bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncovering the Roles of MicroRNAs in Major Depressive Disorder: From Candidate Diagnostic Biomarkers to Treatment Response Indicators
Authors: Homorogan Claudia , Nitusca Diana , Seclaman Edward , Enatescu Virgil , Marian Catalin
Published: October 2021

Major depressive disorder (MDD) is a recurrent debilitating illness that represents a major health burden due to its increasing worldwide prevalence, unclear pathological mechanism, nonresponsive treatment, and lack of reliable and specific diagnostic biomarkers. Recently, microRNA species (miRs) have gained particular interest because they have the ability to post-transcriptionally regulate gene expression by modulating mRNA stability and translation in a cohesive fashion. By regulating entire genetic circuitries, miRs have been shown to have dysregulated expression levels in blood samples from MDD patients, when compared to healthy subjects. In addition, antidepressant treatment (AD) also appears to alter the expression pattern of several miRs. Therefore, we critically and systematically reviewed herein the studies assessing the potential biomarker role of several candidate miRs for MDD, as well as treatment response monitoring indicators, in order to enrich the current knowledge and facilitate possible diagnostic biomarker development for MDD, which could aid in reducing both patients’ burden and open novel avenues toward a better understanding of MDD neurobiology.
An Integrated Fuzzy Model for Selecting Resilient Suppliers in Electronics Industry of Iran
Authors: Aghababayi Hamzeh , Shafiei Nikabadi Mohsen
Published: October 2021

Selecting appropriate and resilient suppliers is an important issue in supply chain management (SCM) literature. Making an effective decision on this issue can decrease external risks and disruptions, purchase costs, and delay times and also guarantees business continuity in the event of disruptions and, consequently, increases company competitiveness and customer satisfaction. This paper aims to provide a model based on identifying and investigating related criteria to evaluate suppliers’ resilience and select the most resilient suppliers in Iran’s electronic industry. To this purpose, the screening technique, the best-worst methodology (BWM), and goal programming (GP) have been applied in the fuzzy environment. The proposed model has been implemented and demonstrated by a case study of the electronic industry, as a real-life example. The results show that agility (0.227), compatibility (0.153), and vulnerability (0.102) are the most important factors for a resilient supplier.
E-Business Strategy for Logistics Companies: Achieving Success through Information Systems Planning
Authors: Kamariotou Maria , Kitsios Fotis , Madas Michael
Published: October 2021

Background: E-business and Information Technology (IT) are critical components in the improvement of logistics functions. As logistics contributes to the entire strategic planning of a firm, e-business and IT applications support the implementation of strategic planning in a more efficient and effective manner. According to this view, previous scholars have ignored the importance of Information Systems (IS) planning in the selection and implementation of appropriate IS as per situation. This paper explores the Information Systems Planning (ISP) phases that influence the success of the process. Methods: Data were collected and analyzed using Regression Analysis by 73 IT managers for Greek Small and Medium Enterprises (SMEs) in the logistics sector. Results: The outcomes of the analysis show that executives ought to be informed about the strategic utilization of IS planning in order to improve competitive advantage. Furthermore, managers must also select the suitable IT facilities to align business strategy with the business structure. Conclusions: The outcomes support managers to focus on logistics functions and realize the importance of such ISP in logistics. As a result, selecting appropriate IS leads to increased competitive advantage, faster communication, support for the storage and retrieval of more accurate data, cost reduction and increased customer value.
An Injectable Chitosan-Based Self-Healable Hydrogel System as an Antibacterial Wound Dressing
Authors: Wang Xiaoyu , Song Rijian , Johnson Melissa , A Sigen , He Zhonglei , Milne Cameron , Wang Xianqing , Lara-Sáez Irene , Xu Qian , Wang Wenxin
Published: October 2021

Due to their biodegradability and biocompatibility, chitosan-based hydrogels have great potential in regenerative medicine, with applications such as bacteriostasis, hemostasis, and wound healing. However, toxicity and high cost are problems that must be solved for chitosan-based hydrogel crosslinking agents such as formaldehyde, glutaraldehyde, and genipin. Therefore, we developed a biocompatible yet cost-effective chitosan-based hydrogel system as a candidate biomaterial to prevent infection during wound healing. The hydrogel was fabricated by crosslinking chitosan with dialdehyde chitosan (CTS–CHO) via dynamic Schiff-base reactions, resulting in a self-healable and injectable system. The rheological properties, degradation profile, and self-healable properties of the chitosan-based hydrogel were evaluated. The excellent antibacterial activity of the hydrogel was validated by a spread plate experiment. The use of Live/Dead assay on HEK 293 cells showed that the hydrogel exhibited excellent biocompatibility. The results demonstrate that the newly designed chitosan-based hydrogel is an excellent antibacterial wound dressing candidate with good biocompatibility.
Tensile Properties and Damping Capacity of Cold-Rolled Fe-20Mn-12Cr-3Ni-3Si Damping Alloy
Authors: Kim Jae-Hwan , Jung Jong-Min , Shim Hyunbo
Published: October 2021

