bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticancer Activities of Tetrasubstituted Imidazole‐Pyrimidine‐Sulfonamide Hybrids as Inhibitors of EGFR Mutants
Authors: Alghamdi Eman M. , Alamshany Zahra M. , El Hamd Mohamed A. , Taher Ehab S. , Farrag El‐Behairy Mohammed , Norcott Philip L. , Marzouk Adel A.
Published: February 2023

A new series of tetrasubstituted imidazole derivatives carrying pyrimidine sulfonamide pharmacophores has been synthesized and evaluated for their anticancer activities. In‐vitro screening of these hybrids against a full 60‐cell‐line panel at a single dose of 10 μM showed significant growth inhibition of up to 95 %. The most active compound showed in‐vitro anticancer activities against (i) abnormal HER2 and (ii) two mutants for EGFR. Apoptotic gene expression revealed that lead compounds induced MCF‐7 cell line apoptosis together with considerable change in the Bax/Bcl‐2 expression ratio. One lead compound led to a significant cell‐cycle S‐phase arrest, while another blocked the cell cycle at G1/S‐phase causing the accumulation of cells. Docking analysis of these two hybrids adopted the orientation and binding interactions with a higher liability to enter the active side pocket of HER2, L858R, and T790 M, preferable to that of co‐crystallized ligands. Modelling simulation was consistent with the acquired biological evaluation.
Epistemic equity in oncology: Opportunities to leverage patient‐centric implementation in clinical trial design
Authors: Patel Tej A. , Ting Frederic Ivan L. , Jain Bhav , Eala Michelle Ann B. , Jacomina Luisa E. , Mejia Michael Benedict A. , Dee Edward Christopher
Published: February 2023

In addition to the ethical imperative to combat epistemic injustice in cancer research, work from differently resourced settings may shed light on questions of implementation and access. This piece discusses several recent randomized controlled trials whose findings advance not only clinical science but also the implementation of care. One trial demonstrates the efficacy of dose‐reduced immunotherapy and another demonstrates the utility of oral chemotherapy, respectively tackling issues of cost and ease of access. This commentary explores the implications of these and similar studies in light of financial, geographic, and social barriers to access experienced by many people with cancer in low‐ and middle‐income countries, proposes actionable next steps to improve epistemic equity in cancer research, and calls for patient‐centric implementation in clinical trial design.
Estrous cycle impacts on dendritic spine plasticity in rat nucleus accumbens core and shell and caudate–putamen
Authors: Beeson Anna L. S. , Meitzen John
Published: February 2023

An important factor that can modulate neuron properties is sex‐specific hormone fluctuations, including the human menstrual cycle and rat estrous cycle in adult females. Considering the striatal brain regions, the nucleus accumbens (NAc) core, NAc shell, and caudate–putamen (CPu), the estrous cycle has previously been shown to impact relevant behaviors and disorders, neuromodulator action, and medium spiny neuron (MSN) electrophysiology. Whether the estrous cycle impacts MSN dendritic spine attributes has not yet been examined, even though MSN spines and glutamatergic synapse properties are sensitive to exogenously applied estradiol. Thus, we hypothesized that MSN dendritic spine attributes would differ by estrous cycle phase. To test this hypothesis, brains from adult male rats and female rats in diestrus, proestrus AM, proestrus PM, and estrus were processed for Rapid Golgi–Cox staining. MSN dendritic spine density, size, and type were analyzed in the NAc core, NAc shell, and CPu. Overall spine size differed across estrous cycle phases in female NAc core and NAc shell, and spine length differed across estrous cycle phase in NAc shell and CPu. Consistent with previous work, dendritic spine density was increased in the NAc core compared to the NAc shell and CPu, independent of sex and estrous cycle. Spine attributes in all striatal regions did not differ by sex when estrous cycle was disregarded. These results indicate, for the first time, that estrous cycle phase impacts dendritic spine plasticity in striatal regions, providing a neuroanatomical avenue by which sex‐specific hormone fluctuations can impact striatal function and disorders.
Inflammatory myofibroblastic tumor of the mesentery with a SQSTM1::ALK fusion responding to alectinib
Authors: Sunga Cass G. G. , Higgins Michael S. , Ricciotti Robert W. , Liu Yajuan J. , Cranmer Lee D.
Published: February 2023

Background

Inflammatory myofibroblastic tumor (IMT) is an ultra‐rare soft tissue neoplasm associated with fusion proteins encompassing the anaplastic lymphoma kinase (ALK) protein fused to a variety of partner proteins. Data regarding response to ALK‐targeting agents based on fusion partner is limited.

Case

A 30‐year‐old female sought emergency care after onset of abdominal and lower back pain in 2019. Computed tomography (CT) demonstrated a cystic, mesenteric mass within the pelvis measuring up to 8.9 cm. Complete laparoscopic excision of the mass from the mesentery of the right colon and terminal ileum was performed. Pathologic assessment revealed IMT with a fusion between sequestosome 1 and ALK (SQSTM1::ALK), described in only two other cases of IMT. Four months after surgery, CT revealed multi‐focal, unresectable disease recurrence. She was referred to the University of Washington/Fred Hutchinson Cancer Center and placed on therapy with alectinib, after which she experienced a partial response. Three years after IMT recurrence, disease remains under control.

