alena , Lepik Kirill , Shuvalov Oleg , Zaritskey Andrey , Daks Alexandra , Fedorova Olga
Published: December 2021

Despite the outstanding results of treatment using autologous chimeric antigen receptor T cells (CAR-T cells) in hematological malignancies, this approach is endowed with several constraints. In particular, profound lymphopenia in some patients and the inability to manufacture products with predefined properties or set of cryopreserved batches of cells directed to different antigens in advance. Allogeneic CAR-T cells have the potential to address these issues but they can cause life-threatening graft-versus-host disease or have shorter persistence due to elimination by the host immune system. Novel strategies to create an “off the shelf” allogeneic product that would circumvent these limitations are an extensive area of research. Here we review CAR-T cell products pioneering an allogeneic approach in clinical trials.
Novel Insights Into Gene Signatures and Their Correlation With Immune Infiltration of Peripheral Blood Mononuclear Cells in Behcet’s Disease
Authors: Zhan Haoting , Li Haolong , Cheng Linlin , Yan Songxin , Zheng Wenjie , Li Yongzhe
Published: December 2021

Background

Behcet’s disease (BD) is a chronic inflammatory disease that involves systemic vasculitis and mainly manifests as oral and genital ulcers, uveitis, and skin damage as the first clinical symptoms, leading to gastrointestinal, aortic, or even neural deterioration. There is an urgent need for effective gene signatures for BD’s early diagnosis and elucidation of its underlying etiology.

Methods

We identified 82 differentially expressed genes (DEGs) in BD cases compared with healthy controls (HC) after combining two Gene Expression Omnibus datasets. We performed pathway analyses on these DEGs and constructed a gene co-expression network and its correlation with clinical traits. Hub genes were identified using a protein–protein interaction network. We manually selected CCL4 as a central hub gene, and gene-set enrichment and immune cell subset analyses were applied on patients in high- and low-CCL4 expression groups. Meanwhile, we validated the diagnostic value of hub genes in differentiating BD patients from HC in peripheral blood mononuclear cells using real-time PCR.

Results

Twelve hub genes were identified, and we validated the upregulation of CCL4 and the downregulation of NPY2R mRNA expression. Higher expression of CCL4 was accompanied by larger fractions of CD8 + T cells, natural killer cells, M1 macrophages, and activated mast cells. Receiver operator characteristic curves showed good discrimination between cases and controls based on the expression of these genes.

Conclusion

CCL4 and NPY2R could be diagnostic biomarkers for BD that reveal inflammatory status and predict vascular involvement in BD, respectively.
Technical Considerations for Development of Policy and Approvals for In-Water Cleaning of Ship Biofouling
Authors: Tamburri Mario N. , Georgiades Eugene T. , Scianni Christopher , First Matthew R. , Ruiz Gregory M. , Junemann Carolyn E.
Published: December 2021

Submerged ship surfaces are often inhabited by diverse sessile and sedentary marine organisms, which can directly impact vessel operations and increase the likelihood of non-indigenous species (NIS) establishment and impacts. Ship in-water cleaning (IWC) systems are now being incorporated into biofouling policy, and rigorous, transparent, and predictive verification testing is vital to regulatory success. Performance criteria for IWC approval should focus on environmental protection goals by including: qualified and independent testing; quantitative, robust, and statistically sound data, rather than qualitative observations; water sampling at all critical control points to characterize the release of harmful materials, including dissolved and particulate biocides; measurable and protective endpoints, rather than percent reductions; determinations of presence or absence of macro-organisms, irrespective of species origins or physiological state; and appropriately trained IWC operators.
Preparation of ZnO/Brucite Functional Composite Powder by the Mechanochemical Method
Authors: Shuai Huan , Wang Jiao , Ren Fengguo , Du Gaoxiang
Published: December 2021