The tensile properties and damping capacity of cold-rolled Fe–20Mn–12Cr–3Ni–3Si alloys were investigated. The martensitic transformation was identified, including surface relief with a specific orientation and partial intersection. Besides, as the cold rolling degree increased, the volume fraction of ε-martensite increased, whereas α’-martensite started to form at the cold rolling degree of 15% and slightly increased to 6% at the maximum cold rolling degree. This difference may be caused by high austenite stability by adding alloying elements (Mn and Ni). As the cold rolling degree increased, the tensile strength linearly increased, and the elongation decreased due to the fractional increment in the volume of martensite. However, the damping capacity increased until a 30% cold rolling degree was approached, and then decreased. The irregular tendency of the damping capacity was confirmed, depicting that it increased to a specific degree and then decreased as the tensile strength and elongation increased. Concerning the relationship between the tensile properties and the damping capacity, the damping capacity increased and culminated, and then decreased as the tensile properties and elongation increased. The damping capacity in the high-strength area tended to decrease because it is difficult to dissipate vibration energy into thermal energy in alloys with high strength. In the low-strength area, on the other hand, the damping capacity increased as the strength increased since the increased volume fraction of ε-martensite is attributed to the increase in the damping source.
Synthesis, Self-Assembly and In Vitro Cellular Uptake Kinetics of Nanosized Drug Carriers Based on Aggregates of Amphiphilic Oligomers of N-Vinyl-2-pyrrolidone
Authors: Kulikov Pavel P. , Luss Anna L. , Nelemans Levi C. , Shtilman Mikhail I. , Mezhuev Yaroslav O. , Kuznetsov Igor A. , Sizova Oksana Yu. , Christiansen Gunna , Pennisi Cristian P. , Gurevich Leonid
Published: October 2021

Development of nanocarrier-based drug delivery systems is a major breakthrough in pharmacology, promising targeted delivery and reduction in drug toxicity. On the cellular level, encapsulation of a drug substantially affects the endocytic processes due to nanocarrier–membrane interaction. In this study we synthesized and characterized nanocarriers assembled from amphiphilic oligomers of N-vinyl-2-pyrrolidone with a terminal thiooctadecyl group (PVP-OD). It was found that the dissolution free energy of PVP-OD depends linearly on the molecular mass of its hydrophilic part up to M¯n = 2 × 104, leading to an exponential dependence of critical aggregation concentration (CAC) on the molar mass. A model hydrophobic compound (DiI dye) was loaded into the nanocarriers and exhibited slow release into the aqueous phase on a scale of 18 h. Cellular uptake of the loaded nanocarriers and that of free DiI were compared in vitro using glioblastoma (U87) and fibroblast (CRL2429) cells. While the uptake of both DiI/PVP-OD nanocarriers and free DiI was inhibited by dynasore, indicating a dynamin-dependent endocytic pathway as a major mechanism, a decrease in the uptake rate of free DiI was observed in the presence of wortmannin. This suggests that while macropinocytosis plays a role in the uptake of low-molecular components, this pathway might be circumvented by incorporation of DiI into nanocarriers.
Modification of the Structure and Properties of Lightweight Cement Composite with PVA Fibers
Authors: Sikarskas Donatas , Antonovič Valentin , Malaiškienė Jurgita , Boris Renata , Stonys Rimvydas , Šahmenko Genadijs
Published: October 2021

This study addresses the application of polyvinyl alcohol (PVA) fibers to improve the performance of lightweight cement composites with pozzolans. Blended cement mixes based on expanded glass granules were modified with PVA fibers (Type A: Ø40 µm, L = 8 mm and Type B: Ø200 µm, L = 12 mm). The following research methods were used to analyse the effect of the fibers on the structure of cement matrix and physical-mechanical properties of lightweight composite: SEM, XRD, DTG, calorimetry tests, and standard test methods of physical and mechanical properties. Results from the tests showed that a denser layer of hydrates was formed around the PVA fiber and the amounts of portlandite, CSH, and CASH formed in the specimens with PVA were found to be higher. PVA fibers of Type A accelerated hydration of the cement paste, slightly increased the compressive strength of the lightweight composite, but had no significant effect on the values of density, ultrasonic pulse velocity and flexural strength. The shrinkage of cement composite was significantly reduced using both types of PVA fiber and both types of PVA fibers increased the fracture energy of lightweight cement composite with expanded granules.
Fatigue Damage Map of AZ31B-F Magnesium Alloys under Multiaxial Loading Conditions
Authors: Anes Vitor , Reis Luis , Freitas Manuel
Published: October 2021

In this work, the mechanical behavior of the AZ31B-F magnesium alloy under cyclic loading is analyzed with the goal of contributing to the advancement of its use in the design of AZ31B-F components and structures. To achieve this goal, an experimental program was implemented to evaluate the cyclic response of the AZ31B-F under specific proportional loads with different stress amplitude ratios. Afterwards, regression methods were applied to extend the experimental data to a wide range of proportional loads. As a result, the AZ31B-F damage map, a material property that stablishes the damage scale between normal and shear stresses for finite life loading regimes, was obtained. In addition, a safety factor was developed for the AZ31B-F material when subjected to proportional loading. The achieved results have a direct application in mechanical design of components/structures made of AZ31B-F contributing to its reliability.
Orange Pickeringite from the Algares 30-Level Adit, Aljustrel Mine, Iberian Pyrite Belt, Portugal
Authors: Silva Teresa P. , Matos João X. , de Oliveira Daniel , Morais Igor , Gonçalves Pedro , Albardeiro Luís , Carvalho Fernanda , Menda Ugur D. , Veiga João P.
Published: October 2021

