bluuebunny/crossref_metadata_2025 huggingface dataset:
A low‐cost, in silico nutritional genomics course‐based undergraduate research experience applicable to multiple disciplines
Authors: Good Deborah J.
Published: April 2020

This article describes the development and assessment of a Nutritional Genomics course, designed to be held in a regular classroom during normal class periods, with few extra costs to the students or the department. The course was run as an upper‐level undergraduate and lower‐level graduate student course. Student taking the course spent 11 weeks learning and then 4 weeks using various in silico methods to independently characterize genes of interest in the field. During the last 4 weeks of the course, students combined their methods to test a hypothesis they generated about a gene they have not yet studied and completed a final report in the form of a journal article. Two students have published or are in the process of publishing work from their final project. Validated surveys of genetic knowledge given at least 6 months following the course indicated a very high level of genetic knowledge retainment, and favorable attitudes toward genetics testing and medical use of genetics. Finally, self‐perceived critical thinking skills were high, and students indicated that they perceived these skills to be gained by their participation in the course. Materials and syllabus provided in the manuscript makes this CURE easily transferrable to other disciplines.
Long noncoding RNA MEG3 decreases the growth of head and neck squamous cell carcinoma by regulating the expression of miR‐421 and E‐cadherin
Authors: Ji Yefeng , Feng Guanying , Hou Yunwen , Yu Yang , Wang Ruixia , Yuan Hua
Published: April 2020

Background

Maternally expressed 3 (MEG3), a long chain noncoding RNA (lncRNA), has verified its function as a suppressor in several kinds of cancers. However, the downstream mechanism of MEG3 in regulating the molecular mechanism of epithelial‐mesenchymal transformation (EMT) in head and neck squamous cell carcinoma (HNSCC) progression demands further investigation.

Methods

Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to determine the expression level of MEG3 in HNSCC and adjacent normal tissues of 51 cases. Luciferase report assay was used to detect the correlation between miR‐421 and MEG3, and miR‐421 and E‐cadherin in HNSCC cell lines. Cell invasion and proliferation capacity were assessed through transwell and CCK8 assays. Scratch wound assay was used to assess cell migration capacity.

Results

Firstly, this study demonstrated that the expression of MEG3 was significantly downregulated in HNSCC compared to adjacent normal tissues. Overexpressed MEG3 inhibited cell proliferation, migration, and invasion in vitro. Secondly, MEG3 upregulated the expression of E‐cadherin, which was instead downregulated by miR‐421. MiR‐421 was negatively regulated by MEG3 in HNSCC. Therefore, MEG3 regulated EMT by sponging miR‐421 targeting E‐cadherin in HNSCC.

Conclusions

This study indicated that the MEG3‐miR‐421‐E‐cadherin axis could be a new therapeutic target for HNSCC.
Friedel–Crafts Type Methylation with Dimethylhalonium Salts
Authors: Hämmerling Sebastian , Voßnacker Patrick , Steinhauer Simon , Beckers Helmut , Riedel Sebastian
Published: April 2020

The dimethylchloronium salt [Me2Cl][Al(OTeF5)4] is used to methylate electron‐deficient aromatic systems in Friedel–Crafts type reactions as shown by the synthesis of N‐methylated cations, such as [MeNC5F5]+, [MeNC5F4I]+, and [MeN3C3F3]+. To gain a better understanding of such fundamental Friedel–Crafts reactions, the role of the dimethylchloronium cation has been evaluated by quantum‐chemical calculations.
Footwear and insole design features for offloading the diabetic at risk foot—A systematic review and meta‐analyses
Authors: Collings Richard , Freeman Jennifer , Latour Jos M. , Paton Joanne
Published: April 2020

The aim of this systematic review was to identify the best footwear and insole design features for offloading the plantar surface of the foot to prevent foot ulceration in people with diabetic peripheral neuropathy. We searched multiple databases for published and unpublished studies reporting offloading footwear and insoles for people with diabetic neuropathy and nonulcerated feet. Primary outcome was foot ulcer incidence; other outcome measures considered were any standardized kinetic or kinematic measure indicating loading or offloading the plantar foot. Fifty‐four studies, including randomized controlled studies, cohort studies, case‐series, and a case‐controlled and cross‐sectional study were included. Three meta‐analyses were conducted and random‐effects modelling found peak plantar pressure reduction of arch profile (37 kPa (MD, −37.5; 95% CI, −72.29 to −3.61; P < .03), metatarsal addition (35.96 kPa (MD, −35.96; 95% CI, −57.33 to −14.60; P < .001) and pressure informed design 75.4 kPa (MD, −75.4 kPa; 95% CI, −127.4 to −23.44 kPa; P < .004).The remaining data were presented in a narrative form due to heterogeneity. This review highlights the difficulty in differentiating the effect of different insole and footwear features in offloading the neuropathic diabetic foot. However, arch profiles, metatarsal additions and apertures are effective in reducing plantar pressure. The use of pressure analysis to enhance the effectiveness of the design of footwear and insoles, particularly through modification, is recommended.
Reproducible Visualization of Raw Fisheries Data for 113 Species Improves Transparency, Assessment Efficiency, and Monitoring
Authors: Anderson Sean C , Keppel Elise A , Edwards Andrew M
Published: April 2020

