bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to first‐line treatment predicts progression‐free survival benefit of small‐cell lung cancer patients treated with anlotinib
Authors: Qin Boyu , Xin Lingli , Hou Qingxiang , Yang Bo , Zhang Jing , Qi Xiaoguang , Wei Yingtian , Hu Yi , Xiong Qi
Published: May 2021

Background

Anlotinib significantly extended progression‐free survival (PFS) and overall survival (OS) in small‐cell lung cancer (SCLC) as third or later line treatment.

Methods

In this study, we retrospectively analyzed the efficacy and safety of anlotinib in the clinical practice and aimed to identify risk factors for predicting the clinical benefit of anlotinib in SCLC patients. 29 SCLC patients treated with anlotinib monotherapy or combination therapy as second or later line treatment were included. PFS, OS, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed.

Results

In whole patients, the median PFS was 2.1 months (95% confidence interval (CI): 1.1–3.2 months); The ORR and DCR were 10.3% and 48.3%, respectively; The median OS was 7.2 months (95%CI: 3.2–11.2 months). Cox regression analysis demonstrated that response to first‐line treatment was the independent risk factor for PFS. The ORR (20.0% vs. 0%) and DCR (53.3% vs. 42.9%) were promoted in patients treated with anlotinib combination therapy comparing to anlotinib monotherapy. The most common AEs were hoarseness, fatigue, decreased appetite, oral mucositis, and anemia. No treatment‐related AEs graded 3 or more.

Conclusion

Anlotinib is an effective option for SCLC patients with tolerable toxicity as second or later line treatment. Patients sensitive to first‐line treatment had longer PFS when treated with anlotinib. Anloitnib combined with other therapy increased the efficacy without adding toxicity.
Challenges to identity integration amongst sexual minority British Muslim South Asian men
Authors: Mitha Karim , Ali Sheila , Koc Yasin
Published: May 2021

Since the Stonewall uprisings, there has been greater social acceptance of homosexuality within Western contexts. Nevertheless, those who are at the intersection of more than one minority identity continue to face prejudice and discrimination, including homophobia and racism. Though there has been increasing work regarding the experiences of sexual minority people of colour (POC), a lacuna remains regarding the experiences of sexual minority British Muslim South Asian men and the integration of sexual minority and religious identities, particularly within a context of increased societal acceptance towards sexual minorities and societal Islamophobia. In this study, 38 sexual minority British Muslim South Asian men were recruited via snowball sampling and interviewed. Data were examined via reflexive thematic analysis. Five themes were identified: degrees of “outness”, hegemonic Whiteness and the LGBTQ+ community, internalisation of White hegemony, distancing from the sexual minority religio‐cultural ingroup, and attempting to reconcile potential identity conflict between sexual orientation identity and religious and cultural identities. Respondents' experiences highlighted substantial social exclusion due to intersectional disadvantage as well as a lack of intra‐community social support, suggesting substantial isolation, psychological implications and a general eschewing of identity affiliation based on sexual attraction. This has implications on services predicated on identity affiliation which may potentially exclude the needs of hidden and intersectionally disadvantaged populations.
Bosutinib‐associated interstitial lung disease and pleural effusion: A case report and literature review
Authors: Liu Qiuying (Selina) , Ass'ad Nour Ali , Arana Yi Cecilia
Published: May 2021

Bosutinib is a tyrosine kinase inhibitor approved for the management of chronic myeloid leukemia (CML). Interstitial lung disease and pleural effusion are pulmonary side effects of TKIs rarely associated with bosutinib treatment.
Transcatheter management of adult aortic coarctation with “Railway” technique
Authors: Yuan Xun , Mitsis Andreas , Rigby Michael , Nienaber Christoph A.
Published: May 2021

Endografting for atretic coarctation is technically feasible to avoid the risks of open surgery. It requires a strategic and structured endovascular approach such as the “Railway” technique for safe and successful restructuring of complete aortic atresia and avoiding rupture or bleeding.
An enlarging neck mass with dyspnea and left finger pain in a 63‐year‐old woman
Authors: Hoang Thanh D. , Snitchler Andrea N. , Shakir Mohamed K.M.
Published: May 2021

We described a rare presentation of papillary thyroid cancer metastasized to left finger. This case highlights the importance of an early and effective engagement of multidisciplinary team approach to optimize patient care and that papillary thyroid cancer can occasionally pursue an aggressive, lethal course.
Minimally invasive mitral valve repair and ablation of concomitant atrial fibrillation in a patient with severe hemophilia A
Authors: Bogachev‐Prokophiev Alexander , Sharifulin Ravil , Karadzha Anastasiia , Larionova Natalya , Shmyrev Vladimir , Kornilov Igor , Mamaev Andrey , Afanasyev Alexander , Pivkin Alexey
Published: May 2021

Minimally invasive mitral valve repair and ablation of atrial fibrillation, combined with FVIII level‐controlled replacement therapy, can be safely performed in patients with severe hemophilia.
Neurobrucellosis: A differential not to be missed in patients presenting with neuropsychiatric features
Authors: Nepal Gaurav , Balayar Ramesh , Bhatta Suraj , Acharya Sulav , Gajurel Bikram Prasad , Karn Ragesh , Rajbhandari Reema , Paudel Sunanda , Gautam Niraj , Shrestha Ashish , Ojha Rajeev
Published: May 2021