The sheltered environment of the Algares +30 level adit (underground mine gallery) contributes to the preservation of secondary water-soluble minerals formed on the tunnel walls. The massive sulphide and related stockwork zone are hosted by the Mine Tuff volcanic unit and are exposed in the walls of the gallery, showing intense oxidation and hydrothermal alteration. Minerals from the halotrichite group were identified on the efflorescent salts, typically white fine-acicular crystals but also on aggregates with dark orange/brownish colour. Mineral characterization was performed using several methods and analytical techniques (XRD, XRF-WDS, SEM-EDS, DTA-TG), and the chemical formulas were calculated maintaining the ratio A:B ≅ 1:2 in accordance with the general formula of the halotrichite group, AB2(SO4)4·22H2O. This methodology allowed the assignment of the orange colour to the presence of trivalent iron on iron-rich pickeringite in partial substitution of aluminium.
Direct Conversion of 3-(2-Nitroethyl)-1H-Indoles into 2-(1H-Indol-2-yl)Acetonitriles
Authors: Aksenov Alexander V. , Aksenov Nicolai A. , Aleksandrova Elena V. , Aksenov Dmitrii A. , Grishin Igor Yu. , Sorokina Elena A. , Wenger Allison , Rubin Michael
Published: October 2021

The recently discovered [4+1]-spirocyclization of nitroalkenes to indoles provided a convenient new approach to 2-(1H-indol-2-yl)acetonitriles. However, this reaction was complicated by the formation of inert 3-(2-nitroethyl)-1H-indole byproducts. Herein, we offer a workaround this problem that allows for effective transformation of the unwanted byproducts into acetonitrile target molecules.
Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial–Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36
Authors: Ruan Yuan , Yuan Pei-Pei , Wei Ya-Xin , Zhang Qi , Gao Li-Yuan , Li Pan-Ying , Chen Yi , Fu Yang , Cao Yan-Gang , Zheng Xiao-Ke , Feng Wei-Sheng
Published: October 2021

Lipid deposition in the kidney can cause serious damage to the kidney, and there is an obvious epithelial–mesenchymal transition (EMT) and fibrosis in the late stage. To investigate the interventional effects and mechanisms of phenolic compounds from Mori Cortex on the EMT and fibrosis induced by sodium oleate-induced lipid deposition in renal tubular epithelial cells (NRK-52e cells), and the role played by CD36 in the adjustment process, NRK-52e cells induced by 200 μmol/L sodium oleate were given 10 μmoL/L moracin-P-2″-O-β-d-glucopyranoside (Y-1), moracin-P-3′-O-β-d-glucopyranoside (Y-2), moracin-P-3′-O-α-l-arabinopyranoside (Y-3), and moracin-P-3′-O-[β-glucopyranoside-(1→2)arabinopyranoside] (Y-4), and Oil Red O staining was used to detect lipid deposition. A Western blot was used to detect lipid deposition-related protein CD36, inflammation-related protein (p-NF-κB-P65, NF-κB-P65, IL-1β), oxidative stress-related protein (NOX1, Nrf2, Keap1), EMT-related proteins (CD31, α-SMA), and fibrosis-related proteins (TGF-β, ZEB1, Snail1). A qRT-PCR test detected inflammation, EMT, and fibrosis-related gene mRNA levels. The TNF-α levels were detected by ELISA, and the colorimetric method was used to detects SOD and MDA levels. The ROS was measured by flow cytometry. A high-content imaging analysis system was applied to observe EMT and fibrosis-related proteins. At the same time, the experiment silenced CD36 and compared the difference between before and after drug treatment, then used molecular docking technology to predict the potential binding site of the active compounds with CD36. The research results show that sodium oleate can induce lipid deposition, inflammation, oxidative stress, and fibrosis in NRK-52e cells. Y-1 and Y-2 could significantly ameliorate the damage caused by sodium oleate, and Y-2 had a better ameliorating effect, while there was no significant change in Y-3 or Y-4. The amelioration effect of Y-1 and Y-2 disappeared after silencing CD36. Molecular docking technology showed that the Y-1 and Y-2 had hydrogen bonds to CD36 and that, compared with Y-1, Y-2 requires less binding energy. In summary, moracin-P-2″-O-β-d-glucopyranoside and moracin-P-3′-O-β-d-glucopyranoside from Mori Cortex ameliorated lipid deposition, EMT, and fibrosis induced by sodium oleate in NRK-52e cells through CD36.
Methoxy-Monobenzoylmethane Protects Human Skin against UV-Induced Damage by Conversion to Avobenzone and Radical Scavenging
Authors: Termer Michael , Carola Christophe , Salazar Andrew , Keck Cornelia M. , von Hagen Joerg
Published: October 2021

