bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio‐polymer modified nanoclay embedded forward osmosis membranes with enhanced desalination performance
Authors: Mamah Stanley Chinedu , Goh Pei Sean , Ismail Ahmad Fauzi , Yogarathinam Lukka Thuyavan , Suzaimi Nur Diyana , Opia Anthony Chukwunonso , Ojo Samuel , Ngwana Ngouangna Eugene
Published: April 2022

The substrate of forward osmosis (FO) thin‐film composite (TFC) membranes supports the formation of the selective layer. It can remarkably influence the structure as well as the physiochemical characteristics of the selective layer formed atop. Therefore, the improvement of TFC substrates in terms of its thickness, tortuosity and porosity can further fine tune the properties of the resultant TFC membranes. In this present study, TFC membrane comprising of polyamide selective layer and palygorskite‐chitin (PAL‐CH) containing polysulfone substrate was developed for FO desalination. The effects of PAL‐CH on the surface and structural properties of the substrate were examined. The FO desalination performance of the resultant membranes was evaluated in both active‐layer facing feed solution and active‐layer facing draw solution modes using NaCl as draw solution. In comparison with the un‐modified membrane, the TFC membrane with PAL‐CH embedded polysulfone substrate exhibited enhanced water flux and lower structural parameter. The incorporation of PAL‐CH hybrid nanomaterial resulted in improved flux of 34.39 L/m2 h1, which corresponds to improvement by 110% compared to that of pristine membranes. During the antifouling test, PAL‐CH‐S/PA membrane attained 97% water recovery while the pristine membrane attained 90% water recovery.
Design, synthesis, SAR, and biological evaluation of saccharin‐based hybrids as carbonic anhydrase inhibitors
Authors: Chinchilli Krishna K. , Royyala Venkata N. , Thacker Pavitra S. , Angeli Andrea , Danaboina Srikanth , Singh Priti , Nanduri Srinivas , Supuran Claudiu T. , Arifuddin Mohammed
Published: April 2022

Saccharin is a cyclic secondary sulfonamide, which is a selective inhibitor of the tumor‐associated carbonic anhydrase (CA; EC 4.2.1.1) enzymes CA IX and CA XII compared to many primary sulfonamides. In this study, new saccharin‐1,2,3‐triazole and saccharin‐1,2,4‐oxadiazole hybrids were synthesized. All the newly synthesized molecules were screened for their CA‐inhibitory activity against four important human CA (hCA) isoforms: hCA I, hCA II, hCA IX, and hCA XII. Compounds 8a and 8f emerged as potent hCA II inhibitors (Ki = 3 µM). Compounds 6d, 6e and 7a, 7b were highly selective against hCA IX (6d, 6e) and hCA II (7a, 7b), with moderate inhibitory activity. The activity of these compounds was further confirmed by performing in silico docking studies against hCA II and hCA IX.
Hydrogen Peroxide‐triggered Chemical Strategy for Controlling CRISPR systems
Authors: Ji Huimin , Xiong Wei , Zhang Kaisong , Tian Tian , Zhou Xiang
Published: April 2022

The function of the CRISPR system can be conditionally controlled through rationally guided RNA engineering such that the target sequences can be precisely selected and manipulated. In particular, gRNA, as an important component of the CRISPR system, provides a unique tool for multifunctional control of the system based on the structure of the RNA itself. Therefore, we introduced here a protective group on the 2′‐OH position of RNA to inhibit RNA‐guided nucleic acid cleavage. Next, the modified gRNA can restore its original function under the chemical stimulation of hydrogen peroxide to realize the control of the CRISPR system. The experiment result demonstrated that the operating mechanism of this strategy may be based on chemical modifications that reduce the number of complementary base pairs between RNAs and targets, and the RNA‐protein interaction. This further enriches the toolbox of conditional control of CRISPR function and has broad potential for gene editing in living cells and disease treatment using endogenous hydrogen peroxide.
In Vivo Functional Ultrasound (fUS) Real‐Time Imaging and Dosimetry of Mice Brain Under Radiofrequency Exposure
Authors: Orlacchio Rosa , Percherancier Yann , Poulletier De Gannes Florence , Hurtier Annabelle , Lagroye Isabelle , Leveque Philippe , Arnaud‐Cormos Delia
Published: April 2022

This study aims to analyze in real‐time the potential modifications induced by low‐level continuous‐wave and Global System for Mobile Communications radiofrequency (RF) exposure at 1.8 GHz on brain activation in anesthetized mice. A specific in vivo experimental setup consisting of a dipole antenna for the local exposure of the brain was fully characterized. A unique neuroimaging technique based on a functional ultrasound (fUS) probe was used to observe the areas of mice brain activation simultaneously to the RF exposure with unprecedented spatial and temporal resolution (~100 μm, 1 ms) following manual whisker stimulation using a brush. Numerical and experimental dosimetry was carried out to characterize the exposure and to guarantee the validity of the biological results. Our results show that the fUS probe can be efficiently used during in vivo exposure without interference with the dipole. In addition, we conclude that exposure to brain‐averaged specific absorption rate levels of 2 and 6 W/kg does not introduce significant changes in the time course of the evoked fUS response in the left barrel field cortex. The proposed technique represents a valuable instrument for providing new insights into the possible effects induced on brain activation under RF exposure. For the first time, brain activity under mobile phone exposure was evaluated in vivo with fUS imaging, paving the way for more realistic exposure configurations, i.e. awake mice and new signals such as the 5 G networks. © 2022 Bioelectromagnetics Society.
Effects of Moderate to High Static Magnetic Fields on Reproduction
Authors: Song Chao , Yu Biao , Wang Junjun , Zhu Yiming , Zhang Xin
Published: April 2022