Modern survey and fishery observation programs generate vast quantities of data. However, regulatory agencies often lack the capacity to translate those data into effective monitoring information. Here, we describe an approach of automated visualization of raw fisheries data and demonstrate it with a report on 113 groundfish species in Pacific Canadian waters. Our implementation consists of two pages per species that show standardized visualizations of temporal trends and spatial distributions of commercial catches and survey indices, along with analyses of age, size, maturity, and growth. The approach facilitates discussions on stock assessment and survey prioritization, increases transparency about data holdings, and makes data available for regular review by interested parties. We encourage other agencies to consider similar approaches for their own data.
Aggressive morphologic variants of mantle cell lymphoma characterized with high genomic instability showing frequent chromothripsis, CDKN2A/B loss, and TP53 mutations: A multi‐institutional study
Authors: Streich Lukas , Sukhanova Madina , Lu Xinyan , Chen Yi‐Hua , Venkataraman Girish , Mathews Stephanie , Zhang Shanxiang , Kelemen Katalin , Segal Jeremy , Gao Juehua , Gordon Leo , Chen Qing , Behdad Amir
Published: April 2020

Aggressive morphologic variants of mantle cell lymphoma (MCL), including blastoid and pleomorphic (B/P‐MCL), are rare and associated with poor clinical outcomes. The genomic landscape of these variants remains incompletely explored. In this multi‐institutional study, we describe recurrent mutations and novel genomic copy number alterations (CNAs) in B/P‐MCL, using next generation sequencing and SNP‐array. Chromothripsis, a recently described phenomenon of massive chromosomal rearrangements, was identified in eight of 13 (62%) B/P MCL cases, and a high degree of genomic complexity with frequent copy number gains and losses was also seen. In contrast, a comparative cohort of nine cases of conventional MCL (C‐MCL) showed no chromothripsis and less complexity. Twelve of 13 (92%) B/P‐MCL cases showed loss of CDKN2A/B (6 biallelic and 6 monoallelic losses); while only one C‐MCL showed monoallelic CDKN2A/B loss. In B/P‐MCL, TP53 was the most commonly mutated gene, with mutations present in eight cases (62%), six of which showed concurrent loss of chromosome 17p. Of the eight cases with chromothripsis, six (85%) harbored TP53 mutations. Other recurrent mutations in B/P‐MCL included ATM (7, 53%), CCND1 (5, 38%), NOTCH1 (2, 18%), NOTCH2, and BIRC3 (each in 3, 23%). Here, we describe high genomic instability associated with chromothripsis and a high frequency of CDKN2A/B and TP53 alterations in the aggressive variants of MCL. The nonrandom chromothripsis events observed in B/P‐MCL may be an indicator of clinically aggressive MCL. In addition, frequent CDKN2A deletion and high genomic instability may provide potential targets for alternative treatment.
ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice
Authors: Sala Margaux , Gonzales Delphine , Leste‐Lasserre Thierry , Dugot‐Senant Nathalie , Paradis Valérie , Di Tommaso Sylvaine , Dupuy Jean‐William , Pitard Vincent , Dourthe Cyril , Sciarra Amedeo , Sempoux Christine , Ferrell Linda D. , Clouston Andrew D. , Miller Gregory , Yeh Mathew M. , Thung Swan , Gouw Annette S.H. , Quaglia Alberto , Han Jing , Huan Ji , Fan Cathy , Crawford James , Nakanuma Yasuni , Harada Kenichi , le Bail Brigitte , Castain Claire , Frulio Nora , Trillaud Hervé , Possenti Laurent , Blanc Jean‐Frédéric , Chiche Laurence , Laurent Christophe , Balabaud Charles , Bioulac‐Sage Paulette , Raymond Anne Aurélie , Saltel Frédéric
Published: April 2020

Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico‐pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis.
Effect of inclined and low magnetic field in gaseous slip flow in two‐dimensional rectangular microchannel using first‐order boundary conditions
Authors: Kharouf Duaa M. , Al‐Khasawneh Khaleel , Tarawneh Mohammad
Published: April 2020

In the present work, the effect of an oriented low magnetic field on near‐continuum gaseous slip flow inside a two‐dimensional rectangular microchannel has been studied using first‐order boundary conditions. The flow was assumed to be compressible, laminar, and steady. The governing equations were solved analytically to obtain the solutions of velocity, temperature, and the pressure of the flow. The influence of different parameters such as Knudsen number, aspect ratio, Hartmann number, and pressure ratio were studied and analyzed. It was found that the electric and magnetic field with an inclined angle had significant effects on the flow properties. The results showed that the velocity increases and the temperature decreases as the inclination angle of the magnetic field decreases. The velocity increases as the Knudsen number, pressure ratio, and aspect ratio increase, while it decreases with increasing of the Hartmann number. The temperature decreases with increasing of the Knudsen number, pressure ratio, and aspect ratio, while the temperature increases as the Hartmann number increases. The results of the present study were validated with published results in the literature.
ABCC4/MRP4 contributes to the aggressiveness of Myc‐associated epithelial ovarian cancer
Authors: Jung Moonsun , Gao Jixuan , Cheung Leanna , Bongers Angelika , Somers Klaartje , Clifton Molly , Ramsay Emma E. , Russell Amanda J. , Valli Emanuele , Gifford Andrew J. , George Joshy , Kennedy Catherine J. , Wakefield Matthew J. , Topp Monique , Ho Gwo‐Yaw ,   Australian Ovarian Cancer Study, Scott Clare L. , Bowtell David D. , deFazio Anna , Norris Murray D. , Haber Michelle , Henderson Michelle J.
Published: April 2020

