bluuebunny/crossref_metadata_2025 huggingface dataset:
TagSeq for gene expression in non‐model plants: A pilot study at the Santa Rita Experimental Range NEON core site
Authors: Marx Hannah E. , Scheidt Stephen , Barker Michael S. , Dlugosch Katrina M.
Published: November 2020

Premise

TagSeq is a cost‐effective approach for gene expression studies requiring a large number of samples. To date, TagSeq studies in plants have been limited to those with a high‐quality reference genome. We tested the suitability of reference transcriptomes for TagSeq in non‐model plants, as part of a study of natural gene expression variation at the Santa Rita Experimental Range National Ecological Observatory Network (NEON) core site.

Methods

Tissue for TagSeq was sampled from multiple individuals of four species (Bouteloua aristidoides and Eragrostis lehmanniana [Poaceae], Tidestromia lanuginosa [Amaranthaceae], and Parkinsonia florida [Fabaceae]) at two locations on three dates (56 samples total). One sample per species was used to create a reference transcriptome via standard RNA‐seq. TagSeq performance was assessed by recovery of reference loci, specificity of tag alignments, and variation among samples.

Results

A high fraction of tags aligned to each reference and mapped uniquely. Expression patterns were quantifiable for tens of thousands of loci, which revealed consistent spatial differentiation in expression for all species.

Discussion

TagSeq using de novo reference transcriptomes was an effective approach to quantifying gene expression in this study. Tags were highly locus specific and generated biologically informative profiles for four non‐model plant species.
Effect of human immunodeficiency virus on the brain: A review
Authors: Cilliers Karen , Muller Christo J. F.
Published: November 2020

Thirty million people are infected with human immunodeficiency virus (HIV) worldwide, and HIV‐associated neurocognitive disorder (HAND) is one of the most common comorbidities of HIV. However, the effect of HIV on the brain has not been fully investigated. This article aimed to review the changes to the brain due to HIV in terms of atrophy, diffusion changes, and hyperintensities. Studies have observed significant atrophy in subcortical gray matter, as well as in cortical white and gray matter. Moreover, the ventricles enlarge, and the sulci widen. Although HIV causes changes to the white and gray matter of the brain, few diffusion tensor imaging studies have investigated the changes to gray matter integrity. White and gray matter hyperintensities have frequently been observed in HIV‐positive individuals, with the subcortical gray matter (caudate nucleus and putamen) and periventricular white matter frequently affected. In conclusion, subcortical gray matter is the first brain region to be affected and is affected most severely. Additionally, this review highlights the gaps in the literature, since the effect of HIV on the brain is not fully known. Future studies should continue to investigate the effect of HIV on the brain in different stages of the disease, and alternate therapies should be developed since highly active antiretroviral therapy is currently ineffective at treating HAND.
Habits and the electronic herd: The psychology behind social media’s successes and failures
Authors: Anderson Ian A. , Wood Wendy
Published: November 2020

If platforms such asFacebook, Instagram,andTwitterare the engines of social media use, what is the gasoline? The answer can be found in the psychological dynamics behind consumer habit formation and performance. In fact, the financial success of different social media sites is closely tied to the daily‐use habits they create among users. We explain how the rewards of social media sites motivate user habit formation, how social media design provides cues that automatically activate habits and nudge continued use, and how strong habits hinder quitting social media. Demonstrating that use habits are tied to cues, we report a novel test of a 2008 change inFacebookdesign, showing that it impeded posting only of frequent, habitual users, suggesting that the change disrupted habit automaticity. Finally, we offer predictions about the future of social media sites, highlighting the features most likely to promote user habits.
Disagreement between patient‐ and physician‐reported outcomes on symptomatic adverse events as poor prognosis in patients treated with first‐line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial
Authors: Ooki Akira , Morita Satoshi , Tsuji Akihito , Iwamoto Shigeyoshi , Hara Hiroki , Tanioka Hiroaki , Satake Hironaga , Kataoka Masato , Kotaka Masahito , Kagawa Yoshinori , Nakamura Masato , Shingai Tatsushi , Ishikawa Masashi , Miyake Yasuhiro , Suto Takeshi , Hashiguchi Yojiro , Yabuno Taichi , Ando Masahiko , Sakamoto Junichi , Yamaguchi Kensei
Published: November 2020

