bluuebunny/crossref_metadata_2025 huggingface dataset:
The lncRNA ALMS1‐IT1 may promote malignant progression of lung adenocarcinoma via AVL9‐mediated activation of the cyclin‐dependent kinase pathway
Authors: Luan Tian , Zhang Tian‐Ye , Lv Zhong‐Hua , Guan Bi‐Xi , Xu Jian‐Yu , Li Jian , Li Ming‐Xu , Hu Song‐Liu
Published: March 2021

Lung adenocarcinoma (LUAD) is the primary epithelial tumor of the lung. The lack of clinical symptoms and specific molecular diagnostic indicators during the early stages of LUAD mean that the disease may not be detected until late stages, and the 5‐year survival rate is only approximately 15%. Long non‐coding RNA ALMS1 intronic script 1 (ALMS1‐IT1) was previously reported to be correlated with the poor prognosis of head and neck squamous cell carcinoma patients. Here, we investigated whether ALMS1‐IT1 has prognostic potential for LUAD. Bioinformatics analyses were performed to examine the expression and prognostic value of ALMS1 and AVL9 (for which gene expression is positively correlated with ALMS1‐IT1 expression in LUAD) in LUAD based on TCGA and Oncomine databases. We report that ALMS1‐IT1 and AVL9 were both highly expressed in LUAD and correlated with poor outcomes in LUAD patients. Of note, the prognosis of LUAD patients with low expression of both ALMS1‐IT1 and AVL9 was superior to that of other patients. Furthermore, the proliferation, migration and invasion of LUAD cells were decreased in cells lacking ALMS1‐IT1, and this decrease could be almost completely reversed through overexpression of AVL9. Gene set enrichment analysis revealed that expression of genes related to the cell cycle pathway is closely related to both the high expression of ALMS1‐IT1 and AVL9 in LUAD. Finally, up‐regulation of ALMS1‐IT1 can activate the cyclin‐dependent kinase pathway, whereas absence of AVL9 can reverse this activation, as shown by western blotting. In summary, ALMS1‐IT1/AVL9 may promote the malignant progression of LUAD, at least in part by regulating the cyclin‐dependent kinase pathway.
Macroporous Superhydrophobic Coatings with Switchable Wettability Enabled by Smart Shape Memory Polymers
Authors: Leverant Calen J. , Zhang Yifan , Cordoba Maria A. , Leo Sin‐Yen , Charpota Nilesh , Taylor Curtis , Jiang Peng
Published: March 2021

Here, a facile bottom‐up nanofabrication technology for making smart superhydrophobic coatings with switchable wettability and tunable optical properties by integrating shape memory polymers (SMPs) with templated macroporous photonic crystals is reported. Thermoresponsive shape memory efforts exhibited by a polyurethane‐based shape memory copolymer enable reversible microstructural transitions between a “memorized” permanent configuration composing of highly ordered arrays of macropores and a temporary deformed structure with collapsed macropores. The unique macroporous SMP photonic crystal arrays with large surface roughness can entrap a large portion of air in the interconnecting macropores, resulting in superior superhydrophobic properties including high apparent water contact angle (CA > 160°) and low CA hysteresis. Importantly, the shape memory‐enabled microstructural transitions lead to drastic wettability switching from superhydrophobic (CA > 160°) to hydrophobic (CA ≈ 110°) or from oleophobic (CA ≈139° for hexadecane) to oleophilic (CA ≈ 80°). The large CA tunability (>50°) coupled with the simultaneous color change from shining iridescence to colorless associated with the same microstructural transition can not only provide a noninvasive means for visually indicating the surface wetting states, this favorable coupling between the wetting and optical behaviors of macroporous SMP photonic crystal membranes can also pave the way for developing new tunable nanooptical devices.
Amalgamation‐Assisted Control of Profile of Liquid Metal for the Fabrication of Microfluidic Mixer and Wearable Pressure Sensor
Authors: Hu Weiping , Li Yuxing , Tang Shi‐Yang , Li Lin , Niu Q. Jason , Yan Sheng
Published: March 2021

The presence of microdomes can significantly increase the surface roughness, contact area, and deformability of materials, which have been adopted in many fields including microfluidics, wearable devices, and microanalysis systems. However, the shape of liquid metal (LM) droplet is defined by the density and surface energy, which has very limited room to tune. In this work, a simple, low‐cost method to effectively control the profile of LM using the masked amalgamation is presented. The LM amalgamates the masked copper surface to create the complex microdomes with various aspect ratios, sizes, profiles, and structures. The concave dome replicated from the LM mold has been demonstrated to enhance the microfluidic mixing performance. With a pattern transfer technique, the microconvex domes can be patterned on the surface of stretchable conductive composites to develop a flexible and sensitive pressure sensor. This sensor exhibits a fast response time, a wide working range, and an enhanced sensitivity for detecting small strains. As such, the fabricated microdomes exhibit a great potential to enable the fabrication of high‐performance sensors, microfluidic platforms, and micro total analysis systems.
High‐Efficiency Terahertz Nonreciprocal One‐Way Transmission and Active Asymmetric Chiral Manipulation Based on Magnetoplasmon/Dielectric Metasurface
Authors: Tan Zhiyu , Fan Fei , Zhao Dan , Ji Yunyun , Cheng Jierong , Chang Shengjiang
Published: March 2021

