bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystallographic Characteristic Effect of Cu Substrate on Serrated Cathode Dissolution in Cu/Sn–3.0Ag–0.5Cu/Cu Solder Joints during Electromigration
Authors: Yue Wu , Ding Chao , Qin Hongbo , Gong Chenggong , Zhang Junxi
Published: May 2021

The crystallographic characteristic effect of Cu substrate on cathode dissolution behavior in line-type Cu/Sn–3.0Ag–0.5Cu (SAC305)/Cu solder joints during electromigration (EM) was investigated by scanning electron microscope (SEM), electron backscatter diffraction (EBSD), and first-principles calculations. The SEM and EBSD results show that the crystallographic characteristic of Cu substrate is crucial to cathode dissolution behavior under a direct current of 1.5 × 104 A/cm2 at 125 °C ± 2 °C. When the (001) plane of copper grain adjacent to the Cu3Sn/Cu interface is perpendicular or nearly perpendicular to the current direction, local cathode dissolution tips are easily formed, whereas the (111) plane remains mostly undissolved, which finally leads to the inhomogeneous cathode serrated dissolution in the substrate. The first-principles calculation results reveal that the different surface energies and energy barriers of the different crystallographic planes of Cu grains in the substrate are responsible for the local cathode dissolution tips. Adjusting the copper grain in a substrate to a crystal plane or direction that is difficult to dissolve during EM is a promising method for improving the reliability of solder joints in the future.
Effect of Chemical Composition on Magnetic and Electrical Properties of Ferroelectromagnetic Ceramic Composites
Authors: Bochenek Dariusz , Niemiec Przemysław , Chrobak Artur
Published: May 2021

In this paper, ferroelectric–ferrimagnetic ceramic composites based on multicomponent PZT-type (PbZr1−xTixO3-type) material and ferrite material with different percentages in composite compositions were obtained and studied. The ferroelectric component of the composite was a perovskite ceramic material with the chemical formula Pb0.97Bi0.02(Zr0.51Ti0.49)0.98(Nb2/3Mn1/3)0.02O3 (P), whereas the magnetic component was nickel-zinc ferrite with the chemical formula Ni0.5Zn0.5Fe2O4 (F). The process of sintering the composite compounds was carried out by the free sintering method. Six ferroelectric-ferrimagnetic ceramic P-F composite compounds were designed and obtained with different percentages of its components, i.e., 90/10 (P90-F10), 85/15 (P85-F15), 80/20 (P80-F20), 60/40 (P60-F40), 40/60 (P40-F60), and 20/80 (P20-F80). X-ray diffraction patterns, microstructural, ferroelectric, dielectric, magnetic properties, and DC electrical conductivity of the composite materials were investigated. In this study, two techniques were used to image the microstructure of P-F composite samples: SB (detection of the signals from the secondary and backscattered electron detectors) and BSE (detection of backscattered electrons), which allowed accurate visualization of the presence and distribution of the magnetic and ferroelectric component in the volume of the composite samples. The studies have shown that at room temperature, the ceramic composite samples exhibit good magnetic and electrical properties. The best set of physical properties and performance of composite compositions have ceramic samples with a dominant phase of ferroelectric component and a small amount of the ferrite component (P90-F10). Such a composition retains the high ferroelectric properties of the ferroelectric component in the composite while also acquiring magnetic properties. These properties can be prospectively used in new types of memory and electromagnetic converters.
High-Order Accurate Flux-Splitting Scheme for Conservation Laws with Discontinuous Flux Function in Space
Authors: Xiang Tingting , Wang Guodong , Zhang Suping
Published: May 2021

A new modified Engquist–Osher-type flux-splitting scheme is proposed to approximate the scalar conservation laws with discontinuous flux function in space. The fact that the discontinuity of the fluxes in space results in the jump of the unknown function may be the reason why it is difficult to design a high-order scheme to solve this hyperbolic conservation law. In order to implement the WENO flux reconstruction, we apply the new modified Engquist–Osher-type flux to compensate for the discontinuity of fluxes in space. Together the third-order TVD Runge–Kutta time discretization, we can obtain the high-order accurate scheme, which keeps equilibrium state across the discontinuity in space, to solve the scalar conservation laws with discontinuous flux function. Some examples are given to demonstrate the good performance of the new high-order accurate scheme.
Chiral Capillary Electrokinetic Chromatography: Principle and Applications, Detection and Identification, Design of Experiment, and Exploration of Chiral Recognition Using Molecular Modeling
Authors: El Deeb Sami , Silva Camilla Fonseca , Junior Clebio Soares Nascimento , Hanafi Rasha Sayed , Borges Keyller Bastos
Published: May 2021