The status and prognostic value of the disagreement between physician and patient assessments of symptomatic adverse events (AEs) remain unclear for patients with metastatic colorectal cancer treated with first‐line cetuximab plus chemotherapy. Paired data on patient‐reported outcomes using the EORTC QLQ‐C30 and physician‐reported outcomes using the NCI‐CTCAE for eight symptomatic AEs (fatigue, pain, insomnia, dyspnea, constipation, appetite loss, nausea/vomiting, and diarrhea) were collected from a prospective trial assessing the relationships between treatment efficacy, AEs, and quality of life. The overall agreement rates between patient and physician reporting at 4 weeks ranged from 40.2% to 76.5% for 129 patients. The level of agreement based on Cohen's κ statistics was slight to poor for dyspnea, pain, fatigue, and insomnia, while it was moderate to fair for the remaining AEs. No clinicopathological characteristics of disagreement were found. The underreporting by physicians ranged from 12.5% (nausea/vomiting) to 56.7% (fatigue). The 2‐year overall survival (OS) rate was more favorable for patients with high agreement than for those with low agreement (71.2% vs. 46.5%, p = .016), and the agreement status was an independent factor of OS (HR, 2.31; 95% CI, 1.13–4.71; p = .022). For patients who were reported as asymptomatic by the physician, the presence of patient‐reported symptoms resulted in a trend toward poor prognostic outcomes for appetite loss, dyspnea, diarrhea, and constipation. These findings provide the clinical importance of the monitoring of patient‐reported symptoms that can be complementary to physician‐reported data to ensure more accurate clinical outcomes.
Endovascular removal of a misplaced ureteral stent in the vena cava: a complication of ultrasound‐guided percutaneous nephrolithotomy
Authors: Hu Chao , Zhu Anyi , Zhu Xianhua , Liang Ting , Lu Xiongbing
Published: November 2020

Intravascular migration of a double J stent into the inferior vena cava is an uncommon complication. Active prevention, timely diagnosis, and early intervention are crucial for this complication. Intravascular interventional therapy is relatively easy, less traumatic, and has a high success rate. It can be used to select patients for intravascular ectopic DJS treatment.
Spontaneous rupture of a degenerated leiomyoma causing peritonitis and ileus during pregnancy: A case report
Authors: Odagami Mizuha , Makino Mutsuko , Miyagi Etsuko , Aoki Shigeru
Published: November 2020

Degenerated leiomyomas can rupture during pregnancy, and leakage of the fluid causes peritonitis in rare cases. If peritonitis associated with a degenerated leiomyoma is observed, the occurrence of rupture of the leiomyoma should be considered.
Surface Modified Persistent Luminescence Probes for Biosensing and Bioimaging: A Review
Authors: Luo Qiang , Wang Wenjie , Tan Jie , Yuan Quan
Published: November 2020

Persistent luminescence materials (PLMs) are a class of unique luminescent materials that can remain luminescent for a few milliseconds to days without constant excitation. By virtue of the super long decay time, PLMs have been extensively explored in biosensing and bioimaging applications to elimin ate autofluorescence interference and improve signal‐to‐noise ratio in complex samples and tissues. However, nude PLMs often suffer from the poor stability, selectivity, and biocompatibility in biological system and in vivo, which greatly impedes their applications in biomedicine and bioanalysis. Remarkably, surface modification is a viable solution that endows PLMs with span‐new features and can make PLMs suitable for organisms by altering PLMs’ interaction with biological system. In this review, commonly used strategies for surface modification of PLMs are briefly introduced, and the applications of surface modified PLMs in biosensing and bioimaging as well as their challenges are summarized.

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Extended cubic B‐spline collocation method for singularly perturbed parabolic differential‐difference equation arising in computational neuroscience
Authors: Daba Imiru Takele , Duressa Gemechis File
Published: November 2020

A parameter uniform numerical method is presented for solving singularly perturbed parabolic differential‐difference equations with small shift arguments in the reaction terms arising in computational neuroscience. To approximate the terms with the shift arguments, Taylor's series expansion is used. The resulting singularly perturbed parabolic differential equation is solved by applying the implicit Euler method in temporal direction and extended cubic B‐spline basis functions consisting of a free parameter λ for the resulting system of ordinary differential equations in the spatial direction. The proposed method is shown to be accurate of order by preserving an ε− uniform convergence. To demonstrate the applicability of the proposed method, two test examples are solved by the method and the numerical results are compared with some existing results. The obtained numerical results agreed with the theoretical results.
3D Oral and Cervical Tissue Models for Studying Papillomavirus Host‐Pathogen Interactions
Authors: Jackson Robert , Maarsingh Jason D. , Herbst‐Kralovetz Melissa M. , Van Doorslaer Koenraad
Published: November 2020

Human papillomavirus (HPV) infection occurs in differentiating epithelial tissues. Cancers caused by high‐risk types (e.g., HPV16 and HPV18) typically occur at oropharyngeal and anogenital anatomical sites. The HPV life cycle is differentiation‐dependent, requiring tissue culture methodology that is able to recapitulate the three‐dimensional (3D) stratified epithelium. Here we report two distinct and complementary methods for growing differentiating epithelial tissues that mimic many critical morphological and biochemical aspects of in vivo tissue. The first approach involves growing primary human epithelial cells on top of a dermal equivalent consisting of collagen fibers and living fibroblast cells. When these cells are grown at the liquid‐air interface, differentiation occurs and allows for epithelial stratification. The second approach uses a rotating wall vessel bioreactor. The low‐fluid‐shear microgravity environment inside the bioreactor allows the cells to use collagen‐coated microbeads as a growth scaffold and self‐assemble into 3D cellular aggregates. These approaches are applied to epithelial cells derived from HPV‐positive and HPV‐negative oral and cervical tissues. The second part of the article introduces potential downstream applications for these 3D tissue models. We describe methods that will allow readers to start successfully culturing 3D tissues from oral and cervical cells. These tissues have been used for microscopic visualization, scanning electron microscopy, and large omics‐based studies to gain insights into epithelial biology, the HPV life cycle, and host‐pathogen interactions. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Establishing human primary cell–derived 3D organotypic raft cultures

