bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facile preparation of tetra‐polyethylene glycol hydrogel microspheres for drug delivery by cross‐flow membrane emulsification
Authors: Henise Jeff , Yao Brian , Ashley Gary W. , Santi Daniel V. 
Published: May 2021

AbstractThe purpose of this work was to develop technology for facile, large‐scale production of tetra‐polyethylene glycol (PEG) hydrogel amino‐microspheres to serve as intermediates for injectable microsphere‐drug conjugates produced under cGMP guidelines. Here we developed equipment and procedures utilizing tubular cross‐flow membrane emulsification to produce the amino‐microspheres. The equipment comprised a polyether ether ketone tube containing 1000 evenly spaced pores encased in a cylindrical stainless steel jacket. The dispersed phase – an aqueous solution of two polymerizable tetra‐PEG prepolymers – is delivered into the outer jacket of the assembly by a pulse dampened pump, and the continuous phase – decane and surfactant – is delivered into the bore of the microporous tube from a pressurized tank. As the dispersed phase is pressed through the pores, the continuous phase induces the detachment of small, uniform droplets of ˜60 μm diameter at the mouths of the pores. After collection of the emulsified droplets, they are allowed to self‐polymerize and are then sieved to remove aberrantly small and large particles. The polymerized amino‐microspheres – obtained in ˜70% yield – are well within acceptance specifications, and show excellent injectability. Using this approach, we could prepare about 30 L of swollen amino‐microspheres per day which could be forwarded to production of microsphere‐drug substance under cGMP guidelines.
Control of dissolved oxygen significantly increases the yield of skin‐derived Schwann cells during expansion in stirred suspension bioreactors
Authors: Walsh Tylor , Biernaskie Jeff , Midha Rajiv , Kallos Michael S. 
Published: May 2021

AbstractPeripheral nerve and spinal cord injuries affect millions of people worldwide often leading to lifelong disability and pain. Cell therapy using autologous Schwann cells are currently being investigated for the treatment of these injuries and are showing great potential. In particular, skin‐derived Schwann cells offer a non‐invasive option for highly therapeutic cells that have been shown to regenerate tissue and restore function. However, it is estimated that for an effective therapy, hundreds of millions of Schwann cells are needed, and current static and spinner flask methods cannot generate these clinical numbers. Therefore, this study utilizes control systems facilitated by stirred suspension bioreactors to monitor and maintain the pH and dissolved oxygen at levels that promote cell proliferation and survival. By adapting the current culture practices to scalable bioreactor platforms, we were able to control the dissolved oxygen creating new expansion protocols that enabled the bioreactor process to grow to clinical scale, producing 667 × 106 cells in a single 500 mL bioreactor in 7 days. Since individual injury is different in terms of complexity and severity, and therefore cell needs, by changing the available surface area in the bioreactor, this developed process is highly adjustable to meet the cell quantity needs for each individual treatment. Following the bioprocess, cells that were harvested from the microcarriers continue to express typical Schwann cell markers suggesting that they retain phenotypic stability. By increasing the production potential of skin‐derived Schwann cells, this therapy is one step closer to the clinic with the hope for ultimately restoring function and improving quality of life to patients with neural injuries.
Investigation on the characteristics and mechanisms of ACE inhibitory peptides by a thorough analysis of all 8000 tripeptides via binding free energy calculation
Authors: Chen Ruiyao , Miao Yulu , Hao Xuan , Gao Bei , Ma Mingzhe , Zhang John Z.H. , Wang Rui , Li Sha , He Xiao , Zhang Lujia 
Published: May 2021

