bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of HPV Genotypes Differs Depending on Behavioural Factors among Young Women
Authors: Bergqvist Laura , Kalliala Ilkka , Aro Karoliina , Auvinen Eeva , Jakobsson Maija , Kiviharju Mari , Virtanen Seppo , Dillner Joakim , Nieminen Pekka , Louvanto Karolina
Published: April 2021

Risk factors for the different human papillomavirus (HPV) genotypes are not well understood, although the risk of cancer is known to vary among them. Our aim was to evaluate the association of diverse behavioral and reproductive factors with genotype-specific HPV prevalence among 879 unvaccinated women aged 18–75 years referred to the colposcopy clinic at Helsinki University Hospital in Finland. Cervical swabs for HPV genotyping were collected in the first visit and assessed for 34 high-risk (hr) and low-risk (lr) HPV genotypes. Participants completed a questionnaire on behavioral, reproductive, and lifestyle factors. Differences in genotype-specific HPV prevalence were analyzed overall and in age groups using binary logistic regression. Smoking was associated with higher prevalence in HPV16 compared with other hrHPV genotypes together with decreasing age, being highest among younger women <30 years old, odds ratio (OR) 3.74 (95% CI 1.42–9.88). The later the sexual debut, the more it seemed to protect from HPV16 infection. The best protection was achieved when the sexual debut took place at >20 years of age, with an OR of 0.43 (95% CI 0.23–0.83). This association was not seen with other hrHPV genotypes. Methods of contraception seemed not to have an effect on hrHPV positivity, regardless of the HPV genotype. The genotype specific hrHPV prevalence differs, depending on behavioral factors, especially among younger women referred to colposcopy.
Identification of a Toxin–Antitoxin System That Contributes to Persister Formation by Reducing NAD in Pseudomonas aeruginosa
Authors: Zhou Jingyi , Li Shouyi , Li Haozhou , Jin Yongxin , Bai Fang , Cheng Zhihui , Wu Weihui
Published: April 2021

Bacterial persisters are slow-growing or dormant cells that are highly tolerant to bactericidal antibiotics and contribute to recalcitrant and chronic infections. Toxin/antitoxin (TA) systems play important roles in controlling persister formation. Here, we examined the roles of seven predicted type II TA systems in the persister formation of a Pseudomonas aeruginosa wild-type strain PA14. Overexpression of a toxin gene PA14_51010 or deletion of the cognate antitoxin gene PA14_51020 increased the bacterial tolerance to antibiotics. Co-overexpression of PA14_51010 and PA14_51020 or simultaneous deletion of the two genes resulted in a wild-type level survival rate following antibiotic treatment. The two genes were located in the same operon that was repressed by PA14_51020. We further demonstrated the interaction between PA14_51010 and PA14_51020. Sequence analysis revealed that PA14_51010 contained a conserved RES domain. Overexpression of PA14_51010 reduced the intracellular level of nicotinamide adenine dinucleotide (NAD+). Mutation of the RES domain abolished the abilities of PA14_51010 in reducing NAD+ level and promoting persister formation. In addition, overproduction of NAD+ by mutation in an nrtR gene counteracted the effect of PA14_51010 overexpression in promoting persister formation. In combination, our results reveal a novel TA system that contributes to persister formation through reducing the intracellular NAD+ level in P. aeruginosa.
Topographic Analysis of Calcite (104) Cleavage Surface Dissolution in Ethanol–Water Solutions
Authors: Ye Shaoxiong , Feng Pan , Liu Jiaping
Published: April 2021

The interaction of organic molecules with calcite surfaces plays a key role in many geochemical, industrial and biomineralization processes, and exploring the influences of organic molecules on calcite reactions is crucial for a fundamental understanding of the reaction mechanisms. Here, we used digital hologram microscopy to explore the in situ evolution of the calcite (104) surfaces when dissolved in ethanol–water solutions, and total organic carbon analysis was applied to confirm the adsorption of ethanol by calcite. The results showed that the bulk dissolution rate of calcite decreases as the volume fraction of ethanol increases, and the topographic features of etch pits were also altered by the presence of ethanol. When exposed to too much ethanol, the etch pits’ growth was inhibited and their shapes tended to change from rhombuses in ultrapure water to triangles. Our results provide insights into the interaction between adsorbed ethanol and evolving calcite crystal, which highlights the dissolution regulation of calcite by organic molecules that could benefit a broad range of fields.
Editorial for Special Issue “Rare Earth Deposits and Challenges of World REE Demand for High-Tech and Green-Tech at the Beginning of the 3rd Millennium”
Authors: Kynický Jindřich , Smith Martin , Salvi Stefano
Published: April 2021

We are living in a time of unprecedented technological innovation [...]
Discovery of Post-Translational Modifications in Emiliania huxleyi
Authors: Duong Van-An , Nam Onyou , Jin EonSeon , Park Jong-Moon , Lee Hookeun
Published: April 2021

