bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunohistochemical Detection of Potential Microbial Antigens in Granulomas in the Diagnosis of Sarcoidosis
Authors: Yamaguchi Tetsuo , Costabel Ulrich , McDowell Andrew , Guzman Josune , Uchida Keisuke , Ohashi Kenichi , Eishi Yoshinobu
Published: March 2021

Sarcoidosis may have more than a single causative agent, including infectious and non-infectious agents. Among the potential infectious causes of sarcoidosis, Mycobacterium tuberculosis and Propionibacterium acnes are the most likely microorganisms. Potential latent infection by both microorganisms complicates the findings of molecular and immunologic studies. Immune responses to potential infectious agents of sarcoidosis should be considered together with the microorganisms detected in sarcoid granulomas, because immunologic reactivities to infectious agents reflect current and past infection, including latent infection unrelated to the cause of the granuloma formation. Histopathologic data more readily support P. acnes as a cause of sarcoidosis compared with M. tuberculosis, suggesting that normally symbiotic P. acnes leads to granuloma formation in some predisposed individuals with Th1 hypersensitivity against intracellular proliferation of latent P. acnes, which may be triggered by certain host or drug-induced conditions. Detection of bacterial nucleic acids in granulomas does not necessarily indicate co-localization of the bacterial proteins in the granulomas. In the histopathologic diagnosis of sarcoidosis, M. tuberculosis-associated and P. acnes-associated sarcoidosis will possibly be differentiated in some patients by immunohistochemistry with appropriate antibodies that specifically react with mycobacterial and propionibacterial antigens, respectively, for each etiology-based diagnosis and potential antimicrobial intervention against sarcoidosis.
Temporal Trend of Conventional Sperm Parameters in a Sicilian Population in the Decade 2011–2020
Authors: Cannarella Rossella , Condorelli Rosita A. , Gusmano Carmelo , Barone Nunziata , Burrello Nunziatina , Aversa Antonio , Calogero Aldo E. , La Vignera Sandro
Published: March 2021

Objective: To evaluate the changes of conventional sperm parameters in men who referred to an andrology reference center in Catania (Eastern Sicily, Italy) in the decade 2011–2020. Methods: For this purpose, we selected–retrospectively and randomly–the reports of 1409 semen analyses performed according to the 2010 WHO criteria. Data on sperm concentration, total sperm count, progressive sperm motility, and percentage of normal forms were analyzed using linear regression of the raw and logarithmic-transformed data. The sperm parameters were subsequently pooled in two five-year periods (2011–2015 and 2016–2020) and compared with each other. Finally, the influence of the city of residence was assessed on five-year pooled data. Main results: A slight but non-significant decline of total sperm count (−2.26 million/year; p = 0.065) and the percentage of spermatozoa with normal morphology (−0.08%/year; p = 0.057) was observed. In contrast, a significant increase of progressive sperm motility (+0.28%/year; p = 0.008) over time was found. The total sperm count of the quinquennium 2016–2020 was significantly lower. and an upward trend of progressive sperm motility was found. compared to the years 2011–2015. No changes in sperm concentration and morphology occurred in the years 2011–2015 vs. 2016–2020. Sperm conventional parameters did not differ when the five-year pooled data were analyzed according to the town of residence. Conclusions: Divergent trends of total sperm count and progressive sperm motility over time were found in patients from Eastern Sicily. This may point out the need of assessing whether a time-dependent change of biofunctional sperm parameters occurs to really understand the trend of sperm quality over time.
The Impact of Antiosteoporotic Drugs on Glucose Metabolism and Fracture Risk in Diabetes: Good or Bad News?
Authors: Anastasilakis Athanasios , Tsourdi Elena , Tabacco Gaia , Naciu Anda , Napoli Nicola , Vescini Fabio , Palermo Andrea
Published: March 2021

Osteoporosis and diabetes mellitus represent global health problems due to their high, and increasing with aging, prevalence in the general population. Osteoporosis can be successfully treated with both antiresorptive and anabolic drugs. While these drugs are clearly effective in reducing the risk of fracture in patients with postmenopausal and male osteoporosis, it is still unclear whether they may have the same efficacy in patients with diabetic osteopathy. Furthermore, as bone-derived cytokines (osteokines) are able to influence glucose metabolism, it is conceivable that antiosteoporotic drugs may have an effect on glycemic control through their modulation of bone turnover that affects the osteokines’ release. These aspects are addressed in this narrative review by means of an unrestricted computerized literature search in the PubMed database. Our findings indicate a balance between good and bad news. Active bone therapies and their modulation of bone turnover do not appear to play a clinically significant role in glucose metabolism in humans. Moreover, there are insufficient data to clarify whether there are any differences in the efficacy of antiosteoporotic drugs on fracture incidence between diabetic and nondiabetic patients with osteoporosis. Although more studies are required for stronger recommendations to be issued, bisphosphonates appear to be the first-line drug for treatment of osteoporosis in diabetic patients, while denosumab seems preferable for older patients, particularly for those with impaired renal function, and osteoanabolic agents should be reserved for patients with more severe forms of osteoporosis.
Maternal and Cord Blood Hemoglobin as Determinants of Placental Weight: A Cross-Sectional Study
Authors: Gragasin Ferrante S. , Ospina Maria B. , Serrano-Lomelin Jesus , Kim Su Hwan , Kokotilo Matthew , Woodman Andrew G. , Renaud Stephen J. , Bourque Stephane L.
Published: March 2021