Conclusion

This is the third reported case of IMT associated with the novel SQSTM1::ALK fusion protein, and the second treated with alectinib. Treatment with the ALK inhibitor alectinib appears to be active in this setting.
Luminescent Lanthanide Complexes for Effective Oxygen‐Sensing and Singlet Oxygen Generation
Authors: Kitagawa Yuichi , Nakai Takuma , Hosoya Shota , Shoji Sunao , Hasegawa Yasuchika
Published: February 2023

Oxygen quantification using luminescence has attracted considerable attention in various fields, including environmental monitoring and clinical analysis. Among the reported luminophores, trivalent lanthanide complexes have displayed characteristic narrow emission bands with high brightness. This bright emission is based on photo‐sensitized energy transfer via organic triplet states. The organic triplet states in lanthanide complexes effectively react with the triplet oxygen, enabling oxygen quantification by lanthanide luminescence. Some TbIII and EuIII complexes with slow deactivation processes have also formed the excited state equilibrium, thus resulting in the emission‐lifetime based oxygen sensing property. The combination of TbIII/EuIII emission, EuIII/SmIII emission, EuIII/ligand phosphorescence, and ligand fluorescence/ligand phosphorescence provide the ratiometric oxygen‐sensing properties. Moreover, the reaction generates singlet oxygen species which exhibit numerous applications in the photo‐medical field. The ligands with large π‐conjugated aromatic systems, such as porphyrin, phthalocyanine, and polyaromatic compounds, induces highly efficient oxygen generation. The combination of effective luminescence with singlet‐oxygen generation by the lanthanide complexes render them suitable for photo‐driven theranostics. This review summarizes the research progress of lanthanide complexes with efficient oxygen‐sensing and singlet‐oxygen generation properties.
Generating the Right Evidence at the Right Time: Principles of a New Class of Flexible Augmented Clinical Trial Designs
Authors: Dunger‐Baldauf Cornelia , Hemmings Rob , Bretz Frank , Jones Byron , Schiel Anja , Holmes Chris
Published: February 2023

To support informed decision making, clear descriptions of the beneficial and harmful effects of a treatment are needed by various stakeholders. The current paradigm is to generate evidence sequentially through different experiments. However, data generated later, perhaps through observational studies, can be difficult to compare with earlier randomized trial data, resulting in confusion in understanding and interpretation of treatment effects. Moreover, the scientific questions these later experiments can serve to answer often remain vague. We propose Flexible Augmented Clinical Trial for Improved eVidence gEneration (FACTIVE), a new class of study designs enabling flexible augmentation of confirmatory randomized controlled trials with concurrent and close‐to‐real‐world elements. Our starting point is to use clearly defined objectives for evidence generation, which are formulated through early discussion with health technology assessment (HTA) bodies and are additional to regulatory requirements for authorization of a new treatment. These enabling designs facilitate estimation of certain well‐defined treatment effects in the confirmatory part and other complementary treatment effects in a concurrent real‐world part. Each stakeholder should use the evidence that is relevant within their own decision‐making framework. High quality data are generated under one single protocol and the use of randomization ensures rigorous statistical inference and interpretation within and between the different parts of the experiment. Evidence for the decision making of HTA bodies could be available earlier than is currently the case.
Simulation of the statistical and formative time delay of Townsend‐mechanism‐governed breakdown in argon at low pressure
Authors: Jovanović Aleksandar P. , Stankov Marjan N. , Marković Vidosav Lj. , Stamenković Suzana N.
Published: February 2023

Understanding the breakdown process is important both from fundamental and practical perspectives. One of the most important quantities that characterize the breakdown is the breakdown time delay. In this article, numerical models for self‐consistent simulation of the statistical and formative time delay of the electric breakdown in argon at low pressure have been proposed. The first model, based on the Monte Carlo simulation of the electron avalanche development, is used to simulate the statistical time delay. The model is designed for low‐pressure breakdowns when the Townsend mechanism is dominant. The electric breakdown is then governed by ion‐induced secondary electron emission from the cathode. In that case, the statistical time delay to breakdown is determined by tracking the waiting time of emission of the primary electron that initiates the electron avalanche and the number of ions produced in it. On the other hand, the formative time delay is determined by simulating the electric current waveform using the fluid model. To test whether the proposed models can be used for discharges operating under various conditions, the voltage dependence is simulated for both the statistical and the formative time delay. The results of the simulations show good agreement with the experimental results and theoretical models.
Bionic surface diode for droplet steering
Authors: Yang Xiaolong , Qi Biao , Lu Yao , Zhang Wang , Wang Xiaolei
Published: February 2023

Control of droplet sliding and its interfacial behavior such as sliding resistance and friction have important applications in microfluidic and energy‐related fields. Nature provides many examples of interface‐driven droplet sliding control; yet, to date, the continuous governing of the multiphase process and precise steering of droplet sliding remain challenging. Here, directional‐dependent ultraslippery patterned surfaces with significant droplet sliding anisotropy were created by coordinating the heterogeneous wettability of the back of the dessert beetle, directional‐dependent architecture of the butterfly wing, and ultraslippery configuration of the Nepenthes alata. Analysis of the sliding resistance on typical ultraslippery patterned surfaces reveals that the directional‐dependent triple phase line (TPL) immigration on the ultraslippery patterns dominates the strong sliding anisotropy, which can be modeled using the classic Furmidge equation. In particular, the sliding anisotropy for the semicircular ultraslippery patterned surface shows threefold higher than that of natural butterfly wings due to the most significant difference in TPL immigration in two opposite directions, which enables the simultaneous handling of multiple droplets without mass loss and steering of droplet sliding/friction. This work may transform the design space for the control of multiphase interface motion and the development of new lab‐on‐a‐chip and droplet‐based microsystems.
DRD4 allele frequencies in greylag geese vary between urban and rural sites
Authors: Mai Sabrina , Wittor Caroline , Merker Stefan , Woog Friederike
Published: February 2023