AbstractFood‐derived angiotensin I‐converting enzyme (ACE) inhibitory peptides represent a potential source of new antihypertensive. However, their characteristics and binding mechanisms were not well understood. In this study, novel energy calculation and experimentation were combined to elucidate the characteristics and mechanisms of ACE inhibitory tripeptides. ACE inhibitory activity of all 8,000 tripeptides was investigated by in silico experiments. IC50 values of the five top‐rated tripeptides ranged from 5.86 to 21.84 μM. Five hundred top‐ranked tripeptides were chosen for detailed structure–activity analysis, and a significant preference for aromatic amino acids at both C‐ and N‐terminus was found. By binding free energy analysis of nine representative tripeptides via MM/GBSA, electrostatic energy was found to be the leading energy that contributed to the binding of ACE with its high affinity tripeptides. Besides, S355, V380, and V518, three residues positioned around the classical binding pockets of ACE, also played a key role in ACE's binding. Therefore, for tripeptides, their binding pockets in ACE were redefined. In conclusion, the characteristics of ACE inhibitory peptides were more deeply illustrated by the thorough analysis of all tripeptides. The energy analysis allows a better understanding of the binding mechanisms of ACE inhibitory peptides, which could be used to redesign the ACE inhibitors for stronger inhibitory activity.
Toward the identification of molecular markers associated with phytochemical traits in the Iranian sumac (Rhus coriaria L.) population
Authors: Mohammadi Alaghuz Rasoul , Darvishzadeh Reza , Alijanpour Ahmad , Razi Mitra 
Published: May 2021

AbstractSumac (Rhus coriaria L.) is one of the important forest species dispersed in the northwest of Iran. It is one of the important spice in Iran and the Middle East because of active components containing organic acids, phenolic acids, flavonoids, anthocyanins, tannins and terpenoids. This study aimed to investigate population structure and linkage disequilibrium (LD) extent within Rhus coriaria L. genotypes using ISSR markers and identify molecular markers associated with phytochemical traits using association analysis. In the molecular part of the experiment, the genetic diversity of 75 sumac genotypes from five different areas of northwest Iran was assessed by 18 ISSR primers. In the phenotypic assessment, the fruits of the sumac genotypes were analyzed using HPLC‐LC/MSMS for determining phytochemical components including maleic acid, ellagic acid, maleic acid hexoside, gallic acid, coumaric acid, quercetin, caftaric acid, and linoleic acid. The phenotypic data analysis revealed the great phenotypic diversity among and within Iranian sumac populations for the studied phytochemical traits. The studied sumac genotypes were divided into two subpopulations based on molecular marker‐based structure analysis. A significant level of LD was observed in 11.64% of the ISSR marker pairs (p < .05). The mixed linear model procedure showed that 12 loci had a significant association with investigated traits. The ISSR loci identified in this study can be potentially used in marker‐assisted selection in sumac breeding programs.
Single nucleotide polymorphism array‐based signature of low hypodiploidy in acute lymphoblastic leukemia
Authors: Creasey Thomas , Enshaei Amir , Nebral Karin , Schwab Claire , Watts Kathryn , Cuthbert Gavin , Vora Ajay , Moppett John , Harrison Christine J. , Fielding Adele K. , Haas Oskar A. , Moorman Anthony V. 
Published: May 2021

AbstractLow hypodiploidy (30–39 chromosomes) is one of the most prevalent genetic subtypes among adults with ALL and is associated with a very poor outcome. Low hypodiploid clones can often undergo a chromosomal doubling generating a near‐triploid clone (60–78 chromosomes). When cytogenetic techniques detect a near triploid clone, a diagnostic challenge may ensue in differentiating presumed duplicated low hypodiploidy from good risk high hyperdiploid ALL (51–67 chromosomes). We used single‐nucleotide polymorphism (SNP) arrays to analyze low hypodiploid/near triploid (HoTr) (n = 48) and high hyperdiploid (HeH) (n = 40) cases. In addition to standard analysis, we derived log2 ratios for entire chromosomes enabling us to analyze the cohort using machine‐learning techniques. Low hypodiploid and near triploid cases clustered together and separately from high hyperdiploid samples. Using these approaches, we also identified three cases with 50–60 chromosomes, originally called as HeH, which were, in fact, HoTr and two cases incorrectly called as HoTr. TP53 mutation analysis supported the new classification of all cases tested. Next, we constructed a classification and regression tree model for predicting ploidy status with chromosomes 1, 7, and 14 being the key discriminators. The classifier correctly identified 47/50 (94%) HoTr cases. We validated the classifier using an independent cohort of 44 cases where it correctly called 7/7 (100%) low hypodiploid cases. The results of this study suggest that HoTr is more frequent among older adults with ALL than previously estimated and that SNP array analysis should accompany cytogenetics where possible. The classifier can assist where SNP array patterns are challenging to interpret.
Dynamic contrast‐enhanced magnetic resonance imaging for differentiating head and neck paraganglioma and schwannoma
Authors: Malla Soumya Ranjan , Bhalla Ashu Seith , Manchanda Smita , Kandasamy Devasenathipathy , Kumar Rakesh , Agarwal Shipra , Shamim Shamim Ahmed , Kakkar Aanchal 
Published: May 2021