Background: Both high and low placental weights are associated with adverse pregnancy outcomes. Maternal hemoglobin levels can influence placental weight, but the evidence is conflicting. Since maternal hemoglobin does not invariably correlate with fetal/neonatal blood hemoglobin levels, we sought to determine whether cord blood hemoglobin or maternal hemoglobin status more closely associates with placental weight in women undergoing elective cesarean section at term. Methods: This was a cross-sectional study conducted at the Royal Alexandra Hospital, Edmonton, Canada, involving 202 women with term singleton pregnancies undergoing elective cesarean section. Maternal blood and mixed cord blood hemoglobin levels were analyzed using a HemoCue Hb201+ system. Birth weight, placental weight, one- and five-minute APGAR scores, American Society of Anesthesiologists physical state classification, maternal age, and maternal height were also recorded. Relationships between maternal and cord blood hemoglobin levels with placental weight, birth weight, and birth weight to placental weight ratio were the main outcome measures. Results: A total of 182 subjects were included in the analysis. Regression analysis showed that cord blood hemoglobin, but not maternal hemoglobin, was inversely related with placental weight (β = −2.4, p = 0.001) and positively related with the birth weight to placental weight ratio (β = 0.015, p = 0.001 and p = 0.63, respectively). Conclusions: Our findings suggest that measuring cord blood hemoglobin levels, rather than maternal hemoglobin levels, may provide important diagnostic information about in utero fetal adaptation to suboptimal placental function and neonatal health.
Influence of Physical Activity on Pain, Depression and Quality of Life of Patients in Palliative Care: A Proof-of-Concept Study
Authors: Myrcik Dariusz , Statowski Wojciech , Trzepizur Magdalena , Paladini Antonella , Corli Oscar , Varrassi Giustino
Published: March 2021

Introduction: Palliative care not only focuses on physical ailments associated with the disease, but also considers the psychological, social and spiritual needs of the patients. The aim of this study is to assess the impact of physical activity on palliative care patients, with special regard to the subjective assessment of severity of total pain and quality of life. Materials and methods: The study was conducted on 92 palliative care patients either in a hospice or at home. The tool used to assess the patients was an original questionnaire focusing on the area of their independence and motor abilities. The study attempted to understand whether an appropriate physical activity and the instruction of palliative care patients and their families in the field of independence would improve the quality of life and reduce the intensity of total pain in the patients. Results: All of the patients were at an advanced stage of cancer. The survey at time “0”, conducted before the start of the instructions for patients and their relatives, showed that a majority of patients (47, 51.09%) often experienced limitations during the performance of daily activities. In the fourth visit, conducted one week after the fourth educational session, there was a significant increase in patients who did not experience any limitations in performing their daily activities or experienced them just sometimes. Conclusions: The ultimate effect of the proposed educational program on physical activity was an increase in the quality of life, a reduction in pain and a mood improvement. These results would need confirmation with more extensive studies.
Local Anesthetic-Induced Central Nervous System Toxicity during Interscalene Brachial Plexus Block: A Case Series Study of Three Patients
Authors: Spitzer Daniel , Wenger Katharina J. , Neef Vanessa , Divé Iris , Schaller-Paule Martin A. , Jahnke Kolja , Kell Christian , Foerch Christian , Burger Michael C.
Published: March 2021

Local anesthetics are commonly administered by nuchal infiltration to provide a temporary interscalene brachial plexus block (ISB) in a surgical setting. Although less commonly reported, local anesthetics can induce central nervous system toxicity. In this case study, we present three patients with acute central nervous system toxicity induced by local anesthetics applied during ISB with emphasis on neurological symptoms, key neuroradiological findings and functional outcome. Medical history, clinical and imaging findings, and outcome of three patients with local anesthetic-induced toxic left hemisphere syndrome during left ISB were analyzed. All patients were admitted to our neurological intensive care unit between November 2016 and September 2019. All three patients presented in poor clinical condition with impaired consciousness and left hemisphere syndrome. Electroencephalography revealed slow wave activity in the affected hemisphere of all patients. Seizure activity with progression to status epilepticus was observed in one patient. In two out of three patients, cortical FLAIR hyperintensities and restricted diffusion in the territory of the left internal carotid artery were observed in magnetic resonance imaging. Assessment of neurological severity scores revealed spontaneous partial reversibility of neurological symptoms. Local anesthetic-induced CNS toxicity during ISB can lead to severe neurological impairment and anatomically variable cerebral lesions.
Overall Complication Rates of DIEP Flap Breast Reconstructions in Germany—A Multi-Center Analysis Based on the DGPRÄC Prospective National Online Registry for Microsurgical Breast Reconstructions
Authors: Heidekrueger Paul I. , Moellhoff Nicholas , Horch Raymund E. , Lohmeyer Jörn A. , Marx Mario , Heitmann Christoph , Fansa Hisham , Geenen Matthias , Gabka Christian J. , Handstein Steffen , Prantl Lukas , von Fritschen Uwe
Published: March 2021