Emiliania huxleyi is a cosmopolitan coccolithophore that plays an essential role in global carbon and sulfur cycling, and contributes to marine cloud formation and climate regulation. Previously, the proteomic profile of Emiliania huxleyi was investigated using a three-dimensional separation strategy combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The current study reuses the MS/MS spectra obtained, for the global discovery of post-translational modifications (PTMs) in this species without specific enrichment methods. Twenty-five different PTM types were examined using Trans-Proteomic Pipeline (Comet and PeptideProphet). Overall, 13,483 PTMs were identified in 7421 proteins. Methylation was the most frequent PTM with more than 2800 modified sites, and lysine was the most frequently modified amino acid with more than 4000 PTMs. The number of proteins identified increased by 22.5% to 18,780 after performing the PTM search. Compared to intact peptides, the intensities of some modified peptides were superior or equivalent. The intensities of some proteins increased dramatically after the PTM search. Gene ontology analysis revealed that protein persulfidation was related to photosynthesis in Emiliania huxleyi. Additionally, various membrane proteins were found to be phosphorylated. Thus, our global PTM discovery platform provides an overview of PTMs in the species and prompts further studies to uncover their biological functions. The combination of a three-dimensional separation method with global PTM search is a promising approach for the identification and discovery of PTMs in other species.
Charge Transfer Complexes of Ketotifen with 2,3-Dichloro-5,6-dicyano-p-benzoquinone and 7,7,8,8-Tetracyanoquodimethane: Spectroscopic Characterization Studies
Authors: Mostafa Gamal A. E. , Bakheit Ahmed , AlMasoud Najla , AlRabiah Haitham
Published: April 2021

The reactions of ketotifen fumarate (KT) with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) as π acceptors to form charge transfer (CT) complexes were evaluated in this study. Experimental and theoretical approaches, including density function theory (DFT), were used to obtain the comprehensive, reliable, and accurate structure elucidation of the developed CT complexes. The CT complexes (KT-DDQ and KT-TCNQ) were monitored at 485 and 843 nm, respectively, and the calibration curve ranged from 10 to 100 ppm for KT-DDQ and 2.5 to 40 ppm for KT-TCNQ. The spectrophotometric methods were validated for the determination of KT, and the stability of the CT complexes was assessed by studying the corresponding spectroscopic physical parameters. The molar ratio of KT:DDQ and KT:TCNQ was estimated at 1:1 using Job’s method, which was compatible with the results obtained using the Benesi–Hildebrand equation. Using these complexes, the quantitative determination of KT in its dosage form was successful.
Graphene Integrated Hydrogels Based Biomaterials in Photothermal Biomedicine
Authors: Phan Le Minh Tu , Vo Thuy Anh Thu , Hoang Thi Xoan , Cho Sungbo
Published: April 2021

Recently, photothermal therapy (PTT) has emerged as one of the most promising biomedical strategies for different areas in the biomedical field owing to its superior advantages, such as being noninvasive, target-specific and having fewer side effects. Graphene-based hydrogels (GGels), which have excellent mechanical and optical properties, high light-to-heat conversion efficiency and good biocompatibility, have been intensively exploited as potential photothermal conversion materials. This comprehensive review summarizes the current development of graphene-integrated hydrogel composites and their application in photothermal biomedicine. The latest advances in the synthesis strategies, unique properties and potential applications of photothermal-responsive GGel nanocomposites in biomedical fields are introduced in detail. This review aims to provide a better understanding of the current progress in GGel material fabrication, photothermal properties and potential PTT-based biomedical applications, thereby aiding in more research efforts to facilitate the further advancement of photothermal biomedicine.
Hygro-Thermal Vibrations of Porous FG Nano-Beams Based on Local/Nonlocal Stress Gradient Theory of Elasticity
Authors: Penna Rosa , Feo Luciano , Lovisi Giuseppe , Fabbrocino Francesco
Published: April 2021

In this manuscript the dynamic response of porous functionally-graded (FG) Bernoulli–Euler nano-beams subjected to hygro-thermal environments is investigated by the local/nonlocal stress gradient theory of elasticity. In particular, the influence of several parameters on both the thermo-elastic material properties and the structural response of the FG nano-beams, such as material gradient index, porosity volume fraction, nonlocal parameter, gradient length parameter, and mixture parameter is examined. It is shown how the proposed approach is able to capture the dynamic behavior of porous functionally graded Bernoulli–Euler nano-beams under hygro-thermal loads and leads to well-posed structural problems of nano-mechanics.
Comparative Overview of the Performance of Cementitious and Non-Cementitious Nanomaterials in Mortar at Normal and Elevated Temperatures
Authors: Khan M. Arsalan , Imam M. Khalid , Irshad Kashif , Ali Hafiz Muhammad , Hasan Mohd Abul , Islam Saiful
Published: April 2021

Nanotechnology has emerged as a field with promising applications in building materials. Nanotechnology-based mortars are examples of such building materials that have widespread applications in the construction industry. The main nanomaterials used in mortars include nano-silica, nano-magnesium oxide, nano-alumina, nano-titanium oxide, nano-zinc oxide, nano-clay, and nano-carbon. This review paper presents a summary of the properties and effects of these nanomaterials on cement mortar in terms of its fresh-state and hard-state properties. The fresh-state properties include the setting time, consistency, and workability, while the hard-state properties include mechanical properties such as compressive, flexural, tensile strengths, as well as the elasticity modulus, in addition to durability properties such as water absorption, shrinkage strain, strength loss due to freeze–thaw cycles, and chloride penetration, among others. Different nanomaterials cause different physical and chemical alterations within the microstructures of cement mortar. Therefore, the microstructural characterization and densification of mortar are discussed in detail at varying temperatures. In general, the involvement of nanomaterials in cement mortar influences the fresh-state properties, enhances the mechanical properties, and impacts the durability properties, while reducing the porosity present in the mortar matrix. Cementitious nanomaterials can create a pathway for the easy injection of binding materials into the internal microstructures of a hydration gel to impact the hydration process at different rates, whereas their non-cementitious counterparts can act as fillers. Furthermore, the research gaps and future outlook regarding the application of nanomaterials in mortar are discussed.
Cascade Effect of Nitrogen on Brazilian Soybean Production Chain
Authors: Rezende Vanessa Theodoro , Bonaudo Thierry , Alves Ricardo Barboza , Nacimento Rafael Araújo , Gameiro Augusto Hauber
Published: April 2021