With the increasing urbanization of the last decades, more and more bird species occur in urban habitats. Birds which thrive in urban habitats often have a higher tolerance toward human disturbance and show behaviors which differ from their rural counterparts. There is increasing evidence that many behaviors have a genetic basis. One candidate gene is the dopamine receptor D4 (DRD4), which has been associated with fear and thus, flight initiation distance (FID). In this study, we analyzed a segment of DRD4 in greylag geese Anser anser, describing the variability of this gene across several geographically distant populations, and comparing its variability between an urban and a rural site in south–west Germany. We additionally measured FIDs of urban and rural geese to test for a possible correlation with DRD4 genotypes. We found a high variation within DRD4, with 10 variable sites leading to 11 alleles and 35 genotypes. Two genotypes occurred in 60% of all geese and were thus defined as common genotypes versus 33 rare genotypes. Population differentiation was very low between the urban and rural sites in Germany but common genotypes occurred more often in the urban area and rare genotypes more often in the rural area. FID was significantly higher at the rural site, but no significant correlation between FID and DRD4 genotypes could be detected. Nevertheless, our results suggest that local site selection may be related to DRD4 genotypes.
Does weather drive habitat use and movement of a nonmigratory bird?
Authors: Neumann L. K. , Davis C. A. , Fuhlendorf S. D. , Elmore R. D.
Published: February 2023

Climate change is predicted to increase the intensity and frequency of weather extremes (e.g., extreme heat and drought), which will likely affect wildlife species in significant ways. Maintaining landscape heterogeneity has been suggested as a potential conservation strategy to buffer animals from weather extremes. Because animal movement influences survival and population connectivity, understanding animal space use and movement in response to shifts in weather is useful for the conservation of wildlife. Nonmigratory species are predicted to be more negatively affected by climate change because they have a limited ability to disperse to find resources. We studied the Northern Bobwhite (Colinus virginianus; hereafter, bobwhite) to understand how weather alters habitat use and movement of a nonmigratory animal across a landscape. We collected telemetry locations on bobwhite across western Oklahoma during 2019–2020 and paired these data with meteorological and vegetation data. We analyzed the data at two temporal scales—hourly locations and 12‐h paths. At the hourly scale, we analyzed tree cover use, shrub cover use, and normalized difference vegetation index (NDVI) use using generalized or linear‐mixed models. At the 12‐h scale, we calculated three different movement metrics: cumulative distance, net displacement, sinuosity and analyzed each movement metric separately using generalized linear‐mixed models. We found that bobwhite used denser tree cover and higher NDVI values as air temperature increased in conjunction with solar radiation. Bobwhite used denser shrub cover as air temperature increased and average wind speed was high as well as when air temperature and average wind speed were low. The interaction between variability in vegetation and climate influenced bobwhite movement. Bobwhite in areas with higher NDVI variance moved farther when mean air temperatures were >0°C than bobwhite in areas with low NDVI variance. When mean air temperatures were ≤0°C, NDVI variance had little effect on the cumulative distance moved of bobwhite. Our findings show that some animals use different vegetation types during different weather conditions and that variability in vegetation on the landscape and weather together alters animal movement. Managing for landscape heterogeneity is a solution that may buffer animals from increased climate variability in the future.
Greening recovery – Overcoming policy incoherence for sustainability transformations
Authors: Gottenhuber Sara , Linnér Björn‐Ola , Wibeck Victoria , Persson Åsa
Published: February 2023

Policy coherence is crucial in the 2030 Agenda's transformative ambitions and heralded as of paramount importance to ensure the successful implementation of the 17 Sustainable Development Goals and climate policy targets. Despite political efforts to achieve policy coherence, apparent trade‐offs and goal conflicts have emerged – even in a proclaimed ‘front‐runner’ country like Sweden. This paper examines the role of ideas in proposing and legitimising policy options and achieving policy coherence in the light of the Swedish recovery debate in 2020 following the COVID‐19 pandemic. Ideas of a green economic recovery put forward in the public debate are examined through thematic text and frame analysis. We show that ideas of a green transition, boosted by economic recovery spending, draw on a synergistic frame in combining social, environmental, and economic policy options, carrying a potential for coherency. However, the absence of a discussion on power, as in who stands to gain what under which circumstances, coupled with an inherent understanding of a temporal hierarchy of policy priorities does not only impact the ability to design coherent policies but may have considerable impacts on the prospects of achieving sustainability transformations.
Dual‐signal immuno‐competitive determination of brain natriuretic peptide based on magnetic nanozyme
Authors: Xu Xiao‐Hui , Xia Junjie , Song Sunfengda , Liu Yawen , Chen Jie , Zhong Suyun , Chen Hongxia , Zhang Zhao‐Huan
Published: February 2023