While autologous breast reconstruction has gained momentum over recent years, there is limited data on the structure and quality of care of microsurgical breast reconstruction in Germany. Using the breast reconstruction database established by the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC), the presented study investigated the overall outcomes of deep inferior epigastric perforator (DIEP) flap reconstructions in Germany. Data of 3926 patients and 4577 DIEP flaps performed by 22 centers were included in this study. Demographics, patient characteristics, perioperative details and postoperative outcomes were accounted for. Centers performing < Ø 40 (low-volume (LV)) vs. ≥ Ø 40 (high-volume (HV)) annual DIEP flaps were analyzed separately. Overall, total and partial flap loss rates were as low as 2.0% and 1.1% respectively, and emergent vascular revision surgery was performed in 4.3% of cases. Revision surgery due to wound complications was conducted in 8.3% of all cases. Mean operative time and length of hospital stay was significantly shorter in the HV group (LV: 385.82 min vs. HV: 287.14 min; LV: 9.04 (18.87) days vs. HV: 8.21 (5.04) days; both p < 0.05). The outcome and complication rates deduced from the national registry underline the high standard of microsurgical breast reconstruction on a national level in Germany.
When Should We Think of Myelodysplasia or Bone Marrow Failure in a Thrombocytopenic Patient? A Practical Approach to Diagnosis
Authors: Bonadies Nicolas , Rovó Alicia , Porret Naomi , Bacher Ulrike
Published: March 2021

Thrombocytopenia can arise from various conditions, including myelodysplastic syndromes (MDS) and bone marrow failure (BMF) syndromes. Meticulous assessment of the peripheral blood smear, identification of accompanying clinical conditions, and characterization of the clinical course are important for initial assessment of unexplained thrombocytopenia. Increased awareness is required to identify patients with suspected MDS or BMF, who are in need of further investigations by a step-wise approach. Bone marrow cytomorphology, histopathology, and cytogenetics are complemented by myeloid next-generation sequencing (NGS) panels. Such panels are helpful to distinguish reactive cytopenia from clonal conditions. MDS are caused by mutations in the hematopoietic stem/progenitor cells, characterized by cytopenia and dysplasia, and an inherent risk of leukemic progression. Aplastic anemia (AA), the most frequent acquired BMF, is immunologically driven and characterized by an empty bone marrow. Diagnosis remains challenging due to overlaps with other hematological disorders. Congenital BMF, certainly rare in adulthood, can present atypically with thrombocytopenia and can be misdiagnosed. Analyses for chromosome fragility, telomere length, and germline gene sequencing are needed. Interdisciplinary expert teams contribute to diagnosis, prognostication, and choice of therapy for patients with suspected MDS and BMF. With this review we aim to increase the awareness and provide practical approaches for diagnosis of these conditions in suspicious cases presenting with thrombocytopenia.
The Use of Animal-Borne Biologging and Telemetry Data to Quantify Spatial Overlap of Wildlife with Marine Renewables
Authors: Isaksson Natalie , Cleasby Ian R. , Owen Ellie , Williamson Benjamin J. , Houghton Jonathan D. R. , Wilson Jared , Masden Elizabeth A.
Published: March 2021

The growth of the marine renewable energy sector requires the potential effects on marine wildlife to be considered carefully. For this purpose, utilization distributions derived from animal-borne biologging and telemetry data provide accurate information on individual space use. The degree of spatial overlap between potentially vulnerable wildlife such as seabirds and development areas can subsequently be quantified and incorporated into impact assessments and siting decisions. While rich in information, processing and analyses of animal-borne tracking data are often not trivial. There is therefore a need for straightforward and reproducible workflows for this technique to be useful to marine renewables stakeholders. The aim of this study was to develop an analysis workflow to extract utilization distributions from animal-borne biologging and telemetry data explicitly for use in assessment of animal spatial overlap with marine renewable energy development areas. We applied the method to European shags (Phalacrocorax aristotelis) in relation to tidal stream turbines. While shag occurrence in the tidal development area was high (99.4%), there was no overlap (0.14%) with the smaller tidal lease sites within the development area. The method can be applied to any animal-borne bio-tracking datasets and is relevant to stakeholders aiming to quantify environmental effects of marine renewables.
Centennial to Multi-Decadal Morphology Change and Sediment Budget Alteration with Consideration of the Impacts of the 2011 Tohoku Earthquake Tsunami along the Nobiru Coast, Japan
Authors: Hiep Nguyen Trong , Tanaka Hitoshi , Tinh Nguyen Xuan
Published: March 2021