Soybean is one of the most traded products. Naturally, soy fixes nitrogen through biological symbiosis. Its cultivation transforms natural inert atomic nitrogen into its reactive forms. The advancement of soybean can have environmental impacts, both locally and globally. This study estimated nitrogen flows and their use efficiency in the Brazilian soybean production chain applying material flow analysis. We innovate proposing a new indicator to estimate the “cascade effect of nitrogen” in a framework of 12 years (2007 to 2019). We hypothesized that it is capable to show accumulated nitrogen emissions through the chain. Besides, the method can show the main sources of nitrogen to the environment. The biological fixation was the largest entry. The efficiency in the use of nitrogen was 81% for grain production, and the nitrogen cascade indicator, which represents the ratio of the nitrogen emission in the environment to the total nitrogen available in the product, was only 5.2% in the soybean meal production chain for the year of 2019, with a clear trend of increasing during the period. Thus, Brazil contributes significantly to global nitrogen emissions in the environment since the country is an important producer and player in the world market.
Adherence to Mediterranean Diet and Selected Lifestyle Elements among Young Women with Type 1 Diabetes Mellitus from Northeast Poland: A Case-Control COVID-19 Survey
Authors: Grabia Monika , Puścion-Jakubik Anna , Markiewicz-Żukowska Renata , Bielecka Joanna , Mielech Anita , Nowakowski Patryk , Socha Katarzyna
Published: April 2021

An appropriate balanced diet and dietary patterns are important at every stage of life, but in the case of young patients with type 1 diabetes mellitus (T1DM), it is especially crucial during the COVID-19 pandemic. The aim of the study was to assess health and nutritional behaviors, mainly adherence to the Mediterranean diet (MD), during the second wave of the COVID-19 pandemic in Poland among women with T1DM, and to compare them with a healthy population. This survey (based on a questionnaire) was conducted in December 2020 and included 219 young women, healthy (n = 106) and with T1DM (n = 113), from northeast Poland. Over 30% of the study group admitted that they did not engage in any physical activity. A large proportion declared that their screen time was 5–7 h a day (48% in control and 40% in T1DM group). High intakes of sweet-beverages, sweets and red meat, but also low intakes of olive oil, fish and nuts were observed. The vast majority of participants (60% vs. 71%) were moderately adherent to the Mediterranean Diet Adherence Screener (MEDAS). The study demonstrated that despite the similarity between the behaviors of healthy people and those with T1DM, negative health and nutritional practices, such as low physical activity, long screen time, medium and high levels of stress and inappropriate eating habits were observed.
Can Healthy and Sustainable Dietary Patterns That Fit within Current Dutch Food Habits Be Identified?
Authors: Heerschop Samantha N. , Biesbroek Sander , Temme Elisabeth H. M. , Ocké Marga C.
Published: April 2021

This study investigated major healthy and sustainable dietary patterns in the Dutch population. Two 24-hour dietary recalls were collected in 2078 participants aged 19–79 years in the Dutch National Food Consumption Survey 2012–2016. Dietary patterns were identified using reduced rank regression. Predictor variables were food groups and response variables were Dutch Healthy Diet index 2015 (DHD15-index) score, greenhouse gas emissions (GHGE), and blue water use. Three patterns were discovered, including a “high fruit and vegetable dietary pattern”, a “low meat dietary pattern”, and a “high dairy, low fruit juices dietary pattern”. Diets in the highest quartile of these patterns had higher DHD15-index score than the average population. However, diets of the “high fruit and vegetable dietary pattern” were associated with higher dietary GHGE (14%) and blue water use (69.2%) compared to the average population. Diets of the “low meat dietary pattern” were associated with lower GHGE (19.6%) and higher blue water use (7.7%). Concluding, the “low meat dietary pattern” was the most healthy and sustainable dietary pattern in this population. The addition of blue water use as an environmental impact indicator shows the difficulty of finding existing dietary patterns that have low environmental impact in all determinants.
Nutrition in Gynecological Diseases: Current Perspectives
Authors: Ciebiera Michał , Esfandyari Sahar , Siblini Hiba , Prince Lillian , Elkafas Hoda , Wojtyła Cezary , Al-Hendy Ayman , Ali Mohamed
Published: April 2021