In this experiment, ZnO/brucite composite powder was prepared through the mechanochemical method; further, the properties, particle morphology, and structure of the composite powder were characterized. The results show that mechanical grinding action can promote the production of a large number of surface ions with unsaturated coordination number on the surface of brucite and ZnO particles, thereby promoting hydroxylation of the particle surfaces. The addition of NaOH to the composite system can also aid the further activation of the surface of the brucite and ZnO particles and the formation of more associated hydroxyl groups. Finally, a core–shell composite powder is formed with weak forces such as hydrogen bonds and van der Waals forces as the connecting bonds.
Macular Vascular Geometry Changes With Sex and Age in Healthy Subjects: A Fundus Photography Study
Authors: Feng Ziqing , Wang Gengyuan , Xia Honghui , Li Meng , Liang Guoxia , Dong Tingting , Xiao Peng , Yuan Jin
Published: December 2021

Purpose: To characterize the sex- and age-related alterations of the macular vascular geometry in a population of healthy eyes using fundus photography.

Methods: A cross-sectional study was conducted with 610 eyes from 305 healthy subjects (136 men, 169 women) who underwent fundus photography examination and was divided into four age groups (G1 with age ≤ 25 years, G2 with age 26–35 years, G3 with age 36–45 years, and G4 with age ≥ 46 years). A self-developed automated retinal vasculature analysis system allowed segmentation and separate multiparametric quantification of the macular vascular network according to the Early Treatment Diabetic Retinopathy Study (ETDRS). Vessel fractal dimension (Df), vessel area rate (VAR), average vessel diameter (Dm), and vessel tortuosity (τn) were acquired and compared between sex and age groups.

Results: There was no significant difference between the mean age of male and female subjects (32.706 ± 10.372 and 33.494 ± 10.620, respectively, p > 0.05) and the mean age of both sexes in each age group (p > 0.05). The Df, VAR, and Dm of the inner ring, the Df of the outer ring, and the Df and VAR of the whole macula were significantly greater in men than women (p < 0.001, p < 0.001, p < 0.05, respectively). There was no significant change of τn between males and females (p > 0.05). The Df, VAR, and Dm of the whole macula, the inner and outer rings associated negatively with age (p < 0.001), whereas the τn showed no significant association with age (p > 0.05). Comparison between age groups observed that Df started to decrease from G2 compared with G1 in the inner ring (p < 0.05) and Df, VAR, and Dm all decreased from G3 compared with the younger groups in the whole macula, inner and outer rings (p < 0.05).

Conclusion: In the healthy subjects, macular vascular geometric parameters obtained from fundus photography showed that Df, VAR, and Dm are related to sex and age while τn is not. The baseline values of the macular vascular geometry were also acquired for both sexes and all age groups.
The Impact of Bartonella VirB/VirD4 Type IV Secretion System Effectors on Eukaryotic Host Cells
Authors: Fromm Katja , Dehio Christoph
Published: December 2021

Bartonella spp. are facultative intracellular pathogens that infect a wide range of mammalian hosts including humans. The VirB/VirD4 type IV secretion system (T4SS) is a key virulence factor utilized to translocate Bartonella effector proteins (Beps) into host cells in order to subvert their functions. Crucial for effector translocation is the C-terminal Bep intracellular delivery (BID) domain that together with a positively charged tail sequence forms a bipartite translocation signal. Multiple BID domains also evolved secondary effector functions within host cells. The majority of Beps possess an N-terminal filamentation induced by cAMP (FIC) domain and a central connecting oligonucleotide binding (OB) fold. FIC domains typically mediate AMPylation or related post-translational modifications of target proteins. Some Beps harbor other functional modules, such as tandem-repeated tyrosine-phosphorylation (EPIYA-related) motifs. Within host cells the EPIYA-related motifs are phosphorylated, which facilitates the interaction with host signaling proteins. In this review, we will summarize our current knowledge on the molecular functions of the different domains present in Beps and highlight examples of Bep-dependent host cell modulation.
Characteristics of Mucormycosis in Hematological Patients and a Death Prediction Model
Authors: Ma Xiaoxu , Li Ang , Cao Weijie , Li Huiling , Zhang Suping , Li Li , Xing Haizhou , Tian Wenliang , Jiao Pengfei , Chen Jiajun , Zhang Qingxian , Xu Aiguo , Xing Lihua
Published: December 2021