The lack of low‐loss and high‐efficiency nonreciprocal isolators has become one of the limitations in the development of terahertz (THz) application systems. This work demonstrates that the longitudinally magnetized InSb can achieve one‐way transmission for one photonic spin state but not for linear polarization (LP) state due to the chiral mirror‐symmetry of the two spin states. To solve this issue, a silicon microstructure is fabricated on the InSb substrate to form a magnetoplasmon/dielectric metasurface, where both the time‐reversal and mirror‐reversal symmetric transmission of the two spin states can be broken. In this device, the forward LP state is efficiently transformed into one of the spin states and output with low loss, but the backward wave is forbidden, which achieves the one‐way transmission for the LP incidence with over 30 dB isolation and only 1.7 dB insertion loss. When a THz polarizer is added behind the device to obtain the LP output, the isolation can reach 40 dB, significantly better than the previous reports. This study is significant to understand the nonreciprocal transmission and manipulation mechanism of THz spin states in the magnetized semiconductor and promotes the development of high‐performance THz isolators under the weak magnetic field.
Machine Learning Identifies Metabolic Signatures that Predict the Risk of Recurrent Angina in Remitted Patients after Percutaneous Coronary Intervention: A Multicenter Prospective Cohort Study
Authors: Cui Song , Li Li , Zhang Yongjiang , Lu Jianwei , Wang Xiuzhen , Song Xiantao , Liu Jinghua , Li Kefeng
Published: March 2021

Recurrent angina (RA) after percutaneous coronary intervention (PCI) has few known risk factors, hampering the identification of high‐risk populations. In this multicenter study, plasma samples are collected from patients with stable angina after PCI, and these patients are followed‐up for 9 months for angina recurrence. Broad‐spectrum metabolomic profiling with LC‐MS/MS followed by multiple machine learning algorithms is conducted to identify the metabolic signatures associated with future risk of angina recurrence in two large cohorts (n = 750 for discovery set, and n = 775 for additional independent discovery cohort). The metabolic predictors are further validated in a third cohort from another center (n = 130) using a clinically‐sound quantitative approach. Compared to angina‐free patients, the remitted patients with future RA demonstrates a unique chemical endophenotype dominated by abnormalities in chemical communication across lipid membranes and mitochondrial function. A novel multi‐metabolite predictive model constructed from these latent signatures can stratify remitted patients at high‐risk for angina recurrence with over 89% accuracy, sensitivity, and specificity across three independent cohorts. Our findings revealed reproducible plasma metabolic signatures to predict patients with a latent future risk of RA during post‐PCI remission, allowing them to be treated in advance before an event.
All‐Inkjet‐Printed 3D Alveolar Barrier Model with Physiologically Relevant Microarchitecture
Authors: Kang Dayoon , Park Ju An , Kim Woojo , Kim Seongju , Lee Hwa‐Rim , Kim Woo‐Jong , Yoo Joo‐Yeon , Jung Sungjune
Published: March 2021

With the outbreak of new respiratory viruses and high mortality rates of pulmonary diseases, physiologically relevant models of human respiratory system are urgently needed to study disease pathogenesis, drug efficacy, and pharmaceutics. In this paper, a 3D alveolar barrier model fabricated by printing four human alveolar cell lines, namely, type I and II alveolar cells (NCI‐H1703 and NCI‐H441), lung fibroblasts (MRC5), and lung microvascular endothelial cells (HULEC‐5a) is presented. Automated high‐resolution deposition of alveolar cells by drop‐on‐demand inkjet printing enables to fabricate a three‐layered alveolar barrier model with an unprecedented thickness of ≈10 µm. The results show that the 3D structured model better recapitulate the structure, morphologies, and functions of the lung tissue, compared not only to a conventional 2D cell culture model, as expected, but also a 3D non‐structured model of a homogeneous mixture of the alveolar cells and collagen. Finally, it is demonstrated that this thin multilayered model reproduce practical tissue‐level responses to influenza infection. Drop‐on‐demand inkjet‐printing is an enabling technology for customization, scalable manufacturing, and standardization of their size and growth, and it is believed that this 3D alveolar barrier model can be used as an alternative to traditional test models for pathological and pharmaceutical applications.
AIEgen‐enhanced protein imaging: Probe design and sensing mechanisms
Authors: Naghibi Sanaz , Chen Tong , Jamshidi Ghahfarokhi Amin , Tang Youhong
Published: March 2021

Proteins are the building blocks of life, regarded as one of the most complex and crucial biomacromolecules in biological systems, and playing a significant role in executing genes and transferring genetic information. According to recent research, due to the structural intricacy of proteins and their sensitivity to physical and chemical degradation processes, they could be utilized as biomarkers or therapeutic agents in the diagnosis, treatment, or even prevention of different diseases. Therefore, modern pathways have been developed for understanding the function of proteins, resulting in intriguing approaches in the field of protein‐related diseases. The diagnostic strategies to deal with such diseases, including protein analysis, protein quantification, and protein imaging, were argued in depth. Meanwhile, the aggregation‐induced emission (AIE) concept and its potential applications for real‐time imaging make AIE luminogens (AIEgen) attractive for protein imaging. In general, AIEgens refer to those luminogenic chemicals that are nonluminescent in solution, but luminescent in either the aggregated or solid states. This review is focused on the emergence of AIE materials in protein tracking, detecting, and imaging for medical applications.
Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys)
Authors: Chenbhanich Jirat , Hu Yan , Hetts Steven , Cooke Daniel , Dowd Christopher , Devine Patrick ,   UCLA Clinical Genomics Center, Russell Bianca , Kang Sung Hae L. , Chang Vivian Y. , Abla Adib A. , Cornett Patricia , Yeh Iwei , Lee Hane , Martinez‐Agosto Julian A. , Frieden Ilona J. , Shieh Joseph T.
Published: March 2021