Diet and nutrition are fundamental in maintaining the general health of populations, including women’s health. Health status can be affected by nutrient deficiency and vice versa. Gene–nutrient interactions are important contributors to health management and disease prevention. Nutrition can alter gene expression, as well as the susceptibility to diseases, including cancer, through several mechanisms. Gynecological diseases in general are diseases involving the female reproductive system and include benign and malignant tumors, infections, and endocrine diseases. Benign diseases such as uterine fibroids and endometriosis are common, with a negative impact on women’s quality of life, while malignant tumors are among the most common cause of death in the recent years. In this comprehensive review article, a bibliographic search was performed for retrieving information about nutrients and how their deficiencies can be associated with gynecological diseases, namely polycystic ovary syndrome, infertility, uterine fibroids, endometriosis, dysmenorrhea, and infections, as well as cervical, endometrial, and ovarian cancers. Moreover, we discussed the potential beneficial impact of promising natural compounds and dietary supplements on alleviating these significant diseases.
Adiponectin: Structure, Physiological Functions, Role in Diseases, and Effects of Nutrition
Authors: Khoramipour Kayvan , Chamari Karim , Hekmatikar Amirhosein Ahmadi , Ziyaiyan Amirhosein , Taherkhani Shima , Elguindy Nihal M. , Bragazzi Nicola Luigi
Published: April 2021

Adiponectin (a protein consisting of 244 amino acids and characterized by a molecular weight of 28 kDa) is a cytokine that is secreted from adipose tissues (adipokine). Available evidence suggests that adiponectin is involved in a variety of physiological functions, molecular and cellular events, including lipid metabolism, energy regulation, immune response and inflammation, and insulin sensitivity. It has a protective effect on neurons and neural stem cells. Adiponectin levels have been reported to be negatively correlated with cancer, cardiovascular disease, and diabetes, and shown to be affected (i.e., significantly increased) by proper healthy nutrition. The present review comprehensively overviews the role of adiponectin in a range of diseases, showing that it can be used as a biomarker for diagnosing these disorders as well as a target for monitoring the effectiveness of preventive and treatment interventions.
Exclusive Breastfeeding Is Not Associated with Maternal–Infant Bonding in Early Postpartum, Considering Depression, Anxiety, and Parity
Authors: Fukui Naoki , Motegi Takaharu , Watanabe Yuichiro , Hashijiri Koyo , Tsuboya Ryusuke , Ogawa Maki , Sugai Takuro , Egawa Jun , Enomoto Takayuki , Someya Toshiyuki
Published: April 2021

It is important to clarify how the breastfeeding method affects women’s mental health, and how women’s mental health affects the breastfeeding method in the early postpartum period when major depression and other psychiatric problems are most likely to occur. This study aimed to examine this bidirectional relationship in the early postpartum period. Participants were 2020 postpartum women who completed the Hospital Anxiety and Depression Scale (HADS) and Mother-to-Infant Bonding Scale (MIBS). We obtained data for participants’ breastfeeding method for four weeks after childbirth. We performed a path analysis with factors including breastfeeding method (exclusive breastfeeding or non-exclusive breastfeeding), parity (primipara or multipara), the two HADS subscales (anxiety and depression), and the two MIBS subscales (lack of affection and anger and rejection). The path analysis showed that breastfeeding method did not significantly affect depression, anxiety, and maternal–infant bonding in the early postpartum period. Women with higher anxiety tended to use both formula-feeding and breastfeeding. Our study suggests that exclusive breastfeeding is not associated with maternal-fetal bonding in early postpartum, considering depression, anxiety, and parity.
Mapping Sub-Metre 3D Land-Sea Coral Reefscapes Using Superspectral WorldView-3 Satellite Stereoimagery
Authors: Collin Antoine , Andel Mark , Lecchini David , Claudet Joachim
Published: April 2021

Shallow coral reefs ensure a wide portfolio of ecosystem services, from fish provisioning to tourism, that support more than 500 million people worldwide. The protection and sustainable management of these pivotal ecosystems require fine-scale but large-extent mapping of their 3D composition. The sub-metre spaceborne imagery can neatly produce such an expected product using multispectral stereo-imagery. We built the first 3D land-sea coral reefscape mapping using the 0.3 m superspectral WorldView-3 stereo-imagery. An array of 13 land use/land cover and sea use/sea cover habitats were classified using sea-, ground- and air-truth data. The satellite-derived topography and bathymetry reached vertical accuracies of 1.11 and 0.89 m, respectively. The value added of the eight mid-infrared (MIR) channels specific to the WorldView-3 was quantified using the classification overall accuracy (OA). With no topobathymetry, the best combination included the eight-band optical (visible + near-infrared) and the MIR8, which boosted the basic blue-green-red OA by 9.58%. The classes that most benefited from this MIR information were the land use “roof” and land cover “soil” classes. The addition of the satellite-derived topobathymetry to the optical+MIR1 produced the best full combination, increasing the basic OA by 9.73%, and reinforcing the “roof” and “soil” distinction.
First Report of Ixodes scapularis Ticks Parasitizing a North American Porcupine in Canada
Authors: Scott John D.
Published: April 2021