With the wide application of magnetic resonance imaging in hospitals and permanent magnets in household items, people have increased exposure to various types of static magnetic fields (SMFs) with moderate and high intensities, which has caused a considerable amount of public concern. Studies have shown that some aspects of gametogenesis and early embryonic development can be significantly affected by SMFs, while others have shown no effects. This review summarizes the experimental results of moderate to high‐intensity SMFs (1 mT–16.7 T) on the reproductive development of different model animals, and we find that the effects of SMFs are variable depending on experimental conditions. In general, the effects of inhomogeneous SMFs seem to be more significant compared to that of homogeneous SMFs, which is likely due to magnetic forces generated by the magnetic field gradient. Moreover, some electromagnetic fields may have induced bioeffects because of nonnegligible gradient and heat effect, which are much reduced in superconducting magnets. We hope this review can provide a starting point for more in‐depth analysis of various SMFs on reproduction, which is indispensable for evaluating the safety and potential applications of SMFs on living organisms in the future. © 2022 Bioelectromagnetics Society.
Lymph node ratio predicts efficacy of postoperative radiation therapy in nonmetastatic Merkel cell carcinoma: A population‐based analysis
Authors: Lamberti Giuseppe , Andrini Elisa , Siepe Giambattista , Mosconi Cristina , Ambrosini Valentina , Ricci Claudio , Marchese Paola Valeria , Ricco Gianluca , Casadei Riccardo , Campana Davide
Published: April 2022

Background

After radical resection of a nonmetastatic Merkel cell carcinoma (M0 MCC), postoperative radiation therapy (RT) is recommended as it improves survival. However, the role of RT in specific subgroups of M0 MCC is unclear. We sought to identify whether there is a differential survival benefit from RT in specific M0 MCC patient subgroups.

Methods

M0 MCC patients from the Surveillance, Epidemiology, and End Results (SEER) database registry were collected. The best prognostic age, tumor size, and lymph node ratio (LNR, ratio between positive lymph nodes and resected lymph nodes) cutoffs were calculated. The primary endpoint was overall survival (OS).

Results

A total of 5644 M0 MCC patients (median age 77 years, 62% male) were included: 4022 (71%) node‐negative (N0) and 1551 (28%) node‐positive (N+). Overall, 2682 patients (48%) received RT. Age > 76.5 years, tumor size >13.5 mm, and LNR >0.215 were associated with worse OS. RT was associated with longer OS in the M0 MCC, N0, and N+ group and independently associated with a 25%, 27%, and 26% reduction in the risk for death, respectively. RT benefit on survival was increased in tumor size >13.5 mm in the N0 group and LNR >0.215 in the N+ group. No OS benefit from RT was observed in T4 tumors (N0 and N+ groups).

Conclusions

RT was associated with improved survival in M0 MCC, irrespective of the nodal status. LNR >0.215 is a useful prognostic factor for clinical decision‐making and for stratification and interpretation of clinical trials.
Isolation, Structural Analysis and Anti‐Inflammatory Activity of a Polysaccharide from Ilex cornuta Fruits
Authors: Cui Mingxiao , Tian Junya , Sun Jun , Li Xinyuan , Xu Qiaohong , Ma Jian , Liu Kehai , Liu Kewu
Published: April 2022

In the present study, a polysaccharide from Ilex cornuta fruits (LCFP‐3) was obtained by hot water extraction, Diethyaminoethyl cellulose‐52 (DEAE‐52) chromatography column and Sephadex G‐100 gel column purification. Its structural characteristics were further explored using high performance anion exchange chromatography (HPAEC), gas chromatography and mass spectrometry (GC/MS), scanning electron microscopy (SEM), Fourier transform infrared (FT‐IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. Monosaccharide composition analysis revealed LCFP‐3 contained mainly Galactose (31.92 %), Arabinose (25.87 %) and Galacturonic acid (23.35 %) while small percentage of Rhamnose, Glucose, Mannose and Xylose. Chemical composition analysis showed that the total sugar content of LCFP‐3 was 90.31 % and the protein content was 0.246 %. Gel permeation chromatography (GPC) analysis showed that its average molecular weight was 41.199 kDa. Structural analysis showed that LCFP‐3 may be composed of residues, T‐α‐Arap, T‐α‐Rhap, 1,3‐α‐Arap, 1,4‐α‐Arap, T‐β‐Galp, 1,4‐α‐GalpA(OMe), 1,4‐β‐Glcp, 1,3‐β‐Galp, 1,3,6‐β‐Manp, 1,6‐β‐Galp, 1,3,4‐β‐GalpA, 1,4,6‐β‐Manp, 1,3,6‐β‐Glcp, 1,2,3,4‐α‐Xylp. The anti‐inflammatory activity of LCFP‐3 was evaluated using lipopolysaccharide (LPS)‐induced RAW246.7 macrophages. The results showed that 1–200 μg/mL LCFP‐3 could dose‐dependently protect against LPS‐induced toxicity and 1 μg/mL LCFP‐3 could significantly inhibit LPS‐induced NO production. Therefore, LCFP‐3 exerted an anti‐inflammatory activity and has great potential as a functional ingredient.
Essential Oils from Different Myrtaceae Species from Brazilian Atlantic Forest Biome – Chemical Dereplication and Evaluation of Antitrypanosomal Activity
Authors: Silva Maiolini Tatiane Cristina , Rosa Welton , de Oliveira Miranda Daniel , Costa‐Silva Thais A. , Tempone Andre G. , Pires Bueno Paula Carolina , Ferreira Dias Danielle , Aparecida Chagas de Paula Daniela , Sartorelli Patricia , Lago João Henrique G. , Gomes Soares Marisi
Published: April 2022