Activating variants in the platelet‐derived growth factor receptor β gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome. A recently described phenotype with fusiform aneurysm has been associated with mosaic PDGFRB c.1685A > G p.(Tyr562Cys) variant. Few reports however have examined the vascular phenotypes and mosaic effects of PDGFRB variants. We describe clinical characteristics of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant identified via next‐generation sequencing‐based genetic testing. We observed intracranial fusiform aneurysm in one patient and found an additional eight patients with aneurysms and phenotypes associated with PDGFRB‐activating variants through literature search. The conditions caused by PDGFRB‐activating variants share overlapping features including overgrowth, premature aged skin, and vascular malformations including aneurysms. Aneurysms are progressive and can result in morbidities and mortalities in the absence of successful intervention. Germline and/or somatic testing for PDGFRB gene should be obtained when PDGFRB activating variant‐related phenotypes are present. Whole‐body imaging of the arterial tree and echocardiography are recommended after diagnosis. Repeating the imaging study within a 6‐ to 12‐month period after detection is reasonable. Finally, further evaluation for the effectiveness and safety profile of kinase inhibitors in this patient population is warranted.
Traditional Chinese medicine for dementia
Authors: Li Song , Wu Zhengzhi , Le Weidong
Published: March 2021

In Western medicine, dementia refers to a spectrum of diseases affecting cognition, mental health, and physical abilities. Ancient medical literatures of traditional Chinese medicine (TCM) also recorded dementia‐like symptoms, but described the disease from a totally distinct theoretical point of view. The earliest records of memory loss in ancient China can be traced back 2000 years earlier. In TCM, dementia can be attributed mainly to the Brain dystrophy, Spleen‐Kidney weakness, Blood stasis, and Phlegm stagnation. Of interest, ancient Chinese physicians have proposed that dementia manifests as not only cognitive but also noncognitive symptoms including psychiatric disorders and sleep disturbance, which have been investigated widely nowadays in Western medicine. Various TCM prescriptions, herbal medicines, and acupunctures have also been proposed for dementia prevention and therapy. Some of these strategies are still used in current clinical practice. Reviewing and highlighting the unique TCM recognition of treating dementia may shed light on future dementia research.
Electrochemical performance of polydopamine modified PANI/rGO composites: Dependency on preparation sequence
Authors: Zhao Xueyan , Pionteck Jürgen
Published: March 2021

Compounding polyaniline (PANI) and reduced graphite oxide (rGO) is a fascinating cost‐effective way to combine the high energy density of faradic material and high power density of carbonaceous material. In this study, in‐situ polymerization of dopamine was used to reduce graphite oxide and to modify the rGO product with polydopamine (PDA) simultaneously. This modification prevented restacking of rGO, and enhanced the interactions between PANI and rGO. The partial reduction of GO during the polymerization of dopamine was proven by X‐ray diffraction, Fourier transform infrared attenuated total reflectance, and UV–vis spectroscopy. Surprisingly, the electrochemical performance of the composites depends strongly on the preparation sequence. PANI/(rGO‐PDA) composites obtained by the synthesis of PANI in the presence of rGO‐PDA show better electrochemical performance than (PANI/rGO)‐PDA composites, which were produced by polymerizing dopamine in the presence of PANI/GO composite. At a given scan rate of 20 mV s−1, the highest specific capacity of PANI/(rGO‐PDA) composites was 230.7 F g−1, which was higher than those of all (PANI/rGO)‐PDA composites. This phenomenon is tightly related to the differences in morphologies, conductivities and specific surface areas of the two types of composites.
Withdrawing Ixekizumab in Patients With Psoriatic Arthritis Who Achieved Minimal Disease Activity: Results From a Randomized, Double‐Blind Withdrawal Study
Authors: Coates Laura C. , Pillai Sreekumar G. , Tahir Hasan , Valter Ivo , Chandran Vinod , Kameda Hideto , Okada Masato , Kerr Lisa , Alves Denise , Park So Young , Adams David H. , Gallo Gaia , Hufford Matthew M. , Hojnik Maja , Mease Philip J. , Kavanaugh Arthur ,   for the SPIRIT‐P3 Study Group
Published: March 2021

Objective

To evaluate the effect of withdrawing ixekizumab in patients with psoriatic arthritis (PsA) in whom minimal disease activity (MDA) has been achieved after open‐label ixekizumab treatment.

Methods

SPIRIT‐P3 was a multicenter, randomized, double‐blind withdrawal study of biologic treatment–naive adult patients with PsA who were treated with open‐label ixekizumab for 36 weeks (160 mg at week 0, then 80 mg every 2 weeks). Patients in whom MDA was sustained for >3 consecutive months were randomized 1:1, between weeks 36 and 64, to undergo blinded withdrawal of ixekizumab treatment (placebo) or to continue ixekizumab treatment every 2 weeks up to week 104. The primary efficacy end point was time to relapse (loss of MDA) for randomized patients. Patients who experienced a relapse were re‐treated with ixekizumab every 2 weeks up to week 104.

Results

A total of 394 patients were enrolled and received open‐label ixekizumab every 2 weeks. Of those patients, 158 (40%) achieved sustained MDA and were randomized to undergo withdrawal of ixekizumab treatment (placebo every 2 weeks; n = 79) or to continue ixekizumab treatment every 2 weeks (n = 79). Disease relapse occurred more rapidly with treatment withdrawal (median 22.3 weeks [95% confidence interval (95% CI) 16.1–28.3]) compared to those who continued treatment with ixekizumab (median not estimable; P < 0.0001). Sixty‐seven patients (85%) compared to 30 patients (38%) experienced relapse in the placebo group and the continued treatment group, respectively. Median time to achieving MDA again with re‐treatment was 4.1 weeks (95% CI 4.1–4.3); in 64 of 67 patients (96%) who experienced relapse with treatment withdrawal, MDA was achieved again with re‐treatment. Safety was consistent with the known safety profile for ixekizumab.

