bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissolution Behavior and Varied Mesoporosity of Zeolites by NH4F Etching
Authors: Qin Zhengxing , You Zhenchao , Bozhilov Krassimir N. , Kolev Stefan K. , Yang Wei , Shen Yanfeng , Jin Xin , Gilson Jean‐Pierre , Mintova Svetlana , Vayssilov Georgi N. , Valtchev Valentin
Published: February 2022

The mesopores formation in zeolite crystals has long been considered to occur through the stochastic hydrolysis and removal of framework atoms. Here, we investigate the NH4F etching of representative small, medium, and large pore zeolites and show that the zeolite dissolution behavior, therefore the mesopore formation probability, is dominated by zeolite architecture at both nano‐ and sub‐nano scales. At the nano‐scale, the hidden mosaics of zeolite structure predetermine the spatio‐temporal dissolution of the framework, hence the size, shape, location, and orientation of the mesopores. At the sub‐nano scale, the intrinsic micropore size and connectivity jointly determine the diffusivity of reactant and dissolved products. As a result, the dissolution propensity varies from removing small framework fragments to consuming nanodomains and up to full digestion of the outmost part of zeolite crystals. The new knowledge will lead to new understanding of zeolite dissolution behavior and new adapted strategies for tailoring hierarchical zeolites.
Topologically‐Interlocked Minicircles as Probes of DNA Topology and DNA‐Protein Interactions
Authors: Rajendran Arivazhagan , Krishnamurthy Kirankumar , Park Seojeong , Nakata Eiji , Kwon Youngjoo , Morii Takashi
Published: February 2022

DNA minicircles exist in biological contexts, such as kinetoplast DNA, and are promising components for creating functional nanodevices. They have been used to mimic the topological features of nucleosomal DNA and to probe DNA‐protein interactions such as HIV‐1 and PFV integrases, and DNA gyrase. Here, we synthesized the topologically‐interlocked minicircle rotaxane and catenane inside a frame‐shaped DNA origami. These minicircles are 183 bp in length, constitute six individual single‐stranded DNAs that are ligated to realize duplex interlocking, and adopt temporary base pairing of single strands for interlocking. To probe the DNA‐protein interactions, restriction reactions were carried out on DNAs with different topologies such as free linear duplex or duplex constrained inside origami and free or topologically‐interlocked minicircles. Except the free linear duplex, all tested structures were resistant to restriction digestion, indicating that the topological features of DNA, such as flexibility, curvature, and groove orientation, play a major role in DNA‐protein interactions.
Optimization of asymmetric reduction conditions of 2‐bromo‐1‐(naphthalen‐2‐yl)ethanone by Enterococcus faecium BY48 biocatalyst with A‐optimal design‐embedded model
Authors: Özdemir Akın , Şahin Engin
Published: February 2022

Aromatic α‐halohydrins, especially 2‐haloethanols, which are a common pharmacological precursor, may be readily transformed to chiral β‐adrenergic receptor blockers. Studies including the synthesis of (S)‐2‐bromo‐1‐(naphthalen‐2‐yl)ethanol ((S)‐2), an α‐halohydrin, in high conversion, enantiomeric excess (ee), and yield by biocatalytic asymmetric reduction of 2‐bromo‐1‐(naphthalen‐2‐yl)ethanone (1) are still insufficient. Moreover, asymmetric reduction of substrate 1 using a mathematical optimization method is not explored in the current literature. In this article, the four asymmetric bioreduction conditions, which are (1) pH, (2) temperature, (3) incubation period, and (4) agitation speed, of substrate 1 were optimized to obtain (S)‐2 with A‐optimal design‐embedded model in the presence of Enterococcus faecium BY48. Optimum bioreduction conditions were determined by the A‐optimal design‐embedded model as follows: pH = 7, temperature = 25°C, incubation period = 24 h, and agitation speed = 200 rpm. And then, it was suggested that (S)‐2 could be obtained with 98.88% ee and 100% conversion rate (cr) under these optimum conditions. As a result of the experimental reaction performed under the optimization conditions suggested by the model, (S)‐2 was obtained with 99% ee and 100% cr. The study revealed that E. faecium BY48 could be used as a biocatalyst in asymmetric reduction reactions. Also, the A‐optimal design‐embedded model could have the great potential to obtain the optimum asymmetric bioreduction conditions.
Computational Fluid Dynamics of Reacting Flows at Surfaces: Methodologies and Applications
Authors: Micale Daniele , Ferroni Claudio , Uglietti Riccardo , Bracconi Mauro , Maestri Matteo
Published: February 2022

This review presents the numerical algorithms and speed‐up strategies developed to couple continuum macroscopic simulations and detailed microkinetic models in the context of multiscale approaches to chemical reactions engineering. CFD simulations and hierarchical approaches are discussed both for fixed and fluidized systems. The foundations of the methodologies are reviewed together with specific examples to show the applicability of the methods. These concepts play a pivotal role to enable the first‐principles multiscale approach to systems of technological relevance.
Epilepsy disorder detection and diagnosis using empirical mode decomposition and deep learning architecture
Authors: Srinath Rajagopalan , Gayathri Rajagopal
Published: March 2022