Chagas Disease (CD), caused by flagellate protozoan Trypanosoma cruzi, is a Neglected Tropical Diseases (NTD) that affect approximately seven million people worldwide with a restrict therapeutical arsenal. In the present study, the essential oils from 18 Myrtaceae species were extracted, chemically dereplicated, and evaluated in vitro against T. cruzi. From these, eight essential oils were considered promising (IC50<10 μg/mL and SI>10) against the protozoan: Eugenia florida, E. acutata, E. widgrenii, Calyptranthes brasilienses, C. widgreniana, Plinia cauliflora, Campomanesia xanthocarpa, and Psidium guajava. Multivariate data analysis pointed out (E)‐caryophyllene, α‐humulene, limonene, caryophyllene oxide, and α‐copaene playing an important role in the anti‐T. cruzi activity. The obtained results demonstrated the potential of essential oils of Myrtaceae species as valuable sources of bioactive compounds against T. cruzi.
Simultaneous proteasome and autophagy inhibition synergistically enhances cytotoxicity of doxorubicin in breast cancer cells
Authors: Loh Jian Sheng , Rahim Nusaibah Abdul , Tor Yin Sim , Foo Jhi Biau
Published: April 2022

Ubiquitin–proteasome system (UPS) and autophagy are interconnected proteolysis pathways implicated in doxorubicin resistance of breast cancer cells. Following anticancer treatments, autophagy either plays a cytoprotective role or augments treatment‐induced cytotoxicity. However, the role of autophagy in breast cancer cells cotreated with doxorubicin and ixazomib remains unclear. The expression of autophagy proteins (LC3A/B and Beclin‐1) and UPS protein (ubiquitin) in MDA‐MB‐231 and MCF‐7 cells following doxorubicin, ixazomib, and/or hydroxychloroquine were determined by western blot. The combinatorial effects and combination index (CI) of triple‐combination were determined by cell viability assay and CompuSyn software, respectively. Doxorubicin and ixazomib cotreatment increased Beclin‐1 (3.8‐ and 3.5‐fold) and LC3‐II expression (13.5‐ and 1.9‐fold) in MDA‐MB‐231 and MCF‐7 cells, respectively. Adding lysosomal inhibitor hydroxychloroquine to doxorubicin and ixazomib further increased LC3‐II expression to 45.0‐ and 16.5‐fold in MDA‐MB‐231 and MCF‐7 cells, respectively, confirming autophagy induction. The triple‐combination synergistically inhibited cell growth, achieving CI 0.672 and 0.157 in MDA‐MB‐231 and MCF‐7 cells, respectively. The triple‐combination also induced ubiquitinated proteins accumulation (2.5‐fold and 3.0‐fold) in MDA‐MB‐231 and MCF‐7 cells, respectively. These results suggest that the autophagy induced by doxorubicin and ixazomib cotreatment serves cytoprotective role in breast cancer cells. Simultaneous UPS and autophagy inhibition synergistically enhanced doxorubicin‐mediated cytotoxicity.
Case series of closure devices complications
Authors: Chami Tarek , Janus Scott E. , Shishehbor Mehdi H. , Li Jun
Published: April 2022

Vascular closure devices (VCD) are effective at achieving hemostasis. VCD failure is attributed to underlying arterial disease, leading to a hazardous situation for obtaining contralateral femoral access. Radial‐to‐peripheral (R2P) access has emerged as a safe option to rescue these procedural complications. Here, we present two cases of VCD failure rescue utilizing R2P and outline this approach step‐by‐step.
Novel Fe‐modified CeO2 Nanorod Catalyst for the Dimethyl Carbonate Formation from CO2 and Methanol
Authors: Luo Mingsheng , Qin Tong , Liu Qinglong , Yang Zhi , Wang Fengli , Li Hong
Published: April 2022

A series of Fe‐modified CeO2 catalysts with nanoparticle, nanorod, nanocube and nano‐octahedron morphologies were synthesized and applied for direct synthesis of dimethyl carbonate (DMC) from CO2 and methanol. The Fe‐modification shows a remarkably promoting effect on the formation of DMC over Fe‐modified CeO2 nanorod. The DMC yield was improved from 0.202 to 2.568 mmol DMC per gcat by 2 %Fe‐modification of CeO2 nanorod. A synergistic effect among the moderate acid‐basic sites, specific surface area and surface composition resulted from Fe‐modification was proposed to be crucial to obtaining the high reactivity of DMC formation.
Fluorinated Ether‐Based Electrolyte for Supercapacitors with Increased Working Voltage and Suppressed Self‐discharge
Authors: Yao Jing , Shi Mingwei , Li Wenshi , Han Qiankun , Wu Maosheng , Yang Wei , Wang Engui , Lu Xianmao
Published: April 2022