Support Protocol 1: Isolation of epithelial cells from patient‐derived tissues

Support Protocol 2: Growth and maintenance of primary human epithelial cells in monolayer culture

Support Protocol 3: PCR‐based HPV screening of primary cell cultures

Basic Protocol 2: Establishing human 3D cervical tissues using the rotating wall vessel bioreactor

Support Protocol 4: Growth and maintenance of human A2EN cells in monolayer culture

Support Protocol 5: Preparation of the slow‐turning lateral vessel bioreactor

Support Protocol 6: Preparation of Cytodex‐3 microcarrier beads

Basic Protocol 3: Histological assessment of 3D organotypic raft tissues

Basic Protocol 4: Spatial analysis of protein expression in 3D organotypic raft cultures

Basic Protocol 5: Immunofluorescence imaging of RWV‐derived 3D tissues

Basic Protocol 6: Ultrastructural visualization and imaging of RWV‐derived 3D tissues

Basic Protocol 7: Characterization of gene expression by RT‐qPCR
Public Workshop Summary Report on Fiscal Year 2021 Generic Drug Regulatory Science Initiatives: Data Analysis and Model‐Based Bioequivalence
Authors: Lee Jieon , Gong Yuqing , Bhoopathy Sid , DiLiberti Charles E. , Hooker Andrew C. , Rostami‐Hodjegan Amin , Schmidt Stephan , Suarez‐Sharp Sandra , Lukacova Viera , Fang Lanyan , Zhao Liang
Published: November 2020

On May 4, 2020, the US Food and Drug Administration (FDA) hosted an online public workshop titled “FY 2020 Generic Drug Regulatory Science Initiatives Public Workshop” to provide an overview of the status of the science and research priorities and to solicit input on the development of Generic Drug User Fee Amendments fiscal year 2021 priorities. This report summarizes the podium presentations and the outcome of discussions along with innovative ways to overcome challenges and significant opportunities related to model‐based approaches in bioequivalence assessment for breakout session 4 titled, “Data analysis and model‐based bioequivalence (BE).” This session focused on the application of model‐based approaches in the generic drug development, with a vision of accelerating regulatory decision making for abbreviated new drug application assessments. The session included both podium presentations and panel discussions with three topics of interest: (i) in vitro study evaluation methods and their clinical relevance, (ii) challenges in model‐based BE, (iii) emerging expertise and tools in implementing new BE approaches.
Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch–Schönlein purpura nephritis
Authors: Imai Takashi , Nishiyama Kei , Ueki Kenji , Tanaka Tamami , Kaku Yoshitsugu , Hara Toshiro , Ohga Shouichi
Published: November 2020

Objectives

Immunoglobulin A vasculitis/Henoch–Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose‐deficient IgA1 was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear.

Methods

We compared gene expressions of peripheral blood mononuclear cells (PBMCs) among healthy controls (n = 10), IgAV/HSP patients (n = 21) and HSPN patients (n = 8), which required nephritis development within 3 months of IgAV/HSP onset. Immunohistochemistry analysis and flow cytometry were performed to assess renal biopsy specimens and PBMCs, respectively. Serum CX3CL1 levels were measured by ELISA.

Results

GNLY and GZMB expressions increased in HSPN patients, consistent with increased number of glomerular granulysin‐ and/or granzyme B‐positive cells demonstrated by immunohistochemistry analysis. Additionally, circulating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells were activated with the up‐regulated surface expressions of human leucocyte antigen DR (HLA‐DR) and CX3CR1 in HSPN patients with severe proteinuria. Renal biopsies demonstrated increased number of CD8+ cells and/or CD56+ cells and up‐regulated expression of glomerular CX3CL1, a specific ligand for CX3CR1, along with increased serum CX3CL1 level.

Conclusion

Activated CTLs and NK cells play roles in the development of nephritis in IgAV/HSP patients and can be used as novel biomarkers for HSPN.
The application of community ecology theory to co‐infections in wildlife hosts
Authors: Ramsay Chloe , Rohr Jason R.
Published: November 2020

Priority effect theory, a foundational concept from community ecology, states that the order and timing of species arrival during species assembly can affect species composition. Although this theory has been applied to co‐infecting parasite species, it has almost always been with a single time lag between co‐infecting parasites. Thus, how the timing of parasite species arrival affects co‐infections and disease remains poorly understood. To address this gap in the literature, we exposed postmetamorphic Cuban tree frogs (Osteopilus septentrionalis) to Ranavirus, the fungus Batrachochytrium dendrobatidis (Bd), a nematode Aplectana hamatospicula, or pairs of these parasites either simultaneously or sequentially at a range of time lags and quantified load of the secondary parasite and host growth, survival, and parasite tolerance. Prior exposure to Bd or A. hamatospicula significantly increased viral loads relative to hosts singly infected with Ranavirus, whereas A. hamatospicula loads in hosts were higher when coexposed to Bd than when coexposed to Ranavirus. There was a significant positive relationship between time since Ranavirus infection and Bd load, and prior exposure to A. hamatospicula decreased Bd loads compared to simultaneous co‐infection with these parasites. Infections with Bd and Ranavirus either singly or in co‐infections decreased host growth and survival. This research reveals that time lags between co‐infections can affect parasite loads, in line with priority effects theory. As co‐infections in the field are unlikely to be simultaneous, an understanding of when co‐infections are impacted by time lags between parasite exposures may play a major role in controlling problematic co‐infections.
Ventricular tachycardia, premature ventricular contractions, and mortality in unselected patients with lung, colon, or pancreatic cancer: a prospective study
Authors: Anker Markus S. , von Haehling Stephan , Coats Andrew J.S. , Riess Hanno , Eucker Jan , Porthun Jan , Butler Javed , Karakas Mahir , Haverkamp Wilhelm , Landmesser Ulf , Anker Stefan D.
Published: November 2020