The Nobiru Coast is situated on the southwest of the Ishinomaki Bay. The 2011 Great East Japan Tsunami severely devastated the Nobiru Coast and the adjacent Naruse River mouth. In this study, an investigation was conducted based on the available historic maps and images combined with in situ surveys that revealed the century-to-decade morphology change and sediment budget alteration in the Nobiru Coast. During the past two centuries, the longshore transport on the northeast coast and sediment supply from the Naruse River were the principal sediment supply onto the Nobiru Coast and the estimated annual net sediment input into the coast was 87,000 m3/y. Until several decades ago, the construction of the Ishinomaki Port and the erosion preventing constructions (breakwaters, headlands) along the Ohmagari Coast on the northeast areas caused a dramatic reduction of longshore transport to the Nobiru Coast. Hence, the net sediment input fell to 46,000 m3/y. After the tsunami, the sediment input was further reduced to 29,000 m3/y and this loss was closely related to the intruded sediment into the Naruse River. The outcomes of this study are highly valuable for the government authorities to manage the long-term coastal and riverine morphological changes after the 2011 tsunami.
Early Warning Scores in Patients with Suspected COVID-19 Infection in Emergency Departments
Authors: Martín-Rodríguez Francisco , Martín-Conty José L. , Sanz-García Ancor , Rodríguez Virginia Carbajosa , Rabbione Guillermo Ortega , Cebrían Ruíz Irene Cebrían , Oliva Ramos José R. , Castro Portillo Enrique , Polonio-López Begoña , Enríquez de Salamanca Gambarra Rodrigo , Gómez-Escolar Pérez Marta , López-Izquierdo Raúl
Published: March 2021

Early warning scores (EWSs) help prevent and recognize and thereby act as the first signs of clinical and physiological deterioration. The objective of this study is to evaluate different EWSs (National Early Warning Score 2 (NEWS2), quick sequential organ failure assessment score (qSOFA), Modified Rapid Emergency Medicine Score (MREMS) and Rapid Acute Physiology Score (RAPS)) to predict mortality within the first 48 h in patients suspected to have Coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study in patients over 18 years of age who were treated by the advanced life support units and transferred to the emergency departments between March and July of 2020. Each patient was followed for two days registering their final diagnosis and mortality data. A total of 663 patients were included in our study. Early mortality within the first 48 h affected 53 patients (8.3%). The scale with the best capacity to predict early mortality was the National Early Warning Score 2 (NEWS2), with an area under the curve of 0.825 (95% CI: 0.75–0.89). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients presented an area under the curve (AUC) of 0.804 (95% CI: 0.71–0.89), and the negative ones with an AUC of 0.863 (95% CI: 0.76–0.95). Among the EWSs, NEWS2 presented the best predictive power, even when it was separately applied to patients who tested positive and negative for SARS-CoV-2.
The Importance of Low-Intensive Agricultural Landscape for Birds of Prey
Authors: Baltag Emanuel Ștefan , Pocora Viorel , Bolboaca Lucian Eugen , Ion Constantin
Published: March 2021

Low-intensive agricultural areas of Romania sustain high species diversity. Together with natural habitats, these areas are very important for European biodiversity. The ecosystem´s health is reflected in the predator status because of their position at the top of the trophic networks. The Common Buzzard (Buteo buteo) is the most common bird of prey species in Europe. During the first survey census conducted in Eastern Romania (2011–2012 breeding seasons), 8.55–10.35 breeding pairs/100 square km have been counted. The Common Buzzard density varies between breeding seasons and with differences in habitat structure. Their density is positively influenced by the density of forest edge and Simpson diversity index of habitats but is negatively influenced by the total habitat fragmentation and mean daily temperature. According to this analysis, the selection of breeding territories by common buzzards is positively influenced by a heterogeneous landscape in an area with low-intensive agriculture and with large areas of open habitats made up of natural or semi-natural vegetation.
Influence of Compression Rings on the Dynamic Characteristics and Sealing Capacity of the Combustion Chamber in Diesel Engines
Authors: Hernández-Comas Brando , Maestre-Cambronel Daniel , Pardo-García Carlos , Fonseca-Vigoya Marlen Del Socorro , Pabón-León Jhon
Published: March 2021

Internal combustion engines are widely implemented in several applications; however, they still face significant challenges due to the sealing capacity of the compression rings. Gas leakage through the crankcase, also known as blow-by, directly impacts power losses, overall efficiency, and global emissions. Therefore, the present study investigates the influence of parameters such as the ring gap, ring masses, and twist angle of the compression rings on the sealing capacity of the combustion chamber. A mathematical model is proposed to account for geometric, dynamic, and operational characteristics in a single-cylinder diesel engine. The results indicated that the greatest gas losses to the crankcase occur during the compression and combustion stages as a consequence of extreme pressure conditions. Specifically, at least 0.5% of the gases locked in the combustion chamber are released on each cycle, while increasing the mass of the compression rings boosts the gas leakage due to higher inertial forces in the rings. In contrast, a positive twist angle of the compression rings reduced the combustion gases leakage by 7.33×10−5 g/cycle. Additionally, a combined reduction in the gap of both compression rings minimized the leakage flows by 37%. In conclusion, the proposed model served as a robust tool to evaluate different parameters on the sealing capacity of the combustion chamber that contribute to minimizing global emissions. Secondary piston motion and ring distortion represent significant opportunities in future studies.
Finite Plane Strain Bending under Tension of Isotropic and Kinematic Hardening Sheets
Authors: Strashnov Stanislav , Alexandrov Sergei , Lang Lihui
Published: March 2021