When a patient presents with undulating fever and neuropsychiatric features, neurobrucellosis should be considered as a differential diagnosis. If diagnosed early, neurobrucellosis is a treatable disease with a favorable outcome.
Thermodynamic Assessment of Chemical Equilibrium for the Synthesis of Solketal in the Liquid Phase
Authors: Perez Federico M. , Nichio Nora , Pompeo Francisco
Published: May 2021

The synthesis of solketal is one of the innovative routes of glycerol valorization to value‐added products, and the simulation of the process requires the knowledge of thermodynamic properties that are not still available in the literature. In this work, the specific heat capacity as a function of temperature and the enthalpy and entropy of formation of all compounds involved in the reaction were calculated by employing a second‐order group‐additivity method. Expressions for the enthalpy of reaction and equilibrium constant as a function of temperature were also obtained. The glycerol conversion at equilibrium was calculated at different temperatures, pressures, acetone/glycerol molar ratios, and initial water contents, considering the nonideality of the liquid phase.
Mechanistic Study of the Activation and the Electrocatalytic Reduction of Hydrogen Peroxide by Cu‐tmpa in Neutral Aqueous Solution
Authors: Langerman Michiel , Hetterscheid Dennis G. H.
Published: May 2021

Hydrogen peroxide plays an important role as an intermediate and product in the reduction of dioxygen by copper enzymes and mononuclear copper complexes. The copper(II) tris(2‐pyridylmethyl)amine complex (Cu‐tmpa) has been shown to produce H2O2 as an intermediate during the electrochemical 4‐electron reduction of O2. We investigated the electrochemical hydrogen peroxide reduction reaction (HPRR) by Cu‐tmpa in a neutral aqueous solution. The catalytic rate constant of the reaction was shown to be one order of magnitude lower than the reduction of dioxygen. A significant solvent kinetic isotope effect (KIE) of 1.4 to 1.7 was determined for the reduction of H2O2, pointing to a Fenton‐like reaction pathway as the likely catalytic mechanism, involving a single copper site that produces an intermediate copper(II) hydroxo species and a free hydroxyl radical anion in the process.
Machine learning in prediction of intrinsic aqueous solubility of drug‐like compounds: Generalization, complexity, or predictive ability?
Authors: Lovrić Mario , Pavlović Kristina , Žuvela Petar , Spataru Adrian , Lučić Bono , Kern Roman , Wong Ming Wah
Published: May 2021

We present a collection of publicly available intrinsic aqueous solubility data of 829 drug‐like compounds. Four different machine learning algorithms (random forests [RF], LightGBM, partial least squares, and least absolute shrinkage and selection operator [LASSO]) coupled with multistage permutation importance for feature selection and Bayesian hyperparameter optimization were used for the prediction of solubility based on chemical structural information. Our results show that LASSO yielded the best predictive ability on an external test set with a root mean square error (RMSE) (test) of 0.70 log points, anR2(test) of 0.80, and 105 features. Taking into account the number of descriptors as well, an RF model achieves the best balance between complexity and predictive ability with an RMSE(test) of 0.72 log points, anR2(test) of 0.78, and with only 17 features. On a more aggressive test set (principal component analysis [PCA]‐based split), better generalization was observed for the RF model. We propose a ranking score for choosing the best model, as test set performance is only one of the factors in creating an applicable model. The ranking score is a weighted combination of generalization, number of features, and test performance. Out of the two best learners, a consensus model was built exhibiting the best predictive ability and generalization with RMSE(test) of 0.67 log points and aR2(test) of 0.81.
A review of halide charge carriers for rocking‐chair and dual‐ion batteries
Authors: Sandstrom Sean K. , Chen Xin , Ji Xiulei
Published: May 2021

This review discusses how halide ion species have been used as charge carriers in both anion rocking‐chair and dual‐ion battery (DIB) systems. The anion rocking‐chair batteries based on fluoride and chloride have emerged over the past decade and are garnering increased research interest due to their large theoretical energy density values and the natural abundance of halide‐containing materials. Moreover, DIBs that use halide species as their anionic charge carrier are seen as one of the promising next‐generation battery technologies due to their low cost and high working potentials. Although numerous polyatomic anions have been studied as charge carriers, the use of single halide ions (i.e., F− and Cl−) and metal‐based superhalides (e.g., [MgCl3]−) as anionic charge carriers in DIBs has been considerably less explored. Herein, we provide an overview of some of the key advances and recent progress that has been made with regard to halide ion charge carriers in electrochemical energy storage. We offer our perspectives on the current state of the field and provide a roadmap in hopes that it helps researchers toward making new advances in these promising and emerging areas.
Malignant transformation of salivary gland pleomorphic adenoma: proof of principle
Authors: Valstar Matthijs H , Mast Hetty , ten Hove Ivo , Moonen Laura R , Balm Alfons JM , Smeele Ludi E , Koljenović Senada , Dinjens Winand NM , van Velthuysen Marie‐Louise F
Published: May 2021

Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for aggressive retreatment in recurrent pleomorphic adenoma (RPA). However, although the diagnostic category ‘carcinoma ex‐pleomorphic adenoma’ suggests that malignant transformation of a pleomorphic adenoma is a regular event, this has to date not been shown to occur in sequential lesions of one patient. Here, we show the molecular events in transformation to malignancy of a pleomorphic adenoma of the parotid gland. Detailed molecular analysis revealed an LIFR/PLAG1 translocation characteristic for pleomorphic adenoma and, next to this, a PIK3R1 frameshift mutation and several allelic imbalances. In subsequent malignant recurrences, the same LIFR/PLAG1 translocation, PIK3R1 frameshift mutation, and allelic imbalances were present in addition to TP53 mutations. Thus, this case not only shows malignant transformation of SGPA, but also demonstrates that molecular analysis can be of help in recognising malignancy in the rare instance of RPA.
H5P videos in chemical didactics
Authors: Zeller Diana , Gökkuş Yasemin , Kremer Richard , Bohrmann‐Linde Claudia
Published: May 2021