The application of supercapacitors for long‐term energy storage is largely limited by their low energy density and self‐discharge behavior. Finding a way to effectively increase the voltage window (and thus the energy density) and suppress the self‐discharge of supercapacitors is a huge research challenge. Herein, by introducing a fluorinated ether, 1,1,2,2‐tetrafluoroethyl‐2,2,3,3‐tetrafluoropropyl ether (TTE), in triethyl ammonium tetrafluoroborate/acetonitrile solution as the electrolyte of supercapacitors, improved electrolyte stability could be achieved. As a result, a working voltage of 3.6 V was obtained, much higher than the typical working voltage of 2.7 V for acetonitrile‐based electrolytes without TTE. In addition, reduced self‐discharge was attained after adding TTE in the electrolyte. When charged to 3.6 V, the supercapacitors using TTE‐based electrolyte exhibited an open circuit voltage (OCV) decay of 2.03 V after 24 h, lower than that of the supercapacitors without TTE (2.60 V). Mechanistic analysis indicated that the slower self‐discharge could be attributed to the suppressed activation‐controlled faradaic reaction process caused by electrolyte decomposition.
Unravelling Temperature Ramping Rates in Fabricating NaCl‐Induced Porous Co/N‐C Electrocatalysts for Oxygen Reduction Reaction
Authors: Sun Junting , Jin Jiaxiang , Chang Yatao , Wang Jing , Zhang Qindong , Guo Junjie
Published: April 2022

Pyrolysis is a necessary procedure for synthesizing carbon‐based nonprecious metal electrocatalysts via stimulating interaction and carbonization of precursors. In this work, ramping rates that correlated with thermal gradient has been investigated to reveal the configuration evolution of the precursors. Spectra characterizations demonstrated that ramping rates affected decomposition and aromatization of precursors. Increasing ramping rates improved the percentage of doped nitrogen and defects, promoting dispersion of Co atoms in the carbonaceous matrix and increasing density of active sties. In addition, the size variation of NaCl template under different ramping rates modifies the porous structure of Co/N−C electrocatalysts, greatly increasing the percentage of macropores and micropores at rapid ramping rates. As a result, electrocatalysts obtained at 5 °C min−1 exhibit comparable catalytic activity to that of Pt/C due to highly dispersed active sites and rational percentage of porosity, facilitating the sufficient reaction of oxygen along the catalysts. These results shed lights on regulating physical properties of carbonaceous electrocatalysts.
Progress and perspectives on electrospinning techniques for solid‐state lithium batteries
Authors: Lei Wen , Li Heng , Tang Yuxin , Shao Huaiyu
Published: April 2022

Solid‐state electrolytes (SSEs), being the key component of solid‐state lithium batteries, have a significant impact on battery performance. Rational materials structure and composition engineering on SSEs are promising to improve their Li+ conductivity, interfacial contact, and mechanical integrity. Among the fabrication approaches, the electrospinning technique has attracted tremendous attention due to its own merits in constructing a three‐dimensional framework of SSEs with precise porosity structure, tunable materials composition, easy operation, and superior physicochemical properties. To this end, in this review, we provide a comprehensive summary of the recent development of electrospinning techniques for high‐performance SSEs. Firstly, we introduce the historical development of SSEs and summarize the fundamentals, including the Li+ transport mechanism and materials selection principle. Then, the versatility of electrospinning technologies in the construction of the three main types of SSEs and stabilization of lithium metal anodes is comprehensively discussed. Finally, a perspective on future research directions based on previous work is highlighted for developing high‐performance solid‐state lithium batteries based on electrospinning techniques.
Robustness analysis of chemical process systems based on complex network non‐linear load capacity model
Authors: Dong Ran , Wang Zheng , Liu Ruijie , Li Huapeng , Jia Xiaoping , Wang Fang
Published: April 2022

In the complex network of chemical process systems, if a node fails, it may trigger cascading failures and affect normal operation. To enhance the ability of chemical process systems to maintain normal operation after the cascading failure, this paper presents cascading failure modelling and robustness analysis of chemical process systems based on the complex network non‐linear load capacity model. First, based on complex network theory, a complex network model of the chemical process is constructed; then, three cascading failure models are constructed using a combination of linear and non‐linear load capacity models and initial load and initial residual capacity redistribution strategies; and finally, the nodes with the maximum node degree are deliberately attacked to analyze the robustness of the chemical process system in response to cascading failure. The case study shows that the proposed models are valid and feasible, and the robustness of the chemical process system is enhanced as the load and capacity parameters are increased. By reasonably setting the initial load and adjusting the model parameters, the robustness can be effectively improved, providing a theoretical reference for improving the robustness of the actual chemical process system in response to cascading failure.
Lewis Acid Catalyzed Synthesis of Vinylene Linked Two Dimensional Covalent Organic Frameworks
Authors: Bin Bai , Ren Xiao‐Rui , Wang Dong , Wan Li‐Jun
Published: April 2022

Comprehensive Summary

Vinylene linked covalent organic frameworks (COFs) have drawn extensive attention due to their desirable stability, carbon conjugation and opto‐electronic properties. Suitable catalyst is a key factor in the synthesis of vinylene linked COFs, and proton acids and bases are widely reported as catalysts so far. Herein, we report the synthesis of vinylene linked COFs using Lewis acid ZnCl2 as catalyst for the first time. Four COFs with hexagonal pores of different sizes are synthesized by the reaction of 2,4,6‐trimethyl triazine and a series of aromatic aldehydes.
Spatial analysis of tumor‐infiltrating lymphocytes in histological sections using deep learning techniques predicts survival in colorectal carcinoma
Authors: Xu Hongming , Cha Yoon Jin , Clemenceau Jean R , Choi Jinhwan , Lee Sung Hak , Kang Jeonghyun , Hwang Tae Hyun
Published: April 2022