Adult females of the blacklegged tick, Ixodes scapularis (Acari: Ixodidae), were collected from a North American porcupine, Erethizon dorsatum, in eastern Ontario, Canada. This porcupine parasitism indicates that an established population of I. scapularis is present in the local vicinity. This tick species is known to parasitize more than 150 different vertebrate hosts, including the North American porcupine. The presence of I. scapularis ticks parasitizing a North American porcupine constitutes a new tick-host record in Canada.
Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)
Authors: Dasgupta Shatavisha , Koljenović Senada , van den Bosch Thierry , Swagemakers Sigrid , van der Hoeven Nick , van Marion Ronald , van der Spek Peter , van Doorn Helena , van Kemenade Folkert , Ewing-Graham Patricia
Published: April 2021

Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC—the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN (n = 56), de-VIL (n = 8), and non-dysplastic vulvar tissues (n = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN (n = 8) and de-VIL (n = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues (p < 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, TP53 mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.
Citicoline: A Candidate for Adjunct Treatment of Multiple Sclerosis
Authors: Grieb Paweł , Świątkiewicz Maciej , Kamińska Agnieszka , Jünemann Anselm , Rejdak Robert , Rejdak Konrad
Published: April 2021

In remitting–relapsing multiple sclerosis (RR-MS), relapses are driven by autoreactive immune cells that enter the brain and spinal cord and damage myelin sheaths of axons in white and grey matter, whereas during remissions myelin is repaired by activated oligodendroglial cells. Disease-modifying therapies (DMTs) may either retard/attenuate myelin damage or promote/enhance/speed up myelin repair. Almost all currently approved DMTs inhibit myelin damage and are considerably toxic. Enhancement of myelin repair is considered an unmet medical need of MS patients. Citicoline, known for many years as a nootropic and neuroprotective drug and recently pronounced food supplement, has been found to be significantly efficacious in two complementary rodent models of MS, experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced myelin toxicity. Moreover, citicoline treatment improves visual evoked potentials (VEPs) in glaucoma patients, which is relevant because VEP monitoring is frequently used as an indicator of remyelination in MS. Although over-the-counter availability of citicoline may impede its formal translation to the clinic of MS, evaluation of its efficacy for supporting remyelination in this disease is strongly indicated.
pH Dependence of T2 for Hyperpolarizable 13C-Labelled Small Molecules Enables Spatially Resolved pH Measurement by Magnetic Resonance Imaging
Authors: Grashei Martin , Hundshammer Christian , van Heijster Frits H. A. , Topping Geoffrey J. , Schilling Franz
Published: April 2021

Hyperpolarized 13C magnetic resonance imaging often uses spin-echo-based pulse sequences that are sensitive to the transverse relaxation time T2. In this context, local T2-changes might introduce a quantification bias to imaging biomarkers. Here, we investigated the pH dependence of the apparent transverse relaxation time constant (denoted here as T2) of six 13C-labelled molecules. We obtained minimum and maximum T2 values within pH 1–13 at 14.1 T: [1-13C]acetate (T2,min = 2.1 s; T2,max = 27.7 s), [1-13C]alanine (T2,min = 0.6 s; T2,max = 10.6 s), [1,4-13C2]fumarate (T2,min = 3.0 s; T2,max = 18.9 s), [1-13C]lactate (T2,min = 0.7 s; T2,max = 12.6 s), [1-13C]pyruvate (T2,min = 0.1 s; T2,max = 18.7 s) and 13C-urea (T2,min = 0.1 s; T2,max = 0.1 s). At 7 T, T2-variation in the physiological pH range (pH 6.8–7.8) was highest for [1-13C]pyruvate (ΔT2 = 0.95 s/0.1pH) and [1-13C]acetate (ΔT2 = 0.44 s/0.1pH). Concentration, salt concentration, and temperature alterations caused T2 variations of up to 45.4% for [1-13C]acetate and 23.6% for [1-13C]pyruvate. For [1-13C]acetate, spatially resolved pH measurements using T2-mapping were demonstrated with 1.6 pH units accuracy in vitro. A strong proton exchange-based pH dependence of T2 suggests that pH alterations potentially influence signal strength for hyperpolarized 13C-acquisitions.
Peptide-Based Strategies for Targeted Tumor Treatment and Imaging
Authors: Ayo Abiodun , Laakkonen Pirjo
Published: April 2021

Cancer is one of the leading causes of death worldwide. The development of cancer-specific diagnostic agents and anticancer toxins would improve patient survival. The current and standard types of medical care for cancer patients, including surgery, radiotherapy, and chemotherapy, are not able to treat all cancers. A new treatment strategy utilizing tumor targeting peptides to selectively deliver drugs or applicable active agents to solid tumors is becoming a promising approach. In this review, we discuss the different tumor-homing peptides discovered through combinatorial library screening, as well as native active peptides. The different structure–function relationship data that have been used to improve the peptide’s activity and conjugation strategies are highlighted.
A Model-Informed Drug Development (MIDD) Approach for a Low Dose of Empagliflozin in Patients with Type 1 Diabetes
Authors: Johnston Curtis K. , Eudy-Byrne Rena J. , Elmokadem Ahmed , Nock Valerie , Marquard Jan , Soleymanlou Nima , Riggs Matthew M. , Liesenfeld Karl-Heinz
Published: April 2021