Avobenzone, one of the most commonly used UV filters in topical sunscreens, is susceptible to photodegradation with a consequential reduction of its UV absorbing properties. This loss of function may lead to skin irritation, photodermatosis, and photoallergic reactions caused by photodegradation byproducts. In this work, we aim to address this issue with a substance named methoxy-monobenzoylmethane (MeO-MBM), which is neither a UVB nor a UVA filter, but which converts to avobenzone, a known and approved UVA filter, under mainly UVB light irradiation. The antioxidant and intracellular radical formation properties of MeO-MBM were compared to the ones of avobenzone. The UV irradiation of MeO-MBM led to an increase in UV absorption primarily in the UVA range after conversion, both in vitro and in vivo. HPTLC and UHPLC studies illustrate the conversion of MeO-MBM to avobenzone in vitro after irradiation at 250 kJ/m2, reaching a conversion rate of 48.8%. A stable molecular antioxidant activity was observed, since 100-µM MeO-MBM was measured to be 11.2% in the DPPH assay, with a decrease to 9.7% after irradiation. In comparison, the molecular antioxidant activity of 100-µM avobenzone was determined to be 0.8%. In keratinocytes, MeO-MBM reduces the intracellular ROS by 90% and avobenzone by 75% with tBHP as the inducer and by 53% and 57%, respectively, when induced by pyocyanin, indicating the redox scavenging capacity of both these molecules. These results indicate that MeO-MBM functions initially as an antioxidant material and as a photoantioxidant during its conversion process to avobenzone. This research provides insight into the development of active ingredients for topical applications with dynamic functionalities. Using this approach, we demonstrate the possibility to extend the UV protection offered to skin cells while combating cellular stress in parallel.
Improving Detection of Client Complexity in the Community (Impact): A Study Protocol of a Pragmatic Randomized Controlled Trial
Authors: Boak Jennifer , Blackberry Irene , Rasekaba Tshepo
Published: October 2021

Background: Community-dwelling older clients are becoming increasingly complex. Detecting this complexity in clinical practice is limited, with greater reliance on community nurses’ clinical judgment and skills. The lack of a consistent approach to complexity impacts the level of care and support for older clients to remain in their homes for longer. Objective: To examine the effectiveness of the Patient Complexity Instrument (PCI) in addition to nurses’ clinical judgment to enhance detection of complexity, and subsequent older clients’ resource allocation compared to usual nursing assessment. Design: A pragmatic randomized controlled trial will be conducted within a community nursing service in regional Victoria, Australia. Clients 65 years and over referred to the service who are eligible for Commonwealth Home Support Programme (CHSP) funding will be randomized into Control group: usual nursing assessment or Intervention group: usual nursing assessment plus the PCI. Nurse participants are Registered Nurses currently employed in the community nursing service. Results: This study will explore whether introducing the PCI in a community nursing service enhances detection of complexity and client care resource allocation compared to nurses’ clinical judgment based on usual nursing assessment. Conclusion: This protocol outlines the study to enhance the detection of complexity by nurses delivering care for community-dwelling older people in the regional Australian context. The findings will inform the use of a standardized tool to detect complexity among community-dwelling older Australians.
SARS-CoV-2 Multi-Antigen Serology Assay
Authors: Mazhari Ramin , Ruybal-Pesántez Shazia , Angrisano Fiona , Kiernan-Walker Nicholas , Hyslop Stephanie , Longley Rhea J. , Bourke Caitlin , Chen Catherine , Williamson Deborah A. , Robinson Leanne J. , Mueller Ivo , Eriksson Emily M.
Published: October 2021

Serology tests are extremely useful for assessing whether a person has been infected with a pathogen. Since the onset of the COVID-19 pandemic, measurement of anti-SARS-CoV-2-specific antibodies has been considered an essential tool in identifying seropositive individuals and thereby understanding the extent of transmission in communities. The Luminex system is a bead-based technology that has the capacity to assess multiple antigens simultaneously using very low sample volumes and is ideal for high-throughput studies. We have adapted this technology to develop a COVID-19 multi-antigen serological assay. This protocol described here carefully outlines recommended steps to optimize and establish this method for COVID-19-specific antibody measurement in plasma and in saliva. However, the protocol can easily be customized and thus the assay is broadly applicable to measure antibodies to other pathogens.
Design of Hierarchical NiCo2O4 Nanocages with Excellent Electrocatalytic Dynamic for Enhanced Methanol Oxidation
Authors: Li Xue , He Gege , Zeng Chong , Zhou Dengmei , Xiang Jing , Chen Wenbo , Tian Liangliang , Yang Wenyao , Cheng Zhengfu , Song Jing
Published: October 2021

Although sheet-like materials have good electrochemical properties, they still suffer from agglomeration problems during the electrocatalytic process. Integrating two-dimensional building blocks into a hollow cage-like structure is considered as an effective way to prevent agglomeration. In this work, the hierarchical NiCo2O4 nanocages were successfully synthesized via coordinated etching and precipitation method combined with a post-annealing process. The nanocages are constructed through the interaction of two-dimensional NiCo2O4 nanosheets, forming a three-dimensional hollow hierarchical architecture. The three-dimensional supporting cavity effectively prevents the aggregation of NiCo2O4 nanosheets and the hollow porous feature provides amounts of channels for mass transport and electron transfer. As an electrocatalytic electrode for methanol, the NiCo2O4 nanocages-modified glassy carbon electrode exhibits a lower overpotential of 0.29 V than those of NiO nanocages (0.38 V) and Co3O4 nanocages (0.34 V) modified glassy carbon electrodes. The low overpotential is attributed to the prominent electrocatalytic dynamic issued from the three-dimensional hollow porous architecture and two-dimensional hierarchical feature of NiCo2O4 building blocks. Furthermore, the hollow porous structure provides sufficient interspace for accommodation of structural strain and volume change, leading to improved cycling stability. The NiCo2O4 nanocages-modified glassy carbon electrode still maintains 80% of its original value after 1000 consecutive cycles. The results demonstrate that the NiCo2O4 nanocages could have potential applications in the field of direct methanol fuel cells due to the synergy between two-dimensional hierarchical feature and three-dimensional hollow structure.
Long Non-Coding RNAs in Cardiovascular Diseases: Potential Function as Biomarkers and Therapeutic Targets of Exercise Training
Authors: Correia Camila Caldas Martins , Rodrigues Luis Felipe , de Avila Pelozin Bruno Rocha , Oliveira Edilamar Menezes , Fernandes Tiago
Published: October 2021