Aims

Many cancer patients die due to cardiovascular disease and sudden death, but data on ventricular arrhythmia prevalence and prognostic importance are not known.

Methods and results

Between 2005 and 2010, we prospectively enrolled 120 unselected patients with lung, colon, or pancreatic cancer due to one of three diagnoses: colorectal (n = 33), pancreatic (n = 54), or non‐small cell lung cancer (n = 33). All were free of manifest cardiovascular disease. They were compared to 43 healthy controls similar in age and sex distribution. Each participant underwent 24 h electrocardiogram recording and cancer patients were followed for up to 12.5 years for survival (median 21 months). Ninety‐six cancer patients (80%) died during follow‐up [5‐year survival: 27% (95% confidence interval 19–35%)]. Non‐sustained ventricular tachycardia (NSVT) was more frequent in cancer patients vs. controls (8% vs. 0%, P = 0.021). The number of premature ventricular contractions (PVCs) over 24 h was not increased in cancer patients vs. controls (median 4 vs. 9, P = 0.2). In multivariable analysis, NSVT [hazard ratio (HR) 2.44, P = 0.047] and PVCs (per 100, HR 1.021, P = 0.047) were both significant predictors of mortality, independent of other univariable mortality predictors including tumour stage, cancer type, potassium concentration, prior surgery, prior cardiotoxic chemotherapy, and haemoglobin. In patients with colorectal and pancreatic cancer, ≥50 PVCs/24 h predicted mortality (HR 2.30, P = 0.0024), and was identified in 18% and 26% of patients, respectively.

Conclusions

Non‐sustained ventricular tachycardia is more frequent in unselected patients with colorectal, pancreatic, and non‐small cell lung cancer and together with PVCs predict long‐term mortality. This raises the prospect of cardiovascular mortality being a target for future treatment interventions in selected cancers.
Association between renin–angiotensin–aldosterone system inhibitor use and COVID‐19 hospitalization and death: a 1.4 million patient nationwide registry analysis
Authors: Savarese Gianluigi , Benson Lina , Sundström Johan , Lund Lars H.
Published: November 2020

Aims

Renin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19). We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population.

Methods and results

Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID‐19 cases were defined based on hospitalization/death for COVID‐19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81–0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82–0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.

Conclusions

In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19.
Analysis of mutational signatures with yet another package for signature analysis
Authors: Hübschmann Daniel , Jopp‐Saile Lea , Andresen Carolin , Krämer Stephen , Gu Zuguang , Heilig Christoph E. , Kreutzfeldt Simon , Teleanu Veronica , Fröhling Stefan , Eils Roland , Schlesner Matthias
Published: November 2020

Different mutational processes leave characteristic patterns of somatic mutations in the genome that can be identified as mutational signatures. Determining the contributions of mutational signatures to cancer genomes allows not only to reconstruct the etiology of somatic mutations, but can also be used for improved tumor classification and support therapeutic decisions. We here present the R package yet another package for signature analysis (YAPSA) to deconvolute the contributions of mutational signatures to tumor genomes. YAPSA provides in‐built collections from the COSMIC and PCAWG SNV signature sets as well as the PCAWG Indel signatures and employs signature‐specific cutoffs to increase sensitivity and specificity. Furthermore, YAPSA allows to determine 95% confidence intervals for signature exposures, to perform constrained stratified signature analyses to obtain enrichment and depletion patterns of the identified signatures and, when applied to whole exome sequencing data, to correct for the triplet content of individual target capture kits. With this functionality, YAPSA has proved to be a valuable tool for analysis of mutational signatures in molecular tumor boards in a precision oncology context. YAPSA is available at R/Bioconductor (http://bioconductor.org/packages/3.12/bioc/html/YAPSA.html).
Tumor‐only sequencing for oncology management: Germline‐focused analysis and implications
Authors: George Angela , Turnbull Clare
Published: November 2020

As patients are now routinely having large somatic genomic testing panels undertaken as part of routine management, there is the rising likelihood of uncovering the presence of a germline pathogenic variant. This may be found on testing undertaken on plasma (ctDNA) or tissue. This has led to the need for clear guidelines for oncologists about how to manage such results, including which variants require validation, how this should be undertaken, and what potential problems may arise. This requires an understanding of the limits of testing, and the pitfalls that may be encountered. In this review, we assess the frequency of detecting germline variants through tumor‐only sequencing, the necessary considerations for such information to be analyzed and the role of the molecular tumor board in considering results. We assess the additional considerations for interpretation of the underlying tumor, use of ctDNA or tissue for testing, clonal hematopoiesis, and hypermutation.
Neurophysiological mechanisms underlying motor feature binding processes and representations
Authors: Takacs Adam , Bluschke Annet , Kleimaker Maximilian , Münchau Alexander , Beste Christian
Published: November 2020

