bluuebunny/crossref_metadata_2025 huggingface dataset:
“Dental Cluster” Versus “Metabolic Cluster”: Analyzing the Associations of Planned and Delivered Dental Procedures with Metabolic Syndrome, Utilizing Data from the Dental, Oral, Medical Epidemiological (DOME) Cross-Sectional Record-Based Nationwide Study
Authors: Abramovitz Itzhak , Zini Avraham , Pribluda Pablo , Kedem Ron , Zur Dorit , Protter Noam E. , Almoznino Galit
Published: July 2021

There are conflicting results existing regarding the association between dental status and metabolic syndrome (MetS). The present research analyzed the associations of the sum of the standard dental unit (SDU) scores of planned (SDU-P) and delivered (SDU-D) dental procedures per patient with MetS components, consequences, and related conditions. The SDU score of each dental procedure represents the time and complexity of the executed procedure. This cross-sectional study analyzed data from the Dental, Oral, Medical Epidemiological (DOME) repository, which includes comprehensive socio-demographic, medical, and dental databases of a nationally representative sample of 132,529 military personnel. Univariate analyses revealed that SDU-P had statistically significant positive associations with all systemic morbidities related to MetS, while the SDU-D exhibited positive associations with some of the systemic morbidities and with lower ORs. SDU-P and SDU-D were associated with worse scores of auxiliary examinations used in the assessment of MetS components. SDU-P retained significant positive associations in the multivariate analysis with impaired glucose tolerance (IGT) (OR = 7.40 (1.91–28.57)), deep vein thrombosis (DVT) (OR = 5.61 (1.53–20.83)), obstructive sleep apnea (OSA) (OR = 5.05 (2.40–10.63)), and fatty liver (OR = 1.82 (1.17–2.84)). In contrast, obesity was the only systemic parameter retaining a significant association with SDU-D following multivariate analysis (OR = 1.47 (1.23–1.76)). It can be concluded that SDU-P, but not SDU-D, is a better predictor of systemic morbidities related to MetS. In other words, MetS is associated with a higher dental treatment needs burden, rather than with dental treatments performed de facto. Dental and general health authorities should collaborate and share information and focus on reducing common health-related risk factors, such as smoking and sugar consumption, in particular among high-risk populations, such as immigrants and those with lower SES and rural locality.
GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties
Authors: Park Robin , Coveler Andrew L. , Cavalcante Ludimila , Saeed Anwaar
Published: July 2021

Glycogen synthase kinase-3 beta is a ubiquitously and constitutively expressed molecule with pleiotropic function. It acts as a protooncogene in the development of several solid tumors including pancreatic cancer through its involvement in various cellular processes including cell proliferation, survival, invasion and metastasis, as well as autophagy. Furthermore, the level of aberrant glycogen synthase kinase-3 beta expression in the nucleus is inversely correlated with tumor differentiation and survival in both in vitro and in vivo models of pancreatic cancer. Small molecule inhibitors of glycogen synthase kinase-3 beta have demonstrated therapeutic potential in pre-clinical models and are currently being evaluated in early phase clinical trials involving pancreatic cancer patients with interim results showing favorable results. Moreover, recent studies support a rationale for the combination of glycogen synthase kinase-3 beta inhibitors with chemotherapy and immunotherapy, warranting the evaluation of novel combination regimens in the future.
Dental Students in Germany throughout the COVID-19 Pandemic: A Psychological Assessment and Cross-Sectional Survey
Authors: Mekhemar Mohamed , Attia Sameh , Dörfer Christof , Conrad Jonas
Published: July 2021

Multiple investigations have reported high psychological distress among students since the coronavirus (COVID-19) outbreak started. This survey examined the associations between psychological features, and several demographic and social factors among dental students in German universities. Dental students registered in German universities nationwide were asked to join this survey via a self-directed online questionnaire, from July 2020 to January 2021. This study assembled data on demographic statistics, the depression anxiety stress scales (DASS-21), and the impact of events scale—revised (IES-R) instrument. The relationships between demographic-related variables and mental consequences of depression, anxiety, stress, intrusion, avoidance, and hyperarousal were inspected. Two hundred and eleven students contributed to the questionnaire and conveyed overall normal or mild outcomes of depression, anxiety, stress, intrusion, avoidance, and hyperarousal. In addition, female gender, cardiovascular diseases, smoking habits, and seeing the COVID-19 outbreak as a financial risk were stated as significant related factors (p < 0.05), with increased IES-R and DASS-21 scores. These results highlight the features that should be considered to better protect dental students’ mental health in German universities during the crisis.
Therapeutic Potential of Luteolin on Impaired Wound Healing in Streptozotocin-Induced Rats
Authors: Chen Li-You , Cheng Hsin-Lin , Kuan Yu-Hsiang , Liang Tang-Jun , Chao Yun-Yi , Lin Hsing-Chun
Published: July 2021