Epithelial ovarian cancer (EOC) is a complex disease comprising discrete histological and molecular subtypes, for which survival rates remain unacceptably low. Tailored approaches for this deadly heterogeneous disease are urgently needed. Efflux pumps belonging to the ATP‐binding cassette (ABC) family of transporters are known for roles in both drug resistance and cancer biology and are also highly targetable. Here we have investigated the association of ABCC4/MRP4 expression to clinical outcome and its biological function in endometrioid and serous tumors, common histological subtypes of EOC. We found high expression of ABCC4/MRP4, previously shown to be directly regulated by c‐Myc/N‐Myc, was associated with poor prognosis in endometrioid EOC (P = .001) as well as in a subset of serous EOC with a “high‐MYCN” profile (C5/proliferative; P = .019). Transient siRNA‐mediated suppression of MRP4 in EOC cells led to reduced growth, migration and invasion, with the effects being most pronounced in endometrioid and C5‐like serous cells compared to non‐C5 serous EOC cells. Sustained knockdown of MRP4 also sensitized endometrioid cells to MRP4 substrate drugs. Furthermore, suppression of MRP4 decreased the growth of patient‐derived EOC cells in vivo. Together, our findings provide the first evidence that MRP4 plays an important role in the biology of Myc‐associated ovarian tumors and highlight this transporter as a potential therapeutic target for EOC.
CEO horizon problem and characteristics of board of directors and compensation committee
Authors: Liu Ruonan , Liu Zhenfeng
Published: April 2020

Extant research finds inconclusive evidence about the CEO horizon problem. One possible explanation is that board of directors, especially compensation committees, intervene to mitigate the CEO horizon problem. In this study, we examine whether the characteristics of board of directors and compensation committee affect their effectiveness in mitigating the CEO horizon problem. We find that retiring CEOs are more likely to reduce R&D expenditures when CEOs have more power, and director tenure is longer; retiring CEOs in firms with large board of directors and compensation committee are less likely to manage accruals.
Hsa_circ_0031288/hsa‐miR‐139‐3p/Bcl‐6 regulatory feedback circuit influences the invasion and migration of cervical cancer HeLa cells
Authors: Xu Ya Jie , Yu He , Liu  Guang Xin
Published: April 2020

Circular RNA (circRNA) molecules contain microRNA (miRNA) response elements that are able to competitively bind miRNAs as well as function as miRNA sponges within cells, which can reduce miRNA inhibition of target genes, thereby increasing their expression. TargetScan and miRanda bioinformatic tools were used to analyze the binding sites between genes. The relative levels of gene expression in tissues and cells were verified using quantitative reverse transcription‐polymerase chain reaction. Inhibition of cell proliferation was detected using a WST‐8 method. Cell invasion ability and migration ability were assessed using a Transwell migration assay and a scratch assay, respectively. The binding of miRNA and circRNA was detected using an RNA pull‐down assay. Bifluorescence reporter gene vectors were constructed to verify the binding of miRNA to messenger RNA. A tumor model of cervical cancer cell transplantation in mice was constructed to observe the effect of the genes on tumor growth. hsa_circ_0031288 and B‐cell CLL/lymphoma 6 (Bcl‐6) exhibited high expression in cervical cancer cells and tissue, while hsa‐miR‐139‐3p exhibited low expression. Reducing hsa_circ_0031288 and Bcl‐6 expression or increasing hsa‐miR‐139‐3p expression significantly inhibited the migration, invasion, proliferation, and growth of xenograft and HeLa cells. hsa_circ_0031288 had a regulatory effect on hsa‐miR‐139‐3p, and hsa‐miR‐139‐3p targeted the 3′ untranslated region of Bcl‐6. Reducing hsa_circ_0031288 expression promoted hsa‐miR‐139‐3p expression, while overexpressing miR‐139‐3p inhibited the transcription of Bcl‐6. In the cervical cancer HeLa cell line, the hsa_circ_0031288/hsa‐miR‐139‐3p/Bcl‐6 regulatory axis affects cell migration and proliferation, and its mechanism may involve hsa_circ_0031288 acting as a sponge for hsa‐miR‐139‐3p, thereby relieving the transcriptional inhibition of Bcl‐6. This suggests an approach for elucidating the pathogenesis of cervical cancer while offering new intervention targets for cervical cancer treatment.
Long noncoding RNA SOX21‐AS1 regulates the progression of triple‐negative breast cancer through regulation of miR‐520a‐5p/ORMDL3 axis
Authors: Liu Xia , Song Jingyong , Kang Yu , Wang Yaojia , Chen Anyue
Published: April 2020