Mucormycosis is an angioinvasive fungal infection, associated with high mortality. The aim of our study was to explore the high-risk factors and predict the death of hematological disease complicated with mucormycosis. We retrospectively analyzed clinical data of 31 patients with hematological disease complicated with mucormycosis, adopted random forest to establish the death prediction model, and validated the model in another 15 patients. The median age of the 31 cases was 46 (28–51) years, male to female ratio 1.38:1, and 90-day mortality rate 54.8%. The most common underlying disease was acute myeloid leukemia (58.1%). The main clinical symptoms were fever (100%), cough (87.1%), sputum (80.6%), chest pain (61.3%), and hemoptysis (19.4%). Reversed halo sign (83.9%) was the most common computed tomography sign. A total of 48.4% of patients also had aspergillus or bacterial infections. Discriminative models were constructed by random forest with 17 non-survivors and 14 survivors. Procalcitonin, the duration of intravenous administration of amphotericin B or amphotericin B liposomes, and neutropenia at death or 90 days of survival were the leading risk factors for poor prognosis, with area under the curve of 0.975 (95% CI 0.934–1). We chose 0.6775 as death prediction threshold (with 82.3% sensitivity and 100% specificity) and validated the model successfully in another 15 patients. Chest pain and reversed halo sign are specific clinical and image signs of hematological disease complicated with mucormycosis. Neutropenia, elevated procalcitonin, and insufficient use time of amphotericin B or amphotericin B liposomes are risk factors for death.
Magnetoencephalography Studies of the Envelope Following Response During Amplitude-Modulated Sweeps: Diminished Phase Synchrony in Autism Spectrum Disorder
Authors: Roberts Timothy P. L. , Bloy Luke , Liu Song , Ku Matthew , Blaskey Lisa , Jackel Carissa
Published: December 2021

Prevailing theories of the neural basis of at least a subset of individuals with autism spectrum disorder (ASD) include an imbalance of excitatory and inhibitory neurotransmission. These circuitry imbalances are commonly probed in adults using auditory steady-state responses (ASSR, driven at 40 Hz) to elicit coherent electrophysiological responses (EEG/MEG) from intact circuitry. Challenges to the ASSR methodology occur during development, where the optimal ASSR driving frequency may be unknown. An alternative approach (more agnostic to driving frequency) is the amplitude-modulated (AM) sweep in which the amplitude of a tone (with carrier frequency 500 Hz) is modulated as a sweep from 10 to 100 Hz over the course of ∼15 s. Phase synchrony of evoked responses, measured via intra-trial coherence, is recorded (by EEG or MEG) as a function of frequency. We applied such AM sweep stimuli bilaterally to 40 typically developing and 80 children with ASD, aged 6–18 years. Diagnoses were confirmed by DSM-5 criteria as well as autism diagnostic observation schedule (ADOS) observational assessment. Stimuli were presented binaurally during MEG recording and consisted of 20 AM swept stimuli (500 Hz carrier; sweep 10–100 Hz up and down) with a duration of ∼30 s each. Peak intra-trial coherence values and peak response frequencies of source modeled responses (auditory cortex) were examined. First, the phase synchrony or inter-trial coherence (ITC) of the ASSR is diminished in ASD; second, hemispheric bias in the ASSR, observed in typical development (TD), is maintained in ASD, and third, that the frequency at which the peak response is obtained varies on an individual basis, in part dependent on age, and with altered developmental trajectories in ASD vs. TD. Finally, there appears an association between auditory steady-state phase synchrony (taken as a proxy of neuronal circuitry integrity) and clinical assessment of language ability/impairment. We concluded that (1) the AM sweep stimulus provides a mechanism for probing ASSR in an unbiased fashion, during developmental maturation of peak response frequency, (2) peak frequencies vary, in part due to developmental age, and importantly, (3) ITC at this peak frequency is diminished in ASD, with the degree of ITC disturbance related to clinically assessed language impairment.
Anthocyanins, Anthocyanin-Rich Berries, and Cardiovascular Risks: Systematic Review and Meta-Analysis of 44 Randomized Controlled Trials and 15 Prospective Cohort Studies
Authors: Xu Lin , Tian Zezhong , Chen Hong , Zhao Yimin , Yang Yan
Published: December 2021