This study aimed to explore the prognostic impact of spatial distribution of tumor‐infiltrating lymphocytes (TILs) quantified by deep learning (DL) approaches based on digitalized whole‐slide images stained with hematoxylin and eosin in patients with colorectal cancer (CRC). The prognostic impact of spatial distributions of TILs in patients with CRC was explored in the Yonsei cohort (n = 180) and validated in The Cancer Genome Atlas (TCGA) cohort (n = 268). Two experienced pathologists manually measured TILs at the most invasive margin (IM) as 0–3 by the Klintrup–Mäkinen (KM) grading method and this was compared to DL approaches. Inter‐rater agreement for TILs was measured using Cohen's kappa coefficient. On multivariate analysis of spatial TIL features derived by DL approaches and clinicopathological variables including tumor stage, microsatellite instability, and KRAS mutation, TIL densities within 200 μm of the IM (f_im200) remained the most significant prognostic factor for progression‐free survival (PFS) (hazard ratio [HR] 0.004 [95% confidence interval, CI, 0.0001–0.15], p = 0.0028) in the Yonsei cohort. On multivariate analysis using the TCGA dataset, f_im200 retained prognostic significance for PFS (HR 0.031 [95% CI 0.001–0.645], p = 0.024). Inter‐rater agreement of manual KM grading was insignificant in the Yonsei (κ = 0.109) and the TCGA (κ = 0.121) cohorts. The survival analysis based on KM grading showed statistically significant different PFS in the TCGA cohort, but not the Yonsei cohort. Automatic quantification of TILs at the IM based on DL approaches shows prognostic utility to predict PFS, and could provide robust and reproducible TIL density measurement in patients with CRC.
A coupled computational framework for bone fracture healing and long‐term remodelling: Investigating the role of internal fixation on bone fractures
Authors: Quinn Conall , Kopp Alexander , Vaughan Ted J.
Published: April 2022

In this study, a coupled computational modelling framework for bone fracture repair is presented that enables predictions of both healing and remodelling phases of the fracture region and is used to investigate the role of an internal fixation plate on the long‐term healing performance of a fracture tibia under a range of different conditions. It was found that introduction of a titanium plate allowed the tibia to undergo successful healing at higher loading conditions and fracture gaps, compared with the non‐plated versions. While these plated cases showed faster rates of repair in the healing phase, their performance was substantially different once they entered the remodelling phase, with substantial regions of stress shielding predicted. This framework is one of the few implementations of both fracture healing and remodelling phases of bone repair and includes several innovative approaches to smoothing, time‐averaging and time incrementation in its implementation, thereby avoiding any unwanted abrupt changes between tissue phenotypes. This provides a better representation of tissue development in the fracture site when compared with fracture healing models alone and provides a suitable platform to investigate the long‐term performance of orthopaedic fixation devices. This would enable the more effective design of permanent fixation devices and optimisation of the spatial and temporal performance of bioabsorbable implants.
A novel EHD1/CD44/Hippo/SP1 positive feedback loop potentiates stemness and metastasis in lung adenocarcinoma
Authors: Liu Yuechao , Song Yang , Cao Mengru , Fan Weina , Cui Yaowen , Cui Yimeng , Zhan Yuning , Gu Ruixue , Tian Fanglin , Zhang Shuai , Cai Li , Xing Ying
Published: April 2022

Background

There is growing evidence that endocytosis plays a pivotal role in cancer metastasis. In this study, we first identified endocytic and metastasis‐associated genes (EMGs) and then investigated the biological functions and mechanisms of EMGs.

Methods

Cancer stem cells (CSCs)‐like characteristics were evaluated by tumour limiting dilution assays, three‐dimensional (3D) spheroid cancer models. Microarray analysis was used to identify the pathways significantly regulated by mammalian Eps15 homology domain protein 1 (EHD1) knockdown. Mass spectrometry (MS) was performed to identify EHD1‐interacting proteins. The function of EHD1 as a regulator of cluster of differentiation 44 (CD44) endocytic recycling and lysosomal degradation was determined by CD44 biotinylation and recycling assays.

Results

EHD1 was identified as a significant EMG. Knockdown of EHD1 suppressed CSCs‐like characteristics, epithelial–mesenchymal transition (EMT), migration and invasion of lung adenocarcinoma (LUAD) cells by increasing Hippo kinase cascade activation. Conversely, EHD1 overexpression inhibited the Hippo pathway to promote cancer stemness and metastasis. Notably, utilising MS analysis, the CD44 protein was identified as a potential binding partner of EHD1. Furthermore, EHD1 enhanced CD44 recycling and stability. Indeed, silencing of CD44 or disruption of the EHD1/CD44 interaction enhanced Hippo pathway activity and reduced CSCs‐like traits, EMT and metastasis. Interestingly, specificity protein 1 (SP1), a known downstream target gene of the Hippo‐TEA‐domain family members 1 (TEAD1) pathway, was found to directly bind to the EHD1 promoter region and induce its expression. Among clinical specimens, the EHD1 expression level in LUAD tissues of metastatic patients was higher than that of non‐metastatic patients.

Conclusions

Our findings emphasise that EHD1 might be a potent anti‐metastatic target and present a novel regulatory mechanism by which the EHD1/CD44/Hippo/SP1 positive feedback circuit plays pivotal roles in coupling modules of CSCs‐like properties and EMT in LUAD. Targeting this loop may serve as a remedy for patients with advanced metastatic LUAD.
Cutaneous cancers in the Africans: Systematic review
Authors: Ayanlowo Olusola O. , Adegbulu Abigail A. , Cole‐Adeife Olufolakemi
Published: April 2022

Introduction

Skin cancers are uncommon in Africans and dark‐skinned people but when diagnosed they often have a poor prognosis. Darker skin has increased photoprotection against the high‐intensity ultraviolet radiation (UVR) of the tropics and the subtropics due to high eumelanin content. While UVR has been found to play a significant role in the pathogenesis of cutaneous malignancies in Caucasians, it is of less significance in Africans.