Conclusion

Continued ixekizumab therapy is superior to ixekizumab withdrawal in maintaining low disease activity in biologic treatment–naive patients with PsA. Re‐treatment with ixekizumab following a relapse may restore disease control in cases of treatment interruption.
Identification‐Based Multiple‐Choice Assessments in Anatomy can be as Reliable and Challenging as Their Free‐Response Equivalents
Authors: Douglas‐Morris Jan , Ritchie Helen , Willis Catherine , Reed Darren
Published: March 2021

Multiple‐choice (MC) anatomy “spot‐tests” (identification‐based assessments on tagged cadaveric specimens) offer a practical alternative to traditional free‐response (FR) spot‐tests. Conversion of the two spot‐tests in an upper limb musculoskeletal anatomy unit of study from FR to a novel MC format, where one of five tagged structures on a specimen was the answer to each question, provided a unique opportunity to assess the comparative validity and reliability of FR‐ and MC‐formatted spot‐tests and the impact on student performance following the change of test format to MC. Three successive year cohorts of health science students (n = 1,442) were each assessed by spot‐tests formatted as FR (first cohort) or MC (following two cohorts). Comparative question difficulty was assessed independently by three examiners. There were more higher‐order cognitive skill questions and more of the course objectives tested in the MC‐formatted tests. Spot‐test reliability was maintained with Cronbach’s alpha reliability coefficients ≥ 0.80 and 80% of the MC items of high quality (having point‐biserial correlation coefficients > 0.25). These results also demonstrated guessing was not an issue. The mean final score for the MC‐formatted cohorts increased by 4.9%, but did not change for the final theory examination that was common to all three cohorts. Subgroup analysis revealed that the greatest change in spot‐test marks was for the lower‐performing students. In conclusion, our results indicate spot‐tests formatted as MC are suitable alternatives to FR tests. The increase in mean scores for the MC‐formatted spot‐tests was attributed to the lower demand of the MC format.
Psychological predictors of protective behaviours during the Covid‐19 pandemic: Theory of planned behaviour and risk perception
Authors: Trifiletti Elena , Shamloo Soraya E. , Faccini Martina , Zaka Agustina
Published: March 2021

The Covid‐19 outbreak was declared a public health emergency by the World Health Organization in January 2020. As a consequence, several protective measures were urged by national governments in order to limit the spread of the pandemic. Drawing on the literature on health behaviours, in the present study, we investigated the psychological factors (i.e., attitudes, social norms, perceived behavioural control, intentions, and risk perception) that were associated with two highly recommended behaviours: frequent hand washing and social distancing (i.e., staying at home except for essential reasons). The study employed a correlational design with a follow‐up. A questionnaire including measures of psychological predictors was administered via social media to a sample of 403 adults residing in Italy during the lockdown. Self‐reported behaviours were assessed one week later. Findings showed that attitudes, social norms, perceived behavioural control were significantly related to hand washing and social distancing through intentions. Risk perception was a significant predictor of social distancing but not of hand washing. These findings suggest that intervention and communication strategies aimed at encouraging preventive measures during the Covid‐19 pandemic should be organized taking into account multiple factors which partially differ depending on the type of behaviour considered. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.
Methanol Synthesis with Steel Mill Gases: Performance Investigations in an On‐Site Technical Center
Authors: Girod Kai , Lohmann Heiko , Kaluza Stefan
Published: March 2021

An on‐site laboratory with direct access to cleaned and conditioned steel mill gases was recently put into operation. The long‐term performance and stability of Clariant's MegaMax®800 methanol synthesis catalyst utilizing steel mill gases is currently being investigated. First test results revealed that in order to investigate deactivation mechanisms arising from particular properties of the cleaned steel mill gases, the overlaying effect of thermal deactivation of the catalyst has to be minimized.
Synthesis of low‐cost Co‐Sn‐Pd/rGO catalysts via ultrasonic irradiation and their electrocatalytic activities toward oxygen reduction reaction
Authors: Wang Huihua , Li Lin , Sheng Shizhan , Wang Channa , Qu Tianpeng , Hou Dong , Wang Deyong , Sheng Minqi
Published: March 2021

Reduced graphene supported Co‐Sn‐Pd nanoparticle catalysts(Co0.2SnxPdy/rGO, x + y = 0.4) were successfully synthesized by reducing the trace amounts of ions (Pd2+, Sn2+, and Co2+) in the presence of reduced graphene via an ultrasonic irradiation method. Characterization of the Co0.2SnxPdy/rGO catalysts by X‐ray diffraction (XRD) and transmission electron microscopy (TEM) indicates that the Co0.2Sn0.2Pd0.2/rGO catalyst with a mean diameter of ~3.8 nm is close to a single‐phase solid solution. X‐ray photoelectron spectroscopy (XPS) shows the binding energy of metallic Pd shifts to a higher angle in the Co0.2SnxPdy/rGO (x + y = 0.4) catalysts, indicating a shift of Pd electronic centre upon alloying with Co and Sn. Conventionally, ternary Co‐Sn‐Pd/rGO catalysts show greater oxygen reduction reaction (ORR) activities and durability than binary Pd‐Co/rGO catalyst and 20 wt% Pt/C catalyst even at a very low Pd content. Among of the synthetic catalysts, the Co0.2Sn0.2Pd0.2/rGO catalyst exhibits the best ORR activity (E1/2 = 0.91 V, k = −57 mV · dec−1) and dominates a 4‐electron pathway in the ORR process (n = 3.95 ± 0.09, H2O2<4%). Also, the Co0.2SnxPdy/rGO (x + y = 0.4) catalysts display a remarkable advantage of high methanol tolerance compared to that of the commercial 20 wt% Pt/C catalyst, which make them potential candidates for direct methanol fuel cells.
Penalized high‐dimensional M‐quantile regression: From L1 to Lp optimization
Authors: Hu Jie , Chen Yu , Zhang Weiping , Guo Xiao
Published: March 2021