Objective: The associations between intake of anthocyanins and anthocyanin-rich berries and cardiovascular risks remained to be established. We aimed to quantitatively summarize the effects of purified anthocyanins and anthocyanin-rich berries on major surrogate markers of cardiovascular diseases (CVDs) and the longitudinal associations between dietary anthocyanins and CVD events.

Methods: Meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies.

Results: We included 44 eligible RCTs and 15 prospective cohort studies in this study. Pooled analysis of RCTs showed that purified anthocyanin supplementation could significantly reduce blood LDL cholesterol (weighted mean difference (WMD): −5.43 mg/dL, 95% CI: −8.96, −1.90 mg/dL; p = 0.003) and triglyceride (WMD: −6.18 mg/dL, 95% CI: −11.67, −0.69 mg/dL; p = 0.027) while increase HDL cholesterol (WMD: 11.49 mg/dL, 95% CI: 7.43, 15.55 mg/dL; p < 0.001) concentrations. Purified anthocyanins also markedly decreased circulating tumor necrosis factor alpha (WMD: −1.62 pg/mL, 95% CI: −2.76, −0.48 pg/mL; p = 0.005) and C-reactive protein (WMD: −0.028 mg/dL, 95% CI: −0.050, −0.005 mg/dL; p = 0.014). Besides, administration of anthocyanin-rich berries could significantly lower blood total cholesterol (WMD: −4.48 mg/dL, 95% CI: −8.94, −0.02 mg/dL; p = 0.049) and C-reactive protein (WMD: −0.046 mg/dL, 95% CI: −0.070, −0.022 mg/dL; p < 0.001). Neither purified anthocyanins nor anthocyanin-rich berries could cause any substantial improvements in BMI, blood pressure, or flow-mediated dilation. In addition, meta-analysis of prospective cohort studies suggested that high dietary anthocyanins were related to lower risk of coronary heart disease (CHD) (relative risk (RR): 0.83, 95% CI: 0.72, 0.95; p = 0.009), total CVD incidence (RR: 0.73, 95% CI: 0.55, 0.97; p = 0.030), and total CVD deaths (RR: 0.91, 95% CI: 0.87, 0.96; p < 0.001).

Conclusion: Habitual intake of anthocyanins and anthocyanin-rich berries could protect against CVDs possibly via improving blood lipid profiles and decreasing circulating proinflammatory cytokines.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020208782.
Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment
Authors: Hafner Hannah , Mulcahy Molly C. , Carlson Zach , Hartley Phillip , Sun Haijing , Westerhoff Maria , Qi Nathan , Bridges Dave , Gregg Brigid
Published: December 2021

Maternal metabolic disease and diet during pregnancy and lactation have important implications for the programming of offspring metabolic disease. In addition, high-fat diets during pregnancy and lactation can predispose the offspring to non-alcoholic fatty liver disease (NAFLD), a rising health threat in the U.S. We developed a model of maternal high-fat feeding exclusively during the lactation period. We previously showed that offspring from dams, given lactational high-fat diet (HFD), are predisposed to obesity, glucose intolerance, and inflammation. In separate experiments, we also showed that lactational metformin treatment can decrease offspring metabolic risk. The purpose of these studies was to understand the programming implications of lactational HFD on offspring metabolic liver disease risk. Dams were fed a 60% lard-based HFD from the day of delivery through the 21-day lactation period. A subset of dams was also given metformin as a co-treatment. Starting at weaning, the offspring were fed normal fat diet until 3 months of age; at which point, a subset was challenged with an additional HFD stressor. Lactational HFD led male offspring to develop hepatic insulin resistance. The post-weaning HFD challenge led male offspring to progress to NAFLD with more severe outcomes in the lactational HFD-challenged offspring. Co-administration of metformin to lactating dams on HFD partially rescued the offspring liver metabolic defects in males. Lactational HFD or post-weaning HFD had no impact on female offspring who maintained a normal insulin sensitivity and liver phenotype. These findings indicate that HFD, during the lactation period, programs the adult offspring to NAFLD risk in a sexually dimorphic manner. In addition, early life intervention with metformin via maternal exposure may prevent some of the liver programming caused by maternal HFD.
Comparative Study of Astaxanthin, Cholesterol, Fatty Acid Profiles, and Quality Indices Between Shrimp Oil Extracted From Hepatopancreas and Cephalothorax
Authors: Raju Navaneethan , Gulzar Saqib , Buamard Natchaphol , Ma Lukai , Ying Xiaoguo , Zhang Bin , Benjakul Soottawat
Published: December 2021