Aim

This study aims to highlight the burden of cutaneous cancers in Africans, the predisposing factors, clinical features, and management challenges.

Methodology

This is a systematic review of literature on skin cancers in Africans. The search included PubMed, African Journal online, Medline, and Google scholar on articles published between January 1968 and December 2017 (a 50‐year period). Reports from institutions, pathology departments, skin clinics, cancer registries, and databases were reviewed. Articles were excluded if they do not specify types of skin cancers and frequencies of occurrence.

Result

Squamous cell carcinoma (SCC) was the most documented skin cancer in Sub‐Saharan African countries with darker skin color; and BCC in North African countries with lighter skin color. The highest frequency of cutaneous melanoma was documented in Tanzania. Cancer registries in Uganda and Zimbabwe reported very high prevalence of KS. Albinism is the most common genetic predisposition for cutaneous cancers in Africans. There has been a general increase in the prevalence of skin cancers with the advent of human immunodeficiency virus infection. Africans with albinism present mostly with aggressive, invasive, and multiple SCC. Pigmented BCC and acral lentiginous melanoma were mostly documented in the dark skinned Africans. Management is mostly hindered by high cost and poor infrastructures.

Conclusion

Squamous cell carcinoma, BCC, and cutaneous melanoma were the most documented skin cancers. Oculocutaneous albinism, immune suppression (HIV), and oncogenic viruses were important risk factors for skin cancers in Africans. Public health strategies such as skin cancer screening programs for susceptible groups; training of health care workers and infrastructure development will help reduce severity.
Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non‐ischaemic dilated cardiomyopathy
Authors: Mirelis Jesús G. , Escobar‐Lopez Luis , Ochoa Juan Pablo , Espinosa María Ángeles , Villacorta Eduardo , Navarro Marina , Casas Guillem , Mora‐Ayestarán Nerea , Barriales‐Villa Roberto , Mogollón‐Jiménez María Victoria , García‐Pinilla José M. , García‐Granja Pablo E. , Climent Vicente , Palomino‐Doza Julian , García‐Álvarez Ana , Álvarez‐Barredo María , Cabrera‐Borrego Eva , Ripoll‐Vera Tomás , Peña‐Peña María Luisa , Rodríguez‐González Elena , Gallego‐Delgado María , Gonzalez‐Carrillo Josefa , Fernández‐Ávila Ana , Rodríguez‐Palomares José F. , Brugada Ramón , Bayes‐Genis Antoni , Dominguez Fernando , García‐Pavía Pablo
Published: April 2022

Aims

Genotype and left ventricular scar on cardiac magnetic resonance (CMR) are increasingly recognized as risk markers for adverse outcomes in non‐ischaemic dilated cardiomyopathy (DCM). We investigated the combined influence of genotype and late gadolinium enhancement (LGE) in assessing prognosis in a large cohort of patients with DCM.

Methods and results

Outcomes of 600 patients with DCM (53.3 ± 14.1 years, 66% male) who underwent clinical CMR and genetic testing were retrospectively analysed. The primary endpoints were end‐stage heart failure (ESHF) and malignant ventricular arrhythmias (MVA). During a median follow‐up of 2.7 years (interquartile range 1.3–4.9), 24 (4.00%) and 48 (8.00%) patients had ESHF and MVA, respectively. In total, 242 (40.3%) patients had pathogenic/likely pathogenic variants (positive genotype) and 151 (25.2%) had LGE. In survival analysis, positive LGE was associated with MVA and ESHF (both, p < 0.001) while positive genotype was associated with ESHF (p = 0.034) but not with MVA (p = 0.102). Classification of patients according to genotype (G+/G−) and LGE presence (L+/L−) revealed progressively increasing events across L−/G−, L−/G+, L+/G− and L+/G+ groups and resulted in optimized MVA and ESHF prediction (p < 0.001 and p = 0.001, respectively). Hazard ratios for MVA and ESHF in patients with either L+ or G+ compared with those with L−/G− were 4.71 (95% confidence interval: 2.11–10.50, p < 0.001) and 7.92 (95% confidence interval: 1.86–33.78, p < 0.001), respectively.

Conclusion

Classification of patients with DCM according to genotype and LGE improves MVA and ESHF prediction. Scar assessment with CMR and genotyping should be considered to select patients for primary prevention implantable cardioverter‐defibrillator placement.
Precision Glycodendrimers for DC‐SIGN Targeting**
Authors: Goti Giulio , Colombo Cinzia , Achilli Silvia , Vivès Corinne , Thépaut Michel , Luczkowiak Joanna , Labiod Nuria , Delgado Rafael , Fieschi Franck , Bernardi Anna
Published: April 2022

