bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Hypothyroidism Onset and Alzheimer Disease Onset in Adults with Down Syndrome
Authors: Lai Florence , Mercaldo Nathaniel D. , Wang Cassandra M. , Hersch Micaela S. , Hersch Giovi G. , Rosas Herminia Diana
Published: September 2021

Adults with Down syndrome (DS) have an exceptionally high frequency of Alzheimer disease (AD) with a wide variability in onset, from 40 to 70 years of age. Equally prevalent in DS is hypothyroidism. In this study, we sought to quantify the relationship between the two. A total of 232 adults with DS and AD were stratified into three AD onset age groups: early (<47 years), typical (48–59), and late (>59). Among patients with available data, differences in the distributions of demographics, hypothyroidism variables (presence, age of onset), thyroid function tests, thyroid autoantibodies, and APOE genotypes were assessed (e.g., chi-squared, Mann–Whitney tests). Spearman and partial Spearman correlations and ordinal logistic regression models were constructed to quantify the association between ages of AD and hypothyroidism onset with and without covariate adjustments. We observed a positive association between the ages of AD and hypothyroidism onset after accounting for APOE-Ɛ4 (correlation: 0.44, 0.24, 0.60; odds ratio: 1.09, 1.05–1.14). However, an early age of hypothyroidism onset and the presence of the APOE-Ɛ4 allele were independently associated with the early age of AD onset. Similar findings were observed when accounting for other factors. Our study provides evidence for the importance of hypothyroidism and associated pathological mechanisms for risk of AD in DS.
A Lifespan Development Theory of Insecure Attachment and Internalizing Symptoms: Integrating Meta-Analytic Evidence via a Testable Evolutionary Mis/Match Hypothesis
Authors: Dagan Or , Groh Ashley , Madigan Sheri , Bernard Kristin
Published: September 2021

Attachment scholars have long argued that insecure attachment patterns are associated with vulnerability to internalizing symptoms, such as depression and anxiety symptoms. However, accumulating evidence from the past four decades, summarized in four large meta-analyses evaluating the link between insecure attachment subtypes and internalizing symptoms, provide divergent evidence for this claim. This divergent evidence may be accounted for, at least in part, by the developmental period under examination. Specifically, children with histories of deactivating (i.e., insecure/avoidant) but not hyperactivating (i.e., insecure/resistant) attachment patterns in infancy and early childhood showed elevated internalizing symptoms. In contrast, adolescents and adults with hyperactivating (i.e., insecure/preoccupied) but not deactivating (i.e., insecure/dismissing) attachment classifications showed elevated internalizing symptoms. In this paper, we summarize findings from four large meta-analyses and highlight the divergent meta-analytic findings that emerge across different developmental periods. We first present several potential methodological issues that may have contributed to these divergent findings. Then, we leverage clinical, developmental, and evolutionary perspectives to propose a testable lifespan development theory of attachment and internalizing symptoms that integrates findings across meta-analyses. According to this theory, subtypes of insecure attachment patterns may be differentially linked to internalizing symptoms depending on their mis/match with the developmentally appropriate orientation tendency toward caregivers (in childhood) or away from them (i.e., toward greater independence in post-childhood). Lastly, we offer future research directions to test this theory.
Improving Comfort and Health: Green Retrofit Designs for Sunken Courtyards during the Summer Period in a Subtropical Climate
Authors: Han Gang , Wen Yueming , Leng Jiawei , Sun Lijun
Published: September 2021

The sunken courtyard has long been used in underground spaces and provides an important outdoor environment. It introduces natural elements to create a pleasant space for human activities. However, this study measured a typical sunken courtyard and found potential problems of excessive solar radiation and accumulated air pollutants in summer when at an acceptable outdoor temperature for human activities. To improve the comfort and health of a sunken courtyard, this research proposes some green retrofit designs. Firstly, compared with green wall, water and a tree, sunshade is a primary measure to improve thermal comfort. Combining sunshade, a green wall and water reduces the temperature by up to 5.6 °C in the activity zone during the hottest hour. Secondly, blocking/guiding wind walls can effectively improve the wind environment in a sunken courtyard, but only when the wind direction is close to the prevailing wind. A blocking wind wall was better at affecting velocity and uniformity, while the guiding wind wall was more efficient at discharging air pollutants. This study initially discusses the climate-adaptive design of underground spaces in terms of green, thermal comfort and natural ventilation. Designers should generally integrate above/underground and indoor/outdoor spaces using natural and artificial resources to improve comfort and health in underground spaces.
Cancer Cell Fusion and Post-Hybrid Selection Process (PHSP)
Authors: Hass Ralf , von der Ohe Juliane , Dittmar Thomas
Published: September 2021