Despite advances in treatments and therapies, cardiovascular diseases (CVDs) remain one of the leading causes of death worldwide. The discovery that most of the human genome, although transcribed, does not encode proteins was crucial for focusing on the potential of long non-coding RNAs (lncRNAs) as essential regulators of cell function at the epigenetic, transcriptional, and post-transcriptional levels. This class of non-coding RNAs is related to the pathophysiology of the cardiovascular system. The different expression profiles of lncRNAs, in different contexts of CVDs, change a great potential in their use as a biomarker and targets of therapeutic intervention. Furthermore, regular physical exercise plays a protective role against CVDs; on the other hand, little is known about its underlying molecular mechanisms. In this review, we look at the accumulated knowledge on lncRNAs and their functions in the cardiovascular system, focusing on the cardiovascular pathology of arterial hypertension, coronary heart disease, acute myocardial infarction, and heart failure. We discuss the potential of these molecules as biomarkers for clinical use, their limitations, and how the manipulation of the expression profile of these transcripts through physical exercise can begin to be suggested as a strategy for the treatment of CVDs.
Impact of Body Mass Index on the Age of Relapsing-Remitting Multiple Sclerosis Onset: A Retrospective Study
Authors: Siokas Vasileios , Katsiardanis Konstantinos , Aloizou Athina-Maria , Bakirtzis Christos , Liampas Ioannis , Koutlas Evangelos , Rudolf Jobst , Ntinoulis Konstantinos , Kountouras Jannis , Dardiotis Efthimios , Deretzi Georgia
Published: October 2021

A Backround: Multiple sclerosis (MS) is a complex chronic disease of the central nervous system (CNS). Body mass index (BMI), a component of metabolic syndrome (MetS), is considered among the risk factors for MS. However, its role in MS remains ambiguous. Objective: To examine the impact of BMI on the age of onset in patients with relapsing-remitting MS (RRMS) in a Greek cohort. Methods: Data from 821 Greek patients with RRMS were collected. The BMI values were considered as quartiles. Comparisons for the demographic characteristics between the quartiles were made by Pearson’s chi-square test for the categorical variables and by ANOVA for the continuous variables. An overall p-value was calculated corresponding to trend for association. In case of significant association, further post-hoc analysis was performed in order to identify differences in demographic characteristics between specific BMI quartiles groups. Linear regression analyses were used to assess the relationship between BMI and age at onset of MS. Results: Comparisons of participant characteristics by quartiles of BMI revealed that participants with the highest BMI had an older age of disease onset. Results from linear regression analysis showed that with each increase of 1 BMI unit, the age of RRMS onset increases by 0.255 (95% CI 0.136 to 0.374) years, p < 0.001. Conclusions: Patients with higher BMI, as a parameter of MetS, exhibit increased age of RRMS onset. Our results may present an alternative personalized approach for diagnosis, prognosis, and/or prevention of RRMS.
Winter Malting Barley Growth, Yield, and Quality following Leguminous Cover Crops in the Northeast United States
Authors: Siller Arthur , Darby Heather , Smychkovich Alexandra , Hashemi Masoud
Published: October 2021

There is growing interest in malting barley (Hordeum vulgare L.) production in the Northeastern United States. This crop must meet high quality standards for malting but can command a high price if these quality thresholds are met. A two-year field experiment was conducted from 2015 to 2017 to evaluate the impact of two leguminous cover crops, sunn hemp (Crotalaria juncea L.) and crimson clover (Trifolium incarnatum L.), on subsequent winter malting barley production. Four cover crop treatments—sunn hemp (SH), crimson clover (CC), sunn hemp and crimson clover mixture (SH + CC), and no cover crop (NC)—were grown before planting barley at three seeding rates (300, 350, and 400 seeds m−2). SH and SH + CC produced significantly more biomass and residual nitrogen than the CC and NC treatments. Higher barley seeding rates led to higher seedling density and winter survival. However, the subsequent spring and summer barley growth metrics, yield, and malting quality were not different in any of the treatments. There is much left to investigate in determining the best malting barley production practices in the Northeastern United States, but these results show that winter malting barley can be successfully integrated into crop rotations with leguminous plants without negative impacts on barley growth, yield, and grain quality.
A Systematic Review of Diet Quality Index and Obesity among Chinese Adults
Authors: Kadam Isma’il , Neupane Sudeep , Wei Jingkai , Fullington Lee Ann , Li Tricia , An Ruopeng , Zhao Li , Ellithorpe Amy , Jiang Xinyin , Wang Liang
Published: October 2021