Long-term hyperglycemia may lead to diabetic microvascular and macrovascular complications that can affect the peripheral vascular system, particularly in wound healing capacity. Impaired angiogenesis and delayed wound healing are significant clinically. Luteolin (3′, 4′, 5, 7-tetrahydroxyflavone) is a naturally occurring flavonoid that is ubiquitously found in plants. Recent evidence has shown that luteolin is an anti-inflammatory and anti-oxidative agent. However, the effect of systemic luteolin administration on diabetic wound restoration remains unclear. Herein, we explored the effectiveness of luteolin for improving delayed and impaired healing of skin wound and further clarified the underlying mechanisms. The results indicated that luteolin significantly attenuates blood glucose concentration, improves impaired healing and accelerates re-epithelization of skin wound in streptozotocin (STZ)-induced diabetic rats. Histopathological staining and immunoblotting revealed an inhibitory effect of luteolin on inflammatory cell and cytokine production. We also observed remarkable decreases in protein expressions of inflammatory factors including matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α, interleukin (IL-6), and IL1-β and downregulation of nuclear factor (NF)-κB, as well as increases in anti-oxidative enzymes such as superoxide dismutase 1 (SOD1) and glutathione peroxidase (GSH-Px) induced by nuclear factor erythroid 2-related factor (Nrf)-2 following luteolin supplementation. Furthermore, luteolin decreased the expression of vascular endothelial growth factor (VEGF) and increased the expression of ubiquitin carboxy-terminal hydrolase (UCH)-L1, as evidenced by angiogenesis and neuronal regeneration in completely healed wound. In conclusion, systemic administration of luteolin promotes wound restoration by ameliorating inflammation and oxidative stress through the inactivation of NF-κB and upregulation of Nrf2 in STZ-induced diabetic rats.
Plasmonic Interferometers as TREM2 Sensors for Alzheimer’s Disease
Authors: Li Dingdong , Odessey Rachel , Li Dongfang , Pacifici Domenico
Published: July 2021

We report an effective surface immobilization protocol for capture of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a receptor whose elevated concentration in cerebrospinal fluid has recently been associated with Alzheimer’s disease (AD). We employ the proposed surface functionalization scheme to design, fabricate, and assess a biochemical sensing platform based on plasmonic interferometry that is able to detect physiological concentrations of TREM2 in solution. These findings open up opportunities for label-free biosensing of TREM2 in its soluble form in various bodily fluids as an early indicator of the onset of clinical dementia in AD. We also show that plasmonic interferometry can be a powerful tool to monitor and optimize surface immobilization schemes, which could be applied to develop other relevant antibody tests.
Lipid–Polymer Hybrids Encapsulating Iron-Oxide Nanoparticles as a Label for Lateral Flow Immunoassays
Authors: Bazsefidpar Shayesteh , Moyano Amanda , Gutiérrez Gemma , Matos María , Blanco-López María Carmen
Published: July 2021

The feasibility of using Superparamagnetic Iron Oxide Nanoparticles (SPIONs) encapsulated by lipid–polymer nanoparticles as labels in lateral flow immunoassays (LFIA) was studied. First, nanoparticles were synthesized with average diameters between 4 and 7 (nm) through precipitation in W/O microemulsion and further encapsulated using lipid–polymer nanoparticles. Systems formulated were characterized in terms of size and shape by DLS (Nanozetasizer from Malvern) and TEM. After encapsulation, the average size was around (≈20 and 50 nm). These controlled size agglomerates were tested as labels with a model system based on the biotin–neutravidin interaction. For this purpose, the encapsulated nanoparticles were conjugated to neutravidin using the carbodiimide chemistry, and the LFIA was carried out with a biotin test line. The encapsulated SPIONs showed that they could be promising candidates as labels in LFIA test. They would be useful for immunomagnetic separations, that could improve the limits of detection by means of preconcentration.
Sex Differences and the Role of Gaming Experience in Spatial Cognition Performance in Primary School Children: An Exploratory Study
Authors: van Dun Claudia , van Kraaij Alex , Wegman Joost , Kuipers Jorrit , Aarts Esther , Janzen Gabriele
Published: July 2021

Sex differences are repeatedly observed in spatial cognition tasks. However, the role of environmental factors such as gaming experience remains unclear. In this exploratory study, navigation and object-relocation were combined in a naturalistic virtual reality-based spatial task. The sample consisted of n = 53 Dutch children aged 9–11 years. Overall, girls (n = 24) and boys (n = 29) performed equally accurately, although there was an increase in accuracy with age for boys (ηp2 = 0.09). Boys navigated faster than girls (ηp2 = 0.29), and this difference increased with age (ηp2 = 0.07). More gaming experience in boys versus girls (Cohen’s d = 0.88) did not explain any result observed. We encourage future confirmatory studies to use the paradigm presented here to investigate the current results in a larger sample. These findings could be beneficial for optimizing spatial cognition training interventions.
Myelodysplastic Syndromes in the Postgenomic Era and Future Perspectives for Precision Medicine
Authors: Chanias Ioannis , Stojkov Kristina , Stehle Gregor Th. , Daskalakis Michael , Simeunovic Helena , Njue Linet Muthoni , Schnegg-Kaufmann Annatina S. , Porret Naomi A. , Allam Ramanjaneyulu , Rao Tata Nageswara , Benz Rudolf , Ruefer Axel , Schmidt Adrian , Adler Marcel , Rovo Alicia , Balabanov Stefan , Stuessi Georg , Bacher Ulrike , Bonadies Nicolas
Published: July 2021