Fusion of cancer cells either with other cancer cells (homotypic fusion) in local vicinity of the tumor tissue or with other cell types (e.g., macrophages, cancer-associated fibroblasts (CAFs), mesenchymal stromal-/stem-like cells (MSC)) (heterotypic fusion) represents a rare event. Accordingly, the clinical relevance of cancer-cell fusion events appears questionable. However, enhanced tumor growth and/or development of certain metastases can originate from cancer-cell fusion. Formation of hybrid cells after cancer-cell fusion requires a post-hybrid selection process (PHSP) to cope with genomic instability of the parental nuclei and reorganize survival and metabolic functionality. The present review dissects mechanisms that contribute to a PHSP and resulting functional alterations of the cancer hybrids. Based upon new properties of cancer hybrid cells, the arising clinical consequences of the subsequent tumor heterogeneity after cancer-cell fusion represent a major therapeutic challenge. However, cellular partners during cancer-cell fusion such as MSC within the tumor microenvironment or MSC-derived exosomes may provide a suitable vehicle to specifically address and deliver anti-tumor cargo to cancer cells.
Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma: A Nationwide Cohort Study
Authors: van der Kooij Monique , Dekkers Olaf , Aarts Maureen , van den Berkmortel Franchette , Boers-Sonderen Marye , de Groot Jan , Hospers Geke , Piersma Djura , van Rijn Rozemarijn , Suijkerbuijk Karijn , Westgeest Hans , van der Veldt Astrid , Vreugdenhil Gerard , Wilgenhof Sofie , Wouters Michel , Haanen John , van den Eertwegh Alfonsus , Kapiteijn Ellen
Published: September 2021

Recent meta-analyses show conflicting data on sex-dependent benefit following systemic treatment for advanced melanoma patients. We examined the nationwide Dutch Melanoma Treatment Registry (July 2013–July 2018), assessing sex-dependent differences in advanced melanoma patients (stage IIIC/IV) with respect to clinical characteristics, mutational profiles, treatments initiated, grade 3–4 adverse events (AEs), treatment responses, and mortality. We included 3985 patients, 2363 men (59%) and showed that although men and women with advanced melanoma differ in clinical and tumor characteristics, the safety profile of immune checkpoint inhibition (ICI) is comparable. The data suggest a 10% survival advantage for women, mainly seen in patients ≥60 years of age and patients with BRAF V600 mutant melanoma. Following ICI there was no survival difference.
Development and Validation of an HPLC Method for Analysis of Topotecan in Human Cerebrospinal Fluid and Its Application in Elimination Evaluation of Topotecan after Intraventricular Injection
Authors: Yoshikawa Naoki , Yamada Ai , Yokota Tsubasa , Yamada Yusei , Kinoshita Mariko , Moritake Hiroshi , Ikeda Ryuji
Published: September 2021

Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient’s topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.
Inhibiting the Unconventionals: Importance of Immune Checkpoint Receptors in γδ T, MAIT, and NKT Cells
Authors: Catafal-Tardos Elisa , Baglioni Maria Virginia , Bekiaris Vasileios
Published: September 2021

In recent years, checkpoint inhibitor (CPI) therapy has shown promising clinical responses across a broad range of cancers. However, many patients remain unresponsive and there is need for improvement. CPI therapy relies on antibody-mediated neutralization of immune inhibitory or checkpoint receptors (ICRs) that constitutively suppress leukocytes. In this regard, the clinical outcome of CPI therapy has primarily been attributed to modulating classical MHC-restricted αβ T cell responses, yet, it will inevitably target most lymphoid (and many myeloid) populations. As such, unconventional non-MHC-restricted gamma delta (γδ) T, mucosal associated invariant T (MAIT) and natural killer T (NKT) cells express ICRs at steady-state and after activation and may thus be affected by CPI therapies. To which extent, however, remains unclear. These unconventional T cells are polyfunctional innate-like lymphocytes that play a key role in tumor immune surveillance and have a plethora of protective and pathogenic immune responses. The robust anti-tumor potential of γδ T, MAIT, and NKT cells has been established in a variety of preclinical cancer models and in clinical reports. In contrast, recent studies have documented a pro-tumor effect of innate-like T cell subsets that secrete pro-inflammatory cytokines. Consequently, understanding the mechanisms that regulate such T cells and their response to CPI is critical in designing effective cancer immunotherapies that favor anti-tumor immunity. In this Review, we will discuss the current understanding regarding the role of immune checkpoint regulation in γδ T, MAIT, and NKT cells and its importance in anti-cancer immunity.
Co-Treatment with the Epigenetic Drug, 3-Deazaneplanocin A (DZNep) and Cisplatin after DZNep Priming Enhances the Response to Platinum-Based Therapy in Chondrosarcomas
Authors: Lhuissier Eva , Aury-Landas Juliette , Lenté Marion , Boumediene Karim , Baugé Catherine
Published: September 2021

Background: We have previously shown that 3-Deazaneplanocin A (DZNep) induces apoptosis in chondrosarcomas. Herein, we tested whether the combination of this epigenetic drug to a standard anticancer therapy may enhance the response to each drug in these bone tumors. Methods: Two chondrosarcoma cell lines (SW1353 and JJ012) were cultured in the presence of DZNep and/or cisplatin. Cell growth was evaluated by counting viable cells, and apoptosis was determined by Apo2.7 expression by flow cytometry. In vivo, the antitumoral effect of the DZNep/cisplatin combination was assessed through measurements of tumor volume of JJ012 xenografts in nude mice. Results: In vitro, the DZNep/cisplatin combination reduced cell survival and increased apoptosis compared to each drug alone in chondrosarcomas, but not in normal cells (chondrocytes). This enhancement of the antitumoral effect of the DZNep/cisplatin combination required a priming incubation with DZNep before the co-treatment with DZNep/cisplatin. Furthermore, in the chondrosarcoma xenograft mice model, the combination of both drugs more strongly reduced tumor growth and induced more apoptosis in tumoral cells than each of the drugs alone. Conclusion: Our results show that DZNep exposure can presensitize chondrosarcoma cells to a standard anticancer drug, emphasizing the promising clinical utilities of epigenetic-chemotherapeutic drug combinations in the future treatment of chondrosarcomas.
MicroRNA-Based Risk Score for Predicting Tumor Progression Following Radioactive Iodine Ablation in Well-Differentiated Thyroid Cancer Patients: A Propensity-Score Matched Analysis
Authors: Toraih Eman A. , Fawzy Manal S. , Hussein Mohammad H. , El-Labban Mohamad M. , Ruiz Emmanuelle M. L. , Attia Abdallah A. , Halat Shams , Moroz Krzysztof , Errami Youssef , Zerfaoui Mourad , Kandil Emad
Published: September 2021