Recently, long noncoding RNAs (lncRNAs) have been reported as a new kind of controllers about cancer processes in biology. In spite of the dysregulation of lncRNAs in various kinds of cancers, only a little of the information was effective on the expression configuration and inner effects of lncRNAs in triple‐negative breast cancer (TNBC). This study valued the expression of lncRNA SOX21‐AS1 and the biological role it played in TNBC. In our research, SOX21‐AS1 had a high expression in TNBC cell lines. The functional experiments showed that knockdown of SOX21‐AS1 obviously restrained cell proliferation, migration, invasion, and epithelial‐mesenchymal transition process and promoted cell apoptosis. Mechanistically, SOX21‐AS1 was found to bind with miR‐520a‐5p. Besides, ORMDL3 was identified as a downstream target of miR‐520a‐5p, and the suppressed ORMDL3 expression induced by silenced SOX21‐AS1 could be restored by miR‐520a‐5p inhibition. Further, data from rescue assays revealed that SOX21‐AS1 could regulate the malignancy of TNBC via miR‐520a‐5p/ORMDL3 axis. All in all, we identified that SOX21‐AS1 regulated the cellular process of TNBC cells via antagonizing miR‐520a‐5p availability to upregulate ORMDL3 expression.
LncRNA MALAT1 targeting miR‐124‐3p regulates DAPK1 expression contributes to cell apoptosis in Parkinson's Disease
Authors: Lu Yi , Gong Zhongying , Jin Xiaojie , Zhao Peng , Zhang Yuting , Wang Zhiyun
Published: April 2020

Death associated protein kinase 1 (DAPK1) was initially discovered in the progress of gamma‐interferon induced programmed cell death, it is a key factor in the central nervous system, including Parkinson's disease (PD). However, the underlying mechanisms of DAPK1 in PD remain unclear and this research work aims to explore the potential mechanisms of DAPK1 in PD. In the study, we exposed SH‐SY5Y cells to MPP+ and treated mice with MPTP to investigate the roles of DAPK1 in PD and the underlying mechanisms. The results indicated that the expression of DAPK1 is significantly upregulated and negatively correlated with miR‐124‐3p levels in SH‐SY5Y cells treated by MPP+, and miR‐124‐3p mimics could effectively inhibit DAPK1 expressions and alleviate MPP+‐induced cell apoptosis. In addition, knockdown MALAT1 reduces the levels of DAPK1 and the ratio of SH‐SY5Y cell apoptosis, which is reversed via miR‐124‐3p inhibitor in vitro. Similarly, knockdown MALAT1 could improve behavioral changes and reduce apoptosis by miR‐124‐3p upregulation and DAPK1 downregulation in MPTP induced PD mice. Taken together, our data showed that lncRNA MALAT1 positively regulates DAPK1 expression by targeting miR‐124‐3p, and mediates cell apoptosis and motor disorders in PD. In summary, these results suggest that MALAT1/miR‐124‐3p /DAPK1 signaling cascade mediates cell apoptosis in vitro and in vivo, which may provide experimental evidence of developing potential therapeutic strategies for PD.
Exosomes derived from RPE cells under oxidative stress mediate inflammation and apoptosis of normal RPE cells through Apaf1/caspase‐9 axis
Authors: Ke Yifeng , Fan Xiaoe , Rui Hao , Xinjun Ren , Dejia Wen , Chuanzhen Zheng , Li Xiaorong
Published: April 2020

This study aims to explore the effects of exosomes, secreted by retinal pigment epithelial (RPE) cells under oxidative stress (OS), on apoptosis and inflammation of normal RPE cells. Exosomes secreted by normal RPE cells (named as exo) and rotenone (2.5 µmol/L) stimulated RPE cells (named as rot‐exo) were isolated and extracted by multi‐step differential centrifugation for morphology observation under a transmission electron microscopy. pcDNA3.1a, pcDNA3.1a‐Apaf1, and p3xFlag‐CMV‐caspase‐9 plasmids were constructed and transfected into ARPE‐19 cells. Exosomes secreted by ARPE‐19 cells were injected into the vitreous body of rats to verify the effect of Apaf1 and caspase‐9 on cell apoptosis and inflammation. Co‐immunoprecipitation was applied to clarify the interaction of Apaf1 with caspase‐9. Exosomes secreted by rotenone stimulated ARPE‐19 cells could induce cell apoptosis, oxidative injury, and inflammation in ARPE‐19 cells. Exosomes secreted under OS can damage retinal functions of rats and have upregulated expression of Apaf1. Overexpression of Apaf1 in exosomes secreted under OS can cause the inhibition of cell proliferation, the increase of cell apoptosis and elicitation of inflammatory response in ARPE‐19 cells. Exosomes derived from ARPE‐19 cells under OS regulate Apaf1 expression to increase cell apoptosis and to induce oxidative injury and inflammatory response through a caspase‐9 apoptotic pathway.
Deep cerebral venous blood flow monitoring by transcranial doppler ultrasonography in the treatment of cerebral venous sinus thrombosis: A case report
Authors: Zhang Hui , He Yitao , Zou Liangyu , Deng Jian , Guo Yi
Published: April 2020

We report the case of a patient in whom we used deep cerebral venous blood flow monitoring by transcranial Doppler ultrasonography to monitor the effect of anticoagulation therapy on cerebral venous sinus thrombosis. The blood flow velocity of deep cerebral veins increased in the early stage of cerebral venous sinus thrombosis, then gradually decreased to the normal level as the disease improved. Moreover, the recovery of the blood flow velocity of deep cerebral veins occurred earlier than the morphological recovery demonstrated by magnetic resonance venography.
Evaluating the impact of turf‐care products on soil biological health
Authors: Diera Alexx A. , Raymer Paul L. , Martinez‐Espinoza Alfredo D. , Bauske Ellen , Habteselassie Mussie Y.
Published: April 2020