Brain natriuretic peptide (BNP) has been a disease marker in the diagnosis of heart failure. In this study, gold nanoparticles modified with Hemin (H‐AuNPs) as nanozymes were used to oxidize ABST and MB to amplified colorimetric and electrochemical redox signals respectively. BNP was combined with H‐AuNPs (BNP‐H‐AuNPs) through electrostatic adsorption to construct competitive nanozyme probes. Target BNP in the sample compete with BNP‐H‐AuNPs to bind the antibody‐modified magnetic nanoparticles (AntiBNP‐MNPs). Due to the excellent catalytic performance of the nanozyme, BNP can be observed well by colorimetric and electrochemical assays. Electrochemical method ensured more accurate detection of BNP with a wide detection range (1–200 pg/mL) and a low detection of limit (0.03 pg/mL). Meanwhile, the results of the experiment can be easily observed with the naked eye by simple colorimetric method with a range from 5 ng/mL to 25 ng/mL and a limit of detection down to 80.3 pg/mL. Thus, based on the important role of H‐AuNPs, this assay has exhibited potential value of detection the other small proteins through this competitive nanozyme method.
Predicting customer churn using grey wolf optimization‐based support vector machine with principal component analysis
Authors: Durkaya Kurtcan Betul , Ozcan Tuncay
Published: February 2023

Customer churn is a challenging problem that can lead to a loss of organizational assets. Organizations need to predict customer churn successfully in order to get rid of potential damages and gain a competitive advantage. The aim of this study is to provide a churn prediction model by including feature selection and optimization in classification. The study performs principal component analysis (PCA) to select the best features, support vector machine (SVM) to predict customer churn, and grey wolf optimization (GWO) to optimize the parameters of SVM. In other words, this study proposes a novel hybrid model called PCA‐GWO‐SVM to enhance the prediction ability in customer churn. A comparison experiment is carried out, evaluating the proposed model with the other classification algorithms. Experimental results show that the proposed PCA‐GWO‐SVM hybrid model produces higher accuracy, recall, and F1‐score than other machine learning algorithms such as logit, k‐nearest neighbors, naive Bayes, decision tree, and SVM.
Chinese parents' perceived social change and their organisation of preschoolers' learning activities
Authors: Ren Lixin , Wu Yingqian , Mang Lingyun , Zhang Zhen , Chen Hua
Published: February 2023

China has experienced dramatic transformations over recent decades, which has significant implications for childrearing. This study examined whether Chinese parents' perceived social change would mediate the association between family socioeconomic status (SES) and children's involvement in various learning activities in the home, community and extracurricular contexts. The study included 312 urban Chinese parents with preschool‐aged children. Parents completed measures on perceived social change, their involvement in children's home literacy, numeracy and play activities, as well as children's participation in community‐based activities and commercially provided extracurricular activities (EAs). The results indicated that higher‐SES parents perceived more opportunities and prospects and less work‐related risk and adversity as a function of social change. Parents who perceived more opportunities and prospects were more involved in almost all types of children's learning activities except EAs. Parents who perceived more work‐related risk and adversity only showed decreased involvement in home literacy activities. Parents who endorsed new values more strongly were more likely to enrol their children in EAs and demonstrate greater involvement in children's home literacy activities. The findings revealed substantial within‐group variations in parents' subjective experiences with social change and how parents' perceived social change might shape their ways of organising children's learning environment.
Call to action: Clinical pharmacist roles and opportunities in health disparities research
Authors: Marrs Joel C. , Formea Christine M. , Abdalla Maha , Brual Rochelle L. , Crowe Susie J. , Freibert Kirstie H. , Herink Megan C. , Hoffman Alexander R. , Philbrick Ann M. , Prescott Gina M. , Shahdoost Moghadam Sara , Zhou Crystal
Published: February 2023

The roles clinical pharmacists can play in addressing health equity and eliminating health disparities span the areas of quality of care, access to care, use of care, and health outcomes. Through this call to action, we address the importance of dismantling health disparities and describe the potential barriers and challenges to clinical pharmacists becoming involved with and performing health disparities research. Furthermore, we identify solutions to these barriers and challenges by highlighting opportunities for clinical pharmacists to seek training and identify potential funding sources for health disparities research. In addition, we provide examples of previous health disparities research conducted by pharmacists across a wide spectrum of patient populations, areas of practice, and types of research. The goal moving forward is to continue to promote current training opportunities to allow clinical pharmacists to develop and/or improve on their research skillset to expand pharmacist‐led research within the focus area of health disparities and ultimately serve as leaders and collaborators in the area.
Synthesis of CexZr1‐xO2/SiO2 supports for chromium oxide catalysts of oxidative dehydrogenation of propane with carbon dioxide
Authors: Mashkin Mikhail Yu. , Tedeeva Marina A. , Fedorova Anna A. , Fatula Evgeniya R. , Egorov Alexander V. , Dvoryak Stanislav V. , Maslakov Konstantin I. , Knotko Alexander V. , Baranchikov Alexander E. , Kapustin Gennadii I. , Petukhov Dmitrii I. , Shatalova Tatyana B. , Morozov Igor V. , Kustov Leonid M. , Kustov Alexander L.
Published: February 2023

BACKGROUND

Propane dehydrogenation is an alternative way both to produce propylene and to utilize CO2. Because of the high oxygen mobility in cerium‐zirconium oxide (CexZr1‐xO2), it looks promising as a support for the chromium oxide catalysts of propane dehydrogenation with CO2. Supports of CexZr1‐xO2 on mesoporous silica were synthesized in this work to combine the high oxygen mobility of the former and the pore structure of the latter.