To identify molecular markers that can accurately predict aggressive tumor behavior at the time of surgery, a propensity-matching score analysis of archived specimens yielded two similar datasets of DTC patients (with and without RAI). Bioinformatically selected microRNAs were quantified by qRT-PCR. The risk score was generated using Cox regression and assessed using ROC, C-statistic, and Brier-score. A predictive Bayesian nomogram was established. External validation was performed, and causal network analysis was generated. Within the eight-year follow-up period, progression was reported in 51.5% of cases; of these, 48.6% had the T1a/b stage. Analysis showed upregulation of miR-221-3p and miR-222-3p and downregulation of miR-204-5p in 68 paired cancer tissues (p < 0.001). These three miRNAs were not differentially expressed in RAI and non-RAI groups. The ATA risk score showed poor discriminative ability (AUC = 0.518, p = 0.80). In contrast, the microRNA-based risk score showed high accuracy in predicting tumor progression in the whole cohorts (median = 1.87 vs. 0.39, AUC = 0.944) and RAI group (2.23 vs. 0.37, AUC = 0.979) at the cutoff >0.86 (92.6% accuracy, 88.6% sensitivity, 97% specificity) in the whole cohorts (C-statistics = 0.943/Brier = 0.083) and RAI subgroup (C-statistic = 0.978/Brier = 0.049). The high-score group had a three-fold increased progression risk (hazard ratio = 2.71, 95%CI = 1.86–3.96, p < 0.001) and shorter survival times (17.3 vs. 70.79 months, p < 0.001). Our prognostic microRNA signature and nomogram showed excellent predictive accuracy for progression-free survival in DTC.
Elevating CDCA3 Levels Enhances Tyrosine Kinase Inhibitor Sensitivity in TKI-Resistant EGFR Mutant Non-Small-Cell Lung Cancer
Authors: Sahin Katherine B. , Shah Esha T. , Ferguson Genevieve P. , Molloy Christopher , Kalita-de Croft Priyakshi , Hayes Sarah A. , Hudson Amanda , Colvin Emily , Kamitakahara Hannah , Harvie Rozelle , Hasovits Csilla , Khan Tashbib , Duijf Pascal H. G. , Howell Viive M. , He Yaowu , Bolderson Emma , Hooper John D. , Lakhani Sunil R. , Richard Derek J. , O’Byrne Kenneth J. , Adams Mark N.
Published: September 2021

Tyrosine kinase inhibitors (TKIs) are the first-line therapy for non-small-cell lung cancers (NSCLC) that harbour sensitising mutations within the epidermal growth factor receptor (EGFR). However, resistance remains a key issue, with tumour relapse likely to occur. We have previously identified that cell division cycle-associated protein 3 (CDCA3) is elevated in adenocarcinoma (LUAD) and correlates with sensitivity to platinum-based chemotherapy. Herein, we explored whether CDCA3 levels were associated with EGFR mutant LUAD and TKI response. We demonstrate that in a small-cohort tissue microarray and in vitro LUAD cell line panel, CDCA3 protein levels are elevated in EGFR mutant NSCLC as a result of increased protein stability downstream of receptor tyrosine kinase signalling. Here, CDCA3 protein levels correlated with TKI potency, whereby CDCA3high EGFR mutant NSCLC cells were most sensitive. Consistently, ectopic overexpression or inhibition of casein kinase 2 using CX-4945, which pharmacologically prevents CDCA3 degradation, upregulated CDCA3 levels and the response of T790M(+) H1975 cells and two models of acquired resistance to TKIs. Accordingly, it is possible that strategies to upregulate CDCA3 levels, particularly in CDCA3low tumours or upon the emergence of therapy resistance, might improve the response to EGFR TKIs and benefit patients.
Functional Characteristics and Regulated Expression of Alternatively Spliced Tissue Factor: An Update
Authors: Matiash Kateryna , Lewis Clayton S. , Bogdanov Vladimir Y.
Published: September 2021