Epilepsy neurological disorder is detected and diagnosed in this article using deep learning method by differentiating the focal electroencephalogram (EEG) signals and the non‐focal EEG signals. The proposed method consists of time‐scale signal decomposition, feature extraction, and classification with diagnosis. The empirical mode decomposition (EMD) method is used to decompose the EEG signal into six intrinsic mode function (IMF) sub bands. The external intrinsic features are computed for each of the decomposed IMF sub bands and these features along with the coefficients of each IMF sub bands are then trained and further classified using the proposed convolutional neural networks (CNN) architecture. The CNN classifier classifies the EEG signal into either focal or non‐focal and finally the focal signal is diagnosed as mild case or severe case using the proposed CNN architecture. The proposed framework achieves a Se of 99.8%, Sp of 99.9%, and Acc of 99.8% on the EEG signals which are available in Bern–Barcelona dataset. The proposed framework for diagnosis of severe case signals achieves 99.2% of diagnosis rate (DR) and 99.6% of DR for mild case signals on Bern–Barcelona dataset. The proposed framework achieves a Se of 99.6%, Sp of 99.6%, and Acc of 99.7% on the EEG signals which are available in CHB‐MIT dataset. The proposed framework for diagnosis of severe case signals achieves a DR of 97.3% and DR of 98.0% for mild case signals on CHB‐MIT dataset. The performance of the proposed method is cross validated by k‐fold method.
Turkish durum wheat conserved ex‐situ and in situ unveils a new hotspot of unexplored genetic diversity
Authors: Alsaleh Ahmad , Bektas Harun , Baloch Faheem Shehzad , Nadeem Muhammad Azhar , Özkan Hakan
Published: February 2022

Durum wheat (Triticum turgidum L.) is the 10th most cultivated crop and is a vital food source for human consumption. Genetic diversity in durum wheat is still an unexplored subject, and gene banks are filled with accessions waiting to be screened. Here, four different groups of durum wheat, Turkish and foreign cultivars, and in situ and ex situ landraces were evaluated for population structure and genetic diversity. A collection of 129 durum wheat accessions were genotyped, with a total of 6,357 markers (SilicoDArT, SNP [single‐nucleotide polymorphism], and simple sequence repeats [SSRs]). The highest mean allele number per marker (1.562) was obtained with SNP markers in ex situ landraces; the lowest mean allele number per marker (0.788) was obtained with SSR markers in the foreign cultivars. The minimum percentage of polymorphic loci was 38.70% observed with SSR markers in foreign cultivars; the maximum was 76.20% in SilicoDArT markers in ex situ landraces. According to Neighbor‐Joining analyses, the studied collection was divided into groups of cultivars and landraces, with some level of admixtures. Structure and principal coordinate analysis obtained distinct clusters for ex situ landraces and foreign cultivars, supported by Neighbor‐Joining analysis. A significant level of intergroup and intragroup variation was observed, and Turkish ex situ landraces were found as the most diverse and distinct group in the collection. Turkish landraces may be a promising source of novel allelic diversity that can be used in durum wheat breeding worldwide.
Vitality of primed rice seeds sown under prolonged dry soil conditions in an upland field
Authors: Nakao Yoshihiro , Tamaru Shotaro , Yabuta Shin , Sakagami Jun‐Ichi
Published: February 2022

During rainfed upland rice (Oryza sativa) cultivation, unpredictable drought events can hinder the rice growth. Although drought tolerance is a reported effect of seed priming treatment, we hypothesized that plants from primed seeds would die because they would begin to emerge in dry soil. We also expected that nonemerged primed seeds would show decreased seed vigor because their metabolism was activated by priming before sowing. Therefore, we investigated the vigor of hydroprimed and nonprimed seeds during prolonged drought after sowing during upland rice cultivation. A field experiment was conducted on a rainfed upland field that had insufficient rainfall at the beginning of the season. Plant emergence, establishment, and vigor in resown nongerminated seeds were also investigated. A subsequent growth chamber experiment was conducted to investigate the relationship between sown seed deterioration, soil moisture, and temperature. Contrary to the hypothesis, plants from primed as well as control seeds could survive under prolonged drought after emergence. In the nongerminated primed seeds, oxidative damage was increased. However, the percentage of plant emergence in resown seeds did not differ between treatments. Overall, the performance of primed seeds was better than or similar to that of the control seeds. In conclusion, primed seeds have advantages even under extreme drought conditions in rainfed upland fields.
Collaborative state estimation of lithium‐ion battery based on multi‐time scale low‐pass filter forgetting factor recursive least squares ‐ double extended Kalman filtering algorithm
Authors: Long Tao , Wang Shunli , Cao Wen , Ren Pu , He Mingfang , Fernandez Carlos
Published: February 2022

For the lithium battery management system and real‐time safety monitoring, two issues are of great significance, namely, the ability to accurately update the model parameters in real time and to accurately estimate the state of charge and health. In this context, this thesis adopts the second‐order RC equivalent circuit model and the forgetting factor recursive least squares ‐ double extended Kalman filtering (FFRLS‐DEKF) algorithm with multi‐time scales and low‐pass filter. Forgetting factor recursive least squares is applied to conduct online parameter identification, and the traditional double extended Kalman filtering algorithm is optimized to evaluate the state of charge and model parameters in the micro‐scale and macro‐scale. In this way, the error caused by two different characteristics is reduced, and a low‐pass filter is added to optimize the fluctuation problem of the estimated value of the model parameters. According to the experiment results, the maximum error between the model simulation value and the actual value of the terminal voltage is 0.0459 V. If the initial value of the state of charge deviates from the actual value, the maximum errors under BBDST and HPPC conditions record 0.0235 and 0.0048, respectively, the forgetting factor recursive least squares ‐ double extended Kalman filtering algorithm with multi‐time scales and low‐pass filter is able to track the true value within 40 s. Furthermore, the lithium‐ion battery state of health both reaches 98% under the two conditions. In summary, the experimental analysis shows that the algorithm helps reduce the influence of initial values on the results, thereby reducing error accumulation and improving the robustness.
Therapeutic Misconception about Research Procedures: Does a Simple Information Chart Improve Understanding?
Authors: Campbell Gavin , Dixon Margie D. , Lohani Minisha , Cook John , Hianik Rachel , Thomson Mary Catherine , Abernethy Eli , Lewis Colleen , Switchenko Jeffrey , Harvey R. Donald , Pentz Rebecca D.
Published: February 2022