Coherent, voluntary action requires an integrated representation of these actions and their defining features. Although theories delineate how action integration requiring binding between different action features may be accomplished, the underlying neurophysiological mechanisms are largely elusive. The present study examined the neurophysiological mechanisms underlying binding processes in actions. To this end, we conducted EEG recordings and applied standard event‐related potential analyses, temporal EEG signal decomposition and multivariate pattern analyses (MVPA). According to the code occupation account, an overlap between a planned and a to‐be‐performed action impairs performance. The level, to which performance is attenuated depends on the strength of binding of action features. This binding process then determines the representation of them, the so‐called action files. We show that code occupation and bindings between action features specifically modulate processes preceding motor execution as showed by the stimulus‐locked lateralized readiness potential (LRP). Conversely, motor execution processes reflected by the response‐locked LRP were not modulated by action file binding. The temporal decomposition of the EEG signal, further distinguished between action file related processes: the planned response determining code occupation was reflected in general (voluntary) response selection but not in involuntary (response priming‐related) activation. Moreover, MVPA on temporally decomposed neural signals indicated that action files are represented as a continuous chain of activations. Within this chain, inhibitory and response re‐activation patterns can be distinguished. Taken together, the neurophysiological correlates of action file binding suggest that parallel, stimulus‐ and response‐related pre‐motor processes are responsible for the code occupation in the human motor system.
Organoids and Spheroids as Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma
Authors: Sato Keisaku , Zhang Wenjun , Safarikia Samira , Isidan Abdulkadir , Chen Angela M. , Li Ping , Francis Heather , Kennedy Lindsey , Baiocchi Leonardo , Alvaro Domenico , Glaser Shannon , Ekser Burcin , Alpini Gianfranco
Published: November 2020

Cholangiopathies, such as primary sclerosing cholangitis, biliary atresia, and cholangiocarcinoma, have limited experimental models. Not only cholangiocytes but also other hepatic cells including hepatic stellate cells and macrophages are involved in the pathophysiology of cholangiopathies, and these hepatic cells orchestrate the coordinated response against diseased conditions. Classic two‐dimensional monolayer cell cultures do not resemble intercellular cell‐to‐cell interaction and communication; however, three‐dimensional cell culture systems, such as organoids and spheroids, can mimic cellular interaction and architecture between hepatic cells. Previous studies have demonstrated the generation of hepatic or biliary organoids/spheroids using various cell sources including pluripotent stem cells, hepatic progenitor cells, primary cells from liver biopsies, and immortalized cell lines. Gene manipulation, such as transfection and transduction can be performed in organoids, and established organoids have functional characteristics which can be suitable for drug screening. This review summarizes current methodologies for organoid/spheroid formation and a potential for three‐dimensional hepatic cell cultures as in vitro models of cholangiopathies.
COVID‐19 is increasing Ghanaian pregnant women’s anxiety and reducing healthcare seeking
Authors: Moyer Cheryl A. , Sakyi Kwame S. , Sacks Emma , Compton Sarah D. , Lori Jody R. , Williams John E. O.
Published: November 2020

Synopsis

Pregnant women in Ghana report skipping antenatal care and reconsidering facility delivery due to concerns about COVID‐19.
Stochastic neural network based data analysis‐related talent recruitment optimization via CDN server
Authors: Wang Lei , Dong Yue
Published: November 2020

The competition for talent is always intense, especially in the era of big data, the data analysis‐related talent recruitment plays an important role in promoting the development of enterprises. Regarding resume screening, it is considerably significant during the process of talent recruitment. Consider that Neural Network (NN) has the strong stability on the prediction result and is given a lot of attention, this paper uses Stochastic NN (SNN) to optimize the data analysis‐related talent recruitment. Meanwhile, SNN is used to train resume‐related dataset and make resume screening. In addition, in order to accelerate the training process and decrease the training complexity, this paper uses Locally Linear Embedding (LLE) to do dimension reduction in terms of the extracted data features. Furthermore, in order to guarantee the on‐line resume screening, this paper does resume screening under Content Delivery Network (CDN) scenario, where CDN has two functions, that is, data storage and hot resumes recommendation. The experiments are made based on the collected 7000 resumes, and the result show that this paper has good optimization effect on data analysis‐related talent recruitment.
Changes of lipid profiles in human umbilical vein endothelial cells exposed to zirconia nanoparticles with or without the presence of free fatty acids
Authors: Cheng Xiangjun , Guo Hao , Xian Youqi , Xie Xiaowei
Published: November 2020