This work reviews the literature of chiral capillary electrokinetic chromatography from January 2016 to March 2021. This is done to explore the state-of-the-art approach and recent developments carried out in this field. The separation principle of the technique is described and supported with simple graphical illustrations, showing migration under normal and reversed polarity modes of the separation voltage. The most relevant applications of the technique for enantioseparation of drugs and other enantiomeric molecules in different fields using chiral selectors in single, dual, or multiple systems are highlighted. Measures to improve the detection sensitivity of chiral capillary electrokinetic chromatography with UV detector are discussed, and the alternative aspects are explored, besides special emphases to hyphenation compatibility to mass spectrometry. Partial filling and counter migration techniques are described. Indirect identification of the separated enantiomers and the determination of enantiomeric migration order are mentioned. The application of Quality by Design principles to facilitate method development, optimization, and validation is presented. The elucidation and explanation of chiral recognition in molecular bases are discussed with special focus on the role of molecular modeling.
Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design, Synthesis, Biological, Molecular Docking Studies and In Silico ADME Evaluation
Authors: Kasetti Ashok Babu , Singhvi Indrajeet , Nagasuri Ravindra , Bhandare Richie R. , Shaik Afzal B.
Published: May 2021

Compounds bearing thiazole and chalcone pharmacophores have been reported to possess excellent antitubercular and anticancer activities. In view of this, we designed, synthesized and characterized a novel series of thiazole–chalcone hybrids (1–20) and further evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7, containing 2,4-difluorophenyl and 2,4-dichlorophenyl groups, showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs of 2.43 and 4.41 µM, respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line (DU-145), higher than the standard methotrexate (IC50 = 11 ± 1 µM) with an IC50 value of 6.86 ± 1 µM. Furthermore, cytotoxicity studies of these compounds against normal human liver cell lines (L02) revealed that the target molecules were comparatively less selective against L02. Additional computational studies using AutoDock predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compounds generated through this study, create a way for the optimization and development of novel drugs against tuberculosis infections and prostate cancer.
Preparation of the Key Dolutegravir Intermediate via MgBr2-Promoted Cyclization
Authors: Kong Jiahui , Xia Haijian , He Renbao , Chen Hao , Yu Yongping
Published: May 2021

A novel approach for synthesizing the key dolutegravir intermediate is described via MgBr2-promoted intramolecular cyclization. Condensation of commercially available methyl oxalyl chloride and ethyl 3-(N,N-dimethylamino)acrylate afforded the vinylogous amide in an excellent yield. Subsequent substitution by aminoacetaldehyde dimethyl acetal and methyl bromoacetate gave rise to the expected precursor for cyclization, which was promoted by MgBr2 to highly selectively convert into pyridinone diester. The key dolutegravir intermediate was finally prepared by the selective hydrolysis of the corresponding diester via LiOH.
Steroid Sulphatase and Its Inhibitors: Past, Present, and Future
Authors: Foster Paul A.
Published: May 2021

Steroid sulphatase (STS), involved in the hydrolysis of steroid sulphates, plays an important role in the formation of both active oestrogens and androgens. Since these steroids significantly impact the proliferation of both oestrogen- and androgen-dependent cancers, many research groups over the past 30 years have designed and developed STS inhibitors. One of the main contributors to this field has been Prof. Barry Potter, previously at the University of Bath and now at the University of Oxford. Upon Prof. Potter’s imminent retirement, this review takes a look back at the work on STS inhibitors and their contribution to our understanding of sulphate biology and as potential therapeutic agents in hormone-dependent disease. A number of potent STS inhibitors have now been developed, one of which, Irosustat (STX64, 667Coumate, BN83495), remains the only one to have completed phase I/II clinical trials against numerous indications (breast, prostate, endometrial). These studies have provided new insights into the origins of androgens and oestrogens in women and men. In addition to the therapeutic role of STS inhibition in breast and prostate cancer, there is now good evidence to suggest they may also provide benefits in patients with colorectal and ovarian cancer, and in treating endometriosis. To explore the potential of STS inhibitors further, a number of second- and third-generation inhibitors have been developed, together with single molecules that possess aromatase–STS inhibitory properties. The further development of potent STS inhibitors will allow their potential therapeutic value to be explored in a variety of hormone-dependent cancers and possibly other non-oncological conditions.
Detection of Paratuberculosis in Dairy Herds by Analyzing the Scent of Feces, Alveolar Gas, and Stable Air
Authors: Weber Michael , Gierschner Peter , Klassen Anne , Kasbohm Elisa , Schubert Jochen K. , Miekisch Wolfram , Reinhold Petra , Köhler Heike
Published: May 2021

Paratuberculosis is an important disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). Early detection is crucial for successful infection control, but available diagnostic tests are still dissatisfying. Methods allowing a rapid, economic, and reliable identification of animals or herds affected by MAP are urgently required. This explorative study evaluated the potential of volatile organic compounds (VOCs) to discriminate between cattle with and without MAP infections. Headspaces above fecal samples and alveolar fractions of exhaled breath of 77 cows from eight farms with defined MAP status were analyzed in addition to stable air samples. VOCs were identified by GC–MS and quantified against reference substances. To discriminate MAP-positive from MAP-negative samples, VOC feature selection and random forest classification were performed. Classification models, generated for each biological specimen, were evaluated using repeated cross-validation. The robustness of the results was tested by predicting samples of two different sampling days. For MAP classification, the different biological matrices emitted diagnostically relevant VOCs of a unique but partly overlapping pattern (fecal headspace: 19, alveolar gas: 11, stable air: 4–5). Chemically, relevant compounds belonged to hydrocarbons, ketones, alcohols, furans, and aldehydes. Comparing the different biological specimens, VOC analysis in fecal headspace proved to be most reproducible, discriminatory, and highly predictive.
A Brief Review of the Mechanisms of β-Cell Dedifferentiation in Type 2 Diabetes
Authors: Khin Phyu-Phyu , Lee Jong-Han , Jun Hee-Sook
Published: May 2021