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders caused by sequential accumulation of somatic driver mutations in hematopoietic stem and progenitor cells (HSPCs). MDS is characterized by ineffective hematopoiesis with cytopenia, dysplasia, inflammation, and a variable risk of transformation into secondary acute myeloid leukemia. The advent of next-generation sequencing has revolutionized our understanding of the genetic basis of the disease. Nevertheless, the biology of clonal evolution remains poorly understood, and the stochastic genetic drift with sequential accumulation of genetic hits in HSPCs is individual, highly dynamic and hardly predictable. These continuously moving genetic targets pose substantial challenges for the implementation of precision medicine, which aims to maximize efficacy with minimal toxicity of treatments. In the current postgenomic era, allogeneic hematopoietic stem cell transplantation remains the only curative option for younger and fit MDS patients. For all unfit patients, regeneration of HSPCs stays out of reach and all available therapies remain palliative, which will eventually lead to refractoriness and progression. In this review, we summarize the recent advances in our understanding of MDS pathophysiology and its impact on diagnosis, risk-assessment and disease monitoring. Moreover, we present ongoing clinical trials with targeting compounds and highlight future perspectives for precision medicine.
The Soluble Factor from Oral Cancer Cell Lines Inhibits Interferon-γ Production by OK-432 via the CD40/CD40 Ligand Pathway
Authors: Ohe Go , Kudo Yasusei , Kamada Kumiko , Mouri Yasuhiro , Takamaru Natsumi , Kudoh Keiko , Kurio Naito , Miyamoto Youji
Published: July 2021

(1) Background: OK-432 is a penicillin-killed, lyophilized formulation of a low-toxicity strain (Su) of Streptococcus pyogenes (Group A). It is a potent immunotherapy agent for several types of cancer, including oral cancer. We previously showed that (i) OK-432 treatment induces a high amount of IFN-γ production from peripheral blood mononuclear cells (PBMCs), and (ii) conditioned medium (CM) from oral cancer cells suppresses both the IFN-γ production and cytotoxic activity of PBMCs driven by OK-432. The aim of this study was to determine the inhibitory mechanism of OK-432-induced IFN-γ production from PBMCs by CM. (2) Methods: We performed cDNA microarray analysis, quantitative RT-PCR, and ELISA to reveal the inhibitory mechanism of CM. (3) Results: We found that CD40 plays a key role in IFN-γ production via IL-12 production. Although OK-432 treatment upregulated the expression levels of the IL-12p40, p35, and CD40 genes, CM from oral cancer cells downregulate these genes. The amount of IFN-γ production by OK-432 treatment was decreased by an anti-CD40 neutralizing antibody. (4) Conclusions: Our study suggests that uncertain soluble factor(s) produced from oral cancer cells may inhibit IFN-γ production from PBMCs via suppressing the CD40/CD40L–IL-12 axis.
A Novel Automated Immunoassay Platform to Evaluate the Association of Adiponectin and Leptin Levels with Breast Cancer Risk
Authors: Macis Debora , Aristarco Valentina , Johansson Harriet , Guerrieri-Gonzaga Aliana , Raimondi Sara , Lazzeroni Matteo , Sestak Ivana , Cuzick Jack , DeCensi Andrea , Bonanni Bernardo , Gandini Sara
Published: July 2021

Adiponectin and leptin are adipokines secreted by the adipose tissue that are associated with several chronic diseases including cancer. We aimed to compare the immunoassay platform ELLA with an enzyme-linked immunosorbent assay (ELISA) kit and to assess whether the results of the association analyses with breast cancer risk were dependent on the assay used. We measured adiponectin and leptin with ELLA and ELISA on baseline serum samples of 116 Italian postmenopausal women enrolled in two international breast cancer prevention trials. Results were compared with Deming, Passing–Bablok regression and Bland–Altman plots. Disease-free survival was analyzed with the Cox model. There was a good correlation between the methods for adiponectin and leptin (r > 0.96). We found an increased breast cancer risk for very low adiponectin levels (HR for ELLA = 3.75; 95% CI: 1.37;10.25, p = 0.01), whereas no significant association was found for leptin levels. The disease-free survival curves were almost identical for values obtained with the two methods, for both biomarkers. The ELLA platform showed a good concordance with ELISA for adiponectin and leptin measurements. Our results support the association of very low adiponectin levels with postmenopausal breast cancer risk, irrespective of the method used. The ELLA platform is a time-saving system with high reproducibility, therefore we recommend its use for biomarker assessment.
68Ga-DOTATOC-PET/MRI—A Secure One-Stop Shop Imaging Tool for Robotic Radiosurgery Treatment Planning in Patients with Optic Nerve Sheath Meningioma
Authors: Graef Josefine , Furth Christian , Kluge Anne Kathrin , Acker Gueliz , Kord Melina , Zimmermann Zoe , Amthauer Holger , Makowski Marcus , Loebel Franziska , Vajkoczy Peter , Budach Volker , Senger Carolin
Published: July 2021