RESULTS

Two applied synthetic approaches resulted in materials with different structure and properties. The wet impregnated catalysts demonstrated a higher activity and selectivity to propylene. At the same time, they had larger pore size distribution maxima (~9 nm) than the samples prepared by the introduction of metals simultaneously with Si‐precursor hydrolysis (~2 nm). For the chromium catalysts with the same support, the catalytic activity decreased with varying chromium loading as follows: 5% Cr > 3% Cr ≈ 7% Cr. For the catalysts with different CexZr1‐xO2 supports and equal chromium loading, the activity decreased with x changing as follows: 0.5 > 0.6 > 0.8 for the samples prepared by wet impregnation, and 0.8 ≈ 0.6 > 0.5 for the other synthetic path.

CONCLUSIONS

Catalysts were tested in oxidative dehydrogenation of propane with CO2. The wet impregnation approach turned out to be much more promising in terms of catalytic activity and selectivity to propylene in the reaction of propane dehydrogenation with CO2. The selectivity achieved was ≤80% at a 40% conversion. © 2023 Society of Chemical Industry (SCI).
Expanded carrier screening for reproductive risk assessment: An evidence‐based practice guideline from the National Society of Genetic Counselors
Authors: Sagaser Katelynn G. , Malinowski Jennifer , Westerfield Lauren , Proffitt Jennifer , Hicks Melissa A. , Toler Tomi L. , Blakemore Karin J. , Stevens Blair K. , Oakes Lisa M.
Published: February 2023

Expanded carrier screening (ECS) intends to broadly screen healthy individuals to determine their reproductive chance for autosomal recessive (AR) and X‐linked (XL) conditions with infantile or early‐childhood onset, which may impact reproductive management (Committee Opinion 690, Obstetrics and Gynecology, 2017, 129, e35). Compared to ethnicity‐based screening, which requires accurate knowledge of ancestry for optimal test selection and appropriate risk assessment, ECS panels consist of tens to hundreds of AR and XL conditions that may be individually rare in various ancestries but offer a comprehensive approach to inherited disease screening. As such, the term “equitable carrier screening” may be preferable. This practice guideline provides evidence‐based recommendations for ECS using the GRADE Evidence to Decision framework (Guyatt et al., BMJ, 2008, 336, 995; Guyatt et al., BMJ, 2008, 336, 924). We used evidence from a recent systematic evidence review (Ramdaney et al., Genetics in Medicine, 2022, 20, 374) and compiled data from peer‐reviewed literature, scientific meetings, and clinical experience. We defined and prioritized the outcomes of informed consent, change in reproductive plans, yield in identification of at‐risk carrier pairs/pregnancies, perceived barriers to ECS, amount of provider time spent, healthcare costs, frequency of severely/profoundly affected offspring, incidental findings, uncertain findings, patient satisfaction, and provider attitudes. Despite the recognized barriers to implementation and change in management strategies, this analysis supported implementation of ECS for these outcomes. Based upon the current level of evidence, we recommend ECS be made available for all individuals considering reproduction and all pregnant reproductive pairs, as ECS presents an ethnicity‐based carrier screening alternative which does not rely on race‐based medicine. The final decision to pursue carrier screening should be directed by shared decision‐making, which takes into account specific features of patients as well as their preferences and values. As a periconceptional reproductive risk assessment tool, ECS is superior compared to ethnicity‐based carrier screening in that it both identifies more carriers of AR and XL conditions as well as eliminates a single race‐based medical practice. ECS should be offered to all who are currently pregnant, considering pregnancy, or might otherwise biologically contribute to pregnancy. Barriers to the broad implementation of and access to ECS should be identified and addressed so that test performance for carrier screening will not depend on social constructs such as race.
Simultaneous Highly Efficient Contrast‐Free Lumen and Vessel Wall MR Imaging for Anatomical Assessment of Aortic Disease
Authors: Munoz Camila , Fotaki Anastasia , Hua Alina , Hajhosseiny Reza , Kunze Karl P. , Ismail Tevfik F. , Neji Radhouene , Pushparajah Kuberan , Botnar René M. , Prieto Claudia
Published: February 2023

Background

Bright‐blood lumen and black‐blood vessel wall imaging are required for the comprehensive assessment of aortic disease. These images are usually acquired separately, resulting in long examinations and potential misregistration between images.

Purpose

To characterize the performance of an accelerated and respiratory motion‐compensated three‐dimensional (3D) cardiac MRI technique for simultaneous contrast‐free aortic lumen and vessel wall imaging with an interleaved T2 and inversion recovery prepared sequence (iT2Prep‐BOOST).

Study Type

Prospective.

Population

A total of 30 consecutive patients with aortopathy referred for a clinically indicated cardiac MRI examination (9 females, mean age ± standard deviation: 32 ± 12 years).

Field Strength/Sequence

1.5‐T; bright‐blood MR angiography (diaphragmatic navigator‐gated T2‐prepared 3D balanced steady‐state free precession [bSSFP], T2Prep‐bSSFP), breath‐held black‐blood two‐dimensional (2D) half acquisition single‐shot turbo spin echo (HASTE), and 3D bSSFP iT2Prep‐BOOST.

Assessment

iT2Prep‐BOOST bright‐blood images were compared to T2prep‐bSSFP images in terms of aortic vessel dimensions, lumen‐to‐myocardium contrast ratio (CR), and image quality (diagnostic confidence, vessel sharpness and presence of artifacts, assessed by three cardiologists on a 4‐point scale, 1: nondiagnostic to 4: excellent). The iT2Prep‐BOOST black‐blood images were compared to 2D HASTE images for quantification of wall thickness. A visual comparison between computed tomography (CT) and iT2Prep‐BOOST was performed in a patient with chronic aortic dissection.