Diabetes is a metabolic disease characterized by hyperglycemia. Over 90% of patients with diabetes have type 2 diabetes. Pancreatic β-cells are endocrine cells that produce and secrete insulin, an essential endocrine hormone that regulates blood glucose levels. Deficits in β-cell function and mass play key roles in the onset and progression of type 2 diabetes. Apoptosis has been considered as the main contributor of β-cell dysfunction and decrease in β-cell mass for a long time. However, recent studies suggest that β-cell failure occurs mainly due to increased β-cell dedifferentiation rather than limited β-cell proliferation or increased β-cell death. In this review, we summarize the current advances in the understanding of the pancreatic β-cell dedifferentiation process including potential mechanisms. A better understanding of β-cell dedifferentiation process will help to identify novel therapeutic targets to prevent and/or reverse β-cell loss in type 2 diabetes.
COVID-19 Pandemic and Remote Education Contributes to Improved Nutritional Behaviors and Increased Screen Time in a Polish Population-Based Sample of Primary School Adolescents: Diet and Activity of Youth during COVID-19 (DAY-19) Study
Authors: Kołota Aleksandra , Głąbska Dominika
Published: May 2021

The Coronavirus-19 disease (COVID-19) pandemic has influenced the nutrition of individuals, including the diet followed, food availability, and food security. However, thus far, only a few studies have been published regarding the diet and activity of children and adolescents. The aim of the present study was to analyze the influence of the COVID-19 pandemic and remote education in this period on the diet and physical activity in a Polish population-based sample of primary school adolescents. In June 2020, the Diet and Activity of Youth during COVID-19 (DAY-19) Study was conducted on a population recruited based on stratified random sampling from all regions (schools sampled from counties, and counties from voivodeships). The sample consisted of a total of 1334 adolescents aged 10–16 years. The study assessed the diet and physical activity of the participants using a validated questionnaire which included questions about the period of remote education and the period before the COVID-19 pandemic. The participants were asked about the following: consumption of fruit, vegetables, soft drinks, water, French fries, and fast food; eating meals in front of the television; and the number of days they are physically active and the number of hours they spend watching television. The obtained data were analyzed by stratifying the respondents by the gender, age, size of the city and total COVID-19 morbidity in the voivodeship. It was observed that, during the pandemic and the resultant remote education, the proportion of respondents who declared the recommended intake of fruits and vegetables had increased compared to that before the pandemic—a higher proportion consumed at least three portions of fruit per day (19.0% before pandemic vs. 27.4% during pandemic; p < 0.0001), as well as three and four or more portions of vegetables per day (11.9% vs. 14.5% and 7.5% vs. 11.1%; p = 0.0004). At the same time, the proportion of respondents consuming at least three cups of water per day had increased (41.1% vs. 47.9%; p = 0.0020), whereas the proportion of respondents who never or rarely eat their meals in front of the television had decreased (35.6% vs. 28.9%; p < 0.0001), and the proportion watching television for more than 2 h a day had increased (78.3% vs. 88.4%; p < 0.0001). Based on the results, it may be concluded that, during the period of remote education due to the COVID-19 pandemic, the dietary behaviors of the studied population of Polish adolescents were more beneficial, which included a higher intake of fruit, vegetables, and water, compared to before the pandemic. In spite of the increasing screen time, including eating in front of the television, there was no reduction in the number of days the respondents were physically active.
Low Serum Vitamin E Level Associated with Low Hand Grip Strength in Community-Dwelling Adults: Korean National Health and Nutrition Examination Survey (KNHANES VII) 2016–2018
Authors: Kim Yongjae , Shin Sungjae , Hong Namki , Rhee Yumie
Published: May 2021