The present paper provides a semianalytic solution for finite plane strain bending under tension of an incompressible elastic/plastic sheet using a material model that combines isotropic and kinematic hardening. A numerical treatment is only necessary to solve transcendental equations and evaluate ordinary integrals. An arbitrary function of the equivalent plastic strain controls isotropic hardening, and Prager’s law describes kinematic hardening. In general, the sheet consists of one elastic and two plastic regions. The solution is valid if the size of each plastic region increases. Parameters involved in the constitutive equations determine which of the plastic regions reaches its maximum size. The thickness of the elastic region is quite narrow when the present solution breaks down. Elastic unloading is also considered. A numerical example illustrates the general solution assuming that the tensile force is given, including pure bending as a particular case. This numerical solution demonstrates a significant effect of the parameter involved in Prager’s law on the bending moment and the distribution of stresses at loading, but a small effect on the distribution of residual stresses after unloading. This parameter also affects the range of validity of the solution that predicts purely elastic unloading.
Nonlinear Pantograph-Type Diffusion PDEs: Exact Solutions and the Principle of Analogy
Authors: Polyanin Andrei D. , Sorokin Vsevolod G.
Published: March 2021

We study nonlinear pantograph-type reaction–diffusion PDEs, which, in addition to the unknown u=u(x,t), also contain the same functions with dilated or contracted arguments of the form w=u(px,t), w=u(x,qt), and w=u(px,qt), where p and q are the free scaling parameters (for equations with proportional delay we have 0<p<1, 0<q<1). A brief review of publications on pantograph-type ODEs and PDEs and their applications is given. Exact solutions of various types of such nonlinear partial functional differential equations are described for the first time. We present examples of nonlinear pantograph-type PDEs with proportional delay, which admit traveling-wave and self-similar solutions (note that PDEs with constant delay do not have self-similar solutions). Additive, multiplicative and functional separable solutions, as well as some other exact solutions are also obtained. Special attention is paid to nonlinear pantograph-type PDEs of a rather general form, which contain one or two arbitrary functions. In total, more than forty nonlinear pantograph-type reaction–diffusion PDEs with dilated or contracted arguments, admitting exact solutions, have been considered. Multi-pantograph nonlinear PDEs are also discussed. The principle of analogy is formulated, which makes it possible to efficiently construct exact solutions of nonlinear pantograph-type PDEs. A number of exact solutions of more complex nonlinear functional differential equations with varying delay, which arbitrarily depends on time or spatial coordinate, are also described. The presented equations and their exact solutions can be used to formulate test problems designed to evaluate the accuracy of numerical and approximate analytical methods for solving the corresponding nonlinear initial-boundary value problems for PDEs with varying delay. The principle of analogy allows finding solutions to other nonlinear pantograph-type PDEs (including nonlinear wave-type PDEs and higher-order equations).
Testing the Resilience of CSR Stocks during the COVID-19 Crisis: A Transcontinental Analysis
Authors: Valls Martínez María del Carmen , Martín Cervantes Pedro Antonio
Published: March 2021

Investors and practitioners are increasingly concerned with financial assets within the scope of corporate social responsibility (CSR) meaning that, in recent times, such assets have become enshrined in the preferences of the new generations of investors and consumers. Just when the interest of investors was at its highest, SARS-CoV-2 (COVID-19) affected all international financial markets, so that, at first sight, it might seem that the financial assets assigned to CSR should have suffered collapses that were identical to the rest; however, our work shows the opposite, providing a comparative analysis of how the pandemic has affected the financial markets of each continent to demonstrate its outstanding resilience through the use of the Wavelets methodology. We analyzed the global impact of the registered cases of COVID-19 on the Dow Jones Sustainability World Index (DJSWI), the world’s leading indicator of sustainable companies, in addition to six other financial indices selected from each continent. The empirical results of this research show that the worldwide repercussions of the sudden outbreak of SARS-CoV-2 has had a substantially smaller effect on sustainability-related indices compared to the other considered indices. Similarly, the methodology employed allowed the establishment of a chronogram with details of the dating of COVID-19 expansion through the considered countries, a certain gradation in terms of the impact of the pandemic on these stock indices, and certain common guidelines describing their devastating effects on each of the financial markets represented by the indices in this research.
Tuning Rules for Active Disturbance Rejection Controllers via Multiobjective Optimization—A Guide for Parameters Computation Based on Robustness
Authors: Martínez Blanca Viviana , Sanchis Javier , García-Nieto Sergio , Martínez Miguel
Published: March 2021

A set of tuning rules for Linear Active Disturbance Rejection Controller (LADRC) with three different levels of compromise between disturbance rejection and robustness is presented. The tuning rules are the result of a Multiobjective Optimization Design (MOOD) procedure followed by curve fitting and are intended as a tool for designers who seek to implement LADRC by considering the load disturbance response of processes whose behavior is approximated by a general first-order system with delay. The validation of the proposed tuning rules is done through illustrative examples and the control of a nonlinear thermal process. Compared to classical PID (Proportional-Integral-Derivative) and other LADRC tuning methods, the derived functions offer an improvement in either disturbance rejection, robustness or both design objectives.
Synthesis, Structural and Pharmacological Characterizations of CIC, a Novel α-Conotoxin with an Extended N-Terminal Tail
Authors: Giribaldi Julien , Haufe Yves , Evans Edward R. J. , Wilson David T. , Daly Norelle L. , Enjalbal Christine , Nicke Annette , Dutertre Sébastien
Published: March 2021