In human and mouse, alternative splicing of tissue factor’s primary transcript yields two mRNA species: one features all six TF exons and encodes full-length tissue factor (flTF), and the other lacks exon 5 and encodes alternatively spliced tissue factor (asTF). flTF, which is oftentimes referred to as “TF”, is an integral membrane glycoprotein due to the presence of an alpha-helical domain in its C-terminus, while asTF is soluble due to the frameshift resulting from the joining of exon 4 directly to exon 6. In this review, we focus on asTF—the more recently discovered isoform of TF that appears to significantly contribute to the pathobiology of several solid malignancies. There is currently a consensus in the field that asTF, while dispensable to normal hemostasis, can activate a subset of integrins on benign and malignant cells and promote outside-in signaling eliciting angiogenesis; cancer cell proliferation, migration, and invasion; and monocyte recruitment. We provide a general overview of the pioneering, as well as more recent, asTF research; discuss the current concepts of how asTF contributes to cancer progression; and open a conversation about the emerging utility of asTF as a biomarker and a therapeutic target.
The Evolution and Prognostic Role of Tumour-Infiltrating Lymphocytes and Peripheral Blood-Based Biomarkers in Inflammatory Breast Cancer Patients Treated with Neoadjuvant Chemotherapy
Authors: Van Berckelaer Christophe , Vermeiren Iris , Vercauteren Leonie , Rypens Charlotte , Oner Gizem , Trinh Xuan Bich , Tjalma Wiebren A. A. , Broeckx Glenn , Charafe-Jauffret Emmanuelle , Van Laere Steven , Bertucci François , Colpaert Cecile , van Dam Peter A.
Published: September 2021

Introduction: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer (BC) in which the (prognostic) role of stromal tumour-infiltrating lymphocytes (sTIL) and the peripheral circulating immune cells in patients with residual disease (RD) after neo-adjuvant chemotherapy (NACT) is not clearly established. Methodology: To describe the evolution of sTIL and some peripheral inflammation markers (Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio and Lymphocyte-to-monocyte ratio) after NACT in IBC, we retrospectively collected clinicopathological variables for 125 stage III IBC patients. sTILs were scored by three different researchers on an H&E slide of the mastectomy specimen. A cohort of subtype-matched non-IBC breast cancer patients (nIBC) treated with NACT was included for comparison. Results: There was no significant difference in the pre- and posttreatment sTIL scores between IBC and nIBC and in both groups the number of sTIL was significantly lower after NACT. However, the IBC phenotype did correlate with a stronger decrease of sTIL after NACT (OR: 0.25, 95% CI: 0.073–0.76, p = 0.018). The change in the peripheral immune markers was not significantly different between IBC and nIBC. After NACT, 75 patients had residual disease. In this group, a high number of sTIL before NACT (HR: 0.23, 95% CI: 0.05–1.02, p = 0.05) was prognostic for a longer OS, while a low number of sTIL after NACT (HR: 0.33, 95% CI: 0.11–0.98, p = 0.046) and a low residual cancer cellularity (HR: 0.20, 95% CI: 0.08–0.52, p < 0.001) was associated with a longer DFS. Conclusions: IBC is associated with a significantly stronger decrease of sTIL after NACT compared to nIBC. Furthermore, a high number of sTIL after NACT was associated with a worse prognosis in IBC.
Pediatric Mixed-Phenotype Acute Leukemia: What’s New?
Authors: Batra Sandeep , Ross Anthony John
Published: September 2021

Mixed-phenotype acute leukemias (MPAL) are rare in children and often lack consensus on optimal management. This review examines the current controversies and emerging paradigms in the management of pediatric MPAL. We examine risk stratification, outcomes of recent retrospective and prospective collaborative trials, and the role of transplantation and precision genomics, and outline emerging targets and concepts in this rare entity.
PD-L1 Expression Is Significantly Associated with Tumor Mutation Burden and Microsatellite Instability Score
Authors: Cho Yoon Ah , Lee Hyunwoo , Kim Deok Geun , Kim Hyunjin , Ha Sang Yun , Choi Yoon-La , Jang Kee-Taek , Kim Kyoung-Mee
Published: September 2021

Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), microsatellite instability (MSI), and tumor mutation burden (TMB) have been proposed as a predictive biomarker to predict response to immune checkpoint blockade (ICB). We aimed to find the relationship of PD-L1 IHC to TMB and MSI using a comprehensive cancer panel assay (CCPA) with >500 genes in advanced cancer patients. CCPA results from 588 archived tissue samples were analyzed for TMB and MSI. In seven samples, whole exome sequencing confirmed TMB with Pearson’s correlation coefficient of 0.972 and all MSI-high cases were validated by pentaplex PCR. Association of TMB and MSI with their corresponding PD-L1 IHC was analyzed. The median TMB value of 588 cases was 8.25 mutations (mut)/Mb (range 0–426.8) with different distributions among the tumor types, with high proportions of high-TMB (>10mut/Mb) in tumors from melanoma, colorectal, gastric, and biliary tract. The TMB values significantly correlated with PD-L1 expression, and this correlation was prominent in gastric and biliary tract cancers. Moreover, the MSI score, the proportion of unstable MSI sites to total assessed MSI sites, showed a significant correlation with the TMB values and PD-L1 scores. This study demonstrates that PD-L1 expression is significantly associated with TMB and MSI score and this correlation depends on the location of the primary tumor.
Catalytic Activity Enhancement of Cu-Zn-Based Catalyst for Methanol Steam Reforming with Magnetic Inducement
Authors: Katanyutanon Sasimas , Samarasinghe Dilpium , Lawtrakul Luckhana , Toochinda Pisanu
Published: September 2021