This study assessed the association between serum vitamin E levels and hand grip strength (HGS) in community-dwelling adults data of 1011 men aged 50 years and older and 1144 postmenopausal women were analyzed. Low HGS was defined as HGS below the sex-stratified median value. Proportion of low HGS was the greatest in the lowest quintile of serum vitamin E level (<10.51 mg/L, 57.1%), with a decreasing trend toward the highest vitamin E quintile (>17.81 mg/L, 43.6%; p < 0.001). A one-unit (mg/L) decrease in vitamin E levels was associated with lower HGS in men (adjusted beta coefficient −0.10, 95% confidence interval [CI] −0.18 to −0.02, p = 0.019), but not in women (−0.01, 95% CI −0.06 to 0.03, p = 0.550). Compared with the middle quintile (Q3; 12.59–14.69 mg/L), the lowest vitamin E quintile (Q1) was associated with elevated odds of low HGS (adjusted odds ratio [aOR]: 1.38, p = 0.045), independent of sociodemographic factors, health-related lifestyles, comorbidities, dietary intake, and cholesterol level. However, the odds of low HGS did not differ significantly in other vitamin E quintiles (Q2, aOR 1.12; Q4, aOR 1.38; Q5, aOR 1.12; p > 0.05). Individuals with the lowest quintile vitamin E level had elevated odds of low HGS independent of covariates, findings which merit further validation.
Attenuation of Oxidative Stress and Inflammatory Response by Chronic Cannabidiol Administration Is Associated with Improved n-6/n-3 PUFA Ratio in the White and Red Skeletal Muscle in a Rat Model of High-Fat Diet-Induced Obesity
Authors: Bielawiec Patrycja , Harasim-Symbor Ewa , Sztolsztener Klaudia , Konstantynowicz-Nowicka Karolina , Chabowski Adrian
Published: May 2021

The consumption of fatty acids has increased drastically, exceeding the nutritional requirements of an individual and leading to numerous metabolic disorders. Recent data indicate a growing interest in using cannabidiol (CBD) as an agent with beneficial effects in the treatment of obesity. Therefore, our aim was to investigate the influence of chronic CBD administration on the n-6/n-3 polyunsaturated fatty acids (PUFAs) ratio in different lipid fractions, inflammatory pathway and oxidative stress parameters in the white and red gastrocnemius muscle. All the designed experiments were performed on Wistar rats fed a high-fat diet (HFD) or a standard rodent diet for seven weeks and subsequently injected with CBD (10 mg/kg once daily for two weeks) or its vehicle. Lipid content and oxidative stress parameters were assessed using gas–liquid chromatography (GLC), colorimetric and/or immunoenzymatic methods, respectively. The total expression of proteins of an inflammatory pathway was measured by Western blotting. Our results revealed that fatty acids (FAs) oversupply is associated with an increasing oxidative stress and inflammatory response, which results in an excessive accumulation of FAs, especially of n-6 PUFAs, in skeletal muscles. We showed that CBD significantly improved the n-6/n-3 PUFA ratio and shifted the equilibrium towards anti-inflammatory n-3 PUFAs, particularly in the red gastrocnemius muscle. Additionally, CBD prevented generation of lipid peroxidation products and attenuated inflammatory response in both types of skeletal muscle. In summary, the results mentioned above indicate that CBD presents potential therapeutic properties with respect to the treatment of obesity and related disturbances.
Association of Preoperative Prognostic Nutritional Index and Postoperative Acute Kidney Injury in Patients with Colorectal Cancer Surgery
Authors: Sim Ji-Hoon , Bang Ji-Yeon , Kim Sung-Hoon , Kang Sa-Jin , Song Jun-Gol
Published: May 2021

The prognostic nutritional index (PNI) has been reported to be associated with postoperative complications and prognosis in cancer surgery. However, few studies have evaluated the association between preoperative PNI and postoperative acute kidney injury (AKI) in colorectal cancer patients. This study evaluated association of preoperative PNI and postoperative AKI in patients who underwent colorectal cancer surgery. This study retrospectively analyzed 3543 patients who underwent colorectal cancer surgery between June 2008 and February 2012. The patients were classified into four groups by the quartile of PNI: Q1 (≤43.79), Q2 (43.79–47.79), Q3 (47.79–51.62), and Q4 (≥51.62). Multivariate regression analysis was performed to assess the risk factors for AKI and 1-year mortality. AKI was defined according to Kidney Disease Improving Global Outcomes classification (KDIGO) criteria. Additionally, we assessed surgical outcomes such as hospital stay, ICU admission, and postoperative complications. The incidence of postoperative AKI tended to increase in the Q1 group (13.4%, 9.2%, 9.4%, 8.8%). In the multivariate analysis, high preoperative PNI was significantly associated with low risk of postoperative AKI (adjusted odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93–0.99, p = 0.003) and low 1-year mortality (OR: 0.92, 95% CI: 0.86–0.98, p = 0.011). Male sex, body mass index, diabetes mellitus, and hypertension were risk factors for AKI. The Q1 (≤43.79) group had poor surgical outcomes, such as postoperative AKI (OR: 1.52, 95% CI: 1.18–1.95, p = 0.001), higher rates of ICU admission (OR: 3.13, 95% CI: 1.82–5.39, p < 0.001) and higher overall mortality (OR: 3.81, 95% CI: 1.86–7.79, p < 0.001). In conclusion, low preoperative PNI levels, especially in the Q1 (≤43.79), were significantly associated with postoperative AKI and surgical outcomes, such as hospital stay, postoperative ICU admission, and mortality.
Dietary Changes during the COVID-19 Pandemic: A Longitudinal Study Using Objective Sequential Diet Records from an Electronic Purchase System in a Workplace Cafeteria in Japan
Authors: Nakamura Mieko , Shirai Yoshiro , Sakuma Masae
Published: May 2021