Golf courses require extensive use of inputs to meet the needs of playability and aesthetics. The impact of these inputs on soil biological health is largely unknown. Two field trials were conducted at a golf course in Georgia to evaluate short‐term effects of wetting agents (Cascade Plus and Duplex [C+D], Revolution [Rev]), plant growth regulators (PrimoMaxx [PM] and Cutless [CL]), and a product called PlantHelper (PH) on soil biological health by measuring microbial abundance and function. Quantitative polymerase chain reaction was used to measure microbial abundance, which included total bacteria, total fungi, and ammonia‐oxidizing prokaryotes. Soil respiration and enzyme assays were used as additional indicators of soil health. In bentgrass putting green, total bacteria and ammonia‐oxidizing bacteria decreased in abundance in response to the wetting agents and PH, indicating their sensitivity to the products. Whereas C+D stimulated urease activity, Rev and PH caused a short‐lived but immediate increase in respiration, indicating that they acted as labile carbon sources. In a bermudagrass fairway, PM was the only product that caused an increase in total bacteria abundance. PrimoMaxx and CL caused a delayed increase in respiration, suggesting that they may have affected the microorganisms indirectly through their impact on root growth and exudate production later. Although CL caused a decrease in urease activity, none of the products significantly affected phosphatase activity. Overall, the products did not seem to have a lasting impact on soil biological health, although long‐term studies are needed to confirm these observations.
Understanding access to genomics in an ethnically diverse south Florida population: A comparison of demographics in odyssey and rapid whole genome sequencing programs
Authors: Hussain Saida B. , Quittner Alexandra L. , Brown Marilyn , Li‐Rosi Ana Maria
Published: April 2020

Advances in genomic medicine have evolved to include rapid whole genome sequencing (rWGS) in pediatric intensive care settings. Traditionally, genetic testing was conducted in outpatient clinics, with stepwise genetic testing occurring over several years. This delayed the time to diagnosis, making it more difficult to include underrepresented groups, such as those who identify as Black and Latinx. National genetic sequencing programs have also struggled to engage these participants in their studies, leading to a significant disparity in access to new genetic technologies. The purpose of our study was to compare the demographic characteristics of families enrolled in both an Odyssey Program (N = 46), defined as outpatients in the Genetics Clinic who have had prior genetic testing, and a newly implemented rWGS (N = 52) sequencing program. Despite living in a large, ethnically diverse city, our results indicated that parents in the Odyssey program differed significantly from parents in the rWGS program in level of education, family income, and insurance status. For example, 71.5% of parents in the diagnostic Odyssey program had a college or advanced degree, whereas 42% of parents in the rWGS program had this level of education. Family income and insurance also differed, with 48.6% of families in the Odyssey program earning $100,000 or more versus 28.2% in rWGS; 56% of parents in the Odyssey program had private insurance with 26% on Medicaid whereas only 23% of parents in rWGS had private insurance, with the vast majority of children on Medicaid (69%). Thus, our Odyssey program illustrates some of the common pitfalls in implementing genomic testing in an ethnically diverse community, including lack of referrals, travel to outpatient visits, and a cultural mismatch with providers. The successful enrollment of underrepresented groups in the rWGS program demonstrates that given the opportunity to participate in genetic testing, families are interested and aware of the potential benefits of this testing for their child. As genomic sequencing transitions from outpatient to inpatient settings, an opportunity arises to close the health disparity gap. Recommendations for implementing rWGS in pediatric, intensive care settings that address the common barriers faced by underrepresented families are discussed.
Idiopathic mesenteric phlebosclerosis: A rare cause of chronic diarrhea
Authors: Sze Shun Fung , Lam Polly Woon Yee , Lam Jodis Ting Wa , Chung Cliff Chi Chiu , Lee Yuk Tong
Published: April 2020

We report a 45‐year‐old healthy Chinese woman who presented with chronic diarrhea and iron deficiency anemia, with colonoscopy showing multiple ulcers from cecum to sigmoid on a background of dark‐purple mucosa. She was initially suspected to be suffering from inflammatory bowel disease, but the peculiar colonic biopsy findings and computed tomography (CT) imaging features, together with her habit of using Chinese herbal supplements, supported the rare diagnosis of idiopathic mesenteric phlebosclerosis.
Switching protease inhibitors to rilpivirine in HIV‐positive individuals with complete viral suppression and without prior HIV drug resistance in a resource‐limited setting: a randomized controlled trial
Authors: Palanuphap Kulissara , Sungkanuparph Somnuek
Published: April 2020

Introduction

Prior to the availability of rilpivirine (RPV), patients who could not tolerate efavirenz and nevirapine (NVP) were treated with protease inhibitor (PI)‐based antiretroviral therapy (ART). Dyslipidaemia and other metabolic complications are commonly associated with PI use. This study aimed to compare the efficacy and adverse events between switching from PI‐based to RPV‐based regimen, versus continuing PI‐based regimens in HIV‐positive individuals with complete viral suppression.

Methods

A randomized controlled trial was conducted in HIV‐positive individuals receiving PI‐based regimens with undetectable HIV RNA and without prior HIV drug resistance. Patients were enrolled between July and December 2017 in a university medical centre in Bangkok, Thailand. They were randomized to switch from PIs to RPV (switch group) or continue ritonavir‐boosted PI (control group). Primary endpoint was the proportion of patients with undetectable HIV RNA at 48 weeks. Changes in CD4 cell counts, lipid profiles and adverse events were also analysed.