Magnetic inducement was applied during metal loading to enhance Cu-Zn catalysts for methanol steam reforming in the temperature range of 200–300 °C. The supports used in this study were the γ-Al2O3 support and CeO2-Al2O3 supports prepared under different magnetic environments. Cu-Zn loading between the north and south poles (N-S) on the CeO2-Al2O3 support, prepared between two north poles (N-N), led to the highest H2 production at 300 °C (2796 ± 76 µmol/min), which is triple that of Cu-Zn/CeO2-Al2O3 prepared without magnetic inducement and ~11-fold the activity of the Cu-Zn/Al2O3 reference catalyst. The N-S magnetic environment during metal loading leads to lower reduction temperatures and larger Cu(1+):Cu(2+) ratio. These results showed that the pole arrangement of magnets during metal loading could affect the catalytic activity of the Cu-Zn catalyst owing to its influence on the reducibility and the oxidation state of Cu active metal.
Removal of Tar Contents Derived from Lignocellulosic Biomass Gasification Facilities Using MgAl-LDH@clinoptilolite
Authors: Kim I-Tae , Ahn Kwang-Ho , Jung Jinhong , Jeong Yoonah , Shin Dong-Chul , Lee Ye-Eun
Published: September 2021

Gasification of lignocellulosic biomass requires the effective removal method of tar. This study focused on the application of specially designed Mg/Al-layered double hydroxides clinoptilolite (Mg/Al-LDH@clinoptilolite) to improve the removal efficiency of tar, which would eventually lead to enhancing the power efficiency of gasification, preventing damage to facilities, and deducing durability improvement plans. Zeolite-layered double hydroxides impregnated with clinoptilolite, a natural zeolite, and Mg/Al-layered double hydroxide incorporated into conventional water scrubbers were prepared to enhance the removal efficiency of the tar and improve the quality of the syngas produced during the gasification process. The simultaneous removal of moisture and CO2 in the syngas was also investigated during the removal of the tar. The drastic decrease in tar and CO2 concentration was confirmed, which triggered a relative increase in the effective content of inflammable gas. The findings of the present study provide a practical approach to increasing power efficiency and durability during the gasification of lignocellulosic biomass.
Recent Advances in Catalytic Conversion of Biomass to 2,5-Furandicarboxylic Acid
Authors: Cong Hanyu , Yuan Haibo , Tao Zekun , Bao Hanlin , Zhang Zheming , Jiang Yi , Huang Di , Liu Hongling , Wang Tengfei
Published: September 2021

Converting biomass into high value-added compounds has attracted great attention for solving fossil fuel consumption and global warming. 5-Hydroxymethylfurfural (HMF) has been considered as a versatile biomass-derived building block that can be used to synthesize a variety of sustainable fuels and chemicals. Among these derivatives, 2,5-furandicarboxylic acid (FDCA) is a desirable alternative to petroleum-derived terephthalic acid for the synthesis of biodegradable polyesters. Herein, to fully understand the current development of the catalytic conversion of biomass to FDCA, a comprehensive review of the catalytic conversion of cellulose biomass to HMF and the oxidation of HMF to FDCA is presented. Moreover, future research directions and general trends of using biomass for FDCA production are also proposed.
Valence Regulation of Ultrathin Cerium Vanadate Nanosheets for Enhanced Photocatalytic CO2 Reduction to CO
Authors: Ding Lujia , Han Qiutong , Lu Hong , Yang Yong , Lu Gang , Zhang Hui , Ran Xueqin , Xia Yingdong , Li Ping , Chen Yonghua , Zhou Yong
Published: September 2021

Atomic valence state regulation is an advantageous approach for improving photocatalytic efficiency and product selectivity. However, it is difficult to precisely control the ratio of the different valence states on the surface and the relationship between the surface valence change and catalytic efficiency in the photocatalytic reaction process is unclear. Herein, CeVO4 ultrathin nanosheets were fabricated by one-step solvothermal method with ethanolamine (MEA) as the structure-directing agent. The ratio of the concentrations of intrinsic Ce4+ and Ce3+ ions is precisely modulated from 19.82:100 to 13.33:100 changed by the volume of MEA added without morphology modification. The photocatalytic efficiency increases as the concentrations of intrinsic Ce4+ and Ce3+ ions decrease and CV3 (prepared with 3 mL of MEA) shows the highest CO generation rate approximately 6 and 14 times larger than CV (prepared without MEA) and CV1 (prepared with 1 mL of MEA), respectively, in the photocatalytic CO2 reduction. Interestingly, about 6.8% photo-induced Ce4+ ions were generated on the surface of the catalysts during the photocatalytic CO2 reduction without any phase and morphology changes for CV3. The photocatalytic reaction mechanism is proposed considering the intrinsic and photo-induced Ce4+ ions to obtain efficient photocatalysts.
Conversion of Scenedesmus rubescens Lipid into Biodiesel by Biochar of Different Origin
Authors: Tsavatopoulou Vasiliki D. , Aravantinou Andriana F. , Vakros John , Manariotis Ioannis D.
Published: September 2021