Über den bloßen Einsatz von dokumentierenden und intellektuell inspirierenden Videos in Lehr‐/Lernsettings hinaus bietet die Software H5P die Möglichkeit, zielgruppengerecht durch Integration weiterer Elemente eine interaktive Auseinandersetzung mit Videos zu initiieren. In diesem Beitrag sollen einerseits grundlegende Informationen zu H5P sowie der Einsatz bzw. die Produktion von H5P‐Videos in der chemiedidaktischen Lehre vorgestellt werden.
Perceived risk profile and treatment optimization in heart failure: an analysis from BIOlogy Study to TAilored Treatment in chronic heart failure
Authors: Kobayashi Masatake , Voors Adriaan A. , Ouwerkerk Wouter , Duarte Kevin , Girerd Nicolas , Rossignol Patrick , Metra Marco , Lang Chim C. , Ng Leong L. , Filippatos Gerasimos , Dickstein Kenneth , van Veldhuisen Dirk J. , Zannad Faiez , Ferreira João Pedro
Published: May 2021

Background

Achieving target doses of angiotensin‐converting‐enzyme inhibitor/angiotensin‐receptor blockers (ACEi/ARB) and beta‐blockers in heart failure with reduced ejection fraction (HFrEF) is often underperformed. In BIOlogy Study to TAilored Treatment in chronic heart failure (BIOSTAT‐CHF) study, many patients were not up‐titrated for which no clear reason was reported. Therefore, we hypothesized that perceived‐risk profile might influence treatment optimization.

Methods

We studied 2100 patients with HFrEF (LVEF≤40%) to compare the clinical characteristics and adverse events associated with treatment up‐titration (after a 3‐month titration protocol) between; a) patients not reaching target doses for unclear reason; b) patients not reaching target doses due to symptoms and/or side effects; c) patients reaching target doses.

Results

For ACEi/ARB, (a), (b) and (c) was observed in 51.3%, 25.9% and 22.7% of patients, respectively. For beta‐blockers, (a), (b) and (c) was observed in 67.5%, 20.2% and 12.3% of patients, respectively. By multinomial logistic regression analysis for ACEi/ARB, patients in group (a) and (b) had lower blood pressure and poorer renal function, and patients in group (a) were older and had lower ejection fraction. For beta‐blockers, patients in group (a) and (b) had more severe congestion and lower heart rate. At 9 months, adverse events (i.e., hypotension, bradycardia, renal impairment, and hyperkalemia) occurred similarly among the three groups.

Conclusions

Patients in whom clinicians did not give a reason why up‐titration was missed were older and had more co‐morbidities. Patients in whom up‐titration was achieved did not have excess adverse events. However, from these observational findings, the pattern of subsequent adverse events among patients in whom up‐titration was missed cannot be determined.
Characteristics of central nervous system progression in non‐small cell lung cancer treated with crizotinib or alectinib
Authors: Sakamoto Hiroaki , Yanagitani Noriko , Manabe Ryo , Tsugitomi Ryosuke , Ogusu Shinsuke , Tozuka Takehiro , Yoshida Hiroshi , Amino Yoshiaki , Ariyasu Ryo , Uchibori Ken , Kitazono Satoru , Tasaka Sadatomo , Nishio Makoto
Published: May 2021

Background

Most patients treated with anaplastic lymphoma kinase (ALK)‐tyrosine kinase inhibitors for ALK‐positive non‐small cell lung cancer (NSCLC) develop resistance, leading to metastasis, with progression to the central nervous system (CNS) being a primary concern. Although alectinib has better CNS penetration than crizotinib, patients treated with alectinib also develop CNS progression. CNS metastases more likely occurs during crizotinib treatment due to less blood‐brain barrier (BBB) penetration capability than alectinib. CNS progression pattern may be different during crizotinib and alecitinib treatment. Understanding the characteristics of CNS progression is important for developing treatment strategies.

Aims

We compared the clinical‐radiographic characteristics of CNS metastases among patients undergoing crizotinib and alectinib treatment for ALK‐positive NSCLCs.

Methods and results

We retrospectively analyzed the radiographic and clinical characteristics of CNS progression in ALK‐positive NSCLC patients treated with crizotinib or alectinib at our hospital between July 2011 and May 2020. CNS and systemic tumor progression were evaluated using computed tomography or magnetic resonance imaging. Fifty‐three and 65 patients were treated with crizotinib and alectinib, respectively. Baseline CNS metastasis was observed in 18 and 27 patients in the crizotinib and alectinib groups, respectively. Among the patients in the crizotinib and alectinib groups who developed disease progression, 15/49 (30.6%) and 9/44 (20.5%) had CNS progression, respectively (P = .344). Intra‐CNS progression‐free survival was significantly longer in the alectinib group than in the crizotinib group (median: 14.0 vs 5.6 months, P = .042). The number of CNS metastases sized ≥3 cm, rate of peritumoral brain edema, and the second progression pattern after treatment continuation was not significantly different between the groups.