In phase I trials, some biospecimens are used both for research and patient care and some for research only. Some research participants have therapeutic misconception, assuming all biospecimens are for patient care. This study's aim was to test if a simple information chart would improve understanding of nontherapeutic research procedures. A two‐arm study was conducted. Participants in the control group (C) were asked whether biospecimens were for their care, for research only, or for both. The experimental group (E) was asked the same questions but provided with a study‐specific information chart labeling the purpose of each biospecimen. One hundred one patients were interviewed. In both arms, understanding that pretreatment blood draws were for patient care and research was moderate (49% for C and 62% for E). Understanding that posttreatment blood draws were for research only was significantly higher in the experimental arm (16% for C and 44% for E; p = 0.002). Providing a simple information chart may help alleviate this aspect of therapeutic misconception.
Parameter determination for reducing ESS capacity in PV power smoothing control using spline function
Authors: Takahashi Akiko , Kajitani Tatsuya , Funabiki Shigeyuki
Published: March 2022

This paper comprehensively evaluates the PV power smoothing control method using the spline function. As a result of the verification, it is shown that the ESS capacity can be reduced while maintaining the smoothing effect by PV power smoothing control with energy control and limiting fluctuation rate control. Based on the charging/discharging power of the ESS and the operating conditions of the ESS, the section time that achieves both improvement of the smoothing effect and reduction of the ESS capacity is determined to be 1500 s. Then, the rated capacity of the ESS for a rated power of 1.75MW PV system is 1128 kWh. This is 49.6% of the rated capacity of the ESS, which is required in the PV power smoothing control method with fluctuation rate control. As a result of comparing the proposed method and the moving average method, the proposed method improved the smoothing effect by 49.8% compared to the moving average method.
Smart Photochromic Materials Triggered with Visible Light
Authors: Leistner Anna‐Lena , Pianowski Zbigniew L.
Published: February 2022

Molecular photoswitches reversibly convert the energy of light into a variety of structural changes at the molecular level. They can be integrated into smart materials with broad range of applicability. While most photochromic systems require UV light for activation, application of photoswitches operational entirely within the visible or NIR range of light brings considerable benefits, such as biocompatibility, better light penetration through the material, propelling with sunlight, or a possibility to design dual systems that are mutually activated with UV or visible light frequencies for two distinct functions. In this Review, we discuss the most relevant classes of molecular photoswitches, and demonstrate a selection of photochromic polymers, gels, porous materials, surfaces, energy‐storing materials and other systems triggered with visible light.
Application of an Escherichia coli triple reporter strain for at‐line monitoring of single‐cell physiology during L‐phenylalanine production
Authors: Hoang Manh Dat , Doan Dieu Thi , Schmidt Marlen , Kranz Harald , Kremling Andreas , Heins Anna‐Lena
Published: February 2022

Biotechnological production processes are sustainable approaches for the production of biobased components such as amino acids for food and feed industry. Scale‐up from ideal lab‐scale bioreactors to large‐scale processes is often accompanied by loss in productivity. This may be related to population heterogeneities of cells originating from isogenic cultures that arise due to dynamic non‐ideal conditions in the bioreactor. To better understand this phenomenon, deeper insights into single‐cell physiologies in bioprocesses are mandatory before scale‐up. Here, a triple reporter strain (3RP) was developed by chromosomally integrating the fluorescent proteins mEmerald, CyOFP1, and mTagBFP2 into the L‐phenylalanine producing Escherichia coli strain FUS4 (pF81kan) to allow monitoring of growth, oxygen availability, and general stress response of the single cells. Functionality of the 3RP was confirmed in well‐mixed lab‐scale fed‐batch processes with glycerol as carbon source in comparison to the strain without fluorescent proteins, leading to no difference in process performance. Fluorescence levels could successfully reflect the course of related process state variables, revealed population heterogeneities during the transition between different process phases and potentially subpopulations that exhibit superior process performance. Furthermore, indications were found for noise in gene expression as regulation strategy against environmental perturbation.
Future options of electricity generation for sustainable development: Trends and prospects
Authors: Rashid Fazlur , Joardder Mohammad U. H.
Published: March 2022

Electricity is an important part of our daily life. It is mainly generated from conventional energy sources. Conventional energy sources are diminishing day by day; whereas, energy demand increases significantly. Moreover, less land availability, low budget for energy, and weather‐dependent renewable sources result in poor energy management all over the world. Therefore, proper management of conventional energy and simultaneous finding of potential alternative energy sources are the prime concerns of energy‐related researchers. In this article, literature relating to less‐implemented energy sources is reviewed to demonstrate their current status and future prospects. This review shows that along with current renewable and conventional sources of energy, these less‐implemented energy sources can contribute substantially to overcome the energy scarcity in electricity production. Proper planning and improvement are required to get sufficient benefits from these less‐implement energy sources. In order to clarify the electricity generation from less‐applied energy sources, many figures are adapted using the concept and information of reviewed literature. In those figures and related text, several possible ways of electricity generation using these energy sources and their potential implementation techniques with related challenges have been outlined. The electricity generation rate and their corresponding applications are also depicted. Proper steps to popularize these less‐focused sources of energy would mitigate high energy demand all over the world and offers a cleaner environment for livelihood.
Hollow Carbon Sphere and Polyhedral Carbon Composites Supported Iron Nanoparticles as Excellent Bifunctional Electrocatalysts of Zn–Air Battery
Authors: Wang Yuebing , Yi Ruowei , Chen Aling , Fang Can , Wang Yaping , Yi Qingfeng , Liu Meiyang , Liu Shijie , Zhan Shaoqi , Zhong Bin
Published: February 2022