One of the most recent applications studied in recent years is the use of biochar as a catalyst for the conversion of oils into biodiesel. The scope of this work was to evaluate the efficiency of biochars as heterogeneous catalysts for the conversion of Scenedesmus rubescens lipids into biodiesel. Biochar from different materials were employed, namely, malt spent rootlets (MSR), coffee spent grounds (CSG), and olive kernels (OK). Materials were charred at two temperatures (400 and 850 °C) in order to examine the effect of pyrolysis temperature. Homogeneous catalysts such as sulfuric acid and sodium hydroxide were also employed for comparison purposes. In order to explain the different performance of biochar as catalyst, we conducted detailed characterization of these materials. The results of this study showed that homogeneous catalysts (H2SO4 and NaOH) had similar results to the CSG biochar at 400 °C, which was the most productive tested biochar. The pyrolysis temperatures affected the FAMEs recovery of OK and CSG biochar.
Well-Dispersed MgAl2O4 Supported Ni Catalyst with Enhanced Catalytic Performance and the Reason of Its Deactivation for Long-Term Dry Methanation Reaction
Authors: Wang Fen , Yang Xiumiao , Zhang Jingcai
Published: September 2021

Dry methanation of syngas is a promising route for synthetic natural gas production because of its water and cost saving characteristics, as we reported previously. Here, we report a simple soaking process for the preparation of well-dispersed Ni/MgAl2O4-E catalyst with an average Ni size of 6.4 nm. The catalytic test results showed that the Ni/MgAl2O4-E catalyst exhibited considerably higher activity and better stability than Ni/MgAl2O4-W catalyst prepared by conventional incipient wetness impregnation method in dry methanation reaction. The long-term stability test result of 335 h has demonstrated that the deactivation of the Ni/MgAl2O4-E catalyst is inevitable. With multiple characterization techniques including ICP, EDS, XRD, STEM, TEM, SEM and TG, we reveal that the graphitic carbon encapsulating Ni nanoparticles are the major reasons responsible for catalyst deactivation, and the rate of carbon deposition decreases with reaction time.
Chenodeoxycholic Acid Pharmacology in Biotechnology and Transplantable Pharmaceutical Applications for Tissue Delivery: An Acute Preclinical Study
Authors: Mooranian Armin , Ionescu Corina Mihaela , Wagle Susbin Raj , Kovacevic Bozica , Walker Daniel , Jones Melissa , Chester Jacqueline , Johnston Edan , Danic Maja , Mikov Momir , Dass Crispin , Al-Salami Hani
Published: September 2021

Introduction. Primary bile acids (PBAs) are produced and released into human gut as a result of cholesterol catabolism in the liver. A predominant PBA is chenodeoxycholic acid (CDCA), which in a recent study in our laboratory, showed significant excipient-stabilizing effects on microcapsules carrying insulinoma β-cells, in vitro, resulting in improved cell functions and insulin release, in the hyperglycemic state. Hence, this study aimed to investigate the applications of CDCA in bio-encapsulation and transplantation of primary healthy viable islets, preclinically, in type 1 diabetes. Methods. Healthy islets were harvested from balb/c mice, encapsulated in CDCA microcapsules, and transplanted into the epididymal tissues of 6 syngeneic diabetic mice, post diabetes confirmation. Pre-transplantation, the microcapsules’ morphology, size, CDCA-deep layer distribution, and physical features such as swelling ratio and mechanical strength were analyzed. Post-transplantation, animals’ weight, bile acids’, and proinflammatory biomarkers’ concentrations were analyzed. The control group was diabetic mice that were transplanted encapsulated islets (without PBA). Results and Conclusion. Islet encapsulation by PBA microcapsules did not compromise the microcapsules’ morphology or features. Furthermore, the PBA-graft performed better in terms of glycemic control and resulted in modulation of the bile acid profile in the brain. This is suggestive that the improved glycemic control was mediated via brain-related effects. However, the improvement in graft insulin delivery and glycemic control was short-term.
Sexually Dimorphic Transcriptomic Changes of Developing Fetal Brain Reveal Signaling Pathways and Marker Genes of Brain Cells in Domestic Pigs
Authors: Strawn Monica , Moraes Joao G. N. , Safranski Timothy J. , Behura Susanta K.
Published: September 2021

In this study, transcriptomic changes of the developing brain of pig fetuses of both sexes were investigated on gestation days (GD) 45, 60 and 90. Pig fetal brain grows rapidly around GD60. Consequently, gene expression of the fetal brain was distinctly different on GD90 compared to that of GD45 and GD60. In addition, varying numbers of differentially expressed genes (DEGs) were identified in the male brain compared to the female brain during development. The sex of adjacent fetuses also influenced gene expression of the fetal brain. Extensive changes in gene expression at the exon-level were observed during brain development. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in the female brain, whereas specific receptor-mediated signaling pathways were enriched in the male brain. Marker genes of neurons and astrocytes were significantly differentially expressed between male and female brains during development. Furthermore, comparative analysis of gene expression patterns between fetal brain and placenta suggested that genes related to ion transportation may play a key role in the regulation of the brain-placental axis in pig. Collectively, the study suggests potential application of pig models to better understand influence of fetal sex on brain development.
Fibronectin: Molecular Structure, Fibrillar Structure and Mechanochemical Signaling
Authors: Dalton Caleb J. , Lemmon Christopher A.
Published: September 2021