Optic nerve sheath meningiomas (ONSM) are rare but can lead to irreversible blindness. Hybrid imaging may enhance tumor delineation and diagnostic accuracy via receptor binding. However, relevant clinical data for ONSM are lacking. We evaluated the feasibility of receptor-based hybrid imaging prior to robotic radiosurgery (RRS). We retrospectively analyzed all of our institution’s patients with suspected ONSM who underwent combined positron emission tomography and magnetic resonance imaging (PET/MRI) with gallium-68-labeled (DOTA0-Phe1-Tyr3) octreotide (Ga68-DOTATOC) before RRS between 2018 and 2019. Eight patients with ten suspected ONSM (female = 7; median age, 51.2 years; IQR, 43.0–66.0) were included. Nine out of ten ONSM were deemed PET-positive with a median standard uptake value (SUV) max of 5.6 (IQR, 2.6–7.8). For all nine ONSM that presented 68Ga-DOTATOC uptake, hybrid PET/MRI was used for target volume contouring prior to RSS. At a median follow-up of 11.7 months (IQR, 9.4–16.4), tumor control was achieved in all patients. Radiosurgery resulted in the improvement of visual acuity in two of eight patients, whereas six showed stable vision. Ga68-DOTATOC-PET/MRI can be used for target volume contouring prior to RRS for ONSM as it enables safe treatment planning and improves diagnostic accuracy.
Current Advances in Basic and Translational Research of Cholangiocarcinoma
Authors: Sato Keisaku , Baiocchi Leonardo , Kennedy Lindsey , Zhang Wenjun , Ekser Burcin , Glaser Shannon , Francis Heather , Alpini Gianfranco
Published: July 2021

Cholangiocarcinoma (CCA) is a type of biliary tract cancer emerging from the biliary tree. CCA is the second most common primary liver cancer after hepatocellular carcinoma and is highly aggressive resulting in poor prognosis and patient survival. Treatment options for CCA patients are limited since early diagnosis is challenging, and the efficacy of chemotherapy or radiotherapy is also limited because CCA is a heterogeneous malignancy. Basic research is important for CCA to establish novel diagnostic testing and more effective therapies. Previous studies have introduced new techniques and methodologies for animal models, in vitro models, and biomarkers. Recent experimental strategies include patient-derived xenograft, syngeneic mouse models, and CCA organoids to mimic heterogeneous CCA characteristics of each patient or three-dimensional cellular architecture in vitro. Recent studies have identified various novel CCA biomarkers, especially non-coding RNAs that were associated with poor prognosis or metastases in CCA patients. This review summarizes current advances and limitations in basic and translational studies of CCA.
Epstein–Barr Virus-Associated T- and NK-Cell Lymphoproliferative Diseases: A Review of Clinical and Pathological Features
Authors: Syrykh Charlotte , Péricart Sarah , Lamaison Claire , Escudié Frédéric , Brousset Pierre , Laurent Camille
Published: July 2021

Epstein–Barr virus (EBV) is a ubiquitous virus detected in up to 95% of the general population. Most people are asymptomatic, while some may develop a wide range of EBV-associated lymphoproliferative disorders (LPD). Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV. The 2017 World Health Organization (WHO) classification recognizes the following entities characterized by different outcomes: chronic active EBV infection of T- or NK-cell types (cutaneous and systemic forms), systemic EBV-positive T-cell lymphoma of childhood, EBV-positive aggressive NK-cell leukemia, extra nodal NK/T-cell lymphoma nasal type, and the new provisional entity known as primary EBV-positive nodal T/NK-cell lymphoma. In addition, EBV associated-hemophagocytic lymphohistiocytosis is part of EBV-positive T/NK LPD, but has not been included in the WHO classification due to its reactive nature. Despite novel insights from high-throughput molecular studies, EBV-positive NK/T-cell LPD diagnoses remain challenging, especially because of their rarity and overlap. Until now, an accurate EBV-positive NK/T LPD diagnosis has been based on its clinical presentation and course correlated with its histological features. This review aims to summarize clinical, pathological and molecular features of EBV-positive T/NK LPD subtypes and to provide an overview of new understandings regarding these rare disorders.
A Novel Nanobody Precisely Visualizes Phosphorylated Histone H2AX in Living Cancer Cells under Drug-Induced Replication Stress
Authors: Moeglin Eric , Desplancq Dominique , Stoessel Audrey , Massute Christian , Ranniger Jeremy , McEwen Alastair G. , Zeder-Lutz Gabrielle , Oulad-Abdelghani Mustapha , Chiper Manuela , Lafaye Pierre , Di Ventura Barbara , Didier Pascal , Poterszman Arnaud , Weiss Etienne
Published: July 2021

Histone H2AX phosphorylated at serine 139 (γ-H2AX) is a hallmark of DNA damage, signaling the presence of DNA double-strand breaks and global replication stress in mammalian cells. While γ-H2AX can be visualized with antibodies in fixed cells, its detection in living cells was so far not possible. Here, we used immune libraries and phage display to isolate nanobodies that specifically bind to γ-H2AX. We solved the crystal structure of the most soluble nanobody in complex with the phosphopeptide corresponding to the C-terminus of γ-H2AX and show the atomic constituents behind its specificity. We engineered a bivalent version of this nanobody and show that bivalency is essential to quantitatively visualize γ-H2AX in fixed drug-treated cells. After labelling with a chemical fluorophore, we were able to detect γ-H2AX in a single-step assay with the same sensitivity as with validated antibodies. Moreover, we produced fluorescent nanobody-dTomato fusion proteins and applied a transduction strategy to visualize with precision γ-H2AX foci present in intact living cells following drug treatment. Together, this novel tool allows performing fast screenings of genotoxic drugs and enables to study the dynamics of this particular chromatin modification in individual cancer cells under a variety of conditions.
Green and High Effective Scale Inhibitor Based on Ring-Opening Graft Modification of Polyaspartic Acid
Authors: Zhou Yongsheng , Wang Jie , Fang Yan
Published: July 2021