AbstractBackground and PurposeMorphological assessment with conventional magnetic resonance imaging (MRI) sequences has limited specificity to distinguish between paragangliomas and schwannomas. Assessing the differences in microvascular properties through pharmacokinetic parameters of dynamic contrast‐enhanced (DCE)‐MRI can provide additional information to aid in this differentiation.Materials and MethodsA prospective study on MR characterization of neck masses was performed between January 2017 and March 2019 in our department, out of which 40 patients with head and neck paragangliomas (HNPGLs) (33 lesions) and schwannomas (15 lesions) were included in this analysis. MR perfusion using dynamic axial T1WI fat suppressed fast spoiled gradient recalled sequence with parallel imaging was performed in all the patients, in addition to single‐shot turbo spin‐echo axial diffusion weighted imaging (DWI) and routine MRI. ROI‐based method was used to obtain signal‐time curves, permeability measurements, and mean apparent diffusion coefficient (ADC) to differentiate paragangliomas from schwannomas. Statistical analysis was done to assess the significance and establish a cutoff to distinguish between the two entities. The available images of DOTANOC PET/CT (34 lesions) were analyzed retrospectively. Correlations between the perfusion, diffusion, and molecular PET/CT parameters were done.ResultsParagangliomas had a higher wash‐in rate, wash‐out rate, Ktrans, Kep, and Vp (p < 0.001); while schwannomas had a higher relative enhancement (p < 0.012), time to peak, time of onset, brevity of enhancement, and Ve (p < 0.001). Among the perfusion parameters, Kep (area under curve (AUC) 0.994) and Vp (AUC 0.992) were found to have the highest diagnostic value. In diffusion‐weighted imaging, paragangliomas had a lower mean ADC compared to schwannomas (p < 0.001). The SUVmax and SUVmean were significantly associated with Ktrans, Kep, and Vp in paragangliomas.ConclusionDCE‐MRI in addition to DWI‐MRI can accurately distinguish HNPGL from schwannoma and may replace the need for any additional imaging and preoperative biopsy in most cases.
Deep learningsuper‐resolutionelectron microscopy based on deep residual attention network
Authors: Wang Jia , Lan Chuwen , Wang Caiyong , Gao Zehua 
Published: May 2021

AbstractField‐emission scanning electron microscopy has become a fundamental research tool in the fields of medicine and materials science owing to its effectiveness. However, an inherent contradiction exists between the resolution of field‐emission scanning electron microscopy and its field‐of‐view. To solve this problem, we propose a deep learning‐based method for electron microscopy that can simultaneously obtain a large field‐of‐view and ultrahigh resolution. To solve the super‐resolution problem, a deep residual attention network is designed based on residual learning and the attention mechanism, wherein the backbone network employs several residual groups to effectively extract the features; moreover, attention groups append the backbone part to refine and fuse the features. Besides, a high‐frequency information retention module is added to acquire high‐frequency signals, acting as an effective complement to the deep residual attention network. Owing to the lack of super‐resolution datasets for electron microscopy, we created a microscopic butterfly wing dataset. In the experiments, MixUp was also applied to super‐resolution problem as a simple and effective data augmentation method, to provide more data to train the model. To evaluate the proposed method, we used standard and self‐made datasets with peak signal‐to‐noise ratio (PSNR) and structural similarity (SSIM) as criteria. The results show that the proposed model exhibits a state‐of‐the‐art performance with a PSNR of 25.12 dB and an SSIM of 0.64, and makes field‐emission scanning electron microscopy more practical and promising in the field of optical device optimization.
GPR30 knockdown weakens the capacity of CAF in promoting prostate cancer cell invasion via reducing macrophage infiltration and M2 polarization
Authors: Zhang Ran , Zong Jiaojiao , Peng Yanfei , Shi Jiandang , Du Xiaoling , Liu Haitao , Shen Yongmei , Cao Jiasong , Jia Bona , Liu Feng , Zhang Ju 
Published: May 2021