Cone snails are venomous marine predators that rely on fast-acting venom to subdue their prey and defend against aggressors. The conotoxins produced in the venom gland are small disulfide-rich peptides with high affinity and selectivity for their pharmacological targets. A dominant group comprises α-conotoxins, targeting nicotinic acetylcholine receptors. Here, we report on the synthesis, structure determination and biological activity of a novel α-conotoxin, CIC, found in the predatory venom of the piscivorous species Conus catus and its truncated mutant Δ-CIC. CIC is a 4/7 α-conotoxin with an unusual extended N-terminal tail. High-resolution NMR spectroscopy shows a major influence of the N-terminal tail on the apparent rigidity of the three-dimensional structure of CIC compared to the more flexible Δ-CIC. Surprisingly, this effect on the structure does not alter the biological activity, since both peptides selectively inhibit α3β2 and α6/α3β2β3 nAChRs with almost identical sub- to low micromolar inhibition constants. Our results suggest that the N-terminal part of α-conotoxins can accommodate chemical modifications without affecting their pharmacology.
Effects of Long-Term Nitrogen Fertilization on the Formation of Metabolites Related to Tea Quality in Subtropical China
Authors: Chen Yuzhen , Wang Feng , Wu Zhidan , Jiang Fuying , Yu Wenquan , Yang Jie , Chen Jiaming , Jian Guotai , You Zhiming , Zeng Lanting
Published: March 2021

As a main agronomic intervention in tea cultivation, nitrogen (N) application is useful to improve tea yield and quality. However, the effects of N application on the formation of tea quality-related metabolites have not been fully studied, especially in long-term field trials. In this study, a 10-year field experiment was conducted to investigate the effect of long-term N application treatments on tea quality-related metabolites, their precursors, and related gene expression. Long-term N application up-regulated the expression of key genes for chlorophyll synthesis and promoted its synthesis, thus increasing tea yield. It also significantly increased the contents of total free amino acids, especially l-theanine, in fresh tea leaves, while decreasing the catechin content, which is conducive to enhancing tea liquor freshness. However, long-term N application significantly reduced the contents of benzyl alcohol and 2-phenylethanol in fresh tea leaves, and also reduced (E)-nerolidol and indole in withered leaves, which were not conducive to the formation of floral and fruity aroma compounds. In general, an appropriate amount of N fertilizer (225 kg/hm2) balanced tea yield and quality. These results not only provide essential information on how N application affects tea quality, but also provide detailed experimental data for field fertilization.
Design and Simulation of Air-Breathing Micro Direct Methanol Fuel Cells with Different Anode Flow Fields
Authors: Deng Huichao , Zhou Jiaxu , Zhang Yufeng
Published: March 2021

The design of the anode flow field is critical for yielding better performance of micro direct methanol fuel cells (µDMFCs). In this work, the effect of different flow fields on cell performance was investigated by the simulation method. Compared with grid, parallel and double-serpentine flow fields, a single-serpentine flow field can better improve the mass transfer efficiency of methanol and the emission efficiency of the carbon dioxide by-product. The opening ratio and channel length also have important effects on the cell performance. The cells were manufactured using silicon-based micro-electro-mechanical system (MEMS) technologies and tested to verify the simulation results. The experimental results show that the single-serpentine flow field represents a higher peak power density (16.83 mWcm−2) than other flow fields. Moreover, the results show that an open ratio of 47.3% and a channel length of 63.5 mm are the optimal parameters for the single-serpentine flow field.
Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms
Authors: Ferreira Magda , Pinto Sandra N. , Aires-da-Silva Frederico , Bettencourt Ana , Aguiar Sandra I. , Gaspar Maria Manuela
Published: March 2021

Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one of the most appealing fast-track and cost-effective approaches. In the present work, we assessed the potential therapeutic benefit of three antibiotics, vancomycin, levofloxacin and rifabutin (RFB), through their incorporation in liposomes. Free RFB displayed the utmost antibacterial effect with MIC and MBIC50 below 0.006 µg/mL towards a methicillin susceptible S. aureus (MSSA). RFB was selected for further in vitro studies and the influence of different lipid compositions on bacterial biofilm interactions was evaluated. Although positively charged RFB liposomes displayed the highest interaction with MSSA biofilms, RFB incorporated in negatively charged liposomes displayed lower MBIC50 values in comparison to the antibiotic in the free form. Preliminary safety assessment on all RFB formulations towards osteoblast and fibroblast cell lines demonstrated that a reduction on cell viability was only observed for the positively charged liposomes. Overall, negatively charged RFB liposomes are a promising approach against biofilm S. aureus infections and further in vivo studies should be performed.
Accumulation of Potentially Toxic Elements in Mosses Collected in the Republic of Moldova
Authors: Zinicovscaia Inga , Hramco Constantin , Chaligava Omari , Yushin Nikita , Grozdov Dmitrii , Vergel Konstantin , Duca Gheorghe
Published: March 2021