Polyaspartic acid (PASP)-based green scale inhibitor has great potential application in water treatment. Here, we first synthesized PASP in ionic liquid. Then, an effective PASP-based green scale inhibitor was synthesized by ring-opening graft modification of PASP with both aspartic acid (ASP) and monoethanolamine (MEA). Its chemical composition was characterized by gel chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), and 1H nuclear magnetic resonance (1H NMR). Scale inhibition efficiency was measured by static scale inhibition tests. The results showed that the new PASP-based scale inhibitor has high scale inhibition to both CaCO3 and Ca3(PO4)2. When the concentration was increased to 2 mg/L, the inhibition efficiency of the new PASP-based scale inhibitor was 99% for CaCO3, while when the concentration was raised to only 4 mg/L, its inhibition efficiency increased to 100% for Ca3(PO4)2. Scanning electronic microscopy (SEM) and X-ray diffraction (XRD) were used to analyze the changes of crystal structure for CaCO3 and Ca3(PO4)2 after adding the new PASP-based scale inhibitor. The crystal size of CaCO3 and Ca3(PO4)2 became smaller and the crystal form became amorphous after adding the modified PASPs compared with adding pure PASP. Moreover, the modified PASP showed good biodegradation performance.
Effect of Reaction Time and Hydrothermal Treatment Time on the Textural Properties of SBA-15 Synthesized Using Sodium Silicate as a Silica Source and Its Efficiency for Reducing Tobacco Smoke Toxicity
Authors: Juárez-Serrano Nerea , Berenguer Desiré , Martínez-Castellanos Isabel , Blasco Inmaculada , Beltrán Maribel , Marcilla Antonio
Published: July 2021

The synthesis of SBA-15 has been optimized using sodium silicate, an inexpensive precursor of SBA-15. In this work, the influence of synthesis times of the precipitation and the hydrothermal treatment steps, on the textural properties developed as well as for reducing the toxic compounds generated in tobacco smoking, has been studied. The hydrothermal treatment has been proved to be necessary to obtain materials with adequate performance in this particular application. Twenty-four hours of hydrothermal treatment provide materials with the best properties. Although the reaction stage usually involves the mixing of reagents during 24 h, 40 min is enough to obtain a material with stick-like morphology and typical textural properties. Moreover, between 1 and 2 h of reaction time, the material proved to have the best performance for the purpose of reducing the toxicity of the products generated during the tobacco smoking process. These results are of great significance for an eventual scaling up to industrial scale of the SBA-15 manufacturing process. Results of a pilot plant experiment in a batch of 4 kg of SBA-15 are reported.
Unraveling Structural Details in Ga-Pd SCALMS Systems Using Correlative Nano-CT, 360° Electron Tomography and Analytical TEM
Authors: Wirth Janis , Englisch Silvan , Drobek Dominik , Apeleo Zubiri Benjamin , Wu Mingjian , Taccardi Nicola , Raman Narayanan , Wasserscheid Peter , Spiecker Erdmann
Published: July 2021

We present a comprehensive structural and analytical characterization of the highly promising supported catalytically active liquid metal solutions (SCALMS) system. This novel catalyst shows excellent performance for alkane dehydrogenation, especially in terms of resistance to coking. SCALMS consists of a porous support containing catalytically active low-melting alloy particles (e.g., Ga-Pd) featuring a complex structure, which are liquid at reaction temperature. High-resolution 3D characterization at various length scales is required to reveal the complex pore morphology and catalytically active sites’ location. Nano X-ray computed tomography (nano-CT) in combination with electron tomography (ET) enables nondestructive and scale-bridging 3D materials research. We developed and applied a correlative approach using nano-CT, 360°-ET and analytical transmission electron microscopy (TEM) to decipher the morphology, distribution and chemical composition of the Ga-Pd droplets of the SCALMS system over several length scales. Utilizing ET-based segmentations of nano-CT reconstructions, we are able to reliably reveal the homogenous porous support network with embedded Ga-Pd droplets featuring a nonhomogenous elemental distribution of Ga and Pd. In contrast, large Ga-Pd droplets with a high Ga/Pd ratio are located on the surface of SCALMS primary particles, whereas the droplet size and the Ga/Pd ratio decreases while advancing into the porous volume. Our studies reveal new findings about the complex structure of SCALMS which are required to understand its superior catalytic performance. Furthermore, advancements in lab-based nano-CT imaging are presented by extending the field of view (FOV) of a single experiment via a multiple region-of-interest (ROI) stitching approach.
Aggregated Tau-PHF6 (VQIVYK) Potentiates NLRP3 Inflammasome Expression and Autophagy in Human Microglial Cells
Authors: Panda Chinmaya , Voelz Clara , Habib Pardes , Mevissen Christian , Pufe Thomas , Beyer Cordian , Gupta Sharad , Slowik Alexander
Published: July 2021