AbstractCancer‐associated fibroblasts (CAFs) can promote the development and metastasis of prostate cancer partly by mediating tumor‐associated inflammation. An increasing amount of studies have focused on the functional interactions between CAFs and immune cells in the tumor microenvironment (TME). We previously reported that G protein‐coupled receptor 30 (GPR30) was highly expressed in prostate CAFs and plays a crucial role in prostate stromal cell activation. However, the effect and underlying mechanism of GPR30 expression in prostate CAFs affecting the interaction between CAFs and tumor‐associated macrophages (TAMs) need further elucidation. Here, we found that, compared with CAF‐shControl, CAF‐shGPR30 inhibited macrophage migration through transwell migration assays, which should be attributed to the decreased expression of C‐X‐C motif chemokine ligand 12 (CXCL12). In addition, macrophages treated with a culture medium of CAF‐shGPR30 exhibited attenuated M2 polarization with downregulated M2‐like markers expression. Moreover, macrophages stimulated with a culture medium of CAF‐shGPR30 were less efficient in promoting activation of fibroblast cells and invasion of PCa cells. Finally, cocultured CAF‐shGPR30 and macrophages suppressed PCa cell invasion compared to cocultured CAF‐shControl and macrophages by decreasing interleukin‐6 (IL‐6) secretion, and this effect could be abrogated with rescue expression of IL‐6. Our results pinpoint the function of GPR30 in prostate CAFs on regulating the CAF‐TAM interaction in the TME and provide new insights into PCa therapies via regulating TME.
Combined scaffold hopping, molecular screening with dynamic simulation to screen potent CRBN ligands
Authors: Yan Jian , Sun Shiyang , Zhang Wenjuan , Li Pengyun , Zheng Zhibing 
Published: May 2021

AbstractThalidomide and its derivatives lenalidomide and pomalidomide, known as immunomodulatory drugs, (IMiDs) bind directly to cereblon (CRBN), a substrate receptor of an E3 ubiquitin ligase, resulting in the rapid ubiquitination and degradation of the substrate protein. With the discovery of the protein degradation mechanism of IMiDs, targeted protein degradation mediated by IMiDs via CRBN emerged and developed rapidly for the advantages of overcoming drug resistance and targeting undruggable. To date, almost all CRBN ligands are derived from thalidomide and there are few structural differences between them. Hence, we employed an accurate, effective, and rational approach to screen novel and potential CRBN ligands. In this study, we have built a molecular library by scaffold hopping with thalidomide. ADMET screening, virtual screening, and visual inspection screening were performed step‐by‐step to screen the molecular library and five molecules were hit. Furthermore, docking analysis and a period of 150 ns molecular dynamic (MD) simulation were performed to validate the accuracy of our screen. The docking results showed that molecular A (−10.42 kcal/mol), molecular B (−9.73 kcal/mol), molecular C (−9.25 kcal/mol), molecular D (−9.09 kcal/mol), and molecular E (−10.16 kcal/mol) have lower binding energy than thalidomide (−5.42 kcal/mol), lenalidomide (−5.74 kcal/mol), and pomalidomide (−5.51 kcal/mol). In the MD simulation, all the five screened molecules form key interactions with the active site amino acid residues (Trp380, Trp386, and Trp400) as well as the three marketed IMiDs. Besides, we found and explained that Pro352 was positive for ligand binding to CRBN and Glu377 in reverse, which has not been reported before. We believe that our findings and those five molecules can serve as further optimization of CRBN ligands and development of proteolysis targeting chimeras.
A note on magic rectangle set MRSΓ(2k+1,4;4l+2)
Authors: Cichacz Sylwia , Hinc Tomasz 
Published: May 2021