Results and discussion

A total of 84 patients were enrolled, 42 in each group. Mean age was 47.7 years and 53.6% were males. At 48 weeks, 95.2% of patients in the switch group and 92.9% of control group had maintained undetectable HIV RNA (difference rate 2.4%; 95% CI, −9.6 to 14.7). Means of CD4 cell counts were 611 and 641 cells/mm3 in switch and control groups respectively (p = 0.632). Mean changes in lipid profiles (switch vs. control groups) were: total cholesterol, −12.5 versus + 12.2 (p = 0.024); LDL, −3.4 versus + 6.2 (p = 0.040); HDL, +1.6 versus + 1.9 (p = 0.887); and triglycerides, −82.6 versus − 24.4 mg/dL (p = 0.031). The mean changes of glucose and eGFR were similar (p > 0.05) between the two groups. The mean change of ALT was significantly greater in switch group (18.2 vs. 4.0 U/L, p = 0.017). One patient in switch group had anorexia and elevated ALT at 14 weeks and completely recovered after RPV discontinuation.

Conclusions

Switching PIs to RPV, in patients with complete viral suppression and without prior HIV drug resistance, sustains viral suppression and yields better lipid profiles. This finding supports its use as switching therapy in patients receiving PI‐based regimens due to intolerance to efavirenz and NVP and previous alternatives limited to PI in resource‐limited settings.
Preparation of polydopamine‐coated, graphene oxide/Fe3O4‐ imprinted nanoparticles for selective removal of sulfonylurea herbicides in cereals
Authors: He Jinxing , Lu Yue , Zhao Tao , Li Yingqiu
Published: April 2020

BACKGROUND

Sulfonylureas are potentially toxic broad‐spectrum herbicides. They pose a persistent threat to food safety and the environment. It is therefore important to develop a rapid and efficient pretreatment and detection method to prevent their harmful effects on human health.

RESULTS

In the present work, a novel and highly selective absorbent for chlorosulfuron (CS) detection was prepared by the simple self‐polymerization of dopamine on the surface of magnetic graphene oxide using a CS template. The resultant imprinted nanoparticles (MGO@PDA‐MIPs) were characterized by transmission electron microscopy, X‐ray diffraction, vibrating‐sample magnetometry, thermogravimetric analysis, and nitrogen adsorption–desorption. The adsorption experiments demonstrated that the MGO@PDA‐MIPs have excellent selectivity with regard to CS, with a high imprinting factor of 3.41 compared with a non‐imprinted polymer. The nanoparticles rapidly achieve adsorption equilibrium and efficient desorption because there are numerous binding sites on the thin polydopamine imprinting layer. Under optimized conditions, the MGO@PDA‐MIPs can be used to detect sulfonylurea residues in cereal samples by magnetic solid phase extraction coupled with high performance liquid chromatography (HPLC). The nanoparticles have a satisfactory recovery rate (80.65–101.01%) with a relative standard deviation (RSD) of less than 7.15%, and a limit of detection with regard to CS of 1.61 μg kg−1 (S/N = 3). They can also be re‐used at least seven times.

CONCLUSION

The MGO@PDA‐MIPs have outstanding recognition performance, and can be prepared by a facile, single‐step, and environmentally friendly process. They therefore have excellent potential for the recognition and separation of trace sulfonylurea herbicides in complex matrices. © 2020 Society of Chemical Industry
Chemical profiling and marker characterization of Huangqin decoction prepared with three types of peony root by liquid chromatography with electrospray ionization mass spectrometry
Authors: Du Kang , Yang Jingyi , Yang Li , Wang Zhengtao , Wang Rui , Shi Yanhong
Published: April 2020

Clarification of the quality and biological effect equivalence of traditional Chinese medicines containing multi‐origin species is essential to improve their current quality standards, and also is the core problem to clarify the origins of single herbs with multi‐species in Chinese formulas that will guarantee their clinical application. Huangqin decoction is the typical one of multi‐origin formulas frequently used in traditional Chinese medicine and Kampo medicine. An ultra high performance liquid chromatography with electrospray ionization–tandem mass spectrometry was developed for chemical profiling and marker quantification of Huangqin decoction prepared with two different original types of peony root, white and red peony root. Forty‐seven main peaks in chemical profiling of Huangqin decoction prepared with white and red peony root were identified: nine were from peony root, 20 from baical skullcap root, 17 from licorice root, and one from jujubae fruit. The markers characteristics of the respective types of peony root in Huangqin decoction differ from that in single herbs, especially in terms of monoterpenoids and hydrolysable tannins. Subsequently, 17 representative markers in Huangqin decoction prepared with three types of peony root and their chemical characteristics and content distribution were carried out.
Validation of Abbreviated Four‐ and Eight‐Item Versions of the PTSD Checklist for DSM‐5 in a Traumatically Injured Sample
Authors: Geier Timothy J. , Hunt Joshua C. , Hanson Jessica L. , Heyrman Katelyn , Larsen Sadie E. , Brasel Karen J. , deRoon‐Cassini Terri A.
Published: April 2020