Statistical Tests

Paired t‐tests, Wilcoxon signed‐rank tests, intraclass correlation coefficient (ICC), Bland–Altman analysis. A P value < 0.05 was considered statistically significant.

Results

Bright‐blood iT2Prep‐BOOST resulted in significantly improved image quality (mean ± standard deviation 3.8 ± 0.5 vs. 3.3 ± 0.8) and CR (2.9 ± 0.8 vs. 1.8 ± 0.5) compared with T2Prep‐bSSFP, with a shorter scan time (7.8 ± 1.7 minutes vs. 12.9 ± 3.4 minutes) while providing a complementary 3D black‐blood image. Aortic lumen diameter and vessel wall thickness measurements in bright‐blood and black‐blood images were in good agreement with T2Prep‐bSSFP and HASTE images (<0.02 cm and <0.005 cm bias, respectively) and good intrareader (ICC > 0.96) and interreader (ICC > 0.94) agreement was observed for all measurements.

Data Conclusion

iT2Prep‐BOOST might enable time‐efficient simultaneous bright‐ and black‐blood aortic imaging, with improved image quality compared to T2Prep‐bSSFP and HASTE imaging, and comparable measurements for aortic wall and lumen dimensions.

Evidence Level

2.

Technical Efficacy

Stage 2.
Comparable humoral and cellular immunity against Omicron variant BA.4/5 of once‐boosted BA.1/2 convalescents and twice‐boosted COVID‐19‐naïve individuals
Authors: Kang Chang Kyung , Kim Min‐Gang , Park Seong‐wook , Kim Yong‐Woo , Lee Chan Mi , Choe Pyoeng Gyun , Park Wan Beom , Kim Nam Joong , Kim Minji , Lee Soojin , Kim Ik Soo , Lee Chang‐Han , Shin Hyun Mu , Kim Hang‐Rae , Oh Myoung‐don
Published: February 2023

The fourth vaccination dose confers additional protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in individuals with no prior coronavirus disease‐19 (COVID‐19). However, its immunological benefit against currently circulating BA.4/5 is unclear in individuals who have received a booster shot and been infected with Omicron variant BA.1/2. We analyzed immune responses in whom had been boosted once and did not have COVID‐19 (n = 16), boosted once and had COVID‐19 when BA.1/2 was dominant in Korea (Hybrid‐6M group, n = 27), and boosted twice and did not have COVID‐19 (Vx4 group, n = 15). Antibody binding activities against RBDo BA.1 and RBDo BA.4/5, antigen‐specific memory CD4+ and CD8+ T‐cell responses against BA.4/5, and B‐cell responses against SARS‐CoV‐2 wild‐type did not differ statistically between the Hybrid‐6M and Vx4 groups. The humoral and cellular immune responses of the Hybrid‐6M group against BA.4/5 were comparable to those of the Vx4 group. Individuals who had been boosted and had an Omicron infection in early 2022 may not have high priority for an additional vaccination.
Monkeypox outbreak in Genoa, Italy: Clinical, laboratory, histopathologic features, management, and outcome of the infected patients
Authors: Ciccarese Giulia , Di Biagio Antonio , Bruzzone Bianca , Guadagno Antonio , Taramasso Lucia , Oddenino Giorgio , Brucci Giorgia , Labate Laura , De Pace Vanessa , Mastrolonardo Mario , Broccolo Francesco , Robello Giacomo , Drago Francesco , Bassetti Matteo , Parodi Aurora
Published: February 2023

Since May 2022, multiple human Monkeypox cases were identified in nonendemic countries, mainly among men who have sex with men. We aimed to report the features, clinical course, management, and outcome of the Monkeypox cases diagnosed in the Dermatology and Infectious Disease Units of the San Martino Hospital, Genoa, Italy. We performed an observational study of the Monkeypox cases diagnosed from July 1 until August 31, 2022, collecting clinical, laboratory, and histological data. We studied 16 Monkeypox‐infected men (14 homosexual, 2 bisexual) with a median age of 37 years. Three were HIV‐infected. All patients reported multiple sexual partners and/or unprotected sex in the 2 weeks before the diagnosis. Most patients had prodromal signs/symptoms before the appearance of the skin/mucosal eruption, consisting of erythematous papules/vesicles/pustules in the anogenital area, which tended to erode evolving into crusts and ulcers. Lesions were often associated with local and/or systemic symptoms. Histopathology showed overlapping features in all cases: epidermal ulceration and dermal inflammatory infiltrate consisting of lymphocytes and neutrophils with an interstitial and perivascular/peri‐adnexal pattern and endothelial swelling. Concomitant sexually transmitted infections (STIs) (gonococcal/nongonococcal proctitis and anal high‐risk human papillomavirus [HR‐HPV] infection) were frequent. Four patients were hospitalized, and one received specific treatment. The overall outcome was good. At the follow‐up visit, three patients presented skin scars. Our series confirms the features of the current Monkeypox outbreak; however, different from other studies, we found a considerable rate of concomitant STIs, such as anal HR‐HPV infection, that should be kept in mind because this persistent infection is the main cause of anal cancers.
SARS‐CoV‐2 infection of kidney tissues from severe COVID‐19 patients
Authors: Radovic Shawn , Meng Wen , Chen Luping , Paniz Mondolfi Alberto E. , Bryce Clare , Grimes Zachary , Sordillo Emilia M. , Cordon‐Cardo Carlos , Guo Haitao , Huang Yufei , Gao Shou‐Jiang
Published: February 2023

Background

Coronavirus disease 2019 (COVID‐19) caused by infection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) manifests diverse clinical pathologies involving multiple organs. While the respiratory tract is the primary SARS‐CoV‐2 target, acute kidney injury is common in COVID‐19 patients, displaying as acute tubular necrosis (ATN) resulting from focal epithelial necrosis and eosinophilia, glomerulosclerosis, and autolysis of renal tubular cells. However, whether any renal cells are infected by SARS‐CoV‐2 and the mechanism involved in the COVID‐19 kidney pathology remain unclear.