AbstractA ‐magic rectangle set of order is a set of arrays of size whose entries are elements of a finite Abelian group of order , each appearing once, with all row sums in each rectangle equal to a constant and all column sums in each rectangle equal to a constant . There is known a complete characteristic of a for for positive integers . The case is unsolved for . In this paper we show that a exists if and only if the group has more than one involution.
Association of alpha‐thalassemia and Glucose‐6‐Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia
Authors: Ojewunmi Oyesola Oyewole , Adeyemo Titilope Adenike , Oyetunji Ajoke Idayat , Benn Yewande , Ekpo Mfoniso Godwin , Iwalokun Bamidele Abiodun 
Published: May 2021

AbstractBackgroundStroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha‐thalassemia and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha‐thalassemia and G6PD(A−) variant with abnormal TCD velocities among Nigerian children with SCA.MethodsOne hundred and forty‐one children with SCA were recruited: 72 children presented with normal TCD (defined as the time‐averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha‐thalassemia (the α‐3.7 globin gene deletion) was determined by multiplex gap‐PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism—polymerase chain reaction.ResultsThe frequency of α‐thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α‐/ α α: 41.7%, α ‐/ α ‐: 11.1%] versus 21/69 (30.4%) [α‐/ α α: 27.5%, α ‐/ α ‐: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α‐thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20–0.78, p = 0.007]. However, the frequencies of G6PDA− variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).ConclusionOur study reveals the protective role of α‐thalassemia against the risk of abnormal TCD in Nigerian children with SCA.
Microalgae for nutrient recycling from food waste to aquaculture as feed substitute: a promising pathway to eco‐friendly development
Authors: Deng Yi , Chen Fufeng , Liao Kang , Xiao Yu , Chen Sihua , Lu Qian , Li Jun , Zhou Wenguang 
Published: May 2021

AbstractBACKGROUND: The discharge of food waste and eutrophication in aquaculture could cause environmental pollution and ecological disasters in the hydrosphere. Herein, a novel model of growing microalgae to recover nutrients from food waste and produce feed substitute for aquaculture is proposed.RESULTS: This study developed different methods to pretreat soybean fermentation effluent (SFE) and assessed the contribution of algal growth to nutrient recovery from SFE. Particularly, change of bacterial community was analyzed to explore the interaction between microalgae and bacteria in SFE remediation. In addition, the inclusion level of microalgae in fish diet was optimized and the effect of fresh microalgae on the aquaculture environment was studied. The results showed that unsterilized SFE with appropriate dilution is favorable for microalgal growth and biomass accumulation. Interaction between microalgae and acidogenic bacteria, including Prevotella sp., Acidaminococcus sp. and Lactobacillus sp., favored nutrient recovery from SFE. Removal efficiency of chemical oxygen demand, total nitrogen, total phosphorus and total ammonia‐nitrogen in SFE reached 95.66%, 35.35%, 57.70% and 42.21%, respectively. As the optimal inclusion level of microalgae in fish diet was set as 25%, body length and weight of Micropterus salmoides increased by 13.85 mm and 1.73 g in 44‐day culture. It was also found that fresh microalgae added in fish diet could effectively keep the ammonia concentration in aquaculture system at a lower level.CONCLUSION: The implementation of this model will be of importance to circular economies integrating food waste remediation and eco‐friendly aquaculture. © 2021 Society of Chemical Industry (SCI).
First‐year students’ preparedness for an online dental curriculum
Authors: Patterson Ellen , Barizan Bordin Thaisa , Stephens Mackenzie 
Published: May 2021

AbstractThe COVID‐19 pandemic has forced dental schools to rapidly adapt complex curricula for distance learning. In order to design high‐quality and effective online educational interventions and adapt dental curricula to the postpandemic “new normal,” it is crucial to understand students’ preparedness for and attitudes toward this rapid and unanticipated pedagogical shift. This survey study (58% response rate) explored entering first‐year dental students’ attitudes and beliefs regarding online learning and their prior experiences with various online activities. Students’ experiences varied widely, but concern about the impact of personal or life stressors on their academic performance and fear of cheating on online exams were common. Students in academic programs immediately preceding dental school were significantly more confident in their computer‐based learning skills. Additional interventions may be needed that prepare students for success in future online courses and to lessen potential disparities among students from diverse social and educational backgrounds.