Intra-neuronal misfolding of monomeric tau protein to toxic β-sheet rich neurofibrillary tangles is a hallmark of Alzheimer’s disease (AD). Tau pathology correlates not only with progressive dementia but also with microglia-mediated inflammation in AD. Amyloid-beta (Aβ), another pathogenic peptide involved in AD, has been shown to activate NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3), triggering the secretion of proinflammatory interleukin-1β (IL1β) and interleukin-18 (IL18). However, the effect of tau protein on microglia concerning inflammasome activation, microglial polarization, and autophagy is poorly understood. In this study, human microglial cells (HMC3) were stimulated with the unaggregated and aggregated forms of the tau-derived PHF6 peptide (VQIVYK). Modulation of NLRP3 inflammasome was examined by qRT-PCR, immunocytochemistry, and Western blot. We demonstrate that fibrillar aggregates of VQIVYK upregulated the NLRP3 expression at both mRNA and protein levels in a dose- and time-dependent manner, leading to increased expression of IL1β and IL18 in HMC3 cells. Aggregated PHF6-peptide also activated other related inflammation and microglial polarization markers. Furthermore, we also report a time-dependent effect of the aggregated PHF6 on BECN1 (Beclin-1) expression and autophagy. Overall, the PHF6 model system-based study may help to better understand the complex interconnections between Alzheimer’s PHF6 peptide aggregation and microglial inflammation, polarization, and autophagy.
Apoptosis in the Pancreatic Cancer Tumor Microenvironment—The Double-Edged Sword of Cancer-Associated Fibroblasts
Authors: Pfeifer Ester , Burchell Joy M. , Dazzi Francesco , Sarker Debashis , Beatson Richard
Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. This is attributed to the disease already being advanced at presentation and having a particularly aggressive tumor biology. The PDAC tumor microenvironment (TME) is characterized by a dense desmoplastic stroma, dominated by cancer-associated fibroblasts (CAF), extracellular matrix (ECM) and immune cells displaying immunosuppressive phenotypes. Due to the advanced stage at diagnosis, the depletion of immune effector cells and lack of actionable genomic targets, the standard treatment is still apoptosis-inducing regimens such as chemotherapy. Paradoxically, it has emerged that the direct induction of apoptosis of cancer cells may fuel oncogenic processes in the TME, including education of CAF and immune cells towards pro-tumorigenic phenotypes. The direct effect of cytotoxic therapies on CAF may also enhance tumorigenesis. With the awareness that CAF are the predominant cell type in PDAC driving tumorigenesis with various tumor supportive functions, efforts have been made to try to target them. However, efforts to target CAF have, to date, shown disappointing results in clinical trials. With the help of sophisticated single cell analyses it is now appreciated that CAF in PDAC are a heterogenous population with both tumor supportive and tumor suppressive functions. Hence, there remains a debate whether targeting CAF in PDAC is a valid therapeutic strategy. In this review we discuss how cytotoxic therapies and the induction of apoptosis in PDAC fuels oncogenesis by the education of surrounding stromal cells, with a particular focus on the potential pro-tumorigenic outcomes arising from targeting CAF. In addition, we explore therapeutic avenues to potentially avoid the oncogenic effects of apoptosis in PDAC CAF.
Transcending toward Advanced 3D-Cell Culture Modalities: A Review about an Emerging Paradigm in Translational Oncology
Authors: Farhat Joviana , Pandey Ishan , AlWahsh Mohammad
Published: July 2021

Cancer is a disorder characterized by an uncontrollable overgrowth and a fast-moving spread of cells from a localized tissue to multiple organs of the body, reaching a metastatic state. Throughout years, complexity of cancer progression and invasion, high prevalence and incidence, as well as the high rise in treatment failure cases leading to a poor patient prognosis accounted for continuous experimental investigations on animals and cellular models, mainly with 2D- and 3D-cell culture. Nowadays, these research models are considered a main asset to reflect the physiological events in many cancer types in terms of cellular characteristics and features, replication and metastatic mechanisms, metabolic pathways, biomarkers expression, and chemotherapeutic agent resistance. In practice, based on research perspective and hypothesis, scientists aim to choose the best model to approach their understanding and to prove their hypothesis. Recently, 3D-cell models are seen to be highly incorporated as a crucial tool for reflecting the true cancer cell microenvironment in pharmacokinetic and pharmacodynamics studies, in addition to the intensity of anticancer drug response in pharmacogenomics trials. Hence, in this review, we shed light on the unique characteristics of 3D cells favoring its promising usage through a comparative approach with other research models, specifically 2D-cell culture. Plus, we will discuss the importance of 3D models as a direct reflector of the intrinsic cancer cell environment with the newest multiple methods and types available for 3D-cells implementation.
A Mini-Review of Enhancing Ultrafiltration Membranes (UF) for Wastewater Treatment: Performance and Stability
Authors: Awad Eman Sh. , Sabirova Tamara M. , Tretyakova Natalia A. , Alsalhy Qusay F. , Figoli Alberto , Salih Issam K.
Published: July 2021

The scarcity of freshwater resources in many regions of the world has contributed to the emergence of various technologies for treating and recovering wastewater for reuse in industry, agriculture, and households. Deep wastewater treatment from oils and petroleum products is one of the difficult tasks that must be solved. Among the known technologies, UF membranes have found wide industrial application with high efficiency in removing various pollutants from wastewater. It is shown that the search for and development of highly efficient, durable, and resistant to oil pollution UF membranes for the treatment of oily wastewater is an urgent research task. The key parameters to improve the performance of UF membranes are by enhancing wettability (hydrophilicity) and the antifouling behavior of membranes. In this review, we highlight the using of ultrafiltration (UF) membranes primarily to treat oily wastewater. Various methods of polymer alterations of the UF membrane were studied to improve hydrophilicity, the ability of antifouling the membrane, and oil rejection, including polymer blending, membrane surface modification, and the mixed membrane matrix. The influence of the type and composition of the hydrophilic additives of nanoparticles (e.g., Multiwall carbon nanotubes (MWCNT), graphene oxide (GO), zinc oxide (ZnO), and titanium dioxide (TiO2), etc.) was investigated. The review further provides an insight into the removal efficiency percent.
Novel Colour-Based, Prototype Indicator for Use in High-Pressure Processing (HPP)
Authors: Yusufu Dilidaer , Bingham Michael , Mills Andrew
Published: July 2021