Conclusion

We observed no significant difference in the clinical‐radiographic characteristics of CNS progression between patients undergoing crizotinib and alectinib treatments. Local therapy, including stereotactic radiosurgery, for CNS progression may be suitable and important following alectinib and crizotinib treatment.
Preliminary study on the automatic parallelism optimization model for image enhancement algorithms based on Intel's® Xeon Phi
Authors: Huang Fang , Yang Hao , Tao Jian , Wang Jian , Tan Xicheng
Published: May 2021

In unmanned aerial vehicle (UAV) image‐processing applications, one needs to implement different parallel image‐enhancement algorithms on several high‐performance computing platforms utilizing various programming models. To speed up the parallelization procedure and improve its efficiency, the automatic parallel software package, Par4All, is applied in this work. We find that the performance of the original automatic parallelization algorithm produced with Par4All is inefficient. To resolve this problem, we propose different optimization approaches for Par4All based on Intel®'s Xeon Phi high‐performance computing platform that are based on the structural features of the image‐enhancement algorithms, which can further optimize the original parallel algorithm. These approaches mainly include: (1) Par4All automatic parallel search module optimization, (2) dynamic thread setting optimization, and (3) the collaborative parallelization of both CPU and many integrated core (MIC) processors. According to the results of the comparison experiments involving different algorithms, it is shown that the proposed optimization approaches for these kinds of algorithms can significantly improve the performance of automatic parallel algorithms. The acceleration ratio increases approximately by 30%, 70%, and 80% for the multiscale Retinex, Gaussian‐filtering and median‐filtering algorithms, respectively. As continuation and deepening of our previous research work, this research has the potential to be beneficial for other researchers in image‐processing applications with image‐enhancement algorithms.
Highly Accurate Thickness Determination of 2D Materials
Authors: Xiao Yiping , Zheng Wenwen , Yuan Bin , Wen Chao , Lanza Mario
Published: May 2021

Determining the thickness of two‐dimensional (2D) materials accurately and reliably is highly necessary for multiple investigations, but at the same time it can be quite complex. Most studies in this field measure a topographic map at the edge of the 2D material using an atomic force microscope (AFM), and plot a single‐line cross‐section using the software of the AFM. However, this method is highly inaccurate and can result in high relative errors due to surface roughness and line‐to‐line variability. This is even more important in ultrathin (<4 nm) 2D materials grown by chemical vapor deposition, as these exhibit a larger surface roughness (compared to mechanically exfoliated) due to the high density of local defects. Here it is shown that the thickness of ultrathin 2D materials can be determined statistically with high accuracy and reliability in a very easy way by plotting the histogram height plot. Using this method should enhance the reliability of investigations and research papers in the field of 2D materials.
Influence of low tumor content on tumor mutational burden estimation by whole‐exome sequencing and targeted panel sequencing
Authors: Zhang Wenxin , Wang Ruixia , Fang Huan , Ma Xiangyuan , Li Dan , Liu Tao , Chen Zhenxi , Wang Ke , Hao Shiguang , Yu Zicheng , Chang Zhili , Na Chenglong , Wang Yin , Bai Jian , Zhang Yanyan , Chen Fang , Li Miao , Chen Chao , Wei Liangshen , Li Jinghua , Chang Xiaoyan , Qu Shoufang , Yang Ling , Huang Jie
Published: May 2021

Background

Tumor mutational burden (TMB) is a promising biomarker for stratifying patient subpopulation who would benefit from immune checkpoint blockade (ICB) therapies. Although great efforts have been made for standardizing TMB measurement, mutation calling and TMB quantification can be challenging in samples with low tumor content including liquid biopsies. The effect of varying tumor content on TMB estimation by different assay methods has never been systematically investigated.

Method

We established a series of reference standard DNA samples derived from 11 pairs of tumor–normal matched human cell lines across different cancer types. Each tumor cell line was mixed with its matched normal at 0% (control), 1%, 2%, 5%, and 10% mass‐to‐mass ratio to mimic the clinical samples with low tumor content. TMB of these reference standards was evaluated by both ∼1000× whole‐exome sequencing (wesTMB) and targeted panel sequencing (psTMB) at four different vendors. Both regression and classification analyses of TMB were performed for theoretical investigation and clinical practice purposes.

Results

Linear regression model was established that demonstrated in silico psTMB determined by regions of interest (ROI) as a great representative of wesTMB based on TCGA dataset. It was also true in our reference standard samples as the predicted psTMB interval based on the observed wesTMB captured the intended 90% of the in silico psTMB values. Although ∼1000× deep WES was applied, reference standard samples with less than 5% of tumor proportions are below the assay limit of detection (LoD) of wesTMB quantification. However, predicted wesTMB based on observed psTMB accurately classify (>0.97 AUC) for TMB high and low patient stratification even in samples with 2% of tumor content, which is more clinically relevant, as TMB determination should be a qualitative assay for TMB high and low patient classification. One targeted panel sequencing vendor using an optimized blood psTMB pipeline can further classify TMB status accurately (>0.82 AUC) in samples with only 1% of tumor content.

Conclusions

We developed a linear model to establish the quantitative correlation between wesTMB and psTMB. A set of DNA reference standards was produced in aid to standardize TMB measurements in samples with low tumor content across different targeted sequencing panels. This study is a significant contribution aiming to harmonize TMB estimation and extend its future application in clinical samples with low tumor content including liquid biopsy.
Psychological and eating disorder symptoms as predictors of starting eating disorder treatment
Authors: Martin‐Wagar Caitlin A. , Boswell Rebecca G. , Bennett Brooke L. , Perelman Hayley , Forrest Lauren N.
Published: May 2021

Objective

Little is known about the treatment uptake rate for adults diagnosed with an eating disorder through formal assessment. This study aimed to identify psychological and eating disorder symptoms that predict whether individuals with diagnosed eating disorders start treatment after receiving a diagnostic assessment and recommendation to begin treatment. Identifying barriers to starting treatment can inform interventions to improve the uptake of treatment.

