bluuebunny/crossref_metadata_2025_split huggingface dataset:
DoE‐assisted development and validation of a stability‐indicating HPLC‐DAD method for simultaneous determination of five cannabinoids in Cannabis sativa L. based on analytical quality by design (AQbD) concept
Authors: de Souza Maíra Ribeiro , Koetz Mariana , Limberger Renata Pereira , Henriques Amélia Teresinha 
Published: June 2022

AbstractIntroductionMedical uses of Cannabis sativa L. have gained interest in recent decades, which highlights the need for defining appropriate quality specifications for Cannabis‐based products. However, the complexity of plant matrices and structural similarity between cannabinoids make analytical development a challenging task. Thus, the application of analytical quality by design (AQbD)‐driven approaches can favour the development of fit‐for‐purpose methods.ObjectivesTo develop a high‐performance liquid chromatography diode array detector (HPLC‐DAD) method for simultaneous quantification of cannabidiol, Δ9‐tetrahydrocannabinol, cannabidiolic acid, tetrahydrocannabinolic acid, and cannabinol in C. sativa by applying an AQbD‐driven approach.Materials and MethodsCritical method attributes (CMA) were established following the analytical target profile. Critical method variables (CMV) were categorised based on risk assessment and literature review. Selected CMV regarding sample preparation and chromatographic conditions were optimised using response surface methodology (RSM). The working point was estimated by multiple response optimisation using Deringer's desirability function. The validity of the optimal conditions was confirmed experimentally. Method validation was performed according to ANVISA and ICH guidelines. Relative response factors (RRFs) were also determined.Results and DiscussionBaseline resolution of 12 major cannabinoids was achieved in a 35 min chromatographic analysis. All experimental responses obtained during confirmatory analyses were within the prediction intervals (PI95%). Method's selectivity, linearity (10–100 μg/mL), precision, bias, extraction recovery, and ruggedness were satisfactorily demonstrated.ConclusionsThe application of an AQbD‐driven approach allowed for a better understanding of the effects of the ensemble of CMV on the analyte's behaviour, enabling the definition of appropriate conditions to ensure consistent achievement of the intended method's performance.
Approaches and hurdles of implementing pharmacogenetic testing in the psychiatric clinic
Authors: Maruf Abdullah Al , Bousman Chad A. 
Published: June 2022

AbstractPharmacogenetic (PGx) testing has emerged as a tool for predicting a person's ability to process and react to drugs. Despite the growing evidence‐base, enthusiasm, and successful efforts to implement PGx testing in psychiatry, a consensus on how best to implement PGx testing into practice has not been established and numerous hurdles to widespread adoption remain to be overcome. In this article, we summarize the most used approaches and commonly encountered hurdles when implementing PGx testing into routine psychiatric care. We also highlight effective strategies that have been used to overcome hurdles. These strategies include the development of user‐friendly clinical workflows for test ordering, use, and communication of results, establishment of test standardization and reimbursement policies, and development of tailored curriculums for educating health‐care providers and the public. Although knowledge and awareness of these approaches and strategies to overcome hurdles alone may not be sufficient for successful implementation, they are necessary to ensure the effective spread, scale, and sustainability of PGx testing in psychiatry and other areas of medicine.
MRI in liver cirrhosis
Authors: Alzoubi Osama , Arar Ahmad , Singh Viraj , Erturk Sukru M. , Mozes Ferenc , Pavlides Michael 
Published: June 2022

AbstractLiver magnetic resonance imaging (MRI) has seen a massive increase in its use over the last decades. Since its first description in the early 1980s, contrast‐enhanced MRI is now the gold standard for the diagnosis of hepatocellular cancer in patients with liver cirrhosis. Techniques like magnetic resonance (MR) elastography and combinations of multiple MR parameters in single scanning protocols are now available and these are opening new possibilities for the assessment of multiple aspects of disease in patients with liver cirrhosis. In this narrative review, we provide an overview of the use of MRI in patients with cirrhosis for the diagnosis of and screening for liver cancer, for the diagnosis of cirrhosis and prediction of long‐term outcomes, and for the evaluation of portal hypertension. With the multitude of techniques now available and the number of cirrhosis aspects that can be assessed by single scans make the study and application of MRI an attractive target in the search for a technique for use in this group of patients that often have to attend for multiple appointments and multiple tests, including invasive investigations.
DRAGON – The German Thermo‐Chemical Code Based on the Becker‐Kistiakowsky‐Wilson Equation of State
Authors: Arnold Werner , Rottenkolber Ernst , Hartmann Thomas 
Published: June 2022