Zirconia nanoparticles (NPs) have been widely used in biomedicine, which will likely lead to their interactions with endothelial cells (ECs). However, the toxicity of zirconia NPs to ECs is less investigated and the toxicological data are not consistent. Furthermore, no previous study, to the best of our knowledge, investigated the influence of zirconia NPs on lipid metabolism. This study investigated lipid profiles in human umbilical vein ECs (HUVECs) exposed to zirconia NPs with or without the presence of free fatty acids (FFAs). Incubation with FFA changed the hydrodynamic size, zeta potential, and surface profiles of zirconia NPs, indicating the surface coating effects. Exposure of HUVECs to various concentrations of zirconia NPs with or without the presence of FFA did not significantly decrease cellular viability, but FFA decreased zirconium elemental levels in NP‐exposed cells. Oil Red O staining showed that FFA or zirconia NPs and FFA, but not zirconia NPs alone, significantly increased lipid accumulation in HUVECs. Consistently, lipidomic data suggested that exposure to FFA or zirconia NPs and FFA up‐regulated most lipid classes in HUVECs. As the mechanisms for increased lipid accumulation, exposure to FFA or zirconia NPs and FFA up‐regulated endoplasmic reticulum (ER) stress axis IRE1α–XBP‐1, leading to increased FASN and ACSL3, proteins involved in lipid metabolism. Combined, our results demonstrated that zirconia NPs were noncytotoxic and showed minimal impact on ER stress‐mediated lipid metabolism in HUVECs under both normal and FFA‐challenged conditions, which indicated the relatively high biocompatibility of zirconia NPs to ECs.
Correlations of disease severity and age with hematology parameter variations in patients with COVID‐19 pre‐ and post‐treatment
Authors: Liang Juanying , Nong Shaoyun , Jiang Liejun , Chi Xiaowei , Bi Dewu , Cao Jun , Mo Lida , Luo Xiaolu , Huang Huayi
Published: November 2020

Background

For better understanding of the pathological changes of COVID‐19, benefiting clinical management of the disease and the preparation for future waves of similar pandemics.

Methods

Hematology parameters from a total of 52 cases of COVID‐19 admitted for treatment in a designated hospital were retrospectively analyzed. Data were analyzed by SPSS statistical software.

Results

Pre‐treatment T‐cell subsets, total lymphocytes, red blood cell distribution width (RDW), eosinophils, and basophils were significantly lower than that of post‐treatment, while the inflammatory indexes neutrophils, neutrophil to lymphocyte ratio (NLR), and C‐reactive protein (CRP) levels, as well as red blood cell (RBC) and hemoglobin, were significantly reduced after treatment. The T‐cell subsets, total lymphocytes, and basophils in severely and critically ill patients were significantly lower than those in moderately ill patients. Neutrophils, NLR, eosinophils, procalcitonin (PCT), and CRP was significantly higher in severely and critically ill patients than in moderately ill patients. CD3+, CD8+, total lymphocytes, platelets, and basophils in patients older than 50 were lower than that of those younger than 50, while neutrophils, NLR, CRP, and RDW in patients older than 50 were higher than that of younger than 50. There was a positive correlation among prothrombin time (PT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in severely and critically ill patients.

Conclusions

T‐cell subsets, lymphocyte count, RDW, neutrophils, eosinophils, NLR, CRP, PT, ALT, and AST are important indicators in the management especially for severely and critically ill patients with COVID‐19.
Emerging role of CCN family proteins in fibrosis
Authors: Sun Chao , Zhang Han , Liu Xinhui
Published: November 2020

Fibrosis is a common pathological change characterized by the excessive accumulation of fibrous connective tissue. Once uncontrolled, this pathological progress can lead to irreversible damage to the structure and function of organs, which is a serious threat to human health and life. Actually, the disability and death of patients caused by many chronic diseases have a closed relationship with fibrosis. The CCN protein family, including six members, is a small group of matrix proteins exhibiting structurally similar features. In the past 20 years, different biological functions of CCN proteins have been identified in various diseases. Of note, it has been recently shown that they are implicated in the key pathological process of fibrosis. In this review, we summarize the current status of knowledge regarding the role of CCN proteins involved in the pathogenesis of fibrosis diseases in detail. Furthermore, we highlight some of the underlying interaction mechanisms of CCN protein acting in fibrosis that helps to develop new drugs and determine appropriate clinical strategies for fibrotic diseases.
Evaluation of the dentate gyrus in adult mice exposed to acetaminophen (paracetamol) on postnatal day 10
Authors: Philippot Gaëtan , Hellsten Sofie V. , Viberg Henrik , Fredriksson Robert
Published: November 2020

Acetaminophen (AAP; or paracetamol) is a widely used nonprescription drug with antipyretic and analgesic properties. Alarmingly, there is an increasing body of evidence showing that developmental exposure to AAP is associated with adverse behavioural outcomes later in life. We have previously shown that relevant doses of AAP in 10‐day‐old mice affected memory, learning and locomotor activity in the adult animals. Interestingly, the neurons of the dentate gyrus (DG) have a relatively late time of origin as they are generated during the first two weeks of postnatal life in rodents. Since the generation of these cells, which are important for memory processing, coincides with our AAP exposure, we aim to investigate if the cytoarchitecture of the DG is affected by postnatal day 10 AAP treatment. In addition, we investigate if markers for differentiation and migration in the hippocampus were affected by the same treatment. We did not observe any visual effects in adult DG cytoarchitecture, nor any changes of markers for differentiation/migration in the hippocampus in 24 hr after exposure. Even though a large effect size was estimated on adult DG thickness following AAP exposure, the estimated 95% CIs around the differences of the means reveal no significant effect. Hence, larger sample sizes are warranted to clarify if neonatal AAP exposure affects adult DG thickness in mice.
Development of an efficient, one‐pot, multicomponent protocol for synthesis of 8‐hydroxy‐4‐phenyl‐1,2‐dihydroquinoline derivatives
Authors: Tabassum Rukhsana , Ashfaq Muhammad , Oku Hiroyuki
Published: November 2020