Method

After a diagnostic assessment at an eating disorder specialty clinic, 223 adults were recommended to begin treatment and completed self‐report measures of psychological functioning, clinical impairment, and eating psychopathology. Patient attendance was assessed to determine rates and predictors of starting treatment within 3 months of the assessment.

Results

Of the 223 patients recommended to begin treatment, approximately two‐third started treatment within 3 months of the assessment. Logistic regression identified greater avoidance of eating, greater laxative use frequency, more social eating concerns, and lower weight dissatisfaction as predicting lower likelihood of beginning treatment after assessment. A chi‐square test for independence found no significant differences between diagnostic groups on starting treatment.

Discussion

Findings identify eating disorder symptoms that predict treatment enrollment after diagnostic assessment and recommendation to begin treatment. Assessing for these symptoms at the diagnostic assessment stage is recommended to address potential treatment barriers. Future research should identify strategies that increase treatment uptake at this stage of the process.
Population dynamics of little brown bats (Myotis lucifugus) at summer roosts: Apparent survival, fidelity, abundance, and the influence of winter conditions
Authors: Schorr Robert A. , Siemers Jeremy L.
Published: May 2021

White‐nose syndrome (WNS) has caused the death of millions of bats, but the impacts have been more difficult to identify in western North America. Understanding how WNS, or other threats, impacts western bats may require monitoring other roosts, such as maternity roosts and night roosts, where bats aggregate in large numbers.

Little brown bats (Myotis lucifugus) are experiencing some of the greatest declines from WNS. Estimating survival and understanding population dynamics can provide valuable data for assessing population declines and informing conservation efforts.

We conducted a 5‐year mark–recapture study of two M. lucifugus roosts in Colorado. We used the robust design model to estimate apparent survival, fidelity, and abundance to understand population dynamics, and environmental covariates to understand how summer and winter weather conditions impact adult female survival. We compared the fidelity and capture probability of M. lucifugus between colonies to understand how bats use such roosts.

Overwinter survival increased with the number of days with temperatures below freezing (β > 0.100, SE = 0.003) and decreased with the number of days with snow cover (β < −0.40, SE < 0.13). Adult female fidelity was higher at one maternity roost than the other. Overwinter and oversummer adult female survival was high (>0.90), and based on survival estimates and fungal‐swabbing results, we believe these populations have yet to experience WNS.

Recapture of M. lucifugus using antennas that continuously read passive integrated transponder tags allows rigorous estimation of bat population parameters that can elucidate trends in abundance and changes in survival. Monitoring populations at summer roosts can provide unique population ecology data that monitoring hibernacula alone may not. Because few adult males are captured at maternity colonies, and juvenile males have low fidelity, additional effort should focus on understanding male M. lucifugus population dynamics.
Comparative plastome analysis of Blumea, with implications for genome evolution and phylogeny of Asteroideae
Authors: Abdullah  , Mehmood Furrukh , Rahim Abdur , Heidari Parviz , Ahmed Ibrar , Poczai Péter
Published: May 2021

The genus Blumea (Asteroideae, Asteraceae) comprises about 100 species, including herbs, shrubs, and small trees. Previous studies have been unable to resolve taxonomic issues and the phylogeny of the genus Blumea due to the low polymorphism of molecular markers. Therefore, suitable polymorphic regions need to be identified. Here, we de novo assembled plastomes of the three Blumea species B. oxyodonta, B. tenella, and B. balsamifera and compared them with 26 other species of Asteroideae after correction of annotations. These species have quadripartite plastomes with similar gene content, genome organization, and inverted repeat contraction and expansion comprising 113 genes, including 80 protein‐coding, 29 transfer RNA, and 4 ribosomal RNA genes. The comparative analysis of codon usage, amino acid frequency, microsatellite repeats, oligonucleotide repeats, and transition and transversion substitutions has revealed high resemblance among the newly assembled species of Blumea. We identified 10 highly polymorphic regions with nucleotide diversity above 0.02, including rps16‐trnQ, ycf1, ndhF‐rpl32, petN‐psbM, and rpl32‐trnL, and they may be suitable for the development of robust, authentic, and cost‐effective markers for barcoding and inference of the phylogeny of the genus Blumea. Among these highly polymorphic regions, five regions also co‐occurred with oligonucleotide repeats and support use of repeats as a proxy for the identification of polymorphic loci. The phylogenetic analysis revealed a close relationship between Blumea and Pluchea within the tribe Inuleae. At tribe level, our phylogeny supports a sister relationship between Astereae and Anthemideae rooted as Gnaphalieae, Calenduleae, and Senecioneae. These results are contradictory to recent studies which reported a sister relationship between “Senecioneae and Anthemideae” and “Astereae and Gnaphalieae” or a sister relationship between Astereae and Gnaphalieae rooted as Calenduleae, Anthemideae, and then Senecioneae using nuclear genome sequences. The conflicting phylogenetic signals observed at the tribal level between plastidt and nuclear genome data require further investigation.
How does eDNA decay affect metabarcoding experiments?
Authors: Holman Luke E. , Chng Yi , Rius Marc
Published: May 2021