Herein, we synthesize Fe‐based nanocatalysts supported on the composites composed of hollow carbon spheres (HCSs) and metal–organic frameworks (MOFs) by a facile pyrolysis method. The composites with different ratios of HCSs and MOFs present an interesting phenomenon: the oxygen reduction reaction (ORR) limiting current increases along with the HCSs content, while the onset potential and half‐wave potential show the highest values when the ratio between HCSs and MOFs is optimized. The composite catalysts exhibit superior ORR electrocatalytic performance than Pt/C in alkaline and neutral media. Even in the acidic media, these composite catalysts still present a close catalytic activity to Pt/C. For the oxygen evolution reaction (OER) test, the prepared Fe‐NC@NHCS‐600 shows a reduced overpotential to that of the benchmark IrO2. The rechargeable Zn‐air battery using Fe‐NC@NHCS‐600 as the catalyst of air electrode exhibits superior discharge capability with an open‐circuit voltage of 1.620 V and a maximum power density of 278.97 mW cm−2 in alkaline electrolyte, as well as an open‐circuit voltage of 1.457 V and a maximum power density of 114.96 mW cm−2 in neutral electrolyte. The battery also exhibits steady cycling stability for more than 90 and 70 h at 5 and 10 mA cm−2, respectively.
ZnO electron transporting layer engineering realized over 20% efficiency and over 1.28 V open‐circuit voltage in all‐inorganic perovskite solar cells
Authors: Wu Xiao , Zhang Jianquan , Qin Minchao , Liu Kuan , Lv Ziyu , Qin Zhaotong , Guo Xinlu , Li Yuhao , Xu Jianbin , Li Gang , Yan He , Lu Xinhui
Published: February 2022

Cesium lead based all‐inorganic perovskite solar cells (PSCs) are promising candidates for tandem solar cells owing to their favorable thermal stability and suitable bandgap. However, to exploit the advantage to the full, there is still huge room to reduce energy loss and enhance the VOC. In this work, we developed low‐temperature processed ZnO as an ETL alternative. Incorporation of PbX2 (X = I−, Cl−, and CH3COO−) was found to increase oxygen vacancies in ZnO, which not only promoted the growth of all‐inorganic perovskite layer with improved morphology and orientational order, but also formed a favorable energy level alignment with the perovskite layer, thus facilitating charge extraction and suppressing charge recombination. Consequently, the CsPb(I1−xBrx)3 PSCs based on PbX2:ZnO exhibited enhanced stability and performance. The efficiency was boosted from 17.64% to 20.04% with an improved fill factor of 84.14% and a VOC of 1.28 V, being the highest VOC among highly efficient (>20%) all‐inorganic PSCs to date.
Statistical study on soot volume fractions of buoyant turbulent diffusion fires
Authors: Bi Yubo , Lu Shouxiang , Gao Wei , Bi Mingshu , Cong Haiyong
Published: February 2022

The statistical soot properties of buoyant turbulent diffusion propane fire were experimentally and theoretically studied with different fuel sooting tendencies by nitrogen addition. Results show that nitrogen addition decreases the instantaneous soot volume fraction and increases soot intermittency. The combination of these two factors together leads to a decrease in mean soot volume fraction when nitrogen is added. Both radially integrated and the total soot volume fraction decrease with nitrogen addition. The radially integrated soot volume fraction is found to be a function of fuel concentration. A dimensionless correlation is proposed to predict the total soot volume fraction based on theoretical analysis and in good agreement with the experimental data. The results could provide guidance for predicting soot yield for buoyant turbulent fires.
The influence of two yeast strains on fermentation and flavour composition of cider
Authors: Tangüler Hasan , Erten Hüseyin
Published: March 2022

Two commercial dry strains of Saccharomyces cerevisiae and their different inoculum levels were used to carry out cider fermentation to assess their impact on the quality and volatile flavour composition of cider. Analyses indicated that the composition and production of flavour compounds of ciders are generally significantly affected by the strains and inoculation levels. Additionally, the Uvaferm CM strain produced the lowest amount of relative and total flavour compounds compared to Actiflore PM. According to the PCA, differences in volatile components were observed in ciders obtained from both yeasts. While the 1st and 2nd concentrations of Actiflore PM yeast fall to the same region and the others to the different region, the 1st, 2nd and 3rd concentrations of the Uvaferm CM yeast are located in the same region and the others in the different region. It could be said that the Actiflore PM strain synthesizes compounds (such as ethyl alcohol, relative and total esters) that are effective on the quality of cider, the higher amount that Uvaferm CM. The data obtained can be useful for cider producers.
Response surface optimization of pudding formulation containing fish gelatin and clove (Syzygium aromaticum) and cinnamon (Cinnamomum verum) powder: Effect on color, physicochemical, and sensory attributes of the final pudding product
Authors: Choobkar Nasrin , Daraei Garmakhany Amir , Aghajani Abdolraza R. , Ataee Maryam
Published: February 2022