AbstractWith regard to 100th anniversary of the publication of Richard Becker's famous paper on shock waves and detonation, this article highlights today's relevance of Becker's work on what is known as the BKW EOS. The BKW‐based thermo‐chemical code “Dragon” is presented and the development of the insensitive and blast enhanced PBX “KS23” (RDX/Al/HTPB 58/27/15) is taken as an example to demonstrate the application of Dragon in the design of a modern high explosive. The single experimental development steps of KS23 as well as the underlying and supporting theoretical work are described.
Design, synthesis, and biological evaluation of novel berberine derivatives against phytopathogenic fungi
Authors: Zhou Yong , Yang Cheng‐Jie , Luo Xiong‐Fei , Li An‐Ping , Zhang Shao‐Yong , An Jun‐Xia , Zhang Zhi‐Jun , Ma Yue , Zhang Bao‐Qi , Liu Ying‐Qian 
Published: June 2022

AbstractBACKGROUNDThe abuse of chemical fungicides not only leads to toxic residues and resistance in plant pathogenic fungi, but also causes environmental pollution and side effects on in humans and animals. Based on the antifungal activities of berberine, seven different types of berberine derivatives (A1–G1) were synthesized, and their antifungal activities against six plant pathogenic fungi were evaluated (Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Phytophthora capsici, Sclerotinia sclerotiorum, and Magnaporthe oryzae).RESULTSThe results for antifungal activities in vitro showed that berberine derivative E1 displayed good antifungal activity against R. solani with a median effective concentration (EC50) of 1.77 μg ml−1, and berberine derivatives F1 and G1 demonstrated broad‐spectrum antifungal activities with EC50 values ranging from 4.43 to 42.23 μg ml−1 against six plant pathogenic fungi. Berberine derivatives (E2–E29, F2–F18, and G2–G9) were further synthesized to investigate the structure–activity relationship (SAR), and compound E20 displayed significant antifungal activity against R. solani with an EC50 value of 0.065 μg ml−1. Preliminary mechanism studies showed that E20 could cause mycelial shrinkage, cell membrane damage, mitochondrial abnormalities and the accumulation of harmful reactive oxygen species, resulting in cell death in R. solani. Moreover, in vivo experimental results showed that the protective effect of E20 was 97.31% at 5 μg ml−1, which was better than that of the positive control thifluzamide (50.13% at 5 μg ml−1).CONCLUSIONBerberine derivative E20 merits further development as a new drug candidate with selective and excellent antifungal activity against R. solani. © 2022 Society of Chemical Industry.
Robotic single port anti‐reflux surgery: Initial worldwide experience of two cases with a novel surgical approach to treat gastroesophageal reflux disease
Authors: Cubisino Antonio , Dreifuss Nicolas H. , Schlottmann Francisco , Baz Carolina , Mangano Alberto , Masrur Mario A. , Bianco Francesco M. 
Published: June 2022

AbstractIntroductionTo date, no anti‐reflux operations have been reported with the new da Vinci Single‐Port (single port (SP)) robotic platform. We aimed to describe this novel surgical approach and evaluate its safety and feasibility.MethodsAll robotic SP operations were performed under an Institutional Review Board approved protocol.ResultsTwo patients underwent robotic SP anti‐reflux surgery through a single incision of 2.7 cm (one Nissen‐fundoplication and one re‐Redo Nissen‐fundoplication). The mean docking‐time was 2.5 (2–3) minutes and mean console‐time was 147 (119–155) minutes. No additional ports were needed, and no intraoperative complications occurred. Patients tolerated a soft diet on postoperative day 1 and were discharged on POD‐2 and 3.ConclusionRobotic SP anti‐reflux surgery appears to be safe and feasible. This platform offers similar advantages to the multiport robotic surgery, while adding lower invasiveness and an improved cosmesis. Further studies are needed to confirm our results and evaluate long‐term outcomes of this surgical approach.
4D Printing of Extrudable and Degradable Poly(Ethylene Glycol) Microgel Scaffolds for Multidimensional Cell Culture
Authors: Miksch Connor E. , Skillin Nathaniel P. , Kirkpatrick Bruce E. , Hach Grace K. , Rao Varsha V. , White Timothy J. , Anseth Kristi S. 
Published: June 2022