Quantiles and expectiles have been receiving much attention in many areas such as economics, ecology, and finance. By means of Lp optimization, both quantiles and expectiles can be embedded in a more general class of M‐quantiles. Inspired by this point of view, we propose a generalized regression called Lp‐quantile regression to study the whole conditional distribution of a response variable given predictors in a heterogeneous regression setting. In this article, we focus on the variable selection aspect of high‐dimensional penalized Lp‐quantile regression, which provides a flexible application and makes a complement to penalized quantile and expectile regressions. This generalized penalized Lp‐quantile regression steers an advantageous middle course between ordinary penalized quantile and expectile regressions without sacrificing their virtues too much when 1 < p < 2, that is, offers versatility and flexibility with these ‘quantile‐like’ and robustness properties. We develop the penalized Lp‐quantile regression with scad and adaptive lasso penalties. With properly chosen tuning parameters, we show that the proposed estimators display oracle properties. Numerical studies and real data analysis demonstrate the competitive performance of the proposed penalized Lp‐quantile regression when 1 < p < 2, and they combine the robustness properties of quantile regression with the efficiency of penalized expectile regression. These properties would be helpful for practitioners.
Effect of non‐recommended doses versus recommended doses of direct oral anticoagulants in atrial fibrillation patients: A meta‐analysis
Authors: Liu Xuyang , Huang Manxiang , Ye Caisheng , Xiao Xiujuan , Yan Chengguang
Published: March 2021

Background

Several observational studies have shown that the inappropriate dosing use of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) that does not conform to recommendations is becoming a widespread phenomenon. Therefore, we performed a meta‐analysis and systematic review to assess the effect of non‐recommended doses versus recommended doses of DOACs on the effectiveness and safety outcomes among AF patients.

Methods

The PubMed and Ovid databases were systematically searched to identify the relevant studies until December 2020. The effect estimates were hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using a fixed‐effects model (I2 ≤ 50%) or a random‐effects model (I2 > 50%).

Results

A total of 11 studies were included in this meta‐analysis. Compared with recommended dosing of DOACs, non‐recommended low dosing of DOACs was associated with increased risks of stroke or systemic embolism (SSE, HR = 1.29, 95% CI 1.12–1.49) and all‐cause death (HR = 1.37, 95% CI 1.15–1.62), but not the ischemic stroke, myocardial infarction, gastrointestinal bleeding, intracranial bleeding, and major bleeding. Compared with recommended dosing of DOACs, non‐recommended high dosing of DOACs was associated with increased risks of SSE (HR = 1.44, 95% CI 1.01–2.04), major bleeding (HR = 1.99, 95% CI 1.48–2.68), and all‐cause death(HR = 1.38, 95% CI 1.02–1.87).

Conclusion

Compared with recommended dosing of DOACs, non‐recommended low dosing of DOACs was associated with increased risks of SSE and all‐cause death. Further study should confirm the findings of non‐recommended high dosing versus recommended dosing of DOACs.
Natural and Semisynthetic Pentacyclic Triterpenes for Chronic Myeloid Leukemia Therapy: Reality, Challenges and Perspectives
Authors: Barreto Vianna Débora Renz , Gotardi Jessica , Baggio Gnoatto Simone Cristina , Pilger Diogo André
Published: March 2021

Chronic myeloid leukemia (CML) is a neoplasm characterized by BCR‐ABL1, an oncoprotein with vital role in leukemogenesis. Its inhibition by tyrosine kinase inhibitors represents the main choice of treatment. However, therapeutic failure is worrying given the lack of pharmacological options. Pentacyclic triterpenes are phytochemicals with outstanding antitumoral properties and have also been explored as a basis for the design of potential leads. In this review, we have gathered and discuss data regarding both natural and semisynthetic pentacyclic triterpenes applied to CML cell treatment. We found consistent evidence that the class of pentacyclic triterpenes in general exerts promising pro‐apoptotic and antiproliferative activities in sensitive and resistant CML cells, and thus represents a rich source for drug development. We also analyze the predicted drug‐like properties of the molecules, discuss the structural changes with biological implications and show the great opportunities this class represents, as well as the perspectives they provide on drug discovery for CML treatment.
Tuning of Ionic Liquid Crystal Properties by Combining Halogen Bonding and Fluorous Effect
Authors: Cavallo Gabriella , Abate Antonio , Rosati Marta , Paolo Venuti Giovanni , Pilati Tullio , Terraneo Giancarlo , Resnati Giuseppe , Metrangolo Pierangelo
Published: March 2021