Multivalent ligands of the C‐type lectin receptor DC‐SIGN have emerged as effective antiadhesive agents against various pathogens. Some years ago, we described a hexavalent DC‐SIGN ligand, Polyman‐26, designed to bridge two of the four binding sites displayed by the receptor. In this work, we present our efforts to accomplish simultaneous coordination of all four carbohydrate binding sites of DC‐SIGN through the synthesis of cross‐shaped glycodendrimers. The tailored rigid scaffold allowed multivalent presentation of glycomimetics in a spatially defined fashion, while providing good water solubility to the constructs. Evaluation of the biological activity by SPR assays revealed strong binding avidity towards DC‐SIGN and increased selectivity over langerin. Inhibition of DC‐SIGN binding to SARS‐CoV‐2 spike protein and of DC‐SIGN mediated Ebola virus trans‐infection testifies for the glycodendrimers potential application in infection diseases. The tetravalent platform described here is easily accessible and can be used in modular fashion with different ligands, thus lending itself to multiple applications.
A new multimodality fusion classification approach to explore the uniqueness of schizophrenia and autism spectrum disorder
Authors: Du Yuhui , He Xingyu , Kochunov Peter , Pearlson Godfrey , Hong L. Elliot , van Erp Theo G. M. , Belger Aysenil , Calhoun Vince D.
Published: April 2022

Schizophrenia (SZ) and autism spectrum disorder (ASD) sharing overlapping symptoms have a long history of diagnostic confusion. It is unclear what their differences at a brain level are. Here, we propose a multimodality fusion classification approach to investigate their divergence in brain function and structure. Using brain functional network connectivity (FNC) calculated from resting‐state fMRI data and gray matter volume (GMV) estimated from sMRI data, we classify the two disorders using the main data (335 SZ and 380 ASD patients) via an unbiased 10‐fold cross‐validation pipeline, and also validate the classification generalization ability on an independent cohort (120 SZ and 349 ASD patients). The classification accuracy reached up to 83.08% for the testing data and 72.10% for the independent data, significantly better than the results from using the single‐modality features. The discriminative FNCs that were automatically selected primarily involved the sub‐cortical, default mode, and visual domains. Interestingly, all discriminative FNCs relating to the default mode network showed an intermediate strength in healthy controls (HCs) between SZ and ASD patients. Their GMV differences were mainly driven by the frontal gyrus, temporal gyrus, and insula. Regarding these regions, the mean GMV of HC fell intermediate between that of SZ and ASD, and ASD showed the highest GMV. The middle frontal gyrus was associated with both functional and structural differences. In summary, our work reveals the unique neuroimaging characteristics of SZ and ASD that can achieve high and generalizable classification accuracy, supporting their potential as disorder‐specific neural substrates of the two entwined disorders.
Is a law enough to provide a better prognosis for Brazilian melanoma patients or education is still a gap?
Authors: Marcelino Bruno Aquino , Soares Fernanda Hermeto , Curi Marcela Lima de Castro , Alves Wainstein Alberto Julius , Drummond‐Lage Ana Paula
Published: April 2022

According to Brazilian Law 12.732/12 (“60‐day law”), cancer patients have 60 days after diagnosis for beginning treatment at the Unified Health System (SUS). The study aimed to evaluate the achievement and effectiveness of the ‘60‐day law’ for melanoma patients in a SUS cancer reference unit. A retrospective study analysed 58 medical charts from patients with the initial diagnosis performed before and after the “60‐day law”. The Law does not change the time interval between diagnosis and the beginning of treatment, and after the Law, patients presented a worse overall survival (p < 0.001). In conclusion, the ‘60‐day law’ was not effective.
An index number approach to estimating organic price premia at retail
Authors: Çakır Metin , Beatty Timothy K. M. , Boland Michael A. , Li Qingxiao , Park Timothy A. , Wang Yanghao
Published: April 2022

A full understanding of the retail price premia commanded by organic foods is essential to production, marketing, and public policy decisions. But there is no systematic information on magnitudes of the premia and how they change over time and across space. This article uses index number methods to estimate spatially and temporally consistent retail price premia for organic fresh fruits and vegetables (FFV). The indices are constructed using weekly point‐of‐sale scanner data from grocery stores and mass merchandisers in 24 contiguous metropolitan statistical areas (MSA) between 2009 and 2017. Our main result is that the national average organic price premia in the FFV market are persistent, ranging between 58% and 92%, and trending upward over the study period. The differences in premia across MSAs are large, while they have slightly converged during the study period. The premia also differ substantially across products. Lastly, we construct the price indices and estimate the premia using alternative compositions of index baskets. We show that price premia are substantially overestimated if the price of the conventional product basket is not calculated with the same weights used to calculate the price of the organic basket.
Reliability and validity of using structured visual‐inspection criteria to interpret latency‐based functional analysis outcomes
Authors: Sunde Eleah , Briggs Adam M. , Mitteer Daniel R.
Published: April 2022

Prior research has evaluated the reliability and validity of structured visual inspection (SVI) criteria for interpreting functional analysis (FA) outcomes (Hagopian et al., 1997; Roane et al., 2013). We adapted these criteria to meet the unique needs of interpreting latency‐based FA outcomes and examined the reliability and validity of applying SVI criteria to 43 previously published latency‐based FA datasets. Overall, raters agreed on SVI‐determined FA outcomes (98% of functions and 95% of cases) and these outcomes corresponded well to the interpretations provided by the authors of these 43 datasets (94% of functions and 88% of cases), indicating a high degree of reliability and concurrent validity. Our findings suggest that the use of SVI criteria may (a) serve as an objective aid in the identification of behavioral function(s), (b) produce high levels of agreement among expert raters, and (c) serve as a useful resource when teaching students how to interpret latency‐based FA outcomes.
Availability and characteristics of teaching and learning curriculum programs for first year pharmacy residents: A national perspective
Authors: Thomas Michael C. , Benner Kim , Hughes Peter J.
Published: April 2022

Introduction

Previous surveys on teaching and learning curriculum (TLC) programs focus on specific populations (ie, schools and colleges of pharmacy). However, the prevalence and characteristics of TLC programs available through pharmacy residency programs across the spectrum of postgraduate year one (PGY1) programs is not known.