Methods

Kidney tissues obtained at autopsy from four severe COVID‐19 patients and one healthy subject were examined by hematoxylin and eosin staining. Indirect immunofluorescent antibody assay was performed to detect SARS‐CoV‐2 spike protein S1 and nonstructural protein 8 (NSP8) together with markers of different kidney cell types and immune cells to identify the infected cells.

Results

Renal parenchyma showed tissue injury comprised of ATN and glomerulosclerosis. Positive staining of S1 protein was observed in renal parenchymal and tubular epithelial cells. Evidence of viral infection was also observed in innate monocytes/macrophages and NK cells. Positive staining of NSP8, which is essential for viral RNA synthesis and replication, was confirmed in renal parenchymal cells, indicating the presence of active viral replication in the kidney.

Conclusions

In fatal COVID‐19 kidneys, there are SARS‐CoV‐2 infection, minimally infiltrated innate immune cells, and evidence of viral replication, which could contribute to tissue damage in the form of ATN and glomerulosclerosis.
Persistent circulation of soluble and extracellular vesicle‐linked Spike protein in individuals with postacute sequelae of COVID‐19
Authors: Craddock Vaughn , Mahajan Aatish , Spikes Leslie , Krishnamachary Balaji , Ram Anil K. , Kumar Ashok , Chen Ling , Chalise Prabhakar , Dhillon Navneet K.
Published: February 2023

SARS‐CoV‐2, the causative agent of COVID‐19 disease, has resulted in the death of millions worldwide since the beginning of the pandemic in December 2019. While much progress has been made to understand acute manifestations of SARS‐CoV‐2 infection, less is known about post‐acute sequelae of COVID‐19 (PASC). We investigated the levels of both Spike protein (Spike) and viral RNA circulating in patients hospitalized with acute COVID‐19 and in patients with and without PASC. We found that Spike and viral RNA were more likely to be present in patients with PASC. Among these patients, 30% were positive for both Spike and viral RNA; whereas, none of the individuals without PASC were positive for both. The levels of Spike and/or viral RNA in the PASC+ve patients were found to be increased or remained the same as in the acute phase; whereas, in the PASC−ve group, these viral components decreased or were totally absent. Additionally, this is the first report to show that part of the circulating Spike is linked to extracellular vesicles without any presence of viral RNA in these vesicles. In conclusion, our findings suggest that Spike and/or viral RNA fragments persist in the recovered COVID‐19 patients with PASC up to 1 year or longer after acute SARS‐CoV‐2 infection.
Macaque fossils (Cercopithecidae: Papionini) from the Kumok Cave, Sungho County, North Hwanghae Province, the Democratic People's Republic of Korea
Authors: Han Kum Sik , So Kwang Sik , Ri Jae Nam , Ri Pin , Chol U , Kang Jin Gon
Published: February 2023

The recently discovered macaque fossils, including mandible, maxilla fragments and isolated teeth, from the Kumok Cave, Sungho County, the Democratic People's Republic of Korea can be identified as Macaca mulatta. They represent the first recognised occurrence of fossil M. mulatta in the Kumok Cave. The Kumok Cave sediments include seven layers, of which the macaque fossils were found only in the third layer. Thermoluminescence dating on a calcite sample from Layer 3 is about 86.1 ± 7.7 ka, and geochronology by the accompanying mammal fauna belongs to the Late Pleistocene, Thus, it indicates that Layer 3 was represented by a warm phase at the end of the pre‐Würm interglacial Epoch. The Kumok fossils also contribute to the growing primate fossil record in DPRK, and indicate the need for increased research into fossil primates in that country.
Improved antioxidant activity of rutin via lipase‐mediated esterification with oleic acid
Authors: Liu Yihang , Wang Qingzhi , Liu Chen , Yang Haonan , Jia Li , Zhao Litao , Gong Fayong , Tan Chen , Tao Hongxun , He Wen‐Sen
Published: February 2023

BACKGROUND

Oxidation is a major problem for oils and fats, which can be mitigated by antioxidants. Rutin has excellent antioxidant activity, but its poor lipid solubility greatly limits its practical application. In this study, an efficient enzymatic synthesis route of lipophilic rutin ester was established using oleic acid as an acyl donor, and the antioxidant potential of rutin oleate was evaluated for the first time by proton (1H) nuclear magnetic resonance (NMR) spectroscopy.

RESULTS

The synthesized product was finally identified as rutin oleate by Fourier transform infrared, high‐performance liquid chromatography–mass spectrometry, and 1H, carbon‐13, and DEPT‐135 NMR analyses, and the acylation site was the 4‴‐OH of the rhamnose group in the rutin molecule. The maximum conversion was over 93% after 48 h of reaction using Novozym 435 as catalyst under the best conditions among these tests. The conversion of rutin ester decreased with the increase of carbon chain length and the number of carbon–carbon double bonds of the fatty acid molecule. Most importantly, rutin oleate exhibited antioxidant capacity comparable to butylated hydroxytoluene and its counterparts (rutin and oleic acid) at low temperatures (60° C), but had a significant advantage at high temperatures (120° C).