AbstractGranular synthetic hydrogels are useful bioinks for their compatibility with a variety of chemistries, affording printable, stimuli‐responsive scaffolds with programmable structure and function. Additive manufacturing of microscale hydrogels, or microgels, allows for the fabrication of large cellularized constructs with percolating interstitial space, providing a platform for tissue engineering at length scales that are inaccessible by bulk encapsulation where transport of media and other biological factors are limited by scaffold density. Herein, synthetic microgels with varying degrees of degradability are prepared with diameters on the order of hundreds of microns by submerged electrospray and UV photopolymerization. Porous microgel scaffolds are assembled by particle jamming and extrusion printing, and semi‐orthogonal chemical cues are utilized to tune the void fraction in printed scaffolds in a logic‐gated manner. Scaffolds with different void fractions are easily cellularized post printing and microgels can be directly annealed into cell‐laden structures. Finally, high‐throughput direct encapsulation of cells within printable microgels is demonstrated, enabling large‐scale 3D culture in a macroporous biomaterial. This approach provides unprecedented spatiotemporal control over the properties of printed microporous annealed particle scaffolds for 2.5D and 3D tissue culture.
The Effects of Water Temperature and Simulated Angling on the Physiological Stress Response of Largemouth Bass
Authors: Dinken Colin P. , Keretz Kevin R. , Schramm Harold L. , Petrie‐Hanson Lora , Schilling M. Wes , Allen Peter J. 
Published: June 2022

AbstractThe Largemouth Bass Micropterus salmoides, a popular sport fish, is subjected to multiple sublethal stressors during angling, including high water temperature, exercise, handling, live‐well retention, and weigh‐in procedures. Combined effects of ambient and live‐well temperatures on the stress response and recovery from angling‐induced exercise have not been tested in conditions similar to those encountered in tournaments. Therefore, we assessed the effects of ambient temperature (17, 25, and 33°C) and live‐well temperature differential (−4, 0, and +4°C) on the physiological stress response of Largemouth Bass (mean length = 331 mm) at rest, following a simulated angling stressor, and throughout 8 h of recovery in live wells. Stress variables were measured in whole blood (hematocrit, hemoglobin, pH, partial pressure of oxygen [pO2], partial pressure of carbon dioxide [pCO2], Na+, K+, Ca2+, Cl−, and leukocytes) and plasma (cortisol, glucose, lactate, and osmolality). Fish acclimated to 17°C showed the greatest cortisol response after the chasing stressor; however, higher levels of glucose, lactate, pCO2, K+, and monocyte percentage were found at 33°C, and blood pH, Cl−, and lymphocyte percentage were lower at 33°C than at 17°C. When live‐well temperature was manipulated, cortisol levels were highest in fish subjected to the coldest conditions (acclimated to 17°C and retained in 13°C and 17°C live wells) and the warmest condition (acclimated to 33°C and retained in 37°C live wells). However, all fish subjected to the colder extremes survived, whereas 100% mortality occurred in the warmest condition. Besides cortisol, indicators of stress were less pronounced at colder temperatures. Glucose, lactate, and notably K+ concentrations were highest in 37°C live wells, and blood pH, Ca2+, Na+, and Cl− were lowest. Low blood lymphocytes and high monocytes at the warmest conditions indicate reduced immunocompetence or inflammation. Mortality at high temperature may result from exhaustion of aerobic and anaerobic energy sources, failure to recover from metabolic acidosis, and an inability to regain ionic balance.
Lab‐scale data and microbial community structure suggest shortcut nitrogen removal as the predominant nitrogen removal mechanism in post‐aerobic digestion (PAD)
Authors: Sabba Fabrizio , McNamara Patrick , Redmond Eric , Ruff Caitlin , Young Mike , Downing Leon 
Published: June 2022