The detection of species using environmental DNA (eDNA) relies on our capacity to identify DNA from the sampled environment. Once eDNA is released into the environment, the physical degradation of individual eDNA molecules over time directly affects our ability to detect species (eDNA decay). Therefore, interpreting eDNA data requires an explicit understanding of eDNA decay to accurately infer contemporary presence or absence of a given species in the study ecosystem. Most research to date on eDNA decay has focused on single‐species assays (predominantly quantitative PCR), and thus little is known on how eDNA decay affects the interpretation of metabarcoding datasets. Here, we used eDNA metabarcoding (targeting a section of the eukaryotic cytochrome c oxidase subunit I gene) of water samples from controlled tanks to examine eDNA decay in a wide variety of marine metazoan species. After the stocked organisms were removed from these tanks, we observed a sharp decrease in amplicon sequence variant (ASV) richness within the first 48 hours. Furthermore, there was a substantial change in beta diversity between 24 and 48 hours, and after 48 hours, most stocked species became undetectable. Interestingly, the estimated decay rate for each study species, calculated using a linear regression of reads over time, differed across organisms, with up to 2–3‐fold difference among species. Our results showed that, for marine temperate species, the most substantial change in eDNA metabarcoding detectability occurred within the first 48 h, and after that, eDNA from several taxa became undetectable. These findings inform the ecological interpretation of metabarcoding datasets and provide estimates of eDNA decay rate that are valuable for both simulation studies and the design of future ecological surveys.
Design and rationale of the EMPA‐VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure
Authors: Hundertmark Moritz J. , Agbaje Olorunsola F. , Coleman Ruth , George Jyothis T. , Grempler Rolf , Holman Rury R. , Lamlum Hanan , Lee Jisoo , Milton Joanne E. , Niessen Heiko G. , Rider Oliver , Rodgers Christopher T. , Valkovič Ladislav , Wicks Eleanor , Mahmod Masliza , Neubauer Stefan
Published: May 2021

Aims

Despite substantial improvements over the last three decades, heart failure (HF) remains associated with a poor prognosis. The sodium‐glucose co‐transporter‐2 inhibitor empagliflozin demonstrated significant reductions of HF hospitalization in patients with HF independent of the presence or absence of type 2 diabetes mellitus in the EMPEROR‐Reduced trial and cardiovascular mortality in the EMPA‐REG OUTCOME trial. To further elucidate the mechanisms behind these positive outcomes, this study aims to determine the effects of empagliflozin treatment on cardiac energy metabolism and physiology using magnetic resonance spectroscopy (MRS) and cardiovascular magnetic resonance (CMR).

Methods and results

The EMPA‐VISION trial is a double‐blind, randomized, placebo‐controlled, mechanistic study. A maximum of 86 patients with HF with reduced ejection fraction (n = 43, Cohort A) or preserved ejection fraction (n = 43, Cohort B), with or without type 2 diabetes mellitus, will be enrolled. Participants will be randomized 1:1 to receive either 10 mg of empagliflozin or placebo for 12 weeks. Eligible patients will undergo cardiovascular magnetic resonance, resting and dobutamine stress MRS, echocardiograms, cardiopulmonary exercise tests, serum metabolomics, and quality of life questionnaires at baseline and after 12 weeks. The primary endpoint will be the change in resting phosphocreatine‐to‐adenosine triphosphate ratio, as measured by 31Phosphorus‐MRS.

Conclusions

EMPA‐VISION is the first clinical trial assessing the effects of empagliflozin treatment on cardiac energy metabolism in human subjects in vivo. The results will shed light on the mechanistic action of empagliflozin in patients with HF and help to explain the results of the safety and efficacy outcome trials (EMPEROR‐Reduced and EMPEROR‐Preserved).
c‐Rel employs multiple mechanisms to promote the thymic development and peripheral function of regulatory T cells in mice
Authors: Fulford Thomas S. , Grumont Raelene , Wirasinha Rushika C. , Ellis Darcy , Barugahare Adele , Turner Stephen J. , Naeem Haroon , Powell David , Lyons Paul A. , Smith Kenneth G. C. , Scheer Sebastian , Zaph Colby , Klein Ulf , Daley Stephen R. , Gerondakis Steve
Published: May 2021

The NF‐κB transcription factor c‐Rel is a critical regulator of Treg ontogeny, controlling multiple points of the stepwise developmental pathway. Here, we found that the thymic Treg defect in c‐Rel‐deficient (cRel–/–) mice is quantitative, not qualitative, based on analyses of TCR repertoire and TCR signaling strength. However, these parameters are altered in the thymic Treg‐precursor population, which is also markedly diminished in cRel–/– mice. Moreover, c‐Rel governs the transcriptional programme of both thymic and peripheral Tregs, controlling a core of genes involved with immune signaling, and separately in the periphery, cell cycle progression. Last, the immune suppressive function of peripheral cRel–/– tTregs is diminished in a lymphopenic model of T cell proliferation and is associated with decreased stability of Foxp3 expression. Collectively, we show that c‐Rel is a transcriptional regulator that controls multiple aspects of Treg development, differentiation, and function via distinct mechanisms.
Sensitive and Low‐background Electrochemical Immunosensor Employing Glucose Dehydrogenase and 1,10‐Phenanthroline‐5,6‐dione
Authors: Jiaul Haque Al‐Monsur , Kwon Jungwook , Kim Jihyeon , Kim Gyeongho , Lee Nam‐Sihk , Ho Yoon Young , Yang Haesik
Published: May 2021