Diet quality scores are designed mainly based on Western-style dietary patterns. They were demonstrated to be good indicators of obesity in developed but not developing countries. Several diet quality scores were developed based on the Chinese dietary guidelines, yet no systematic review exists regarding how they were related to obesity. We searched research articles published between 2000 and 2021 in PubMed, CINAHL, and Scopus databases. Both cross-sectional and prospective studies that examined the relationship between a diet quality score and weight, body mass index, obesity, or waist circumference conducted in a Chinese population were selected. From the 602 articles searched, 20 articles were selected (12 are cross-sectional studies and 8 are prospective cohort studies). The relationship between internationally used scores and obesity was inconsistent among studies. Scores tailored to the Chinese diet demonstrated a strong relationship with both being underweight and obesity. The heterogeneity of the populations and the major nutrition transition in China may partially explain the discrepancies among studies. In conclusion, diet quality scores tailored to the Chinese diet may be associated with both undernutrition and overnutrition, as well as being underweight and obesity outcomes.
Relationship between Energy Balance and Circulating Levels of Hepcidin and Ferritin in the Fasted and Postprandial States
Authors: Kimita Wandia , Bharmal Sakina H. , Ko Juyeon , Cho Jaelim , Petrov Maxim S.
Published: October 2021

Markers of iron metabolism are altered in new-onset diabetes, but their relationship with metabolic signals involved in the maintenance of energy balance is poorly understood. The primary aim was to explore the associations between markers of iron metabolism (hepcidin and ferritin) and markers of energy balance (leptin, ghrelin, and the leptin/ghrelin ratio) in both the fasted and postprandial states. These associations were also studied in the sub-groups stratified by diabetes status. This was a cross-sectional study of individuals without disorders of iron metabolism who were investigated after an overnight fast and, in addition, some of these individuals underwent a mixed meal test to determine postprandial responses of metabolic signals. The associations between hepcidin, ferritin, and leptin, ghrelin, leptin/ghrelin ratio were studied using several multiple linear regression models. A total of 76 individuals in the fasted state and 34 individuals in the postprandial state were included. In the overall cohort, hepcidin was significantly inversely associated with leptin (in the most adjusted model, the β coefficient ± SE was −883.45 ± 400.94; p = 0.031) and the leptin/ghrelin ratio (in the most adjusted model, the β coefficient ± SE was −148.26 ± 61.20; p = 0.018) in the fasted state. The same associations were not statistically significant in the postprandial state. In individuals with new-onset prediabetes or diabetes (but not in those with normoglycaemia or longstanding prediabetes or diabetes), hepcidin was significantly inversely associated with leptin (in the most adjusted model, the β coefficient ± SE was −806.09 ± 395.44; p = 0.050) and the leptin/ghrelin ratio (in the most adjusted model, the β coefficient ± SE was −129.40 ± 59.14; p = 0.037). Leptin appears to be a mediator in the link between iron metabolism and new-onset diabetes mellitus. These findings add to the growing understanding of mechanisms underlying the derangements of glucose metabolism.
The Role of Protein and Fat Intake on Insulin Therapy in Glycaemic Control of Paediatric Type 1 Diabetes: A Systematic Review and Research Gaps
Authors: Furthner Dieter , Lukas Andreas , Schneider Anna Maria , Mörwald Katharina , Maruszczak Katharina , Gombos Petra , Gomahr Julian , Steigleder-Schweiger Claudia , Weghuber Daniel , Pixner Thomas
Published: October 2021

Carbohydrate counting (CHC) is the established form of calculating bolus insulin for meals in children with type 1 diabetes (T1DM). With the widespread use of continuous glucose monitoring (CGM) observation time has become gapless. Recently, the impact of fat, protein and not only carbohydrates on prolonged postprandial hyperglycaemia have become more evident to patients and health-care professionals alike. However, there is no unified recommendation on how to calculate and best administer additional bolus insulin for these two macronutrients. The aim of this review is to investigate: the scientific evidence of how dietary fat and protein influence postprandial glucose levels; current recommendations on the adjustment of bolus insulin; and algorithms for insulin application in children with T1DM. A PubMed search for all articles addressing the role of fat and protein in paediatric (sub-)populations (<18 years old) and a mixed age population (paediatric and adult) with T1DM published in the last 10 years was performed. Conclusion: Only a small number of studies with a very low number of participants and high degree of heterogeneity was identified. While all studies concluded that additional bolus insulin for (high) fat and (high) protein is necessary, no consensus on when dietary fat and/or protein should be taken into calculation and no unified algorithm for insulin therapy in this context exists. A prolonged postprandial observation time is necessary to improve individual metabolic control. Further studies focusing on a stratified paediatric population to create a safe and effective algorithm, taking fat and protein into account, are necessary.
Simulated Changes in Tropical Cyclone Size, Accumulated Cyclone Energy and Power Dissipation Index in a Warmer Climate
Authors: Wehner Michael
Published: October 2021

Detection, attribution and projection of changes in tropical cyclone intensity statistics are made difficult from the potentially decreasing overall storm frequency combined with increases in the peak winds of the most intense storms as the climate warms. Multi-decadal simulations of stabilized climate scenarios from a high-resolution tropical cyclone permitting atmospheric general circulation model are used to examine simulated global changes from warmer temperatures, if any, in estimates of tropical cyclone size, accumulated cyclonic energy and power dissipation index. Changes in these metrics are found to be complicated functions of storm categorization and global averages of them are unlikely to easily reveal the impact of climate change on future tropical cyclone intensity statistics.
SARS-CoV-2 Infection as a Cause of Acute Pancreatitis in a Child—A Case Report
Authors: Kopiczko Natalia , Kwiatek-Średzińska Kamila , Uścinowicz Mirosława , Kowalczuk-Krystoń Monika , Lebensztejn Dariusz Marek
Published: October 2021