In clinical trials, sodium-glucose co-transporter (SGLT) inhibitor use as adjunct to insulin therapy in type 1 diabetes (T1D) provides glucometabolic benefits while diabetic ketoacidosis risk is increased. The SGLT2 inhibitor empagliflozin was evaluated in two phase III trials: EASE-2 and EASE-3. A low, 2.5-mg dose was included in EASE-3 only. As the efficacy of higher empagliflozin doses (i.e., 10 and 25 mg) in T1D has been established in EASE-2 and EASE-3, a modeling and simulation approach was used to generate additional supportive evidence on efficacy for the 2.5-mg dose. We present the methodology behind the development and validation of two modeling and simulation frameworks: M-EASE-1, a semi-mechanistic model integrating information on insulin, glucose, and glycated hemoglobin; and M-EASE-2, a descriptive model informed by prior information. Both models were developed independently of data from EASE-3. Simulations based on these models assessed efficacy in untested clinical trial scenarios. In this manner, the models provide supportive evidence for efficacy of low-dose empagliflozin 2.5 mg in patients with T1D, illustrating how pharmacometric analyses can support efficacy assessments in the context of limited data.
Estimating the Oral Absorption from Self-Nanoemulsifying Drug Delivery Systems Using an In Vitro Lipolysis-Permeation Method
Authors: Klitgaard Mette , Müllertz Anette , Berthelsen Ragna
Published: April 2021

The aim of this study was to design an in vitro lipolysis-permeation method to estimate drug absorption following the oral administration of self-nanoemulsifying drug delivery systems (SNEDDSs). The method was evaluated by testing five oral formulations containing cinnarizine (four SNEDDSs and one aqueous suspension) from a previously published pharmacokinetic study in rats. In that study, the pharmacokinetic profiles of the five formulations did not correlate with the drug solubilization profiles obtained during in vitro intestinal lipolysis. Using the designed lipolysis-permeation method, in vitro lipolysis of the five formulations was followed by in vitro drug permeation in Franz diffusion cells equipped with PermeaPad® barriers. A linear in vivo–in vitro correlation was obtained when comparing the area under the in vitro drug permeation–time curve (AUC0–3h), to the AUC0–3h of the plasma concentration–time profile obtained from the in vivo study. Based on these results, the evaluated lipolysis-permeation method was found to be a promising tool for estimating the in vivo performance of SNEDDSs, but more studies are needed to evaluate the method further.
Spinoza in His Time: The 17th-Century Religious Context
Authors: Spaans Joke
Published: April 2021

In one of the last paragraphs of his Tractatus theologico-politicus (1670), Spinoza extolls the harmony between people of a diversity of faiths, maintained by the magistracy of Amsterdam. However, he also seems apprehensive about the possibility of the return of chaos, such as during the Arminian Controversies in the Dutch Republic in the 1610s and the English Civil War in the 1640s and 1650s. The so-called Wolzogen affair in 1668 probably rattled him. Spinoza’s fears would, however, prove groundless. Theological controversy in the public church was often fierce and bitter, but did not threaten the integrity of the State after 1619. Political and ecclesiastical authorities supported discussions and debate in which a new theological consensus could be hammered out. From the examples of Petrus de Witte’s Wederlegginge der Sociniaensche Dwaelingen and Romeyn de Hooghe’s Hieroglyphica, I will argue that such freedom was not limited to the universities, under the aegis of academic freedom, but that Spinoza’s call for free research and open debate was in fact everyday reality.
The Ecological Turn in Design: Adopting a Posthumanist Ethics to Inform Value Sensitive Design
Authors: Umbrello Steven
Published: April 2021

Design for Values (DfV) philosophies are a series of design approaches that aim to incorporate human values into the early phases of technological design to direct innovation into beneficial outcomes. The difficulty and necessity of directing advantageous futures for transformative technologies through the application and adoption of value-based design approaches are apparent. However, questions of whose values to design are of critical importance. DfV philosophies typically aim to enrol the stakeholders who may be affected by the emergence of such a technology. However, regardless of which design approach is adopted, all enrolled stakeholders are human ones who propose human values. Contemporary scholarship on metahumanisms, particularly those on posthumanism, have decentred the human from its traditionally privileged position among other forms of life. Arguments that the humanist position is not (and has never been) tenable are persuasive. As such, scholarship has begun to provide a more encompassing ontology for the investigation of nonhuman values. Given the potentially transformative nature of future technologies as relates to the earth and its many assemblages, it is clear that the value investigations of these design approaches fail to account for all relevant stakeholders (i.e., nonhuman animals). This paper has two primary objectives: (1) to argue for the cogency of a posthuman ethics in the design of technologies; and (2) to describe how existing DfV approaches can begin to envision principled and methodological ways of incorporating non-human values into design. To do this, the paper provides a rudimentary outline of what constitutes DfV approaches. It then takes up a unique design approach called Value Sensitive Design (VSD) as an illustrative example. Out of all the other DfV frameworks, VSD most clearly illustrates a principled approach to the integration of values in design.
Gadamer’s Appropriation of Pietism
Authors: Stephenson Barry
Published: April 2021