Rates of posttraumatic stress disorder (PTSD) are three times higher in traumatically injured populations than the general population, yet limited brief, valid measures for assessing PTSD symptom severity exist. The PTSD Checklist for DSM‐5 (PCL‐5) is a valid, efficient measure of symptom severity, but its completion is time consuming. Subsequently, abbreviated four‐ and eight‐item versions were developed using the Mini‐International Neuropsychiatric Interview–7 PTSD module and validated in Veteran samples. This study aimed to validate these abbreviated versions using the Clinician‐Administered PTSD Scale for DSM‐5 (CAPS‐5), the gold standard for PTSD diagnosis, in a traumatically injured civilian population. Participants were 251 traumatically injured adults (Mage = 42.52 years; 69.3% male; 50.2% Caucasian) recruited from a Level 1 trauma center inpatient unit; 32.3% and 17.9% of participants experienced a motor vehicle crash or gunshot wound, respectively. The CAPS‐5 and PCL‐5 were administered approximately 6.5 months postinjury. We examined whether compared to the full PCL‐5, the abbreviated versions would adequately differentiate between participants with and without a CAPS‐5 PTSD diagnosis. The abbreviated versions were highly correlated with the total scale and showed good‐to‐excellent internal consistency. The diagnostic utility of the abbreviated measures was comparable to that of the total scale regarding sensitivity, suggesting they may be useful as abbreviated screening tools; however, the total scale functioned better regarding specificity. The abbreviated versions of the PCL‐5 may be useful screening instruments in the long‐term care of traumatic injury survivors and may be more likely to be implemented across routine clinical and research contexts.
Haploinsufficiency of the FOXA2 associated with a complex clinical phenotype
Authors: Mohammed Idris , Al‐Khawaga Sara , Bohanna David , Shabani Abdusamea , Khan Faiyaz , Love Donald R. , Nawaz Zafar , Hussain Khalid
Published: April 2020

Background

There are few reports describing the proximal deletions of the short arm of chromosome 20, making it difficult to predict the likely consequences of these deletions. Most previously reported cases have described the association of 20p11.2 deletions with Alagille syndrome, while there are others that include phenotypes such as panhypopituitarism, craniofacial dysmorphism, polysplenia, autism, and Hirschsprung disease.

Methods

Molecular karyotyping, cytogenetics, and DNA sequencing were undertaken in a child to study the genetic basis of a complex phenotype consisting of craniofacial dysmorphism, ocular abnormalities, ectopic inguinal testes, polysplenia, growth hormone deficiency, central hypothyroidism, and gastrointestinal system anomalies.

Results

We report the smallest described de novo proximal 20p11.2 deletion, which deletes only the FOXA2 leading to the above complex phenotype.

Conclusions

Haploinsufficiency of the FOXA2 only gene is associated with a multisystem disorder.
Chronic postoperative complications and donor site morbidity after sural nerve autograft harvest or biopsy
Authors: Ducic Ivica , Yoon Joshua , Buncke Gregory
Published: April 2020

Background

The sural nerve is the most frequently harvested nerve autograft and is most often biopsied in the workup of peripheral neuropathy. While the complication types associated with these two procedures are well known, their clinical significance is poorly understood and there is a paucity of data regarding the complication rates.

Methods

Pubmed search identified studies regarding complications after sural nerve harvest and biopsy. The data was grouped into sensory deficits, chronic pain, sensory symptoms, wound infections, wound complications, other postoperative complications, and complications impacting daily life. The incidence of each complication was calculated, and a chi‐square analysis was performed to determine if there were any differences between nerve biopsies and graft harvest with respect to each complication.

Results

Twelve studies yielded 478 sural nerve procedures. Sensory deficits occurred at a rate of 92.9%, chronic pain at 19.7%, sensory symptoms at 41.1%, wound infections at 5.7%, noninfectious wound complications at 7.8%, and impact on daily life at 5.0%. The differences in wound infections, sensory symptoms, and impact on daily life between biopsies versus graft excisions were found to reach statistical significance (p < .05).

Conclusions

Sural nerve excisions can cause chronic postoperative donor‐site complications. Given these complications, alternative available mediums for nerve reconstruction should be explored and utilized wherever appropriate. If an alternative medium is unavailable and nerve autograft must be harvested for nerve reconstruction, then patients should be counseled about risks for developing donor site complications that may negatively affect quality of life.
The Preventive Effects of Pterostilbene on the Exercise Intolerance and Circadian Misalignment of Mice Subjected to Sleep Restriction
Authors: Liu Yang , Lang Hedong , Zhou Min , Huang Li , Hui Suocheng , Wang Xiaolan , Chen Ka , Mi Mantian
Published: April 2020

Scope

The study investigates the effects of pterostilbene (PTE) on exercise endurance and circadian rhythm in sleep‐restricted (SR) mice.

Methods and results

The SR model is established by keeping mice awake during the first 8 h of light period for 5 d and PTE (100 mg kg−1 d−1) is given once a day. PTE improves endurance in SR mice by significantly prolonging the exhaustive swimming time and ameliorating exercise fatigue biochemical parameters, including creatine kinase and lactate dehydrogenase. It is observed that PTE effectively regained mitochondrial function by improving mitochondrial swelling and maintaining oxidative phosphorylation system–related genes expression, and inhibited the decrease of mitochondrial biogenesis–related genes expression. Furthermore, PTE restores rhythms of AMP‐activated protein kinase (AMPK) phosphorylation activity, silent information regulator 1 (SIRT1) deacetylation activity, and SIRT1‐mediated peroxisome proliferator‐activated receptor coactivator 1α (PGC‐1α) deacetylation in SR mice. Finally, the results demonstrate that the AMPK/SIRT1/PGC‐1α pathway may be correlated with the relationships between mitochondrial function and circadian rhythms, markedly regulating the expression of skeletal muscle clock genes, circadian locomotor output cycles kaput, and brain and muscle arnt‐like 1.