In this study, the response surface methodology (RSM) was used to optimize the pudding formulation ingredients including the fish/bovine gelatin ratio and cinnamon and clove powder and determine the color and physicochemical and sensory attributes’ change in final pudding product. Experiments were carried out based on a central composite design (CCD). The results showed that by increasing the ratio of fish gelatin to bovine gelatin (FG/BG) up to 3%, the moisture content increased slightly and then decreased significantly. Increasing the cinnamon powder to 0.5% reduced the moisture content. Increasing the FG/BG in the formulation of pudding samples reduced the protein content. The effects of cinnamon and clove powder on the protein content were increasing and decreasing, respectively. By increasing the FG/BG ratio, the samples syneresis showed a significant decrease, while the effects of cinnamon and clove powder on the syneresis were nonsignificant. As the level of cinnamon and clove powder increased, the L* value decreased. Cinnamon and clove powder had a linear effect, and the interaction of gelatins and clove powder had a significant effect on changes in redness. The effects of cinnamon and clove powder on b* value were significant. In terms of sensory evaluation, increasing the cinnamon powder concentration increased the appearance scores, while in the case of fish gelatin, this trend was downward. The linear effect of cinnamon powder on taste was significant, while other variables had no significant effect on the taste of the samples. The sample texture was significantly affected by fish gelatin and clove powder. Increasing FG/BG from 0% to 2.5% increased the texture score, but after this range, a decrease in the texture score was observed. The overall acceptance of samples was more affected by spice powder compared to gelatin. By increasing the cinnamon powder and FG/BG, the overall acceptance increased and decreased, respectively. In conclusion, the optimal FG/BG and cinnamon and clove powder were introduced 1.479%, 0.288%, and 0.619% respectively.
N‐terminus DUX4‐immunohistochemistry is a reliable methodology for the diagnosis of DUX4‐fused B‐lymphoblastic leukemia/lymphoma (N‐terminus DUX4 IHC for DUX4‐fused B‐ALL)
Authors: Siegele Bradford J. , Stemmer‐Rachamimov Anat O. , Lilljebjorn Henrik , Fioretos Thoas , Winters Amanda C. , Dal Cin Paola , Treece Amy , Gaskell Alisa , Nardi Valentina
Published: February 2022

B‐lymphoblastic leukemia/lymphoma (B‐ALL) is the most common pediatric malignancy and the most commonly diagnosed adult lymphoblastic leukemia. Recent advances have broadened the spectrum of B‐ALL, with DUX4 gene fusions implicated in a subclass occurring in adolescents and young adults and harboring a favorable prognosis. DUX4 fusions have been challenging to identify. We aimed to determine whether expression of the DUX4 oncoprotein, as detected by targeted immunohistochemistry, might serve as a surrogate for molecular detection of DUX4 fusions in B‐ALL. A cohort of investigational B‐ALLs was generated with enrichment for DUX4 fusions by the inclusion of cases with characteristic demographic features and immunophenotypic properties. B‐ALLs with mutually exclusive cytogenetics were collected. Immunohistochemical staining by a monoclonal antibody raised against the N‐terminus of the DUX4 protein was performed. N‐DUX4 immunohistochemistry demonstrated strong, crisp nuclear staining in blasts of seven investigational cases, six of which had nucleic acid material available for molecular evaluation. Five of these cases demonstrated RNA‐seq DUX4‐fusion positivity. One N‐DUX4 immunohistochemistry positive case lacked a definitive DUX4‐fusion by RNA‐seq, though demonstrated a gene expression profile characteristic of DUX4‐rearranged B‐ALLs, a CD2+ immunophenotype, and a lack of staining by C‐terminus DUX4 antibody immunohistochemistry. At least 83.3% [5/6] positive predictive value. N‐DUX4 immunohistochemistry was negative in blasts of three RNA‐seq DUX4‐fusion‐negative cases (3/3; 100% negative predictive value). B‐ALLs with mutually exclusive cytogenetic profiles were all N‐DUX4 negative (0/10, specificity 100%). N‐DUX4 immunohistochemistry is reliable for the distinction of DUX4‐rearranged B‐ALLs from other B‐ALLs. We recommend its use for subclassification of B‐ALLs in adolescents and young adults and in B‐ALLs that remain “not otherwise specified.”
Presence of SARS‐CoV‐2 in the lower genital tract of women with active COVID‐19 infection: A prospective study
Authors: Khoiwal Kavita , Kalita Deepjyoti , Kumari Reena , Dhundi Deepika , Shankar Ravi , Kumari Ranjeeta , Gaurav Amrita , Bahadur Anupama , Panda Prasan Kumar , Tomy Akhil , Chaturvedi Jaya
Published: February 2022

SARS‐CoV‐2 may present in the lower genital tract of women with active COVID‐19 infection and the probability is significantly higher with high viral load.
The pharmacist's responsibility to ensure appropriate use of direct‐to‐consumer genetic testing
Authors: Gammal Roseann S. , Smith D. Max , Wiisanen Kristin W. , Cusimano Joseph M. , Pettit Rebecca S. , Stephens Julie W. , Walko Christine M. , Yang Rachel Hagyeong , Dunnenberger Henry M.
Published: March 2022