The preparation and testing of a colour-based prototype indicator for high-pressure processing (HPP) are described. The indicator is a layered structure comprising a pressed disc of a mixture of silica gel, which has been previously loaded with a set wt% of acidified water, and polytetrafluoroethylene, PTFE, powders, a water-permeable barrier layer, and a Congo-Red-based pH indicator layer, all vacuum-sealed in a water impermeable plastic film. The value of the wt% is calculated from the ratio of the mass of acidified water added to the mass of originally dry silica gel. The high pressures associated with HPP drive the release of the acidified water from the silica gel and its subsequent transport through the water-permeable barrier layer to the pH indicator, thereby producing a striking red-to-blue colour change. The response of the HPP indicator can be tuned to different HPP conditions by varying the wt% of acidified water used to load the silica gel powder. Indicators, with 61, 63, and 65 wt% acidified water loaded silica gel, are prepared and found to require, respectively, the application of at least, 600, 400, and 300 MPa pressure for 3 min to effect a change colour. To our knowledge, this is the first reported example of a prototype HPP indicator that can be tuned to respond to the very different pressure and time conditions used in HPP to sterilise such very different products as milk, apple and orange juice, and aloe vera gel.
Deformity Reconstruction Surgery for Blount’s Disease
Authors: Robbins Craig A.
Published: July 2021

Blount’s disease is an idiopathic developmental abnormality affecting the medial proximal tibia physis resulting in a multi-planar deformity with pronounced tibia varus. A single cause is unknown, and it is currently thought to result from a multifactorial combination of hereditary, mechanical, and developmental factors. Relationships with vitamin D deficiency, early walking, and obesity have been documented. Regardless of the etiology, the clinical and radiographic findings are consistent within the two main groups. Early-onset Blount’s disease is often bilateral and affects children in the first few years of life. Late-onset Blount’s disease is often unilateral and can be sub-categorized as juvenile tibia vara (ages 4–10), and adolescent tibia vara (ages 11 and older). Early-onset Blount’s disease progresses to more severe deformities, including depression of the medial tibial plateau. Additional deformities in both groups include proximal tibial procurvatum, internal tibial torsion, and limb length discrepancy. Compensatory deformities in the distal femur and distal tibia may occur. When non-operative treatment fails the deformities progress through skeletal maturity and can result in pain, gait abnormalities, premature medial compartment knee arthritis, and limb length discrepancy. Surgical options depend on the patient’s age, weight, extent of physeal involvement, severity, and number of deformities. They include growth modulation procedures such as guided growth for gradual correction with hemi-epiphysiodesis and physeal closure to prevent recurrence and equalize limb lengths, physeal bar resection, physeal distraction, osteotomies with acute correction and stabilization, gradual correction with multi-planar dynamic external fixation, and various combinations of all modalities. The goals of surgery are to restore normal joint and limb alignment, equalize limb lengths at skeletal maturity, and prevent recurrence. The purpose of this literature review is to delineate basic concepts and reconstructive surgical treatment strategies for patients with Blount’s disease.
Assessment of Climatic Parameters for Future Climate Change in a Major Agricultural State in India
Authors: Jha Ranjeet Kumar , Kalita Prasanta K. , Cooke Richard A.
Published: July 2021

The change in future climate will have a prominent impact on crop production and water requirement. Crop production is directly related to climatic variables. Temperature, solar radiation, wind, precipitation, CO2 concentration and other climatic variables dictate crop yield. This study, based on long-term historical data, investigates the patterns and changes in climatic variables (precipitation, temperature, and solar radiation) that would most significantly affect the future crop production in many parts of the world, and especially in India, where most farmers depend on rainfall for rice production. Statistical analyses—box and whisker plot, mean absolute error, Taylor diagram, double mass curve, Mann–Kendall trend test, and projected climate change—were used to assess the significance of the climatic factors for the purpose of agricultural modeling. Large variability in precipitation may cause the flash floods and affect the farming, and at the same time, increase in temperature from baseline period will lead to high water requirement by crops, and may cause drought if rainfall does not occur. Decrease in solar radiation will affect crop growth and development, and thus, would hamper the crop production. The results of this study would be useful in identifying the negative issues arising from climate change in future agricultural practices in Bihar, India. Furthermore, the results can also help in developing management strategies to combat the climate change impact on crop production.
Fabrication and Properties of Electrospun and Electrosprayed Polyethylene Glycol/Polylactic Acid (PEG/PLA) Films
Authors: Ke Weichang , Li Xiang , Miao Mengyu , Liu Bing , Zhang Xiaoyu , Liu Tong
Published: July 2021