As a result of the coronavirus disease 2019 (COVID-19) pandemic-related restrictions, food systems have undergone unprecedented changes, with the potential to affect dietary behavior. We aimed to investigate workers’ dietary changes resulting from the introduction of regulations to combat COVID-19 in a Japanese factory cafeteria. Objective data on daytime dietary intake were automatically collected from electronic purchase system records. The dataset included the weekly data of 890 men from 1 July 2019 to 30 September 2020. The cafeteria regulations came into effect on 10 April 2020; in this context, the purchase of dishes and estimated dietary intake were monitored. The number of cafeteria visits decreased slightly after the introduction of the regulations. The purchase of main and side dishes also decreased, but the purchase of grain dishes was less affected. When compared with summer 2019 (pre-pandemic, no regulations: 1 July to 29 September 2019), in summer 2020 (during the pandemic and with regulations: 29 June to 30 September 2020), the estimated mean grain, meat, fish, and total energy intake was stable; however, vegetable intake decreased by 11%. As the COVID-19 pandemic continues, workplace cafeteria regulations need to be monitored to avoid unfavorable dietary changes in employees.
Botanicals in Postmenopausal Osteoporosis
Authors: Słupski Wojciech , Jawień Paulina , Nowak Beata
Published: May 2021

Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.
Withdrawal Symptoms Following Discontinuation of Vortioxetine—Retrospective Chart Review
Authors: Siwek Marcin , Chrobak Adrian Andrzej , Gorostowicz Aleksandra , Krupa Anna Julia , Dudek Dominika
Published: May 2021

The efficacy of vortioxetine has been proven in many studies, but data concerning discontinuation symptoms (DS) after vortioxetine withdrawal is scarce. The aim of our study is to systematically evaluate the prevalence, determinants, and clinical features of vortioxetine DS in a retrospective chart review. Data were obtained from medical records of 263 adult patients with depressive disorders who discontinued former vortioxetine treatment. DS were observed in eight (3%) patients after 71–375 days (median 272) of treatment. DS emerged after median three days following vortioxetine withdrawal and lasted for median seven days. The clinical presentation of DS involved: emotional lability (100% of patients), irritability (75%), sudden worsening of mood (75%), nervousness (37.5%), and agitation (37.5%). Median DESS score was four (range of four to six). DS were significantly more prevalent after accidental vs. planned discontinuation (adjusted p = 0.011) and were less frequent after switching to a different antidepressant vs. ceasing pharmacotherapy (adjusted p = 0.0165). DS appeared more often if patients discontinued therapy without medical consultation (adjusted p = 0.033). The occurrence of DS was not associated with the dose and way of drug discontinuation (sudden vs. gradual). In sum, our results show that clinicians should be aware that vortioxetine withdrawal is associated with the possibility of DS.
Evaluation of Bacterial Nanocellulose Membranes Loaded or Not with Nisin as a Complementary Treatment in Surgical Dehorning Wounds in Bovines
Authors: Custódio Fábio A. F. , de Castro Leonardo M. , Unterkircher Erick , Porto Ana Carolina R. C. , Braga Iolanda S. , Hataka Alessandre , Jozala Angela F. , Grotto Denise
Published: May 2021

Treatments of postsurgical dehorning in cattle usually includes topical application of healing agents in wounds. The Bacterial Nanocellulose (BNC) may come to a complementary treatment for these wounds. Two new complementary treatments with BNC and BNC loaded with nisin were evaluated for wound healing in surgical dehorning in bovine. Hence, two groups of experiments were run, and 12 animals were used in each group. All animals, in right and left horns, received antisepsis treatment. For the first group, the left horn was the control, and on the right one the BNC was applied. For the second group, BNC was applied on the left horn (control) and on the right ones BNC+nisin was applied. In both experiments, wounds were evaluated macroscopically by photographic images and microscopically by histology. For macroscopic evaluations, a significant difference was observed over time, but only in the comparison within the same groups. Microscopic analyzes did not showed significant differences in any type of comparison. In conclusion, there was a clinical improvement in the wound healing response with the application of BNC. However, there was no significant difference between BNC compared to the nisin loaded in BNC. For the first time it was applied a BNC in surgical dehorning wounds in bovines and evaluated the efficacy of treatment in a real animal handling situation.
Synthesis and Evaluation of Thiol-Conjugated Poloxamer and Its Pharmaceutical Applications
Authors: Zaman Muhammad , Saeed Sadaf , Imtiaz Bajwa Rabia , Shafeeq Ur Rahman Muhammad , Rahman Saeed , Jamshaid Muhammad , Rasool Muhammad , Majeed Abdul , Imran Imran , Alqahtani Faleh , Alshehri Sultan , AlAsmari Abdullah , Ali Nemat , Alasmari Mohammed
Published: May 2021