The novel coronavirus disease (COVID-19) was detected for the first time in China in December 2019. Soon after it was declared a pandemic. Main symptoms include fever, dyspnea, cough, muscle pain, headache, anosmia and ageusia, however a growing body of evidence shows that other organs can be affected. Gastrointestinal manifestations have been observed in a considerable number of patients and include abdominal pain, diarrhea and vomiting. The involvement of liver as well as pancreas has been also described, however there are only a few cases of acute pancreatitis reported in patients with COVID-19. Therefore, we present a case of 6-year-old child with mild acute pancreatitis and COVID-19 pneumonia.
The Cross Talk between Underlying Mechanisms of Multiple Sclerosis and Epilepsy May Provide New Insights for More Efficient Therapies
Authors: Rayatpour Atefeh , Farhangi Sahar , Verdaguer Ester , Olloquequi Jordi , Ureña Jesus , Auladell Carme , Javan Mohammad
Published: October 2021

Despite the significant differences in pathological background of neurodegenerative diseases, epileptic seizures are a comorbidity in many disorders such as Huntington disease (HD), Alzheimer’s disease (AD), and multiple sclerosis (MS). Regarding the last one, specifically, it has been shown that the risk of developing epilepsy is three to six times higher in patients with MS compared to the general population. In this context, understanding the pathological processes underlying this connection will allow for the targeting of the common and shared pathological pathways involved in both conditions, which may provide a new avenue in the management of neurological disorders. This review provides an outlook of what is known so far about the bidirectional association between epilepsy and MS.
Mechanistic Insights into Binding of Ligands with Thiazolidinedione Warhead to Human Histone Deacetylase 4
Authors: Schweipert Markus , Jänsch Niklas , Upadhyay Neha , Tilekar Kalpana , Wozny Ewelina , Basheer Sidra , Wurster Eva , Müller Marlene , C S Ramaa , Meyer-Almes Franz-Josef
Published: October 2021

Recently, we have reported that non-hydroxamate thiazolidinedione (TZD) analogs are capable of inhibiting human deacetylase 4 (HDAC4). This study aims at the dissection of the molecular determinants and kinetics of the molecular recognition of TZD ligands by HDAC4. For this purpose, a structure activity relationship analysis of 225 analogs was combined with a comprehensive study of the enzyme and binding kinetics of a variety of HDAC4 mutant variants. The experimental data were rationalized by docking to the two major conformations of HDAC4. TZD ligands are competitive inhibitors and bind via a two-step mechanism involving principal molecular recognition and induced fit. The residence time of 24 g is (34 ± 3) min and thus much larger than that of the canonical pan-HDAC inhibitor SAHA ((5 ± 2) min). Importantly, the binding kinetics can be tuned by varying the structure of the CAP group.
Activation of Tenofovir Alafenamide and Sofosbuvir in the Human Lung and Its Implications in the Development of Nucleoside/Nucleotide Prodrugs for Treating SARS-CoV-2 Pulmonary Infection
Authors: Li Jiapeng , Liu Shuhan , Shi Jian , Zhu Hao-Jie
Published: October 2021

ProTide technology is a powerful tool for the design of nucleoside/nucleotide analog prodrugs. ProTide prodrug design improves cell permeability and enhances intracellular activation. The hydrolysis of the ester bond of a ProTide is a determinant of the intracellular activation efficiency and final antiviral efficacy of the prodrug. The hydrolysis is dictated by the catalytic activity and abundance of activating enzymes. The antiviral agents tenofovir alafenamide (TAF) and sofosbuvir (SBV) are typical ProTides. Both TAF and SBV have also been proposed to treat patients with COVID-19. However, the mechanisms underlying the activation of the two prodrugs in the lung remain inconclusive. In the present study, we profiled the catalytic activity of serine hydrolases in human lung S9 fractions using an activity-based protein profiling assay. We evaluated the hydrolysis of TAF and SBV using human lung and liver S9 fractions and purified enzymes. The results showed that CatA and CES1 were involved in the hydrolysis of the two prodrugs in the human lung. More specifically, CatA exhibited a nearly 4-fold higher hydrolytic activity towards TAF than SBV, whereas the CES1 activity on hydrolyzing TAF was slightly lower than that for SBV. Overall, TAF had a nearly 4-fold higher hydrolysis rate in human lung S9 than SBV. We further analyzed protein expression levels of CatA and CES1 in the human lung, liver, and primary cells of the two tissues using proteomics data extracted from the literature. The relative protein abundance of CatA to CES1 was considerably higher in the human lung and primary human airway epithelial cells than in the human liver and primary human hepatocytes. The findings demonstrated that the high susceptivity of TAF to CatA-mediated hydrolysis resulted in efficient TAF hydrolysis in the human lung, suggesting that CatA could be utilized as a target activating enzyme when designing antiviral ester prodrugs for the treatment of respiratory virus infection.
Multi-Organs-on-Chips for Testing Small-Molecule Drugs: Challenges and Perspectives
Authors: Cecen Berivan , Karavasili Christina , Nazir Mubashir , Bhusal Anant , Dogan Elvan , Shahriyari Fatemeh , Tamburaci Sedef , Buyukoz Melda , Kozaci Leyla Didem , Miri Amir K.
Published: October 2021