For the second time, the moss biomonitoring technique was applied to evaluate the deposition of potentially toxic elements in the Republic of Moldova. The study was performed in the framework of the International Cooperative Program on Effects of Air Pollution on Natural Vegetation and Crops. Moss Hypnum cupressiforme Hedw. samples were collected in May 2020 from 41 sampling sites distributed over the entire territory of the country. The mass fractions of 35 elements (Na, Mg, Al, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Br, Se, Rb, Sr, Sb, Cs, Ba, Cd, La, Ce, Sm, Eu, Tb, Hf, Ta, Th, Pb, and U) were determined using neutron activation analysis and atomic absorption spectrometry. Comparing with 2015/2016 moss survey data, significant differences in the mass fractions of Cr, As, Se, Br, Sr, Sb, Cd, Pb, and Cu were found. Main air pollution sources (natural processes, transport, industry, agriculture, mining) were identified and characterized using factor and correlation analyses. GIS maps were built to point out the zones with the highest element mass fractions and to relate this to the known sources of contamination. Contamination factor, geo-accumulation index, pollution load index, and potential ecological risk index were calculated to assess the air pollution levels in the country. According to the calculated values, Moldova can be characterized as unpolluted to moderately polluted, with low potential ecological risk related to the degree of atmospheric deposition of potentially toxic elements. The cities of Chisinau and Balti were determined to experience particular environmental stress and are considered moderately polluted.
A Roadmap to Modulated Anthocyanin Compositions in Carrots
Authors: Bæksted Holme Inger , Dionisio Giuseppe , Brinch-Pedersen Henrik
Published: March 2021

Anthocyanins extracted from black carrots have received increased interest as natural colorants in recent years. The reason is mainly their high content of acylated anthocyanins that stabilizes the color and thereby increases the shelf-life of products colored with black carrot anthocyanins. Still, the main type of anthocyanins synthesized in all black carrot cultivars is cyanidin limiting their use as colorants due to the narrow color variation. Additionally, in order to be competitive against synthetic colors, a higher percentage of acylated anthocyanins and an increased anthocyanin content in black carrots are needed. However, along with the increased interest in black carrots there has also been an interest in identifying the structural and regulatory genes associated with anthocyanin biosynthesis in black carrots. Thus, huge progress in the identification of genes involved in anthocyanin biosynthesis has recently been achieved. Given this information it is now possible to attempt to modulate anthocyanin compositions in black carrots through genetic modifications. In this review we look into genetic modification opportunities for generating taproots of black carrots with extended color palettes, with a higher percentage of acylated anthocyanins or a higher total content of anthocyanins.
Digital Twins for Tissue Culture Techniques—Concepts, Expectations, and State of the Art
Authors: Möller Johannes , Pörtner Ralf
Published: March 2021

Techniques to provide in vitro tissue culture have undergone significant changes during the last decades, and current applications involve interactions of cells and organoids, three-dimensional cell co-cultures, and organ/body-on-chip tools. Efficient computer-aided and mathematical model-based methods are required for efficient and knowledge-driven characterization, optimization, and routine manufacturing of tissue culture systems. As an alternative to purely experimental-driven research, the usage of comprehensive mathematical models as a virtual in silico representation of the tissue culture, namely a digital twin, can be advantageous. Digital twins include the mechanistic of the biological system in the form of diverse mathematical models, which describe the interaction between tissue culture techniques and cell growth, metabolism, and the quality of the tissue. In this review, current concepts, expectations, and the state of the art of digital twins for tissue culture concepts will be highlighted. In general, DT’s can be applied along the full process chain and along the product life cycle. Due to the complexity, the focus of this review will be especially on the design, characterization, and operation of the tissue culture techniques.
Clustering-Based Extensions of the Common Age Effect Multi-Population Mortality Model
Authors: Schnürch Simon , Kleinow Torsten , Korn Ralf
Published: March 2021

We introduce four variants of the common age effect model proposed by Kleinow, which describes the mortality rates of multiple populations. Our model extensions are based on the assumption of multiple common age effects, each of which is shared only by a subgroup of all considered populations. This makes the models more realistic while still keeping them as parsimonious as possible, improving the goodness of fit. We apply different clustering methods to identify suitable subgroups. Some of the algorithms are borrowed from the unsupervised learning literature, while others are more domain-specific. In particular, we propose and investigate a new model with fuzzy clustering, in which each population’s individual age effect is a linear combination of a small number of age effects. Due to their good interpretability, our clustering-based models also allow some insights in the historical mortality dynamics of the populations. Numerical results and graphical illustrations of the considered models and their performance in-sample as well as out-of-sample are provided.
Annual Time Series of Global VIIRS Nighttime Lights Derived from Monthly Averages: 2012 to 2019
Authors: Elvidge Christopher D. , Zhizhin Mikhail , Ghosh Tilottama , Hsu Feng-Chi , Taneja Jay
Published: March 2021