CONCLUSION

The antioxidant activity of rutin was significantly enhanced by lipase‐mediated esterification with oleic acid. Therefore, rutin oleate could be further developed as a novel antioxidant for use in oil‑ and fat‐based foods. © 2023 Society of Chemical Industry.
An evaluation of spatial capture‐recapture models applied to ungulate non‐invasive genetic sampling data
Authors: Dupont Pierre P. A. , Bischof Richard , Milleret Cyril , Peters Wibke , Edelhoff Hendrik , Ebert Cornelia , Klamm Alisa , Hohmann Ulf
Published: February 2023

Non‐invasive genetic sampling (NGS) methods are becoming a mainstay in wildlife monitoring and can be used with spatial capture‐recapture (SCR) methods to estimate population density. Yet SCR based on NGS remains relatively underused for ungulate population monitoring, despite the importance of robust density estimates for this ecologically and economically important group of species. This may be in part attributed to biological characteristics of ungulate species and data collection methods that lead to violations of SCR model assumptions. We conducted a simulation study to evaluate the robustness of SCR methods to spatially heterogeneous density (i.e., configuration of individuals into groups of variable sizes and composition), individual heterogeneity in space‐use patterns, and adaptive sampling (i.e., variation in detectability across space that correlates with density). We evaluated each violation separately and in combination. We parameterized our simulations based on published information and preliminary analyses of NGS data sets of 3 ungulate species: chamois (Rupicapra rupicapra), red deer (Cervus elaphus), and wild boar (Sus scrofa). While SCR estimates were robust to grouping and adaptive sampling, abundance estimates could be negatively biased (up to 10% in our simulations) in the presence of unaccounted individual heterogeneity in space use. The degree to which abundance estimates were underestimated depended mostly on the amount of variation in space use and detectability among age classes. This bias was also accompanied by a reduction in precision and coverage probability of the SCR estimators. We discuss the implications of these findings, possible approaches to identify problematic violations in available data sets (goodness‐of‐fit tests), and potential further developments of SCR models to ensure reliable abundance estimates for ungulate populations from NGS data.
Recent Progress in Understanding Polymer Crystallization
Authors: Saalwächter Kay , Thurn‐Albrecht Thomas , Paul Wolfgang
Published: February 2023

Recent developments concerned with elucidating the semicrystalline structure formation in bulk polymer melts, with a focus on possibly important factors that have received less systematic attention, are reviewed. This includes the presence or absence of chain motion through the crystallites, which has a strong impact on the final crystallite thickness, and the effects of entanglements, which limit crystal growth and lower the crystallinity. From the theoretical side, interest is shown in shedding light on the thermodynamic driving forces of polymer crystallization, thus providing a theoretical background against which the kinetic limitations determine the resulting structures in experiments.
On the mapping procedure based on higher‐order Hermite polynomials for laminated thin plates with arbitrary domains in gradient elasticity
Authors: Bacciocchi Michele , Fantuzzi Nicholas
Published: February 2023

The article presents a finite element mapping procedure for the coordinate change via higher‐order derivatives to compute the fundamental matrices of laminated thin plates with arbitrary domains in gradient elasticity. In this context, the approximate solution requires Hermite interpolating functions. Therefore, conforming and nonconforming formulations are needed for both membrane and bending degrees of freedom, which require respectively and continuity. The aim of the current procedure is the possibility to remove the limitations related to the regular rectangular shape which typically characterizes this kind of elements and to introduce arbitrary distortions, discussing the influence of structured and unstructured meshes. The accuracy and convergence features of the methodology are presented through some numerical tests and compared to relevant literature.
FLS2‐RBOHD module regulates changes in the metabolome of Arabidopsis in response to abiotic stress
Authors: Yu Xiaole , Liu Zhixin , Qin Aizhi , Zhou Yaping , Zhao Zihao , Yang Jincheng , Hu Mengke , Liu Hao , Liu Yumeng , Sun Susu , Zhang Yixin , Jan Masood , Bawa George , Sun Xuwu
Published: February 2023

Through crosstalk, FLAGELLIN SENSITIVE 2 (FLS2) and RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) are involved in regulating the homeostasis of cellular reactive oxygen species (ROS) and are linked to the metabolic response of plants toward both biotic and abiotic stress. In the present study, we examined the metabolome of Arabidopsis seedlings under drought and salt conditions to better understand the potential role of FLS2 and RBOHD‐dependent signaling in the regulation of abiotic stress response. We identified common metabolites and genes that are regulated by FLS2 and RBOHD, and are involved in the response to drought and salt stress. Under drought conditions, D‐aspartic acid and the expression of associated genes, such as ASPARAGINE SYNTHASE 2 (ASN2), increased in both fls2 and robed/f double mutants. The accumulation of amino acids, carbohydrates, and hormones, such as L‐proline, D‐ribose, and indoleacetaldehyde increased in both fls2 and rbohd/f double mutants under salt conditions, as did the expression of related genes, such as PROLINE IMINOPEPTIDASE, PHOSPHORIBOSYL PYROPHOSPHATE SYNTHASE 5, and NITRILASE 3. Collectively, these results indicate that the FLS2‐RBOHD module regulates plant response to drought and salt stress through ROS signaling by adjusting the accumulation of metabolites and expression of genes related to metabolite synthesis.