We report a sensitive electrochemical immunosensor with a low electrochemical background level, which results from electrochemical‐enzymatic (EN) redox cycling based on mediated electrochemical oxidation of an electro‐inactive reductant (glucose) at 0.0 V. The EN redox cycling employs flavin adenine dinucleotide‐dependent glucose dehydrogenase and 1,10‐phenanthroline‐5,6‐dione (PD). When PD was compared with five common quinone‐based electron mediators, PD enabled the highest signal‐to‐background ratio, due to a very low electrochemical background level. When EN redox cycling was applied to a sandwich‐type immunosensor, parathyroid hormone (PTH) in serum could be detected with a very low detection limit of ∼0.1 pg/mL.
Native and substituted cyclodextrins as chiral selectors for capillary electrophoresis enantioseparations: Structures, features, application, and molecular modeling
Authors: Peluso Paola , Chankvetadze Bezhan
Published: May 2021

CDs are cyclic oligosaccharides consisting of α‐d‐glucopyranosyl units linked through 1,4‐linkages, which are obtained from enzymatic degradation of starch. The coexistence of hydrophilic and hydrophobic regions in the same structure makes these macrocycles extremely versatile as complexing host with application in food, cosmetics, environmental, agriculture, textile, pharmaceutical, and chemical industries. Due to their inherent chirality, CDs have been also successfully used as chiral selectors in enantioseparation science, in particular, for CE enantioseparations. In the last decades, multidisciplinary approaches based on CE, NMR spectroscopy, X‐ray crystallography, microcalorimetry, and molecular modeling have shed light on some aspects of recognition mechanisms underlying enantiodiscrimination. With the ever growing improvement of computer facilities, hardware and software, computational techniques have become a useful tool to model at molecular level the dynamics of diastereomeric associate formation to sample low‐energy conformations, the binding energies between the enantiomer and the CD, and to profile noncovalent interactions contributing to the stability of CD/enantiomer association. On this basis, the aim of this review is to provide the reader with a critical overview on the applications of CDs in CE. In particular, the contemporary theory of the electrophoretic technique and the main structural features of CDs are described, with a specific focus on techniques, methods, and approaches to model CE enantioseparations promoted by native and substituted CDs. A systematic compilation of all published literature has not been attempted.
Production of biolubricant samples from palm kernel oil using different chemical modification approaches
Authors: Egbuna Samuel O. , Nwachukwu Ukeh J. , Agu Chinedu M. , Asadu Christain O. , Okolo Bernard
Published: May 2021

This work focused on the chemical synthesis and characterization of palm kernel oil (PKO) for biolubricant production using transesterification of palm kernel methyl ester with trimethylolpropane (TMP) and epoxidation‐esterification methods. The PKO was extracted using solvent extraction method. The physicochemical characteristics of the PKO and produced biolubricant samples were determined using standard methods. Fourier transform infrared (FTIR) spectrometry and gas chromatographic (GC) analyses were used to determine the predominant functional groups and fatty acids of PKO and the produced biolubricant samples, respectively. The kernel oil yield of 49.82% (by weight) was obtained at 55°C, 150 min and 0.5 mm particle size. The viscosities at 40°C, 100°C, viscosity index, pour and flash points of the biolubricants produced by transesterification with TMP (PKBLT) and epoxidation‐esterification (PKBLE) methods, were (42.53 cSt, 10.65 cSt, 139, −11°C, 235°C) and (44.69 cSt, 11.42 cSt, 132, −12°C, 240°C), respectively. Time, mole ratio, and temperature effects were the main factors that significantly influenced the transesterification and epoxidation processes. The obtained physicochemical properties of PKBLE and PKBLT samples showed conformity with ISO VG 32 standard, hence their possible application as biolubricant basestock. Furthermore, the presences of the C–H, OH functional groups in the FTIR results, indicate the biodegradability of the produced biolubricant samples; while the GC analyses indicate that the samples were mainly saturated fatty acids.
Spatiotemporal clustering using Gaussian processes embedded in a mixture model
Authors: Vanhatalo Jarno , Foster Scott D. , Hosack Geoffrey R.
Published: May 2021

The categorization of multidimensional data into clusters is a common task in statistics. Many applications of clustering, including the majority of tasks in ecology, use data that is inherently spatial and is often also temporal. However, spatiotemporal dependence is typically ignored when clustering multivariate data. We present a finite mixture model for spatial and spatiotemporal clustering that incorporates spatial and spatiotemporal autocorrelation by including appropriate Gaussian processes (GP) into a model for the mixing proportions. We also allow for flexible and semiparametric dependence on environmental covariates, once again using GPs. We propose to use Bayesian inference through three tiers of approximate methods: a Laplace approximation that allows efficient analysis of large datasets, and both partial and full Markov chain Monte Carlo (MCMC) approaches that improve accuracy at the cost of increased computational time. Comparison of the methods shows that the Laplace approximation is a useful alternative to the MCMC methods. A decadal analysis of 253 species of teleost fish from 854 samples collected along the biodiverse northwestern continental shelf of Australia between 1986 and 1997 shows the added clarity provided by accounting for spatial autocorrelation. For these data, the temporal dependence is comparatively small, which is an important finding given the changing human pressures over this time.
Dynamic malware attack dataset leveraging virtual machine monitor audit data for the detection of intrusions in cloud
Authors: Melvin A. Alfred Raja , Kathrine G. Jaspher W. , Ilango S. Sudhakar , Vimal S. , Rho Seungmin , Xiong Neal N. , Nam Yunyoung
Published: May 2021