A one‐pot quick and efficient multicomponent reaction has been developed for the synthesis of a new series of functionalized 8‐hydroxy‐4‐phenyl‐1,2‐dihydroquinoline derivatives using 30 mol% ammonium acetate in ethanol as solvent. This economical protocol run smoothly to give variety of quinoline derivatives in 55% to 98% yield from inexpensive reagents and catalyst in mild reaction conditions. Various spectroscopic techniques like FTIR, 1H NMR and 13C NMR, MALDI‐TOF‐MS, and EI‐MS were used to study and confirm their structure.
Concise synthesis of chiral pyrazolo[4,3‐f] [1,4]oxazepines and pyrazolo[4,3‐f] [1,4]thiazepines bearing pyrazole unit
Authors: Pitchai Manivel , Ulaganathan Sankar , Venkateshappa Suresh Shagathur , Akunuri Arun , Rampulla Richard , Mathur Arvind , Gupta Anuradha
Published: November 2020

An efficient synthesis of pyrazolo [1,4]‐oxazepines and [1,4]‐thiazepines bearing a variety of alkyl and aryl groups with a chiral center has been developed. The synthesis started with readily available 5‐chloro‐pyrazole‐4‐carbaldehyde and chiral amino alcohols. The key step involves intramolecular imine formation. These classes of compounds are potentially useful as templates for drug discovery.
Regional variation in the use of catheter ablation for patients with arrhythmia in Japan
Authors: Inoue Takahiro , Kuwabara Hiroyo
Published: November 2020

Background

Regional variation in the use of percutaneous coronary intervention (PCI), especially when performed as an elective procedure, was observed in a previous study. The use of a developing technology, catheter ablation (CA), was compared between regions in Japan.

Methods and Results

The Diagnostic Procedure Combination data, which are publicly available, were used for the analysis. The number of CAs was summarized and the rates for CA and PCI were calculated based on the prefecture's population aged ≥40 years. A linear regression model was constructed to identify the factors associated with regional variation in the use of CA. The number of CAs performed per hospital consistently increased from 2009 to 2018. The mean rate of CA across Japan was 119 per 100 000 population aged ≥40 years in 2018. The highest CA rate was 166 per 100 000 and the lowest CA rate was 29 per 100 000 in 2018, while the highest and lowest PCI rates for angina per 100 000 were 361 and 88 in 2018, respectively. The significant factor associated with regional variation in the CA rate was the number of specialists.

Conclusions

A wide regional variation was observed in the use of CA for patients with arrhythmia in Japan. Further research is needed to generate evidence of CA for decision‐making as a treatment option and to appropriately deploy this health service regardless of where patients live.
Pathological changes of frozen shoulder in rat model and the therapeutic effect of PPAR‐γ agonist
Authors: Chen Jinfu , Zhu Junjun , Zhu Tianfei , Cui Jiaming , Deng Zhenhan , Chen Kang , Chang Chongfei , Geng Yiyun , Chen Fei , Ouyang Kan , Xiong Jianyi , Wang Manyi , Wang Daping , Zhu Weimin
Published: November 2020

Frozen shoulder is a common shoulder disorder characterized by a gradual increase of pain and a limited range of motion. However, its pathophysiologic mechanisms remain unclear and there is no consensus as to the most effective treatment. The purpose of the study was to investigate the effect of transforming growth factor‐β (TGF‐β) on fibrosis and inflammatory response of the shoulder joint of rat models and to explore the therapeutic effect of the peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonist. In the study, the effect of PPAR‐γ agonist CDDO‐IM treatment on cell proliferation, migration, and extracellular matrix proteins synthesis (vimentin, α‐smooth muscle actin, collagen I, and collagen III) were tested by cell proliferation test, scratches test, real‐time quantitative polymerase chain reaction, and Western blot analysis. The frozen shoulder was also established on the rat model by injecting adenovirus‐TGF‐β1 into rats' shoulder capsule. Pathological changes of the frozen shoulder tissue of the experimental group and PPAR‐γ agonist treatment group were evaluated. The stiffness of joints of the three groups was tested. Inflammatory mediators' expression including cyclooxygenase‐1, interleukin‐1β, and tumor necrosis factor‐α of the shoulder was tested by enzyme‐linked immunosorbent assay, and the expression of extracellular matrix proteins was evaluated by hematoxylin and eosin staining and immunohistochemistry. The results showed that pathological changes of the frozen shoulder in the rat model include an abnormal proliferation of fibroblasts, infiltration of inflammatory cells, and disorder of fibrous structure, while rosiglitazone reduced the severity of the frozen shoulder in the treatment group. Clinically, PPAR‐γ agonists may be a promising target for the treatment of the frozen shoulder.
Comparison of annulus fibrosus cell collagen remodeling rates in a microtissue system
Authors: Tromp Isabel N. , Foolen Jasper , van Doeselaar Marina , Zhang Ying , Chan Danny , Kruyt Moyo C. , Creemers Laura B. , Castelein Rene M. , Ito Keita
Published: November 2020