Millions of consumers have chosen to pursue direct‐to‐consumer (DTC) genetic testing for personal health‐related and/or non‐health‐related information. However, genetic test results can be complex to interpret, and the regulatory landscape for DTC genetic tests is in flux. Given that these tests are easily accessible and may have implications for health, pharmacists need to be prepared to provide patient education on DTC genetic testing, particularly when the results may provide valuable insights into optimal pharmacotherapy. Pharmacists, regardless of practice site and specialty, are well positioned to provide patient education on the benefits, risks, and limitations of DTC pharmacogenomic tests in clinical practice and to advise patients about pursuing confirmatory clinical testing. This report highlights the responsibility of the pharmacist in the appropriate use of DTC genetic testing, particularly pharmacogenomic testing, using a patient case example across varied health settings.
Characterization of the foreign body response of titanium implants modified with polyphenolic coatings
Authors: Weber Florian , Quach Huy Quang , Reiersen Mathias , Sarraj Sadaf Yosef , Bakir Dyala Nidal , Jankowski Victor Aleksander , Nilsson Per H. , Tiainen Hanna
Published: February 2022

The foreign body response is dictating the outcome of wound healing around any implanted materials. Patients who suffer from chronic inflammatory diseases and impaired wound healing often face a higher risk for implant failure. Therefore, functional surfaces need to be developed to improve tissue integration. For this purpose, we evaluated the impact of surface coatings made of antioxidant polyphenolic molecules tannic acid (TA) and pyrogallol (PG) on the host response in human blood. Our results showed that although the polyphenolic surface modifications impact the initial blood protein adsorption compared to Ti, the complement and coagulation systems are triggered. Despite complement activation, monocytes and granulocytes remained inactivated, which was manifested in a low pro‐inflammatory cytokine expression. Under oxidative stress, both coatings were able to reduce intracellular reactive oxygen species in human gingival fibroblasts (hGFs). However, no anti‐inflammatory effects of polyphenolic coatings could be verified in hGFs stimulated with lipopolysaccharide and IL‐1β. Although polyphenols reportedly inhibit the NF‐κB signaling pathway, phosphorylation of NF‐κB p65 was observed. In conclusion, our results indicated that TA and PG coatings improved the hemocompatibility of titanium surfaces and have the potential to reduce oxidative stress during wound healing.
Amelioration of rotenone‐induced alterations in energy/redox system, stress response and cytoskeleton proteins by octanoic acid in zebrafish: A proteomic study
Authors: Sürmen Mustafa G. , Sürmen Saime , Cansız Derya , Ünal İsmail , Üstündağ Ünsal V. , Alturfan Ahmet A. , Büyükkayhan Derya , Emekli‐Alturfan Ebru
Published: February 2022

Rotenone is used to generate Parkinson's disease (PD)‐like symptoms in experimental animals. Octanoic acid (C8), is the principal fatty acid of medium‐chain triglycerides in ketogenic diets. Beneficial effects of ketogenic diets were shown in PD. We applied proteomic methods to reveal the effects of octanoic acid in rotenone toxicity in zebrafish to gain information on the use of ketogenic diets in PD. Zebrafish were exposed to 5 μg/ml rotenone and octanoic acid (20 and 60 mg/ml) for 30 days. LC‐MS/MS analysis was performed. Raw files were analyzed by Proteome Discoverer 2.4 software, peptide lists were searched against Danio rerio proteins. STRING database was used for protein annotations or interactions. 2317 unique proteins were quantified, 302 proteins were differentially expressed. Proteins involved in cell organization, biogenesis, transport, response to stimulus were most frequently expressed. Our study is first to report that the alterations in the expressions of proteins related to energy and redox system, stress response, and cytoskeleton proteins caused by rotenone exposure were normalized by octanoic acid treatment in zebrafish.
Are we choosing mobilization regimens for autologous stem cell transplantation in multiple myeloma wisely: A single center comparison of GCSF+/−plerixafor vs cyclophosphamide/GCSF+/−plerixafor
Authors: Yang Chloe , Dehghani Mina , Hopman Wilma , Bhella Sita
Published: February 2022

Background

Autologous stem cell transplantation (ASCT) is a standard consolidation treatment for eligible patients with multiple myeloma (MM). There is no standardized mobilization regimen for collection of CD34+ stem cells, which is crucial to the success of ASCT. Cyclophosphamide/GCSF is an effective regimen, although reported associated toxicities include risk of febrile neutropenia (FN). Since plerixafor was introduced in Canada, this mobilization agent has been increasingly used as needed with GCSF at Kingston Health Science Centre (KHSC), with elimination of cyclophosphamide. This single center, retrospective, quality improvement study evaluates mobilization and ASCT outcomes of MM patients who had undergone stem cell mobilization at KHSC with cyclophosphamide/GCSF+/−plerixafor without antibiotics, cyclophosphamide/GCSF+/−plerixafor with antibiotics, and GCSF+/−plerixafor without antibiotics.

Methods

A retrospective chart review was conducted evaluating 137 patients. The primary outcome measure was FN rates with mobilization. Balancing measures include CD34+ cell collected, plerixafor usage, days of apheresis and transplant outcomes. Chi‐square, ANOVA, or Kruskal‐Wallis methods were used to test statistical significance where appropriate.

Results

Our study noted a higher total and day one CD34+ count in the two groups utilizing cyclophosphamide in mobilization. All nine cases of FN occurred in these two groups (P < .05). Addition of antibiotics decreased, but did not eliminate risk of FN. There were no significant differences in the rate of plerixafor usage and number of apheresis days. Difference in transplant outcomes, including engraftment and transfusion support, were statistically but not clinically significant. A larger sample size may be needed to explore this fully. There was no significant difference in length of transplant hospital stay.