We report halogen‐bonded complexes between 1‐polyfluoroalkyl‐3‐alkylimidazolium iodides and mono‐iodoperfluoroalkanes of different chain lengths or di‐iodoperfluorooctane. 19F NMR analyses revealed that the preferred stoichiometry between the donors and acceptors is 1 : 1 in the cases of the mono‐iodoperfluoroalkanes, and 2 : 1 with di‐iodoperfluorooctane, as a result of the monodentate behavior of the iodide anion (halogen bond acceptor). Single crystal X‐ray diffraction analyses showed the presence of a perfluorinated superanion, which interdigitates with the cation fluorinated chains, favoring the formation of lamellar structures. All of the obtained supramolecular complexes exhibit enantiotropic liquid crystalline phases over a broad range of temperatures. Most of the obtained complexes show melting points lower than 100 °C, two of them being liquid at room temperature, thus representing a new family of fluorinated ionic liquid crystals.
Modeling Skin Inflammation Using Human In Vitro Models
Authors: Boarder Erika , Rumberger Beth , Howell Michael D.
Published: March 2021

Skin is made up of an epidermis and, dermis which serve as a barrier against physical and environmental threats. Keratinocytes make up greater than 95% of the epidermis and form different layers based on their level of differentiation. Millions of individuals suffer from skin diseases, which are characterized by significant barrier disruption and inflammation. Investigators previously relied on animal models to investigate inflammatory skin diseases; however, technological advances have enabled the use of physiologically human skin models to investigate the effects of inflammatory mediators on the structure and function of skin cells. In this article, we describe two protocols using keratinocytes to investigate tumor necrosis factor alpha (TNF‐α) and interferon gamma (IFN‐γ) driven skin inflammation as a surrogate for psoriasis, vitiligo, and other autoimmune skin diseases driven by these cytokines. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Preparing a HaCaT keratinocyte culture

Basic Protocol 2: 3‐Dimensional organotypic skin cultures to assess TNF‐α and IFN‐γ driven skin inflammation
Computational immune infiltration analysis of pediatric high‐grade gliomas (pHGGs) reveals differences in immunosuppression and prognosis by tumor location
Authors: Bailey Cavan P. , Wang Ruiping , Figueroa Mary , Zhang Shaojun , Wang Linghua , Chandra Joya
Published: March 2021

Immunotherapy for cancer has moved from pre‐clinical hypothesis to successful clinical application in the past 15 years. However, not all cancers have shown response rates in clinical trials for these new agents. igh‐grade gliomas, in particular, have proved exceedingly refractory to immunotherapy. In adult patients, there has been much investigation into these failures, and researchers have concluded that an immunosuppressive microenvironment combined with low mutational burden renders adult glioblastomas “immune cold.” Pediatric cancer patients develop gliomas at a higher rate per malignancy than adults, and their brain tumors bear even fewer mutations. These tumors can also develop in more diverse locations in the brain, beyond the cerebral hemispheres seen in adults, including in the brainstem where critical motor functions are controlled. While adult brain tumor immune infiltration has been extensively profiled from surgical resections, this is not possible for brainstem tumors that can only be sampled at autopsy. Given these limitations, there is a dearth of information on immune cells and their therapeutic and prognostic impact in pediatric high‐grade gliomas (pHGGs), including hemispheric tumors in addition to brainstem. In this report, we use computational methods to examine immune infiltrate in pHGGs and discover distinct immune patterns between hemispheric and brainstem tumors. In hemispheric tumors, we find positive prognostic associations for regulatory T‐cells, memory B‐cells, eosinophils, and dendritic cells, but not in brainstem tumors. These differences suggest that immunotherapeutic approaches must be cognizant of pHGG tumor location and tailored for optimum efficacy.
Quantitative acetylome analysis reveals histone modifications that may predict prognosis in hepatitis B‐related hepatocellular carcinoma
Authors: Chai Xiaoqiang , Guo Jianfei , Dong Ruizhao , Yang Xuan , Deng Chao , Wei Chuanyuan , Xu JiaJie , Han Weiyu , Lu Jiacheng , Gao Chao , Gao Dongmei , Huang Cheng , Ke Aiwu , Li Shuangqi , Li Huanping , Tian Yingming , Gu Zhongkai , Liu Shuxian , Liu Hang , Chen Qilong , Liu Feng , Zhou Jian , Fan Jia , Shi Guoming , Wu Feizhen , Cai Jiabin
Published: March 2021

Lysine acetylation (Kac) as an important posttranslational modification of histones is essential for the regulation of gene expression in hepatocellular carcinoma (HCC). However, the atlas of whole acetylated proteins in HCC tissues and the difference in protein acetylation between normal human tissues and HCC tissues are unknown. In this report, we characterized the proteome and acetyl proteome (acetylome) profile of normal, paracancerous, and HCC liver tissues in human clinical samples by quantitative proteomics techniques. We identified 6781 acetylation sites of 2582 proteins and quantified 2492 acetylation sites of 1190 proteins in normal, paracancerous, and HCC liver tissues. Among them, 15 proteins were multiacetylated with more than 10 lysine residues. The histone acetyltransferases p300 and CBP were found to be hyperacetylated in hepatitis B virus pathway. Moreover, we found that 250 Kac sites of 214 proteins were upregulated and 662 Kac sites of 451 proteins were downregulated in HCC compared with normal liver tissues. Additionally, the acetylation levels of lysine 120 in histone H2B (H2BK120ac), lysine 18 in histone H3.3 (H3.3K18ac), and lysine 77 in histone H4 (H4K77ac) were increased in HCC. Interestingly, the higher levels of H2BK120ac, H3.3K18ac, and H4K77ac were significantly associated with worse prognosis, such as poorer survival and higher recurrence in an independent clinical cohort of HCC patients. Overall, this study lays a foundation for understanding the functions of acetylation in HCC and provides potential prognostic factors for the diagnosis and therapy of HCC.
A One‐Dimensional Cadmium Coordination Polymer: Synthesis, Structure, and Application as Luminescent Sensor for Cu2+ and CrO42−/Cr2O72− Ions
Authors: Zhang Xiamei , Huang Yuan , Zhang Qian , Li Dawei , Li Yahong
Published: March 2021