A consistently processed annual global nighttime lights time series (2012–2019) was produced using monthly cloud-free radiance averages made from low light imaging day/night band (DNB) data collected by the NASA/NOAA Visible Infrared Imaging Radiometer Suite (VIIRS). The processing steps are modified from the original methods developed to produce annual nighttime lights products from nightly data. Only two years of VIIRS nighttime lights (VNL) were produced with the V.1 methods: 2015 and 2016. Here we report on methods used to produce a V.2 VNL time series from the monthly averages with filtering to remove extraneous features such as biomass burning, aurora, and background. In this case, outlier removal is achieved with a twelve-month median, which discards high and low radiance outliers, thus isolating the background to a narrow range of radiances under 1 nW/cm2/sr. Background areas with no detectable lighting are further isolated using a statistical measure of texture, 3 × 3 data range (DR). The DR threshold for zeroing out background rises as the number of cloud-free observations falls. The V.2 method extends the temporal leverage in the noise filtering by developing the DR threshold from a multiyear maximum DR and a multiyear percent cloud-free grid. Additional noise filtering is achieved by zeroing out grid cells that have low average radiances (<0.6 nW/cm2/sr) and detection in only one or two years out of eight. The spatial extent and average radiance levels are compared for the V.1 and V.2 2015 VNL. For the vast majority of grid cells, the average radiances are nearly the same in the two products. However, the V.2 product has more areas of dim lighting detected. The key advantages of the V.2 time series include consistent processing and threshold levels across all years, thus optimizing the set for change detection analyses.
Improving the Performance of Index Insurance Using Crop Models and Phenological Monitoring
Authors: Afshar Mehdi H. , Foster Timothy , Higginbottom Thomas P. , Parkes Ben , Hufkens Koen , Mansabdar Sanjay , Ceballos Francisco , Kramer Berber
Published: March 2021

Extreme weather events cause considerable damage to the livelihoods of smallholder farmers globally. Whilst index insurance can help farmers cope with the financial consequences of extreme weather, a major challenge for index insurance is basis risk, where insurance payouts correlate poorly with actual crop losses. We analyse to what extent the use of crop simulation models and crop phenology monitoring can reduce basis risk in index insurance. Using a biophysical process-based crop model (Agricultural Production System sIMulator (APSIM)) applied for rice producers in Odisha, India, we simulate a synthetic yield dataset to train non-parametric statistical models to predict rice yields as a function of meteorological and phenological conditions. We find that the performance of statistical yield models depends on whether meteorological or phenological conditions are used as predictors and whether one aggregates these predictors by season or crop growth stage. Validating the preferred statistical model with observed yield data, we find that the model explains around 54% of the variance in rice yields at the village cluster (Gram Panchayat) level, outperforming vegetation index-based models that were trained directly on the observed yield data. Our methods and findings can guide efforts to design smart phenology-based index insurance and target yield monitoring resources in smallholder farming environments.
Linking Entrepreneurial Innovation to Effectual Logic
Authors: Ghorbel Faiez , Hachicha Wafik , Boujelbene Younes , Aljuaid Awad M.
Published: March 2021

The terms “innovation” and “effectuation” are frequently used but not in the same thought. In this order, publications linking innovation to effectuation are presented and discussed through a methodology based on the publish and perish tool. In the last two decades, effectuation has become an active criterion in entrepreneurship research. However, previous studies do not interconnect effectuation to the different innovation approaches. In order to overcome this gap, this paper focuses on studying innovation in an effectual context and linking different innovation approaches to effectual logic. Indeed, effectuation is a way of thinking that serves entrepreneurs in the processes of opportunity identification and new venture creation. Effectuation includes a set of decision-making principles expert entrepreneurs are observed to employ in situations of uncertainty (as defined in Society for Effectual Action). This article outlines the four most-studied innovation approaches from the date of their apparitions until January 2021: frugal innovation, disruptive innovation, lean start-up, and design thinking. In this context, effectuation as the essence of innovation must be clarified as a method that has similarities and differences with frugal and disruptive innovation, lean start-up, and design thinking. To validate the proposed theorical model, a bibliometrics tool, named “Harzing publish” or “perish”, is used. The main finding of this research affirms that the two most linked innovation approaches to effectuation are “lean start-up” and “design thinking”, compared to “frugal innovation” and “disruptive innovation”. In an entrepreneurial innovation context, design thinking and lean start-up are flexible tools that can stimulate and validate the effectual cycle.
Reliability Approaches Affecting the Sustainability of Concrete Structures
Authors: Holický Milan , Sýkora Miroslav
Published: March 2021

The most important reliability approaches affecting sustainability in construction consist of the target reliability levels, verification methods, and construction or intervention procedures. The optimum target reliability levels can be specified based on probabilistic optimisation considering sustainability aspects including building costs, expected economic, social, and environmental consequences of construction, and possible failures. It appears that the derived reliability levels are strongly dependent on sustainability aspects and may be lower for the assessment of existing structures than for the design of new structures. The most efficient verification methods are based on advanced probabilistic approaches, including risk assessment methods considering actual properties of the structure and related failure consequences. It has been shown that sustainability in construction may be significantly affected by the design and assessment methods. The case study demonstrates that advanced reliability approaches commonly save 10–20% of the consumption of structural materials and natural resources.