The extracellular matrix (ECM) plays a key role as both structural scaffold and regulator of cell signal transduction in tissues. In times of ECM assembly and turnover, cells upregulate assembly of the ECM protein, fibronectin (FN). FN is assembled by cells into viscoelastic fibrils that can bind upward of 40 distinct growth factors and cytokines. These fibrils play a key role in assembling a provisional ECM during embryonic development and wound healing. Fibril assembly is also often upregulated during disease states, including cancer and fibrotic diseases. FN fibrils have unique mechanical properties, which allow them to alter mechanotransduction signals sensed and relayed by cells. Binding of soluble growth factors to FN fibrils alters signal transduction from these proteins, while binding of other ECM proteins, including collagens, elastins, and proteoglycans, to FN fibrils facilitates the maturation and tissue specificity of the ECM. In this review, we will discuss the assembly of FN fibrils from individual FN molecules; the composition, structure, and mechanics of FN fibrils; the interaction of FN fibrils with other ECM proteins and growth factors; the role of FN in transmitting mechanobiology signaling events; and approaches for studying the mechanics of FN fibrils.
Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy
Authors: Conte Giorgia , Menéndez-Méndez Aida , Bauer Sebastian , El-Naggar Hany , Alves Mariana , Nicke Annette , Delanty Norman , Rosenow Felix , Henshall David C. , Engel Tobias
Published: September 2021

Circulating molecules have potential as biomarkers to support the diagnosis of epilepsy and to assist with differential diagnosis, for example, in conditions resembling epilepsy, such as in psychogenic non-epileptic seizures (PNES). The P2X7 receptor (P2X7R) is an important regulator of inflammation and mounting evidence supports its activation in the brain during epilepsy. Whether the P2X7R or P2X7R-dependent signaling molecules can be used as biomarkers of epilepsy has not been reported. P2X7R levels were analyzed by quantitative ELISA using plasma samples from controls and patients with temporal lobe epilepsy (TLE) or PNES. Moreover, blood cell P2X7R expression and P2X7R-dependent cytokine signature was measured following status epilepticus in P2X7R-EGFP reporter, wildtype, and P2X7R-knockout mice. P2X7R plasma levels were higher in TLE patients when compared with controls and patients with PNES. Plasma levels of the broad inflammatory marker protein C-Reactive protein (CRP) were similar between the three groups. Using P2X7R-EGFP reporter mice, we identified monocytes as the main blood cell type expressing P2X7R after experimentally evoked seizures. Finally, cytokine array analysis in P2X7R-deficient mice identified KC/GRO as a potential P2X7R-dependent plasma biomarker following status epilepticus and during epilepsy. Our data suggest that P2X7R signaling components may be a promising subclass of circulating biomarkers to support the diagnosis of epilepsy.
Insulin-Degrading Enzyme: Paradoxes and Possibilities
Authors: Leissring Malcolm A.
Published: September 2021

More than seven decades have passed since the discovery of a proteolytic activity within crude tissue extracts that would become known as insulin-degrading enzyme (IDE). Certainly much has been learned about this atypical zinc-metallopeptidase; at the same time, however, many quite fundamental gaps in our understanding remain. Herein, I outline what I consider to be among the most critical unresolved questions within the field, many presenting as intriguing paradoxes. For instance, where does IDE, a predominantly cytosolic protein with no signal peptide or clearly identified secretion mechanism, interact with insulin and other extracellular substrates? Where precisely is IDE localized within the cell, and what are its functional roles in these compartments? How does IDE, a bowl-shaped protein that completely encapsulates its substrates, manage to avoid getting “clogged” and thus rendered inactive virtually immediately? Although these paradoxes are by definition unresolved, I offer herein my personal insights and informed speculations based on two decades working on the biology and pharmacology of IDE and suggest specific experimental strategies for addressing these conundrums. I also offer what I believe to be especially fruitful avenues for investigation made possible by the development of new technologies and IDE-specific reagents. It is my hope that these thoughts will contribute to continued progress elucidating the physiology and pathophysiology of this important peptidase.
Circadian Organelles: Rhythms at All Scales
Authors: Aviram Rona , Adamovich Yaarit , Asher Gad
Published: September 2021

Circadian clocks have evolved in most light-sensitive organisms, from unicellular organisms to mammals. Consequently, a myriad of biological functions exhibits circadian rhythmicity, from behavior to physiology, through tissue and cellular functions to subcellular processes. Circadian rhythms in intracellular organelles are an emerging and exciting research arena. We summarize herein the current literature for rhythmicity in major intracellular organelles in mammals. These include changes in the morphology, content, and functions of different intracellular organelles. While these data highlight the presence of rhythmicity in these organelles, a gap remains in our knowledge regarding the underlying molecular mechanisms and their functional significance. Finally, we discuss the importance and challenges faced by spatio-temporal studies on these organelles and speculate on the presence of oscillators in organelles and their potential mode of communication. As circadian biology has been and continues to be studied throughout temporal and spatial axes, circadian organelles appear to be the next frontier.
Methodology of Selecting the Optimal Receptor to Create an Electrochemical Immunosensor for Equine Arteritis Virus Protein Detection
Authors: Brodowski Mateusz , Kowalski Marcin , Białobrzeska Wioleta , Pałka Katarzyna , Walkusz Rafał , Roguszczak Justyna , Łęga Tomasz , Sosnowska Marta , Biedulska Małgorzata , Kurzawa Joanna Kreczko , Bięga Ewelina , Wysocka Joanna , Lisowska Marta , Niedźwiedzka Katarzyna , Lipiński Tomasz , Żołędowska Sabina , Nidzworski Dawid
Published: September 2021