Organ-on-a-chip technology has been used in testing small-molecule drugs for screening potential therapeutics and regulatory protocols. The technology is expected to boost the development of novel therapies and accelerate the discovery of drug combinations in the coming years. This has led to the development of multi-organ-on-a-chip (MOC) for recapitulating various organs involved in the drug–body interactions. In this review, we discuss the current MOCs used in screening small-molecule drugs and then focus on the dynamic process of drug absorption, distribution, metabolism, and excretion. We also address appropriate materials used for MOCs at low cost and scale-up capacity suitable for high-performance analysis of drugs and commercial high-throughput screening platforms.
Acute Toxicity, Immunotoxicity and Allergenicity of Protease Complex Obtained from Micromycete Sarocladium strictum
Authors: Alipkina Svetlana , Kornienko Elena , Nalobin Denis , Osmolovskiy Alexander
Published: October 2021

The different effects on animals of the thrombolytic protease complex of the new producer S. strictum 203 were studied. The tests of acute toxicity, immunotoxicity and allergenicity should conclude that the studied proteolytic complex is safe for medical usage. For the intravenous and the intraperitoneal routes of administration, the maximum tolerated dose and the median lethal dose were not determined.
The Prevalence of and Documented Indications for Antipsychotic Prescribing in Irish Nursing Homes
Authors: Kelleher Jayne E. , Weedle Peter , Donovan Maria D.
Published: October 2021

Background: Antipsychotic medications are often used ‘off-licence’ to treat neuropsychiatric symptoms and disorders of aging and to manage behavioural and psychological symptoms of dementia despite the warnings of adverse effects. Objective: To establish the prevalence of and documented indication for antipsychotic medication use in the Irish nursing home setting. Setting: This study was conducted in six nursing homes located in Co. Cork, Ireland. Method: A retrospective, cross-sectional study was employed. All patients who met the inclusion criteria (≥65 years, residing in a nursing home on a long-term basis) were eligible for inclusion. There were 120 nursing home residents recruited to the study. Main Outcome Measure: The prevalence of antipsychotic medication use in nursing home residents (with and without dementia). Results: The overall prevalence of antipsychotic prescribing was found to be 48% and patients with dementia were significantly more likely to be prescribed an antipsychotic compared to those without dementia (67% vs. 25%) (χ2 (1, N = 120) = 21.541, p < 0.001). In the cohort of patients with dementia, there was a trend approaching significance (p = 0.052) of decreasing antipsychotic use with increasing age (age 65–74 = 90%; age 75–84 = 71%; age 85 and over = 58%). An indication was documented for 84% of the antipsychotic prescriptions in this cohort. Conclusions: The findings of this study highlight that high rates of antipsychotic medication use remains an issue in Irish nursing homes. Further work should explore factors in influencing prescribing of these medications in such settings.
Outcomes of a National, Cross-Sector Antimicrobial Stewardship Training Initiative for Pharmacists in England
Authors: Ng Vincent , Ashiru-Oredope Diane , Rosado Helena , Ward Beth
Published: October 2021

(1) Background: Pharmacists play a pivotal role in tackling Antimicrobial resistance through antimicrobial stewardship (AMS) and are well placed to lead behaviour change interventions across the healthcare system; (2) Methods: A cross-sector AMS training initiative for pharmacists was implemented across England, with three cohorts between 2019–2021. Each cohort took part in an introductory workshop, followed- by a workplace-based quality improvement project supported by peer-assisted learning sessions. Completion of training was determined by an end of training assessment after three to four months. Outcome data and learner survey results were collated, anonymised, and analysed by the training provider. (3) Results: In total, 118 pharmacists participated in the introductory workshop, 70% of these subsequently undertook an improvement project, and 48% engaged workplace stakeholders in the process. Interventions were designed by 57% of learners and 18% completed a at least one Plan-Do-Study-Act cycle. Approximately a quarter of learners met the requirements for a Certificate of Completion. Knowledge quiz scores were obtained from 115 learners pre-training and 28 learners post-training. Paired t-tests conducted for 28 learners showed a statistically significant improvement in mean score from 67.7% to 81.1% (p < 0.0001). Sixty-two learner survey responses were received during the training and 21 follow-up survey responses 6 to 12 months post training. Of the 21 responses to the follow-up survey, ongoing quality improvement work and improvement outcomes were reported by nine and six learners, respectively. (4) Conclusions: The delivery of workplace-based training at scale can be challenging, however this study demonstrates that coupling learning with workplace implementation and peer support can promote behaviour change in learners. Further study into the impact of providing pharmacists across sectors and geographies with access to this type of training will help inform ongoing workforce development interventions.
Regenerative Collaboration in Higher Education: A Framework for Surpassing Sustainability and Attaining Regeneration
Authors: Armon Chara
Published: October 2021

Many in higher education seek to define how to respond to our environmental crisis. Our 20th and early 21st century failures to resolve the crisis have revealed that a focus on “sustainability” is inadequate in its goals, methods, and public appeal. Higher education must now advance its contribution to preparing graduates to enact the regeneration the damaged natural world requires. We now must teach the deep “why” of caring for our home planet as our life partner, exceed the standard of sustainability to focus on the more enduring and restorative standard of regeneration, and offer our students knowledge and skills for effective regenerative action. Colleges and universities can define their primary goal as teaching students how to tend the flourishing and regeneration of the life community via an emphasis on regenerative collaboration. Regenerative collaboration consists of principles that can guide higher education into a stage of deep contribution to regeneration of the natural world and human well-being. The framework of regenerative collaboration promotes transformation of academic disciplines, academic departments, and courses and calls for development of practical regenerative skills to be part of every degree program. Regenerative collaboration is a means of enacting higher education’s transition from a knowledge focus to a wisdom and regenerative action focus.