In this new era of cloud computing, Intrusion Detection System (IDS) is very essential for the continual monitoring of computing resources for signs of compromise since the number of attack vectors and malware are in increase. Only few IDS datasets are publicly available and those available are outdated, lack cloud‐specific attacks. This article presents a novel dataset based on Virtual Machine Introspected data for the implementation of IDS in cloud. The dataset was generated from the behavioral characteristics of malware and benign sample execution traces on virtual machines using Virtual Machine Introspection (VMI) technique. A vector space model based on system call approach is applied to analyze the behavioral characteristics for the generation of proposed dataset. The purpose of this study is to compare the proposed dataset with existing datasets and evaluate the effectiveness of these datasets by applying Machine Learning (ML) algorithms with 10‐fold cross‐validation. The ML algorithms used in the experiments are C4.5, Random Forest, JRip, NaiveBayes, K‐Nearest Neighbors (KNN), and Support Vector Machine (SVM). The effectiveness of detecting intrusions using proposed dataset is promising compared with other datasets in‐terms of intrusion detection accuracy, recall value, precision, and F1‐score metrics. For example, the intrusion detection accuracy in proposed dataset is 0.11% improved than UNM dataset, 6.28% higher than ADFA dataset, and 1.88% higher than LID dataset with C4.5 algorithm. Therefore, the proposed dataset is best suitable for implementing IDS for cloud.
Effects of structural changes on the prediction of downside volatility in futures markets
Authors: Gong Xu , Lin Boqiang
Published: May 2021

We develop a heterogeneous autoregressive model of downside volatility (HAR‐DV) model with structural changes (HAR‐DV‐SC) model to investigate the effects of structural changes on predicting downside volatility. Then we employ HAR‐DV and HAR‐DV‐SC models to forecast downside volatilities in S&P 500 index, crude oil, gold, copper, and soybean futures markets. The in‐sample analysis shows that structural changes contain in‐sample information for predicting downside volatility. The out‐of‐sample analysis indicates that the HAR‐DV‐SC model outperforms the HAR‐DV model, suggesting that structural changes contain incremental out‐of‐sample information on future downside volatility. These results are robust and have important implications for risk management of stakeholders.
Portfolio of Volatility Smiles versus Volatility Surface: Implications for pricing and hedging options
Authors: Kim Sol
Published: May 2021

In this study, we compare the pricing and hedging performance of options‐pricing models using two parameter‐estimation methods to employ cross‐sectional options data with multiple maturities. In the Portfolio of Volatility Smiles method, each set of parameters that describe the individual volatility smile for each maturity is estimated separately. In the Volatility Surface method, a single‐parameter set that describes the entire volatility surface is estimated, regardless of the time‐to‐maturity. When pricing and hedging options with various times to maturity, the Portfolio of Volatility Smiles method generally outperforms the Volatility Surface method, irrespective of the option‐pricing model used, maturity, and moneyness. Considering the volatility smile individually at each maturity is more effective in pricing and hedging options than is considering the volatility surface simultaneously.
The Spatiotemporal Dynamics of Land Use Land Cover Change, and Its Impact on Soil Erosion in Tagaw Watershed, Blue Nile Basin, Ethiopia
Authors: Melese Tadele , Senamaw Abebe , Belay Tatek , Bayable Getachew
Published: May 2021

The Blue Nile basin is one of the hot‐spots of soil erosion areas in Ethiopia. However, the impact of land use changes on soil erosion is poorly understood in the Tagaw watershed. Hence, the objective of the study is to assess the impact of land use changes on soil erosion in Tagaw watershed over the last 31 years. Rainfall, soil, satellite images and topographic data are acquired from field survey and secondary sources. A Revised Universal Soil Loss Equation (RUSLE) model is used to estimate soil erosion. The mean annual and total potential soil losses of the watershed are 19.3, 22.9, 26 and 0.06–503.56, 0.11–516.67, and 0.00–543.5 tons ha−1 yr−1 for 1995, 2006 and 2016 respectively. The highest soil loss is found for bare land. The RUSLE model further showed that the highest soil erosion occurred in 2016 whereas the lowest soil erosion occurred in 1995.
The COVID‐19 Menace
Authors: Walczak Piotr , Janowski Miroslaw
Published: May 2021

Coronavirus disease 2019 (COVID‐19) is caused by the new severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which binds to ectoenzyme angiotensin‐converting enzyme 2. It is very contagious and is spreading rapidly around the world. Until now, coronaviruses have mainly been associated with the aerodigestive tract due to the presence of a monobasic cleavage site for the resident transmembrane serine protease 2. Notably, SARS‐CoV‐2 is equipped with a second, polybasic cleavage site for the ubiquitous furin protease, which may determine the widespread tissue tropism. Furthermore, the terminal sequence of the furin‐cleaved spike protein also binds to neuropilin receptors. Clinically, there is enormous variability in the severity of the disease. Severe consequences are seen in a relatively small number of patients, most show moderate symptoms, but asymptomatic cases, especially among young people, drive disease spread. Unfortunately, the number of local infections can quickly build up, causing disease outbreaks suddenly exhausting health services’ capacity. Therefore, COVID‐19 is dangerous and unpredictable and has become the most serious threat for generations. Here, the latest research on COVID‐19 is summarized, including its spread, testing methods, organ‐specific complications, the role of comorbidities, long‐term consequences, mortality, as well as a new hope for immunity, drugs, and vaccines.