Conclusion

The elimination of cyclophosphamide from mobilization regimens for MM appears to significantly reduce FN rates, without increasing balancing measures such as total number of apheresis days, plerixafor usage, duration of transplant hospitalization or mortality outcomes.
Deep generative models for ligand‐based de novo design applied to multi‐parametric optimization
Authors: Perron Quentin , Mirguet Olivier , Tajmouati Hamza , Skiredj Adam , Rojas Anne , Gohier Arnaud , Ducrot Pierre , Bourguignon Marie‐Pierre , Sansilvestri‐Morel Patricia , Do Huu Nicolas , Gellibert Françoise , Gaston‐Mathé Yann
Published: February 2022

Multi‐parameter optimization (MPO) is a major challenge in new chemical entity (NCE) drug discovery. Recently, promising results were reported for deep learning generative models applied to de novo molecular design, but, to our knowledge, until now no report was made of the value of this new technology for addressing MPO in an actual drug discovery project. In this study, we demonstrate the benefit of applying AI technology in a real drug discovery project. We evaluate the potential of a ligand‐based de novo design technology using deep learning generative models to accelerate the obtention of lead compounds meeting 11 different biological activity objectives simultaneously. Using the initial dataset of the project, we built QSAR models for all the 11 objectives, with moderate to high performance (precision between 0.67 and 1.0 on an independent test set). Our DL‐based AI de novo design algorithm, combined with the QSAR models, generated 150 virtual compounds predicted as active on all objectives. Eleven were synthetized and tested. The AI‐designed compounds met 9.5 objectives on average (i.e., 86% success rate) versus 6.4 (i.e., 58% success rate) for the initial molecules measured on all objectives. One of the AI‐designed molecules was active on all 11 measured objectives, and two were active on 10 objectives while being in the error margin of the assay for the last one. The AI algorithm designed compounds with functional groups, which, although being rare or absent in the initial dataset, turned out to be highly beneficial for the MPO.
High expression of the ferroptosis‐associated MGST1 gene in relation to poor outcome and maladjusted immune cell infiltration in uterine corpus endometrial carcinoma
Authors: Yan Jianing , Ye Guoliang , Shao Yongfu
Published: February 2022

Background

Uterine corpus endometrial carcinoma (UCEC) tightly correlates with dysregulated iron homeostasis. MGST1 (microsomal glutathione S‐transferase 1) involves in the regulation of oxidative stress and plays a key role in inhibiting iron‐mediated cell death in cancer cells. Hence, we aimed to illuminate the characteristics of MGST1 expression and prognosis in UCEC using bioinformatics prediction to provide novel perspectives for theoretical supplementation and ferroptosis‐based immunotherapy.

Methods

We retrieved MGST1 expression data via several public data portals. The relationships between MGST1 expression and clinicopathologic characteristics as well as survival time were evaluated via multivariate methods and Kaplan–Meier survival curves. The MGST1‐interacting protein–protein interaction was also established by the STRING website. The TIMER and GEPIA databases were used to illustrate the association between MGST1 expression and infiltrated immune cells. We used the MethSurv website and the UALCAN website to determine the relationship between MGST1 expression and DNA methylation.

Results

MGST1 overexpression in UCEC compared with normal tissues correlates with different histological types, a lack of hormone therapy and poor survival time. MGST1 interacts with several ferroptosis‐related proteins. Overexpression of MGST1 was accompanied by lower levels of NK cell and CD8+ T cell infiltration, higher myeloid‐derived suppressor cell infiltration and different immunocytes with corresponding markers. Hypermethylation and low promoter methylation cooperate to regulate MGST1 expression.

Conclusion

Elevated MGST1 expression is related to tumour development and poor prognosis, as well as dysregulated infiltration of immune cells in UCEC, which can be a potential prognostic indicator and ferroptosis‐based immunotherapy target.
A study on factors leading to poor mental health of children in Punjab, Pakistan
Authors: Huda Shamas Ul , Ahmad Liaquat , Rasul Sajid , Aslam Muhammad
Published: February 2022

In this article, the several factors have been investigated relating to the poor mental health of the children in Punjab, Pakistan. Using the data of the survey conducted by the Punjab Bureau of Statistics, different determinants of child malnutrition and poverty were diagnosed based upon sufficient information of the children under 5 year of age. Logistic regression analysis methodology has been applied for screening the most influential factors of the study. It has been observed that the rise in poverty has prejudiced the nutritional position of the children, the mother's education, and the fitness of the youth. It has also been observed that male children are more at risk to poor mental health than female children. A number of policy issues came to light from the findings of the study. The wealth index of all three anthropometric measures, the child malnutrition status of uneducated mothers, and the child diarrhea menace are the significant areas.
Pulmonary artery dopplers for early prediction of risk for bronchopulmonary dysplasia in extremely low birth weight babies
Authors: Lalitha Renjini , Bitar Eyad , Hicks Matthew , Hyderi Abbas , Kumaran Kumar
Published: February 2022

Objective

The early abnormal pulmonary vasoreactivity observed in babies at risk of Bronchopulmonary dysplasia (BPD) increases the pulmonary vascular resistance. This can be assessed non‐invasively using Time to Peak Velocity:Right Ventricular Ejection Time ratio (TPV:RVET) measured from pulmonary artery Doppler waveform obtained using echocardiogram. We postulate that screening for this early can predict BPD in this cohort. The objective of the study was to determine the utility of TPV:RVET in early prediction of BPD in Extremely Low Birth Weight (ELBW) babies born less than 1250grams Birth Weight.

Methods

This was a single‐center retrospective cohort study of ELBW babies born<29 weeks over 4 year period who had echocardiogram between 7‐21 days of life. TPV:RVET ratio was measured from pulmonary artery Doppler waveform obtained using echocardiogram. The main outcome was BPD at 36 weeks corrected gestation. The predictive ability of TPV:RVET (cut off 0.34) for subsequent development of BPD was analyzed using ROC.