Shrimp oil from two different portions of Pacific white shrimp including cephalothorax and hepatopancreas was extracted using the mixture of hexane/isopropanol (1:1). The extracted oils from the cephalothorax (CPO) and hepatopancreas (HPO) were characterized for astaxanthin content, cholesterol levels, and fatty acid profiles. Nutrition indices of CPO and HPO were also compared. CPO had lower extraction yield (3.2 ± 0.1%, wet weight basis) than HPO (11.1 ± 0.5%, wet weight basis). High-performance liquid chromatography results indicated that the astaxanthin content in HPO was higher, compared to that of CPO. Nevertheless, the cholesterol level in HPO was 70% lower than that of CPO. Fatty acid profiles of HPO and CPO demonstrated that the polyunsaturated fatty acid (PUFA) content in HPO was higher than that of CPO. The amount of docosahexaenoic acid in the former was ~2 times higher than that of the latter. HPO contained 42.76 ± 0.36% PUFA, whereas PUFA content of CPO was 35.27 ± 0.19%. On the other hand, saturated fatty acids (SFA) were more pronounced in CPO (38.44 ± 0.26%) than HPO (30.82 ± 0.55%). Based on nutrition indices, namely, atherogenicity index, thrombogenicity index, hypocholesterolemic/hypercholesterolemic (h/H) ratio, and PUFA/SFA ratio, HPO possessed higher health benefit than CPO. The oxidation status of CPO and HPO measured in terms of peroxide value, thiobarbituric acid reactive substances, anisidine value, and conjugated dienes indicated that higher primary oxidation products were present in CPO, whereas HPO exhibited more secondary oxidation compounds. Fourier transform infrared spectra further substantiated the presence of oxidation products in CPO and HPO. Liquid chromatography-mass spectrometry identification showed the enhanced levels of phospholipids and glycolipids in the ethanolic fraction of CPO. Overall, HPO with a higher yield was more beneficial in terms of health benefits than CPO.
Perspectives on PARP Inhibitor Combinations for Ovarian Cancer
Authors: Bonadio Renata Colombo , Estevez-Diz Maria del Pilar
Published: December 2021

Poly (ADP-ribose) polymerase (PARP) inhibitors constitute an important treatment option for ovarian cancer nowadays. The magnitude of benefit from PARP inhibitors is influenced by the homologous recombination status, with greater benefit observed in patients with BRCA mutated or BRCA wild-type homologous recombination deficient (HRD) tumors. Although some PARP inhibitor activity has been shown in homologous recombination proficient (HRP) ovarian tumors, its clinical relevance as a single agent is unsatisfactory in this population. Furthermore, even HRD tumors present primary or secondary resistance to PARP inhibitors. Strategies to overcome treatment resistance, as well as to enhance PARP inhibitors’ efficacy in HRP tumors, are highly warranted. Diverse combinations are being studied with this aim, including combinations with antiangiogenics, immunotherapy, and other targeted therapies. This review discusses the rationale for developing therapy combinations with PARP inhibitors, the current knowledge, and the future perspectives on this issue.