A novel coordination polymer {[Cd4(CPIP)3Cl8]}n (CP1) was constructed from the reaction of CPIP (CPIP=1‐chloro‐3‐(pyridine‐2‐yl)imidazo[1,5‐a]pyridine) and CdCl2⋅2.5H2O under solvothermal conditions. The employment of CPIP as the ligand was based on the consideration that two types of Lewis basic sites (the fused nitrogen atom and the chlorine substituent) are present on the backbone of the ligand. These sites can be utilized for interacting with cations and anions, thus for the sensing functionality. Single‐crystal X‐ray diffraction studies revealed that CP1 exhibits interesting one‐dimensional (1D) polymeric chain structure. The adjacent four CdII ions are connected by one μ3‐Cl and five μ2‐Cl atoms to form a Chinese‐lantern‐like topology. CP1 is an excellent luminescent sensor for detecting Cu2+, CrO42− and Cr2O72− ions with high selectivity, sensitivity, and recyclability. Moreover, CP1 is the first reported chloride‐bridged coordination polymer that is capable of sensing Cu2+ ion. The mechanisms for sensing Cu2+, CrO42− and Cr2O72− ions were investigated and discussed.
Insoluble π‐Conjugated Polyimine as an Organic Adsorbent for Group 10 Metal Ions
Authors: Shirakura Hayato , Hijikata Yuh , Pirillo Jenny , Yoneda Tomoki , Manabe Yumehiro , Murugavel Muthuchamy , Ide Yuki , Inokuma Yasuhide
Published: March 2021

Metal ion adsorbents are indispensable materials for the recovery of noble metal ions in a sustainable society. Herein, we report that poly(isopyrazole‐3,5‐diyl‐trans‐vinylene) (1) effectively adsorbed group 10 metal ions from solution in acetonitrile. Owing to its fully π‐conjugated and rigid structure, polyimine1was virtually insoluble in common organic solvents and water, making it advantageous for metal ion adsorption via a solid/liquid interface. Inductively coupled plasma (ICP) analysis showed that ≥90 % of Ni2+, Pd2+, and Pt2+ions were adsorbed at a concentration of 10 μM (order of ≤2 ppm) after stirring suspensions at room temperature. Metal ion desorption was achieved by treatment with ethylenediaminetetraacetic acid disodium salt (EDTA ⋅ 2Na), and the adsorbent was reused. Theoretical calculations supported that the desolvation energy was an important factor for effective adsorption in acetonitrile.
Strategic Synthesis of ‘Picket Fence’ Porphyrins Based on Nonplanar Macrocycles**
Authors: Norvaiša Karolis , Yeow Kathryn , Twamley Brendan , Roucan Marie , Senge Mathias O.
Published: March 2021

Traditional ‘picket fence’ porphyrin systems have been a topic of interest for their capacity to direct steric shielding effects selectively to one side of the macrocycle. Sterically overcrowded porphyrin systems that adopt macrocycle deformations have recently drawn attention for their applications in organocatalysis and sensing. Here we explore the combined benefits of nonplanar porphyrins and the old molecular design to bring new concepts to the playing field. The challenging ortho‐positions of meso‐phenyl residues in dodecasubstituted porphyrin systems led us to transition to less hindered para‐ and meta‐sites and develop selective demethylation based on the steric interplay. Isolation of the symmetrical target compound [2,3,7,8,12,13,17,18‐octaethyl‐5,10,15,20‐tetrakis(3,5‐dipivaloyloxyphenyl)porphyrin] was investigated under two synthetic pathways. The obtained insight was used to isolate unsymmetrical [2,3,7,8,12,13,17,18‐octaethyl‐5,10,15,20‐tetrakis(2‐nitro‐5‐pivaloyloxyphenyl)porphyrin]. Upon separation of the atropisomers, a detailed single‐crystal X‐ray crystallographic analysis highlighted intrinsic intermolecular interactions. The nonplanarity of these systems in combination with ‘picket fence’ motifs provides an important feature in the design of supramolecular ensembles.
3D time‐domain nonlinear analysis of soil‐structure systems subjected to obliquely incident SV waves in layered soil media
Authors: Zhang Wenyang , Taciroglu Ertugrul
Published: March 2021

Numerous experiments and prior analyses have confirmed that the angle of incidence of a seismic wave can significantly affect ground response and dynamic soil–structure interaction (SSI) behavior. Realistically, obliquely incident waves will be generated due to the soil heterogeneity and stratigraphy, which can lead into complex wave propagation and scattering patterns. In this study, we propose a novel methodology that (i) utilizes the wave potential theory to derive the 3D time‐domain analytical solutions for free‐field response under obliquely incident SV waves in layered soil media; (ii) makes use of high‐fidelity numerical tools—namely, the domain reduction method (DRM) and the perfectly matched layers (PMLs)—to inject the obliquely incident waves into the domain of interest and to absorb the outgoing scattered motions, respectively; (iii) enables nonlinear time‐domain site response and SSI analyses that feature an advanced constitutive model for soil. Finally, a 3D 20‐story steel building is modeled as a case study. The building rests on a two‐layer half‐space and is subjected to an obliquely incident seismic wave. The SV wave's angles of incidence are varied to investigate its effects on structural responses, such as horizontal, vertical, and rotational floor accelerations, as well as interstory drift ratios.
Correlated Ni, Cu, and Zn Sensitivities of 8 Freshwater Algal Species and Consequences for Low-Level Metal Mixture Effects
Authors: Fettweis Andreas , Bergen Benoit , Hansul Simon , De Schamphelaere Karel , Smolders Erik
Published: March 2021