Polylactic acid (PLA) film is an alternative filter material for heat-not-burn (HNB) tobacco, but its controllability in cooling performance is limited. In this work, polyethylene glycol (PEG) was introduced to form a polyethylene glycol/polylactic acid (PEG/PLA) film by electrospinning or electrospraying techniques to enhance the cooling performance, due to its lower glass transition and melting temperatures. The PEG/PLA films with typical electrospun or electrosprayed morphologies were successfully fabricated. One typical endothermic peak at approximately 65 °C was clearly observed for the melting PEG phase in the heating process, and the re-crystallization temperature represented by an exothermic peak was effectively lowered to 90–110 °C during the cooling process, indicating that the cooling performance is greatly enhanced by the introduction of the PEG phase. Additionally, the wetting properties and adsorption properties were also intensively studied by characterizing the contact angles, and the as-prepared PEG/PLA films all showed good affinity to water, 1,2-propandiol and triglyceride. Furthermore, the PEG/PLA film with a PLA content of 35 wt.% revealed the largest elasticity modulus of 378.3 ± 68.5 MPa and tensile strength of 10.5 ± 1.1 MPa. The results achieved in this study can guide the development of other filter materials for HNB tobacco application.
Effect of Microcracks on the Tensile Properties of 3D Woven Composites
Authors: Huang Jian , Zhao Qian , Feng Yubo , Zhou Haili , Sun Fangfang , Wang Kun , Li Chao , Zhang Liquan , Sun Xuekun
Published: July 2021

This study provides an experimental investigation on the effect of microcracks on the tensile properties of 3D woven composites. A four-step experimental procedure using the combination of micro-XCT, acoustic emission (AE) and digital image correlation (DIC) is here proposed. Typical tensile damage behaviors were characterized by the stress–strain curves, AE signal analysis and DIC full field strain measurement. Due to a typical four stages stress–strain behavior, phenomena of stiffness degradation and stiffness hardening were successively found during the tensile process. Samples with various damage levels were produced by the in situ AE monitoring. Their 3D microcrack morphologies show the crack initiation, propagation process and the damage modes. Detectable damages initiated during the stress range from 65.98% to 72.93% σs. The cracks volume fraction (CVF) shows a positive correlation relationship with the corresponding tensile load. Moreover, the CVF was used to characterize the degree of damage. The samples with various phased damages were tested again in the fourth step to obtain their residual modulus and residual strength. Detected microcracks have little influence on the residual strength, while the residual modulus witnesses a regular decrease along with the damage increase. The effect of microcracks on the tensile properties is characterized by the relationships between the gradually increased damages and the corresponding residual properties which provide a foundation for damage evaluation of 3D woven structures in service.
Effect of Pulsed-Plasma Treatment on the Structural-Phase Composition and Tribological Properties of Detonation Coatings Based on Ti–Si–C
Authors: Rakhadilov Bauyrzhan , Buitkenov Dastan , Idrisheva Zhanat , Zhamanbayeva Manira , Pazylbek Sapargali , Baizhan Daryn
Published: July 2021

The structural-phase state and tribological characteristics of detonation coatings based on Ti–Si–C before and after pulsed-plasma exposure have been experimentally investigated. The authors of the research used a detonation set-up of CCDS2000 to obtain coatings. The modification of coating surfaces was carried out by a pulsed-plasma flow using the “Impulse-6” installation. The results of the research have shown that the modification of coatings surface by a pulsed-plasma effect causes an increase in the microhardness of the surface layer and in its wear resistance. It was determined that after such type of treatment, there is an increase in the content of the Ti3SiC2 phase. According to the results of XRD analysis, the improvement in the mechano-tribological properties of detonation spraying coatings of the Ti–Si–C system as a result of pulsed-plasma treatment is associated with an increase in the content of Ti3SiC2 phases in the coatings, as well as the formation of carbide and oxide phases on the surface layer.
Synthesized TiO2 Mesoporous by Addition of Acetylacetone and Graphene for Dye Sensitized Solar Cells
Authors: Chang Chun-Hao , Chuang Chia-Han , Zhong De-Yang , Lin Jun-Cheng , Sung Chia-Chi , Hsu Chun-Yao
Published: July 2021

This study mixed acetylacetone (Acac, 1, 2, and 3 mL) and graphene powder (GP, 0 wt.%, 0.001 wt.%, 0.003 wt.% and 0.005 wt.%) with TiO2 mesoporous (TiO2 powders: 20 g and particle size ~30 nm) to enhance the optoelectronic performances of dye sensitized solar cells (DSSC). Sponge-like structure TiO2 mesoporous layers is a requirement for obtaining high efficiency DSSC, which ia synthesized by spin-coating techniques. The dense TiO2 blocking layer (using peroxo-titanium complex) has a uniform, dense structure and completely adheres to the substrates to avoid charge recombination. The X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses of the TiO2 films display the anatase type phase with preferred orientation along the (101) direction. After being ball milled, the TiO2 mesoporous particle size almost remains unchanged. For mixing the Acac with TiO2, the Raman intensity relatively increased, and the band gap energy (Eg) value decreased from 3.223 eV (for pure TiO2) to 3.076 eV (for 2 mL Acac). Raman spectroscopy is used to evaluate the GP elements. It can be seen the intensity ratio (ID/IG) and (I2D/IG) was enhanced when the GP concentration increased. Using mixed Acac 2 mL and GP 0.003 wt.% with a TiO2 mesoporous, led to increases in the open circuit voltage (VOC), short circuit current density (JSC) and fill factor (FF). If a fluorine-doped tin oxide is used instead of an indium tin oxide glass substrate, the photovoltaic efficiency of DSSC increases from 5.45% to 7.24%.