A foundation stone of Hans Georg Gadamer’s philosophical hermeneutics is the notion of the sensus communis. The philosophical significance of a “sensus communis” (common sense) begins with Aristotle, who offered scattered reflections. The topic was taken up in earnest in Enlightenment thought and in German idealism, but it became more of an individual faculty, lacking the deep sense of community and tradition found in earlier formulations. In this paper, the author demonstrates Gadamer’s debt to Pietist thought, examining his appropriation and use of the theology of Friedrich Christoph Oetinger (1702–1782), a leading figure in Swabian Pietism, whose ideas had a significant impact in theological circles and broader cultural life. Gadamer’s critique of the Enlightenment’s ‘prejudice against prejudice,’ owes a debt to the Pietist conception of the sensus communis and his practical philosophy to Pietism’s emphasis on ‘application’ as a fundamental aspect of a hermeneutical triad.
Glycerol–Water Solution-Assisted Mach–Zehnder Temperature Sensor in Specialty Fiber with Two Cores and One Channel
Authors: Qiu Haiming , Zhao Chunyu , Hu Xuehao , Chen Haijin , Yu Qianqing , Lian Zhenggang , Qu Hang
Published: April 2021

In this paper, we propose an in-fiber Mach–Zehnder temperature sensor based on a dual-core fiber with an eccentric core and a central core. The latter one is beside a fluidic channel embedded in the fiber. The effective refractive index of the guided mode in the central core could be influenced by the glycerol–water solution filled in the fluidic channel. Thus, the transmitted spectrum of the sensor is shifted as a function of temperature. By monitoring the selected spectral dip shifts, an experimental sensitivity of 2.77 nm/°C is obtained in the range of 25 to 40 °C for a solution length of 15 cm. To further improve the temperature sensitivity, the solution length is increased up to 29.5 cm, and a higher sensitivity of 5.69 nm/°C is achieved in the same temperature range. The experimental results agree well with the theoretical ones. The proposed sensor has good robustness and stability, which makes it promising for applications of high precision temperature monitoring.
Considerate Regulation of Output Disturbances
Authors: Eitelberg Eduard
Published: April 2021

Recently, I have considered a multi-variable feedforward control practice in a novel way being called “considerate control”. It was shown how the considerate control is related to Bristol gains, which indicate accurately either the required increase in input scope or the reduced output scope as compared to inconsiderate control. Here, considerate control is expanded to regulating control, necessitating some feedback design. Clearly, high-gain feedback leads to considerate control results in low frequency. Considerate pre-compensation decouples loops also at higher frequencies. However, as an analysis of the included examples demonstrates, such considerate design may insert non-minimum phase-lag into loops that did not have it, thus, reducing the loop bandwidth relative to that achievable in a skillful inconsiderate design, sometimes very significantly. As is often the case, there is a trade-off between consideration and performance.
Designing Self-Sustainable Icephobic Layer by Introducing a Lubricating Un-Freezable Water Hydrogel from Sodium Polyacrylate on the Polyolefin Surface
Authors: Shi Junqi , Cao Chongjian , Zhang Lu , Quan Yiwu , Wang Qingjun , Xie Hongfeng
Published: April 2021

A convenient, environment-friendly, and cost-effective method to keep anti-icing for a long time was highly desirable. Slippery lubricant layers were regarded to be effective and promising for anti-icing on different surfaces, but the drought-out of lubricants and the possible detriments to the environment were inevitable. By combining super-high molecular weight sodium polyacrylate (H-PAAS) with polyolefin through a one-pot method, a self-sustainable lubricating layer with extremely low ice adhesion of un-freezable water hydrogel was achieved at subzero conditions. The lubricant hydrogel layer could auto-spread and cover the surface of polyolefin after encountering supercooled water, frost, or ice. Due to the reduction of storage modulus in the interface, the ice adhesion of the specimen surfaces was far below 20 kPa, varying from 5.13 kPa to 18.95 kPa. Furthermore, the surfaces could preserve the fairly low adhesion after icing/de-icing cycles for over 15 times and thus exhibited sustainable durability. More importantly, this method could be introducing to various polymers and is of great promise for practical applications.
Influence of Post-Core and Crown Type on the Fracture Resistance of Incisors Submitted to Quasistatic Loading
Authors: Uctasli Sadullah , Boz Yakup , Sungur Sercan , Vallittu Pekka K. , Garoushi Sufyan , Lassila Lippo
Published: April 2021

The aim of this paper was to evaluate the fracture resistance and failure type of maxillary incisor teeth, rebuilt with various types of post-core restorations and full crowns made of either direct conventional particulate filler composite (PFC, G-aenial Anterior, GC, Tokyo, Japan) or indirect CAD/CAM restorations (composite Cerasmart 270 and glass ceramic LiSi Block from GC). One hundred (n = 10/group) central incisors were cut and divided into 10 experimental groups restored with different approaches. In approach A, teeth were restored with a core build-up composite (Gradia Core, GC) for a core and full crown of PFC. Approach B had teeth restored using composite core and prefabricated fiber posts, and a complete crown of either PFC or CAD/CAM. Approach C contained teeth restored with a core of short fiber-reinforced composite (everX Flow, GC) and prefabricated fiber posts, and a complete crown of either PFC or CAD/CAM. In approach D, the teeth had a core of short fiber-reinforced composite only, and a complete crown of either PFC or CAD/CAM restorations. The root canals were prepared, and when posts were used, they were luted with either a dual-cure resin cement (LinkForce, GC) or everX Flow. As the control, sound teeth (n = 10) were used. Restorations were quasi-statically loaded until fracture. Failure type was visually investigated. The interface between the fiber post and luting cement was investigated using SEM, before and after completion of the loading test. The data were analyzed by analysis of variance (p = 0.05) followed by Tukey’s test. None of the restorative approaches restored the fracture load strength of intact teeth (p < 0.05). Restorations with additional fiber posts (Approaches B and C) had higher load-bearing capacity (p < 0.05) than restorations without fiber posts (Approaches A and D). Restorations that had short fiber-reinforced composite cores with or without fiber posts presented more repairable failures. Using short fiber-reinforced composite as post-luting and core build-up material with conventional fiber posts proved to be a promising method to strengthen severely damaged incisors.
Revised Atomic Charges for OPLS Force Field Model of Poly(Ethylene Oxide): Benchmarks and Applications in Polymer Electrolyte
Authors: Fang Chan-En , Tsai Yi-Chen , Scheurer Christoph , Chiu Chi-Cheng
Published: April 2021