Predicting metal sensitivities and metal mixture interactions for species within each trophic level is essential to understand the effects of metals at the ecosystem level. The present study was set up to explore the correlations of metal sensitivities among species and if these sensitivities or metal mixture interactions are related to growth or morphological traits. The toxicity of Ni, Cu, and Zn on algal growth was tested for 8 freshwater algal species when dosed singly and in combinations in phosphorus-limiting static systems. The metal sensitivities on specific growth rate (10% effect concentrations expressed as free ion activities) varied 2 to 3 orders of magnitude among species depending on metal. These sensitivities were unrelated (p > 0.05) to their specific growth rate (0.7–1.8 d–1) or cell volume (100–103m3 cell–1). Species-specific differences in one or more toxicokinetic and/or toxicodynamic (TKTD) processes are likely at the basis of this variation. The log-transformed metal sensitivities positively correlated (p < 0.1) among the species in all 3 binary combinations (Ni–Cu, Ni–Zn, and Cu–Zn), suggesting that species have correlated TKTD rates for these metals. Furthermore, they would also predict stronger effects of metal mixtures on algal community biodiversity than what would be expected without a positive correlation. Low-level metal mixture effects varied similarly, largely among species and mixture interactions that were highly variable: ranging from synergistic to antagonistic relative to independent action during exponential growth, whereas mixture interactions at 10% effect shifted toward additivity/synergism relative to concentration addition at carrying capacity. Some evidence was found for stronger synergistic mixture effects in smaller species. Overall, the present study highlights the importance of incorporating more species in sensitivity distributions and accounting for mixture toxicity in risk assessment. Environ Toxicol Chem 2021;40:2013–2023. © 2021 SETAC
Delineating the tacit knowledge‐seeking phase of knowledge sharing: The influence of relational social capital components
Authors: Gubbins Claire , Dooley Lawrence
Published: March 2021

Much knowledge on which performance in practice is based is tacit (Smith, 2001) making it a valuable, rare resource, which is difficult to imitate or substitute (Barney, 1991) and a vital source of organizational competitive advantage. However, there is limited research available delineating tacit from explicit knowledge (Insch et al., 2008; Garcia‐Perez & Mitra, 2007) and thus gaps in our understanding about how to derive the greatest value from it. Knowledge management (KM) is partly a socially constructed phenomenon embedded in people and relationships (Nonaka, 1991). However, KM research has neglected the role of the microlevel of individuals and social interactions (Foss, 2009). Furthermore, knowledge sharing research neglects to explore all phases of what is a bidirectional relationship. Scant research exists on the knowledge‐seeking process—from the seeker to the source (Hansen et al., 2005) as the focus is on the unidirectional notion of knowledge sharing—from the source to the seeker (Kim et al., 2011). This study utilizes the social capital lens, which focuses on social relationships and in particular therelations between, rather than thecharacteristics of, individuals, groups, processes, or organizations, to explore tacit knowledge‐seeking processes. The data are based on five American multinational manufacturing organizations and interviews with 105 operators, technicians, and engineers engaged in tacit knowledge work. The paper discusses the results of the investigation of the relational social capital factors of trust, norms, sanctions and social identification, and their influence on decisions to operationalize a tacit knowledge‐seeking interaction.
Peat depth as a control onSphagnummoisture stress during seasonal drought
Authors: Moore Paul A. , Didemus Benjamin D. , Furukawa Alexander K. , Waddington James M.
Published: March 2021

Peatlands are globally important long‐term sinks of carbon, however there is concern that enhanced peat decomposition and moss moisture stress due to climate change mediated drought will reduce moss productivity making these ecosystems vulnerable to carbon loss and associated long‐term degradation. Peatlands are resilient to summer drought moss stress because of negative ecohydrological feedbacks that generally maintain a wet peat surface, but where feedbacks may be contingent on peat depth. We tested this ‘survival of the deepest’ hypothesis by examining water table (WT) position, near‐surface moisture content, and soil water tension in peatlands that differ in size, peat depth, and catchment area during a summer drought. All shallow sites (<40 cm depth) lost their WT (i.e., the groundwater well was dry) for considerable time during the drought period. Near‐surface soil water tension increased dramatically at shallow sites following WT loss, increasing ~5–7.5× greater at shallow sites compared to deep sites (≥40 cm depth). During a mid‐summer drought intensive field survey, we found that 60–67% of plots at shallow sites exceeded a 100 mb tension threshold used to infer moss water stress. Unlike the shallow sites, tension typically did not exceed this 100 mb threshold at the deep sites. Using species dependent water content – chlorophyll fluorescence thresholds and relations between volumetric water content and WT depth, Monte Carlo simulations suggest that moss had nearly twice the likelihood of being stressed at shallow sites (0.38 ± 0.24) compared to deep sites (0.22 ± 0.18). This study provides evidence that mosses in shallow peatland may be particularly vulnerable to warmer and drier climates in the future, but where species composition may play an important role. We argue that a critical ‘threshold’ peat depth specific for different hydrogeological and hydroclimatic regions can be used to assess what peatlands are especially vulnerable to climate change mediated drought.