Conclusions

PTE ameliorates SR‐induced exercise intolerance associated with circadian misalignment and mitochondrial dysfunction through AMPK/SIRT1/PGC‐1α pathway.
Triacylglycerol‐Rich Oils of Marine Origin are Optimal Nutrients for Induction of Polyunsaturated Docosahexaenoic Acid Ester of Hydroxy Linoleic Acid (13‐DHAHLA) with Anti‐Inflammatory Properties in Mice
Authors: Paluchova Veronika , Vik Anders , Cajka Tomas , Brezinova Marie , Brejchova Kristyna , Bugajev Viktor , Draberova Lubica , Draber Petr , Buresova Jana , Kroupova Petra , Bardova Kristina , Rossmeisl Martin , Kopecky Jan , Hansen Trond Vidar , Kuda Ondrej
Published: April 2020

Scope

The docosahexaenoic acid ester of hydroxy linoleic acid (13‐DHAHLA) is a bioactive lipid with anti‐inflammatory properties from the family of fatty acid esters of hydroxy fatty acids (FAHFA).

Methods and results

To explore the biosynthesis of 13‐DHAHLA from dietary oils, C57BL/6N mice are gavaged for 8 days with various corn oil/marine oil mixtures containing the same amount of DHA. Plasma levels of omega‐3 FAHFAs are influenced by the lipid composition of the mixtures but do not reflect the changes in bioavailability of polyunsaturated fatty acids in plasma. Triacylglycerol‐bound DHA and linoleic acid serve as more effective precursors for 13‐DHAHLA synthesis than DHA bound in phospholipids or wax esters. Both 13(S)‐ and 13(R)‐DHAHLA inhibit antigen and PGE2‐induced chemotaxis and degranulation of mast cells to a comparable extent and 13(S)‐DHAHLA is identified as the predominant isomer in mouse adipose tissue.

Conclusion

Here, the optimal nutritional source of DHA is identified, which supports production of anti‐inflammatory FAHFAs, as triacylglycerol‐based marine oil and also reveals a possible role of triacylglycerols in the synthesis of FAHFA lipokines.
Interdigital capacitor loaded electric‐LC resonator for dielectric characterization
Authors: Kapoor Anush , Varshney Prashant Kumar , Akhtar M. Jaleel
Published: April 2020

A high sensitivity microstrip line‐based sensor loaded with the electric‐LC (ELC) resonator is proposed in this work for the accurate characterization of dielectric materials. The high sensitivity in the present situation is achieved due to usage of novel interdigital capacitor in the ELC resonator topology, which actually provides enhanced electric field for dielectric testing. The proposed sensor is designed in the S band regime, and various standard dielectric samples are tested to validate the proposed design. For retrieving the dielectric constants of these samples, an empirical relationship is proposed relating the dielectric properties with the resonant frequency of the sensor. The proposed empirical model is further improved by introducing two error terms to take into consideration the effect of fabrication tolerance of the sensor and surface roughness of the test specimen. The normalized sensitivity of the proposed sensor using standard procedure is estimated to be 5.14%, which is reasonably higher than that of other sensors reported in literature.
Technical Note: Taking EGSnrc to new lows: Development of egs++ lattice geometry and testing with microscopic geometries
Authors: Martinov Martin P. , Thomson Rowan M.
Published: April 2020

Purpose

This work introduces a new lattice geometry library, egs_lattice, into the EGSnrc Monte Carlo code, which can be used for both modeling very large (previously unfeasible) quantities of geometries (e.g., cells or gold nanoparticles (GNPs)) and establishing recursive boundary conditions. The reliability of egs_lattice, as well as EGSnrc in general, is cross‐validated and tested at short length scales and low energies.

Methods

New Bravais, cubic, and hexagonal lattice geometries are defined in egs_lattice and their transport algorithms are described. Simulations of cells and GNP‐containing cavities are implemented to compare to independent, published Geant4‐DNA and PENELOPE results. Recursive boundary conditions, implemented through a cubic lattice, are used to perform electron Fano cavity tests. The Fano test is performed on three different‐sized cells containing GNPs in the region around the nucleus for three source energies.

Results

Lattices are successfully implemented in EGSnrc, and are used for validation. EGSnrc calculated the dose to cell cytoplasm and nucleus when irradiated by an internal electron source with a median difference of 0.6% compared to published Geant4‐DNA results. EGSnrc calculated the ratio of dose to a microscopic cavity containing GNPs over dose to a cavity containing a homogeneous mixture of gold, and results generally agree (within 1%) with published PENELOPE results. The electron Fano cavity test is passed for all energies and cells considered, with sub‐0.1% discrepancies between EGSnrc‐calculated and expected values. Additionally, the recursive boundary conditions used for the Fano test provided a factor of over a million increase in efficiency in some cases.

Conclusions

The egs_lattice geometry library, currently available as a pull request on the EGSnrc GitHub “develop” branch, is now freely accessible as open‐source code. Lattice geometry implementations cross‐validated with independent simulations in other MC codes and verified with the electron Fano cavity test demonstrate not only the reliability of egs_lattice, but also, by extension, EGSnrc’s ability to simulate transport in nanometer geometries and score in microscopic cavities.