AbstractImplementing an aerobic digestion step after anaerobic digestion, referred to as “post aerobic digestion” (PAD), can remove ammonia without the need for an external carbon source and destroy volatile solids. While this process has been documented at the lab‐scale and full‐scale, the mechanism for N removal and the corresponding microbial community that carries out this process have not been established. This research gap is important to fill because the nitrogen removal pathway has implications on aeration requirements and carbon demand, that is, short‐cut N‐removal requires less oxygen and carbon than simultaneous nitrification–denitrification. The aims of this research were to (i) determine if nitrite (NO2−) or nitrate (NO3−) dominates following ammonia removal and (ii) characterize the microbial community from PAD reactors. Here, lab‐scale PAD reactors were seeded with biomass from two different full‐scale PAD reactors. The lab‐scale reactors were fed with biomass from full‐scale reactors and operated in batch mode to quantify nitrogen species concentrations (ammonia, NH4+, NO2−, and NO3−) over time. Experimental results revealed that NO2−production rates were several orders of magnitude greater than NO3−production rates. Indeed, nitrite accumulation rate (NAR) was greater than 90% at most temperatures, confirming that shortcut nitrogen removal was the dominant NH4+removal mechanism in PAD. Microbial community analysis via 16S rRNA sequencing indicated that ammonia oxidizing bacteria (AOB) were much more abundant than nitrite oxidizing bacteria (NOB). Overall, this study suggests that aeration requirements for post‐aerobic digestion should be based on NO2−shunt and not complete simultaneous nitrification denitrification.Practitioner PointsAOB are a key feature of PAD microbial communitiesNOB are present, but in much lower abundance than AOBHigh nitrite accumulation ratio suggests shortcut nitrite as the main mechanism for nitrogen removalNitritation in PAD reactors is sustained at temperatures as high as 40°CNo ammonia oxidation occurred at 50°C implying different mechanisms of nitrogen removal including ammonia stripping
Seasonal differences in hair growth rates of captive aye‐aye, red ruffed, and black‐and‐white ruffed lemurs
Authors: Guilfoyle Kevin J. , McIntosh Apryl M. , Hatch Kent A. 
Published: June 2022

AbstractHair can be an important source of biological information, providing a record of such things as pollutant exposure, hormonal levels, and stable isotope ratios. Hair as a biological sample is easily accessible, easily stored, and resists degradation. Analysis of hair is particularly useful when studying rare and endangered species, such as lemurs, since it can be sampled noninvasively. However, to better interpret the results of stable isotope or other analyses, it is important to understand hair growth rates. We measured hair growth rates in captive aye‐ayes (Daubentonia madagascariensis), red ruffed lemurs (Varecia rubra), and black‐and‐white ruffed lemurs (Varecia variegata), both in winter (December 23, 2013, to January 13, 2014) and summer (July 10–31, 2013) at the Duke Lemur Center. Hair growth per week in all three species of lemurs differed significantly between the boreal summer and boreal winter. The aye‐aye, black‐and‐white ruffed lemur, red ruffed lemur had a mean weekly hair growth of 0.195, 0.209, and 0.232 cm, respectively, in the summer. While the aye‐aye, black‐and‐white ruffed lemur, and red ruffed lemur had a mean weekly hair growth of 0.239, 0.464, and 0.479 cm, respectively, in winter. We found no effect of age on hair growth rates, neither in the boreal summer, nor in the boreal winter for black‐and‐white ruffed lemurs and red ruffed lemurs. A pregnant black‐and‐white ruffed female displayed negligible hair growth during the northern winter, suggesting that pregnancy may affect the partitioning of resources away from such things as hair growth.
Gearing up for the next generation of LFV experiments, via on-shell methods
Authors: Miró Joan Elias , Fernandez Clara , Gümüş Mehmet Asım , Pomarol Alex 
Published: June 2022