The current study was designed to convert the poloxamer (PLX) into thiolated poloxamer (TPLX), followed by its physicochemical, biocompatibilities studies, and applications as a pharmaceutical excipient in the development of tacrolimus (TCM)-containing compressed tablets. Thiolation was accomplished by using thiourea as a thiol donor and hydrochloric acid (HCl) as a catalyst in the reaction. Both PLX and TPLX were evaluated for surface morphology based on SEM, the crystalline or amorphous nature of the particles, thiol contents, micromeritics, FTIR, and biocompatibility studies in albino rats. Furthermore, the polymers were used in the development of compressed tablets. Later, they were also characterized for thickness, diameter, hardness, weight variation, swelling index, disintegration time, mucoadhesion, and in vitro drug release. The outcomes of the study showed that the thiolation process was accomplished successfully, which was confirmed by FTIR, where a characteristic peak was noticed at 2695.9968 cm−1 in the FTIR scan of TPLX. Furthermore, the considerable concentration of the thiol constituents (20.625 µg/g of the polymer), which was present on the polymeric backbone, also strengthened the claim of successful thiolation. A mucoadhesion test illustrated the comparatively better mucoadhesion strength of TPLX compared to PLX. The in vitro drug release study exhibited that the TPLX-based formulation showed a more rapid (p < 0.05) release of the drug in 1 h compared to the PLX-based formulation. The in vivo toxicity studies confirmed that both PLX and TPLX were safe when they were administered to the albino rats. Conclusively, the thiolation of PLX made not only the polymer more mucoadhesive but also capable of improving the dissolution profile of TCM.
Asymmetry in Drug Permeability through the Cornea
Authors: Toffoletto Nadia , Chauhan Anuj , Alvarez-Lorenzo Carmen , Saramago Benilde , Serro Ana Paula
Published: May 2021

The permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release systems.
Drug Safety in Translational Paediatric Research: Practical Points to Consider for Paediatric Safety Profiling and Protocol Development: A Scoping Review
Authors: Aurich Beate , Jacqz-Aigrain Evelyne
Published: May 2021

Translational paediatric drug development includes the exchange between basic, clinical and population-based research to improve the health of children. This includes the assessment of treatment related risks and their management. The objectives of this scoping review were to search and summarise the literature for practical guidance on how to establish a paediatric safety specification and its integration into a paediatric protocol. PubMed, Embase, Web of Science, and websites of regulatory authorities and learned societies were searched (up to 31 December 2020). Retrieved citations were screened and full texts reviewed where applicable. A total of 3480 publications were retrieved. No article was identified providing practical guidance. An introduction to the practical aspects of paediatric safety profiling and protocol development is provided by combining health authority and learned society guidelines with the specifics of paediatric research. The paediatric safety specification informs paediatric protocol development by, for example, highlighting the need for a pharmacokinetic study prior to a paediatric trial. It also informs safety related protocol sections such as exclusion criteria, safety monitoring and risk management. In conclusion, safety related protocol sections require an understanding of the paediatric safety specification. Safety data from carefully planned paediatric research provide valuable information for children, parents and healthcare providers.
A Whole-Body Physiologically Based Pharmacokinetic Model Characterizing Interplay of OCTs and MATEs in Intestine, Liver and Kidney to Predict Drug-Drug Interactions of Metformin with Perpetrators
Authors: Yang Yiting , Zhang Zexin , Li Ping , Kong Weimin , Liu Xiaodong , Liu Li
Published: May 2021

Transmembrane transport of metformin is highly controlled by transporters including organic cation transporters (OCTs), plasma membrane monoamine transporter (PMAT), and multidrug/toxin extrusions (MATEs). Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition. Drug–drug interactions (DDIs) of metformin occur when co-administrated with perpetrators via inhibiting OCTs or MATEs. We aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model characterizing interplay of OCTs and MATEs in the intestine, liver, and kidney to predict metformin DDIs with cimetidine, pyrimethamine, trimethoprim, ondansetron, rabeprazole, and verapamil. Simulations showed that co-administration of perpetrators increased plasma exposures to metformin, which were consistent with clinic observations. Sensitivity analysis demonstrated that contributions of the tested factors to metformin DDI with cimetidine are gastrointestinal transit rate > inhibition of renal OCT2 ≈ inhibition of renal MATEs > inhibition of intestinal OCT3 > intestinal pH > inhibition of hepatic OCT1. Individual contributions of transporters to metformin disposition are renal OCT2 ≈ renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT. In conclusion, DDIs of metformin with perpetrators are attributed to integrated effects of inhibitions of these transporters.
Heat Stress Impact on Yield and Composition of Quinoa Straw under Mediterranean Field Conditions
Authors: Matías Javier , Cruz Verónica , Reguera María
Published: May 2021

Quinoa (Chenopodium quinoa Willd.) is receiving increasing attention globally due to the high nutritional value of its seeds, and the ability of this crop to cope with stress. In the current climate change scenario, valorization of crop byproducts is required to support a climate-smart agriculture. Furthermore, research works characterizing and evaluating quinoa stems and their putative uses are scarce. In this work, straw yield and composition, and the relative feed value of five quinoa varieties, were analyzed in two consecutive years (2017–2018) under field conditions in Southwestern Europe. High temperatures were recorded during the 2017 growing season resulting in significantly decreased straw yield and improved feed value, associated with compositional changes under elevated temperatures. Crude protein, ash, phosphorus, and calcium contents were higher under high temperatures, whereas fiber contents decreased. The relative feed value was also higher in 2017 and differed among varieties. Differences among varieties were also found in straw yield, and contents of phosphorus, potassium, and calcium. Overall, the results presented here support a sustainable quinoa productive system by encouraging straw valorization and shedding light on the mechanisms underlying heat-stress responses in this crop.
Adsorptive Removal of Anionic Azo Dye New Coccine Using Silica and Silica-gel with Surface Modification by Polycation
Authors: Pham Tien Duc , Bui Viet Phuong , Pham Thuy Nga , Le Thi Mai Dung , Nguyen Kim Thuy , Bui Van Hoi , Nguyen The Dung
Published: May 2021