It has been suggested that curvature progression in adolescent idiopathic scoliosis occurs through irreversible changes in the intervertebral discs. Strains of mice have been identified who differ in their disc wedging response upon extended asymmetrical compression. Annulus fibrosus (AF) tissue remodeling could contribute to the faster disc wedging progression previously observed in these mice. Differences in collagen remodeling capacity of AF cells between these in‐bred mice strains were compared using an in vitro microtissue system. AF cells of 8–10‐week‐old LG/J (“fast‐healing”) and C57BL/6J (“normal healing”) mice were embedded in a microtissue platform and cultured for 48 h. Hereafter, tissues were partially released and cultured for another 96 h. Microtissue surface area and waistcoat contraction, collagen orientation, and collagen content were measured. After 96 h postrelease, microtissues with AF cells of LG/J mice showed more surface area contraction (p < .001) and waistcoat contraction (p = .002) than C57BL/6J microtissues. Collagen orientation did not differ at 24 h after partial release. However, at 96 h, collagen in the microtissues from LG/J AF cells was aligned more than in those from C57BL/6J mice (p < .001). Collagen content did not differ between microtissues at 96 h. AF cells of inbred LG/J mice were better able to remodel and realign their collagen fibers than those from C57BL/6J mice. The remodeling of AF tissue could be contributing to the faster disc wedging progression observed in LG/J mice.
Genome sequencing of cold‐adapted Planococcus bacterium isolated from traditional shrimp paste and protease identification
Authors: Leng Weijun , Gao Ruichang , Wu Xiaoyun , Zhou Jing , Sun Quancai , Yuan Li
Published: November 2020

BACKGROUND

Psychrophiles have evolved to adapt to freezing environments, and cold‐adapted enzymes from these organisms can maintain high catalytic activity at low temperature. The use of cold‐adapted enzymes has great potential for the revolution of food and molecular biology industries.

RESULTS

In this study, four different strains producing protease were isolated from traditional fermented shrimp paste, one of which, named Planococcus maritimus XJ11 by 16S rRNA nucleotide sequence analysis, exhibited the largest protein hydrolysis clear zone surrounding the colonies. Meanwhile, the strain P. maritimus XJ11 was selected for further investigation because of its great adaptation to low temperature, low salinity and alkaline environment. The enzyme activity assay of P. maritimus XJ11 indicated that the optimum conditions for catalytic activity were pH 10.0 and 40 °C. Moreover, the enzyme also showed an increasing activity with temperatures from 10 to 40 °C and retained more than 67% activity of the maximum over a broad range of salinity (50–150 g L−1). Genome sequencing analysis revealed that strain XJ11 possessed one circular chromosome of 3 282 604 bp and one circular plasmid of 67 339 bp, with a total number of 3293 open reading frames (ORFs). Besides, 21 genes encoding protease, including three serine proteases, were identified through the NR database.

CONCLUSION

Cold‐adapted bacterium P. maritimus XJ11 was capable of producing alkaline proteases with high catalytic efficiency at low or moderate temperatures. Furthermore, the favorable psychrophilic and enzymatic characters of strain P. maritimus XJ11 seem to have a promising potential for industrial application. © 2020 Society of Chemical Industry
Effect of different thawing methods on the efficiency and quality attributes of frozen red radish
Authors: Xu Baoguo , Chen Jianan , Yuan Jun , Azam SM Roknul , Zhang Min
Published: November 2020

BACKGROUND

The thawing process is regarded as an essential step before the consumption of frozen foods. This study aimed to evaluate the possibility of ultrasound thawing of frozen red radish and to explore the characteristics of ultrasound thawing. The influence of low‐frequency ultrasound (LFU) on the thawing efficiency of frozen red radish cylinders in air and water mediums was investigated. The effects of different ways of thawing, including air thawing (AT), water thawing (WT), refrigeration thawing (RT), ultrasound‐assisted water thawing (UWT), and microwave thawing (MT) on the thawing time and quality of radish samples was studied.

RESULTS

The results showed that thawing time decreased remarkably in air and water mediums assisted by LFU. As the LFU power level increased, the thawing time decreased and the value of the drip loss increased. The firmness of thawed radish samples also decreased significantly compared with the fresh samples. Microwave thawing had the highest thawing rate, but the microstructure of MT radish samples was damaged severely, resulting in the highest drip loss, and the lowest firmness, and vitamin C content. In comparison with the AT, WT, and RT, a significant reduction in thawing time could be achieved for UWT (P < 0.05). Ultrasound‐assisted water thawing exhibited the highest retention of color and vitamin C, and a lower destructive effect on the microstructure.

CONCLUSION

The results showed that LFU could be used as an efficient method to facilitate the thawing process of frozen red radishes, and better preserve the color, vitamin C, and microstructure of the final product. © 2020 Society of Chemical Industry