Poly(ethylene oxide) (PEO)-based polymers are common hosts in solid polymer electrolytes (SPEs) for high-power energy devices. Molecular simulations have provided valuable molecular insights into structures and ion transport mechanisms of PEO-based SPEs. The calculation of thermodynamic and kinetic properties rely crucially on the dependability of the molecular force fields describing inter- and intra-molecular interactions with the target system. In this work, we reparametrized atomic partial charges for the widely applied optimized potentials for liquid simulations (OPLS) force field of PEO. The revised OPLS force field, OPLSR, improves the calculations of density, thermal expansion coefficient, and the phase transition of the PEO system. In particular, OPLSR greatly enhances the accuracy of the calculated dielectric constant of PEO, which is critical for simulating polymer electrolytes. The reparameterization method was further applied to SPE system of PEO/LiTFSI with O:Li ratio of 16:1. Based on the reparametrized partial charges, we applied separate charge-scaling factors for PEO and Li salts. The charge-rescaled OPLSR model significantly improves the resulting kinetics of Li+ transport while maintaining the accurate description of coordination structures within PEO-based SPE. The proposed OPLSR force field can benefit the future simulation studies of SPE systems.
Preliminary Biocompatibility Tests of Poly-ε-Caprolactone/Silver Nanofibers in Wistar Rats
Authors: Álvarez-Ortega Oskar , Ruiz-Ramírez Luis Roberto , Garibay-Alvarado Jesús Alberto , Donohue-Cornejo Alejandro , Espinosa-Cristóbal León Francisco , Cuevas-González Juan Carlos , Reyes-López Simón Yobanny
Published: April 2021

Currently, nanotechnology is perceived as a promising science that produces materials with diverse unique properties at a nanometric scale. Biocompatibility tests of poly-ε-caprolactone nanofibers, embedded with silver nanoparticles manufactured by means of the electrospinning technique, were carried out in Wistar rats to be used as oral dressings for the eradication of bacteria. Solutions of 12.5, 25, 50 and 100 mM of silver nitrate were made using N-dimethylformamide (DMF) and tetrahydrofuran (THF) as reducing solvents with 8% of poly-ε-caprolactone (PCL) polymer. The solutions were electrospun, and the nanofibers obtained in the process were characterized by infrared spectroscopy, Raman spectroscopy, dark field optical microscopy, scanning electron microscopy and X-ray scattering spectroscopy. The nanofibers had an average diameter of 400 ± 100 nm. Once the characterization of the material was done, three implants of each concentration of the nanofibers were formed and placed in the subcutaneous tissue of the rats. Three experimental subjects were used, leaving the material in them for a length of two, four and six weeks, respectively. The rats showed good healing, with the lesions completely healed at four weeks after implantation. After that time, biopsies were taken, and histopathological sections were made to evaluate the inflammatory infiltrate. The tissues of the rats presented chronic inflammatory infiltrate composed mainly of lymphocytes and giant multinucleated cells. The material was rejected by the rats when a layer of collagen and fibroblasts was produced, coating the material, a process characteristic of a foreign body reaction.
Pulsed Laser Deposition of SWCNTs on Carbon Fibres: Effect of Deposition Temperature
Authors: Moise Călin , Rachmani Lidar , Mihai Geanina , Lazar Oana , Enăchescu Marius , Naveh Naum
Published: April 2021

Single wall carbon nanotubes (SWCNTs) were grown on either sized or desized carbon fabric in a self-designed reactor by Pulsed Laser Deposition (PLD). The uniqueness of the PLD system lies, among other things, in the ability to keep the substrate at a low temperature, compared to the 1100 °C needed for the SWCNTs synthesis, thus, rendering it undamaged. Samples were placed at different positions on a cold finger (CF), where a temperature gradient develops, in the range 25–565 °C. The chemical composition and morphology of desized and surface treatments, as well as SWCNTs grown on carbon fibres, were verified by Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-Ray Spectroscopy (EDX), while the quality of SWCNTs was proven by confocal micro-Raman Spectroscopy and High-Resolution Scanning Transmission Electron Microscopy (HR-STEM). Fibres covered with SWCNTs by PLD were characterized using contact angle and the surface free energy was calculated. A micro-droplet pull-out test was used to evaluate the effect of SWCNTs over interfacial properties of a carbon-epoxy composite. A 20% increase in interfacial shear strength (IFSS) was observed by deposition at 290 °C, compared to the commercial carbon fibre sizing. The carbon fibres kept their tensile properties due to the low deposition temperatures.