In the present work, adsorption of anionic azo dye, new coccine (NCC) on silica and silica-gel in an aquatic environment was discovered. Effective conditions such as adsorption time, pH, the influence of dosage on NCC adsorption using strong polycation, poly-diallyl-dimethylammonium chloride (PDADMAC) modified silica (PMS) and PDADMAC modified silica-gel (PMSG) were systematically studied. The removal of NCC using PMS and PMSG were much higher than that using raw silica and silica-gel without PDADMAC in all pH ranges from 3 to 10. The adsorption of NCC onto PMS and PMSG was achieved maxima at the same conditions of contact time 30 min, pH 6. The optimum adsorbent dosages of PMS and PMSG for NCC removal were 10 and 20 mg·mL−1, respectively. Experimental results of NCC adsorption isotherms onto PMS and PMSG at different ionic strength were fitted by Langmuir and Freundlich models. The NCC removal efficiencies using PMS and PMSG were higher than 87%, indicating that PMS and PMSG are novel and reusable adsorbents for removal of anionic dye. Based on adsorption isotherms, and surface group changes after PDADMAC modification and NCC adsorption examined by Fourier transform infrared spectroscopy (FTIR), we demonstrate that electrostatic interaction between positively charged adsorbents’ surfaces and negative sulfonic groups of NCC are the main driving force for anionic azo dye adsorption onto PMS and PMGS adsorbents.
Identification of the LLDPE Constitutive Material Model for Energy Absorption in Impact Applications
Authors: Hynčík Luděk , Kochová Petra , Špička Jan , Bońkowski Tomasz , Cimrman Robert , Kaňáková Sandra , Kottner Radek , Pašek Miloslav
Published: May 2021

Current industrial trends bring new challenges in energy absorbing systems. Polymer materials as the traditional packaging materials seem to be promising due to their low weight, structure, and production price. Based on the review, the linear low-density polyethylene (LLDPE) material was identified as the most promising material for absorbing impact energy. The current paper addresses the identification of the material parameters and the development of a constitutive material model to be used in future designs by virtual prototyping. The paper deals with the experimental measurement of the stress-strain relations of linear low-density polyethylene under static and dynamic loading. The quasi-static measurement was realized in two perpendicular principal directions and was supplemented by a test measurement in the 45° direction, i.e., exactly between the principal directions. The quasi-static stress-strain curves were analyzed as an initial step for dynamic strain rate-dependent material behavior. The dynamic response was tested in a drop tower using a spherical impactor hitting a flat material multi-layered specimen at two different energy levels. The strain rate-dependent material model was identified by optimizing the static material response obtained in the dynamic experiments. The material model was validated by the virtual reconstruction of the experiments and by comparing the numerical results to the experimental ones.
Leflunomide Loaded Chitosan Nanoparticles for the Preparation of Aliphatic Polyester Based Skin Patches
Authors: Nanaki Stavroula G. , Andrianidou Sophia , Barmpalexis Panagiotis , Christodoulou Evi , Bikiaris Dimitrios N.
Published: May 2021

In the present study, the preparation of controlled-released leflunomide (LFD)-loaded skin patches was evaluated, utilizing the combination of chitosan (CS) nanoparticles (NPs) incorporated into suitable poly(l-lactic acid) (PLLA) or poly(lactic-co-glycolic acid) (PLGA) polyester matrices. Initially, LFD-loaded CS NPs of ~600 nm and a smooth surface were prepared, while strong inter-molecular interactions between the drug and the CS were unraveled. In the following step, the prepared LFD-loaded CS NPs were incorporated into PLLA or PLGA, and thin-film patches were prepared via spin-coating. Analysis of the prepared films showed that the incorporation of the drug-loaded CS NPs resulted in a significant increase in the drug’s release rate and extent as compared to neat LFD-loaded polyester patches (i.e., prepared without the use of CS NPs). In-depth analysis of the prepared formulations showed that the amorphization of the drug within the matrix and the increased wetting properties of the prepared CS NPs were responsible for the improved thin-film patch characteristics.
Enhanced Processing of Regrind as Recycling Material in Single-Screw Extruders
Authors: Thieleke Philipp , Bonten Christian
Published: May 2021