Results

Of 589 ELBW<29 weeks, 207 babies were eligible. BPD was found in 60.4%. The TPV:RVET at 0.34 had sensitivity 76.8% (95%CI 68.4–83.9), specificity 85.4% (95%CI 75.8–92.2), positive predictive value 88.9% (95%CI 81.4–94.1), negative predictive value 70.7% (95%CI 60.7–79), and ROC area 0.811 (95%CI 0.757–0.864). Odds ratio of having BPD for TPV:RVET at 0.34 was 19.9 (95%CI 8.19–48.34) and increased by 1.07 (95%CI 1.05–1.09) with every additional days of mechanical ventilation. TPV:RVET ratio had 92.75% inter‐observer agreement with kappa 0.83.

Conclusion

TPV:RVET ratio is a good and reliable early screening tool for subsequent development of BPD in ELBW babies with substantial inter‐observer agreement.
Characterization of exonic variants of uncertain significance in very long‐chain acyl‐CoA dehydrogenase identified through newborn screening
Authors: D'Annibale Olivia M. , Koppes Erik A. , Sethuraman Meena , Bloom Kaitlyn , Mohsen Al‐Walid , Vockley Jerry
Published: February 2022

Very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is an autosomal recessive disease resulting from mutations in the ACADVL gene and is among the disorders tested for in newborn screening (NBS). Confirmatory sequencing following suspected VLCADD NBS results often identifies variants of uncertain significance (VUS) in the ACADVL gene, leading to uncertainty of diagnosis and providing effective treatment regimen. Currently, ACADVL has >300 VUSs in the ClinVar database that requiring characterization to determine potential pathogenicity. In this study, CRISPR/Cas9 genome editing was used to knock out ACADVL in HEK293T cells, and targeted deletion was confirmed by droplet digital polymerase chain reaction (PCR). No VLCAD protein was detected and an 84% decrease in enzyme activity using the electron transfer flavoprotein fluorescence reduction assay and C21‐CoA as substrate was observed compared to control. Plasmids containing control or variant ACADVL coding sequence were transfected into the ACADVL null HEK293T. While transfection of control ACADVL restored VLCAD protein and enzyme activity, cells expressing the VLCAD Val283Ala mutant had 18% VLCAD enzyme activity and reduced protein compared to control. VLCAD Ile420Leu, Gly179Arg, and Gln406Pro produced protein comparable to control but 25%, 4%, and 5% VLCAD enzyme activity, respectively. Leu540Pro and Asp570_Ala572dup had reduced VLCAD protein and 10% and 3% VLCAD enzyme activity, respectively. VLCADD fibroblasts containing the same variations had decreased VLCAD protein and activity comparable to the transfection experiments. Generating ACADVL null HEK293T cell line allowed functional studies to determine pathogenicity of ACADVL exonic variants. This approach can be applied to multiple genes for other disorders identified through NBS.
Longitudinal Changes in Global Cerebral Blood Flow in Cognitively Normal Older Adults: A Phase‐Contrast MRI Study
Authors: Han Hualu , Lin Zixuan , Soldan Anja , Pettigrew Corinne , Betz Joshua F. , Oishi Kumiko , Li Yang , Liu Peiying , Albert Marilyn , Lu Hanzhang
Published: February 2022

Background

Characterization of blood supply changes in older individuals is important in understanding brain aging and diseases. However, prior studies largely focused on cross‐sectional design, thus change in cerebral blood flow (CBF) could not be assessed on an individual level.

Purpose

To evaluate longitudinal short‐term changes in global CBF in cognitively normal older adults.

Study Type

Prospective, longitudinal, and cohort.

Population

One‐hundred twenty‐seven cognitive‐normal participants (mean age 69 ± 7 years, 47 males) underwent serial MRI with an average follow‐up time of 2.1 years.

Field Strength/Sequence

3 T phase‐contrast (PC), three‐dimensional magnetization‐prepared‐rapid‐acquisition‐of‐gradient‐echo (MPRAGE) and fluid‐attenuated inversion recovery (FLAIR) MRI.

Assessment

Total CBF was measured with PC MRI allowing assessment of quantitative flow in four major feeding arteries by a trained radiologist with >3 years' experience (O.K.). Brain volume was obtained from MPRAGE MRI and measured by T1‐MultiAtlas MRICloud tool. The ratio between total CBF and brain volume yielded global CBF in mL/100 g/min. White matter hyperintensity (WMH) was measured automatically using a Bayesian probability approach on FLAIR.

Statistical Tests

Linear mixed effect model was used to simultaneously assess cross‐sectional age‐differences and longitudinal age‐changes in CBF. Spearman rank correlation was used to evaluate the relationship between CBF change and WMH progression. A P‐value of <0.05 (two‐tailed) was considered significant.

Results

Global CBF decreased with age at a longitudinal rate of −0.56 mL/100 g/min/year (95% confidence interval [CI]: −1.09, −0.03), compared to a cross‐sectional rate of −0.26 mL/100 g/min/year (95% CI: −0.41, −0.11). Changes in CBF were significantly associated with progression of WMH (Spearman rank correlation r = −0.25), as those participants who had a more rapid CBF reduction had greater increases in WMH volumes and the relationship remained significant when adjusting for baseline vascular risk scores. Additionally, age‐related changes in whole‐brain volume were found to be −0.151%/year (95% CI: −0.186, −0.116).

Data Conclusion

These findings suggest that brain aging in older adults is accompanied by a rapid longitudinal reduction in CBF, the rate of which is associated with white matter damage.

Level of Evidence

1

Technical Efficacy Stage

2