The study reports a methodology of selecting the optimal receptor to create an electrochemical immunosensor for equine arteritis virus (EAV) protein detection. The detection was based on antigen recognition by antibodies immobilized on gold electrodes. Modification steps were controlled by electrochemical impedance spectroscopy and cyclic voltammetry measurements. In order to obtain the impedance immunosensor with the best parameters, seven different receptors complementary to equine arteritis virus protein were used. In order to make the selection, a rapid screening test was carried out to check the sensor’s response to blank, extremely low and high concentrations of target EAV protein, and negative sample: M protein from Streptococcus equi and glycoprotein G from Equid alphaherpesvirus 1. F6 10G receptor showed the best performance.
A Scoping Review of Life-Course Psychosocial Stress and Kidney Function
Authors: Estevez-Garcia Jesus Alejandro , Tamayo-Ortiz Marcela , Sanders Alison P.
Published: September 2021

Increased exposure to maternal psychosocial stress during gestation and adverse neonatal environments has been linked to alterations in developmental programming and health consequences in offspring. A programmed low nephron endowment, among other altered pathways of susceptibility, likely increases the vulnerability to develop chronic kidney disease in later life. Our aim in this scoping review was to identify gaps in the literature by focusing on understanding the association between life-course exposure to psychosocial stress, and the risk of reduced kidney function. A systematic search in four databases (PubMed, ProQuest, Wed of Science, and Scopus) was performed, yielding 609 articles. Following abstract and full-text review, we identified 19 articles meeting our inclusion criteria, reporting associations between different psychosocial stressors and an increase in the prevalence of kidney disease or decline in kidney function, mainly in adulthood. There are a lack of studies that specifically evaluated the association between gestational exposure to psychosocial stress and measures of kidney function or disease in early life, despite the overall evidence consistent with the independent effects of prenatal stress on other perinatal and postnatal outcomes. Further research will establish epidemiological studies with clear and more comparable psychosocial stressors to solve this critical research gap.
The Relationship between Metabolic Syndrome and Smoking and Alcohol Experiences in Adolescents from Low-Income Households
Authors: Choi Moonyoung , Han Joungkyue , Kim Yonghwan , Chung Jinwook
Published: September 2021

Metabolic syndrome (MetS) in children and adolescents is increasing globally and the age of onset is gradually decreasing. MetS is associated with serious health problems and presents an early risk for adult morbidity and mortality. From 2014–2019, we investigated the relationship between MetS and health behaviors such as smoking, alcohol consumption, and nutrition education in Korean adolescents (boys: 1235, girls: 1087, age: 13–18 years) based on household income; the relationship with hand grip strength was also evaluated. The prevalence of MetS was 8.8% in boys and 5.1% in girls; in the lowest income households, the risk increased ~1.5-fold for boys and ~4-fold for girls, whereas risks of smoking and alcohol use increased 1.81 vs. 2.34 times, and 2.34 vs. 2.37 times for boys and girls, respectively. In adolescents with the weakest grip strength, the risk of MetS increased 9.62 and 7.79 times in boys and girls, respectively. Girls lacking nutrition education exhibited a 1.67-fold increased risk of MetS, but this was not significant in boys. Low household income increased the risk of unhealthy behaviors such as smoking and alcohol consumption in both sexes, and together with low hand grip strength, was an important predictor for developing MetS.
Parents’ Perspectives on Adaptive Sports in Children with Profound Intellectual and Multiple Disabilities
Authors: Neyroud Marion C. , Newman Christopher J.
Published: September 2021

Children with profound intellectual and multiple disabilities (PIMD) need adaptations to participate in sports and it is more difficult for them to access these activities. We investigated the effects of adaptive sports in children with PIMD as perceived by their parents. The parents answered a postal questionnaire exploring the effects of adaptive sports during the 3 days following an activity. The questionnaire explored twelve domains of children’s daily lives, such as sleep and appetite. We calculated a composite score, including all of these domains, to assess whether the children globally benefited from adaptive sports. Of the families, 27/63 responded (participation 42.9%). Four domains improved after the sports activity in an important proportion of children (improvement in 64.0% of children for wellbeing, 57.6% for mood, 56.0% for comfort and 48.1% for sleep). Among the majority of children, the other eight domains remained mostly stable. Three quarters of parents reported a globally positive effect of adapted physical activities on their child. These findings support the further development and provision of adaptive sports for children with severe neurological impairments.
Prevalence of Iodine Deficiency among School Children from New Settlement in Kyrgyzstan
Authors: Urmatova Begaiym , Shin Hyunsook , Shon Soonyoung , Abdyldayeva Zeinep , Ishaeva Elmira , Knyazeva Valeriya
Published: September 2021

This study assesses the status of iodine deficiency among at risk-children and adolescents living in migrant settlements in the Kyrgyz Republic. Children aged 7–15 years from two regional primary schools in the new settlement regions were screened for cognitive and behavioural signs of iodine deficiency using questionnaires. The functional state of the thyroid gland was assessed using ultrasonography and blood tests. Out of 1058 schoolchildren, 15.8% showed signs of iodine deficiency. Female children aged 10–12 years showed a higher prevalence of iodine deficiency. The families of schoolchildren reported limited use of seafood and iodised salt. Children in the migrant regions were at risk of iodine deficiency disorder. Among children, clinical manifestations of iodine deficiency were observed as negative hormonal levels or the presence of goitre. Further investigation on standardised screening instruments for iodine deficiency and the relationship among multilevel analyses are warranted.