Abstract
Lepton Flavor Violating (LFV) observables such as μ → eγ, μ → 3e and μN → eN are among the best probes for new physics at the TeV scale. In the near future the bounds on these observables will improve by many orders of magnitude. In this work we use the SM EFT to understand the impact of these measurements. The precision reach is such that the interpretation of the bounds requires an analysis of the dimension-six operator mixing up to the two-loop level. Using on-shell amplitude techniques, which make transparent many selection rules, we classify and calculate the different operator mixing chains. At the leading order, on-shell techniques allow to calculate anomalous dimensions of SM EFT operators from the product of tree-level amplitudes, even for two-loop renormalization group mixings. We illustrate the importance of our EFT approach in models with extra vector-like fermions.
Taxation and evasion: a dynamic model
Authors: Biondo A. E. , Burgio G. , Pluchino A. , Puglisi D. 
Published: June 2022

AbstractIn this paper we study tax evasion by means of a unified framework, based on a behavioral approach, where each individual decision with respect to tax compliance is driven by either personal evaluations of the available information, correlated to income and the perception of the quality of the public good, and social influences, derived by the known decision of neighbors. Our model relies on individual utility functions and describes the tax-evasion problem by means of a personal evolutionary scheme, in which each citizen dynamically adapts her behavior as a response to changing economic and social factors. We will show basic economic intuitions on the relevance of penalties, imitation, satisfaction and risk aversion by means of an analytical model and its agent-based companion version, in order to analyse different elements influencing tax evasion and their dynamic effects. In particular, it is shown how the tax-evasion probability changes as a function of the risk-aversion and specific focus is dedicated to the role played by non-monetary elements of utility in inducing high levels of tax compliance also at substantially reduced fines.
Cellular Distribution Pattern of tjp1 (ZO-1) in Xenopus laevis Oocytes Heterologously Expressing Claudins
Authors: Brunner Nora , Stein Laura , Amasheh Salah 
Published: June 2022

AbstractEpithelial barriers constitute a fundamental requirement in every organism, as they allow the separation of different environments and set boundaries against noxious and other adverse effectors. In many inflammatory and degenerative diseases, epithelial barrier function is impaired because of a disturbance of the paracellular seal. Recently, the Xenopus laevis oocyte has been established as a heterologous expression model for the analysis of transmembrane tight junction protein interactions and is currently considered to be a suitable screening model for barrier effectors. A prerequisite for this application is a physiological anchoring of claudins to the cytoskeleton via the major scaffolding protein tjp1 (tight junction protein 1, ZO-1). We have analyzed the oocyte model with regard to the interaction of heterologously expressed claudins and tjp1. Our experiments have revealed endogenous tjp1 expression in protein and mRNA analyses of unfertilized Xenopus laevis oocytes expressing human claudin 1 (CLDN1) to claudin 5 (CLDN5). The amphibian cell model can therefore be used for the analysis of claudin interactions.
Graphical Abstract
Diversity in radiology: the right thing to do, the smart thing to do
Authors: Hall Theodore R. , Brown Kathleen 
Published: June 2022

AbstractIn the 10-year period between the last two U.S. population censuses there have been significant changes in the U.S. population demography. The changes in self-reporting of racial and ethnic identity afforded by the most recent U.S. population census in 2020 have given citizens the opportunity to be represented in ways that truly reflect how they wish to be identified. At the same time, the diversity of the health care workforce in radiology has not reflected a similar change. While there have been small incremental changes for underrepresented groups (African Americans/Blacks, Hispanic ethnicity, and the group American Indian/Alaska Native/Native Hawaiian/Pacific Islander), these changes have not kept pace with the ever-changing demographics of the U.S. population. Part of the answer for these very modest gains must lie with our selection processes for identifying potential candidates from underrepresented in medicine groups (URiM) for acceptance to our medical schools, residency programs and employment opportunities as practicing physicians and faculty members. While the strategies employed have had some measure of success, our best efforts to increase diversity in our specialty, and in medicine in general, are being undermined by our biases and our traditional methods for identifying talents.