Regrind processing poses challenges for single-screw extruders due to the irregularly shaped particles. For grooved feed zones, the output is lessened by the reduction of bulk density in comparison to virgin material. Simultaneously, the melt temperature increases, reducing the extruder’s process window. Through experimental investigations on a test stand, a novel feed zone geometry (nominal diameter 35 mm) is developed. It aligns the regrind’s specific throughput with that of virgin material. The regrind processing window is essentially increased. As the solids conveying in the novel feed zone cannot be simulated with existing methods, numerical simulations using the discrete element method are performed. Since plastic deformation occurs in the novel feed zone geometry, a new hysteresis contact model is developed. In addition to spheres, the regrind and virgin particles are modeled as superquadrics to better approximate the irregular shape. The new contact model’s simulation results show excellent agreement with experimental compression tests. The throughput of the extruder simulations is considerably underestimated when using spheres to represent the real particles than when using irregularly shaped superquadrics. Corresponding advantages can be seen especially for virgin material.
Analysis of Raised Feature Failures on 3D Printed Injection Moulds
Authors: Bagalkot Anurag , Pons Dirk , Symons Digby , Clucas Don
Published: May 2021

Background: Polymer-based 3D Printed Injection Mould (3DIM) inserts are used as a cost-effective method for low volume injection moulding (50–500 parts). However, abrupt failure leading to a short tool life is a common shortcoming of 3DIM. Need: The underlying causes of raised feature failures on 3DIM are not well known. Failure is commonly attributed to bending or shearing of raised features on the tool. Understanding the causes may help in delaying the failure and increasing tool life. Approach: Tool failure was analysed from a first-principles perspective, using pressure and temperature fields as determined by mould flow simulation. Experimental results were also obtained for two types of tool material (Visijet M3-X and Digital ABS) with polycarbonate (Lexan 943A) as the part material. Findings: Results find against the idea that pin failure in 3DIM tools is caused by bending and shear failures induced by injection pressures. We also conclude that failure of raised features is not necessarily an abrupt failure as mentioned in the literature. Originality: The generally accepted explanation for the failure of raised features in 3DIM tooling is that injection pressures cause bending and shear failure. This paper disconfirms this notion on theoretical and experimental grounds.
In Vitro Degradation of Specimens Produced from PLA/PHB by Additive Manufacturing in Simulated Conditions
Authors: Findrik Balogová Alena , Trebuňová Marianna , Ižaríková Gabriela , Kaščák Ľuboš , Mitrík Lukáš , Klímová Jana , Feranc Jozef , Modrák Marcel , Hudák Radovan , Živčák Jozef
Published: May 2021

Biopolymers have been the most frequently studied class of materials due to their biodegradability, renewability, and sustainability. The main aim of the presented study was to evaluate degradability of the polymer material blend which was immersed in different solutions. The present study included the production of three different mixtures of polylactic acid and polyhydroxybutyrate, each with a different content of triacetin, which was used as a plasticiser. Applying 3D printing technology, two types of cylindrical specimen were produced, i.e., a solid and a porous specimen, and subjected to in vitro natural degradation. The biodegradation process ran for 195 days in three different solutions (saline, phosphate-buffered saline (PBS), and Hank’s solution) in stable conditions of 37 °C and a pH of 7.4, while the specimens were kept in an orbital motion to simulate the flow of fluids. The goal was to identify the effects of a solution type, specimen shape and material composition on the biodegradation of the materials. The monitored parameters included changes in the solution quantity absorbed by the specimens; morphological changes in the specimen structure; and mechanical properties. They were measured by compressive testing using the Inspekt5 Table Blue testing device. The experiment revealed that specimen porosity affected the absorption of the solutions. The non-triacetin materials exhibited a higher mechanical resistance to compression than the materials containing a plasticiser. The final result of the experiment indicated that the plasticiser-free specimens exhibited higher values of solution absorption, no formation of block cracks or bubbles, and the pH values of the solutions in which these materials were immersed remained neutral for the entire experiment duration; furthermore, these materials did not reduce pH values down to the alkaline range, as was the case with the solutions with the plasticiser-containing materials. Generally, in applications where high mechanical resistance, earlier degradation, and more stable conditions are required, the use of non-plasticiser materials is recommended.
Time for Solidarity: Liturgical Time in Disaster Capitalism
Authors: Roosien Mark
Published: May 2021

This article identifies the upheaval of many people’s experience of time during the COVID-19 pandemic as part of a larger phenomenon of the 24/7 temporality that can be seen to contribute to the environmental destruction and social fragmentation typical of disaster capitalism. It then proposes liturgical temporality as an alternative to 24/7 temporality, framing it as a fitting context for the cultivation of solidarity between human beings and between human beings and the natural world. It argues that modern Jewish and Christian theologies of Sabbath-keeping as a mode of liturgical and ethical praxis have articulated a liberative vision for shared liturgical temporality but have not paid sufficient attention to concrete, collective modes of liturgical time keeping that could contend with the all-encompassing reality of 24/7 life. It concludes by discussing three ways that a more robust spirituality and praxis of liturgical time could support the cultivation of solidarity: a sense of the present that is mindful of the past and future, the invitation of practitioners into a shared story, and meaningful repetition toward the appropriation of a vision of redemption and liberation for human and non-human life.