Objectives

To determine the national prevalence, requirements, cost, and reasons for offering TLC programs in United States (US).

Methods

After pilot testing, an electronic survey was sent to all pharmacy PGY1 residency program directors in the US. The survey asked respondents if a TLC program was available through their program and, if so, queried additional details about requirements for resident participants and cost considerations. Additionally, participants were asked to rank reasons for not making TLC programs available, if applicable. Data were summarized using descriptive statistics.

Results

There were 419 surveys at least partially completed, which represented a 28.2% response rate and similar geographic distribution of respondents to that of the overall population of residency programs. Nearly 95% of responding residency programs offer a TLC program to their residents. Consistent with recommendations, a variety of teaching activities are completed by residents, with classroom instruction (75.2%) being most common. However, dyssynchrony exists between classroom instruction and didactic assessment (59.3%). Simulation and laboratory teaching opportunities was the least prevalent teaching activity (49%). Most TLC programs are not associated with a fee, but about 25% reported charging at least $25 per resident.

Conclusion

TLC programs are commonly offered through PGY1 pharmacy residency programs in the US. Most programs are facilitated by schools or colleges of pharmacy and offer residents a wide variety of teaching opportunities. However, there remains a gap in assessment and in simulation or lab teaching opportunities. The results of this study can be used by residency and TLC programs for self‐examination and quality improvement efforts.
Perfectionism unbound: An integrated individual and group intervention for those hiding imperfections
Authors: Cheli Simone , Cavalletti Veronica , Flett Gordon L. , Hewitt Paul L.
Published: April 2022

The tendency to hide and mask suffering and one's perceived imperfections is one of the biggest obstacles in treating those with prominent perfectionistic traits. In this single case, we present an integrative form of psychotherapy for patients with recurrent strategies aimed at neither displaying nor disclosing their perfectionism. Emily was a 26‐year‐old woman diagnosed with Major Depressive Disorder and reported a personality pathology as diagnosed through the Alternative Model of Personality Disorders. The intervention comprised of a 4‐month individual therapy and 2‐month group therapy. The former is based on Metacognitive Interpersonal Therapy protocol for personality disorders. The latter is a protocol that integrates the Dynamic Relational Treatment for Perfectionism and Compassion Focused Therapy. At the end of this integrative treatment, Emily remitted from Major Depressive Disorder and personality pathology. Further studies should confirm our promising results in larger samples.
Effect of CD38 on B‐cell function and its role in the diagnosis and treatment of B‐cell‐related diseases
Authors: Zeng Feng , Zhang Jiani , Jin Xi , Liao Qianjin , Chen Zhifang , Luo Gengqiu , Zhou Yanhong
Published: April 2022

CD38 is a multifunctional receptor and enzyme present on the surface of B lymphocytes, which can induce B lymphocytes proliferation and apoptosis by crosslinking related cytokines to affect the function of B cells, thus affecting immune regulation in humans and promoting tumorigenesis. The level of CD38 expression in B cells has become an important factor in the clinical diagnosis, treatment, and prognosis of malignant tumors and other related diseases. Therefore, studying the relationship between CD38 expression on the surface of B cells and the occurrence of the disease is of great significance for elucidating its association with disease pathogenesis and the clinical targeted therapy. In this paper, we review the effects of CD38 on B‐cell activation, proliferation, and differentiation, and elaborate the functional role and mechanism of CD38 expression on B cells. We also summarize the relationship between the level of CD38 expression on the surface of B cells and the diagnosis, treatment, and prognosis of various diseases, as well as the potential use of targeted CD38 treatment for related diseases. This will provide an important theoretical basis for the scientific research and clinical diagnosis and treatment of B‐cell‐related diseases.
Evolution and functionalization of vitellogenin genes in the termite Reticulitermes speratus
Authors: Yaguchi Hajime , Suzuki Shogo , Kanasaki Naoto , Masuoka Yudai , Suzuki Ryutaro , Suzuki Ryouhei H. , Hayashi Yoshinobu , Shigenobu Shuji , Maekawa Kiyoto
Published: April 2022

Eusociality has been commonly observed in distinct animal lineages. The reproductive division of labor is a particular feature, achieved by the coordination between fertile and sterile castes within the same nest. The sociogenomic approach in social hymenopteran insects indicates that vitellogenin (Vg) has undergone neo‐functionalization in sterile castes. Here, to know whether Vgs have distinct roles in nonreproductive castes in termites, we investigated the unique characteristics of Vgs in the rhinotermitid termite Reticulitermes speratus. The four Vgs were identified from R. speratus (RsVg1−4), and RsVg3 sequences were newly identified using the RACE method. Molecular phylogenetic analysis supported the monophyly of the four termite Vgs. Moreover, the termites Vg1−3 and Vg4 were positioned in two different clades. The  dN/dS ratios indicated that the branch leading to the common ancestor of termite Vg4 was under weak purifying selection. Expression analyses among castes (reproductives, workers, and soldiers) and females (nymphs, winged alates, and queens) showed that RsVg1−3 was highly expressed in fertile queens. In contrast, RsVg4 was highly expressed in workers and female nonreproductives (nymphs and winged adults). Localization of RsVg4 messenger RNA was confirmed in the fat body of worker heads and abdomens. These results suggest that Vg genes are functionalized after gene duplication during termite eusocial transition and that Vg4 is involved in nonreproductive roles in termites.