bluuebunny/crossref_metadata_2025 huggingface dataset:
Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion
Authors: Fraune Christoph , Harms Luisa , Büscheck Franziska , Höflmayer Doris , Tsourlakis Maria Christina , Clauditz Till S. , Simon Ronald , Möller Katharina , Luebke Andreas M. , Möller-Koop Christina , Steurer Stefan , Hube-Magg Claudia , Sauter Guido , Weidemann Sören , Lebok Patrick , Dum David , Kind Simon , Minner Sarah , Izbicki Jakob R. , Schlomm Thorsten , Huland Hartwig , Heinzer Hans , Burandt Eike , Haese Alexander , Graefen Markus , Schroeder Cornelia
Published: March 2020

Background

TFAP2D is a transcription factor important for modulating gene expression in embryogenesis. Its expression and prognostic role in prostate cancer has not been evaluated.

Methods

Therefore, a tissue microarray containing 17,747 prostate cancer specimens with associated pathological, clinical, and molecular data was analyzed by immunohistochemistry to assess the role of TFAP2D.

Results

TFAP2D expression was typically increased in prostate cancer as compared to adjacent non-neoplastic glands. TFAP2D staining was considered negative in 24.3% and positive in 75.7% of 13,545 interpretable cancers. TFAP2D staining was significantly linked to advanced tumor stage, high classical and quantitative Gleason grade, lymph node metastasis, and a positive surgical margin (p ≤ 0.0045). TFAP2D positivity was more common in ERG fusion positive (88.7%) than in ERG negative cancers (66.8%; p < 0.0001). Subset analyses in 3776 cancers with and 4722 cancers without TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. Multivariate analysis did not identify TFAP2D protein expression levels as a robust independent prognostic parameter. Positive TFAP2D immunostaining was significantly associated with 10 of 11 previously analyzed chromosomal deletions in ERG negative cancers (p ≤ 0.0244 each) indicating that elevated TFAP2D expression parallels genomic instability in prostate cancer.

Conclusion

These data demonstrate that TFAP2D protein overexpression is linked to prostate cancer progression and genomic instability in ERG negative prostate cancers.
Experimental Research on the Dynamic Lubricating Performance of Slipper/Swash Plate Interface in Axial Piston Pumps
Authors: Zhou Junjie , Zhou Jichen , Jing Chongbo
Published: March 2020

The interface between the slipper/swash plate is one of the most important frication pairs in axial piston pumps. The test of this interface in a real pump is very challenging. In this paper, a novel pump prototype is designed and a test rig is set up to study the dynamic lubricating performance of the slipper/swash-plate interface in axial piston machines. Such an experimental setup can simulate the operating condition of a real axial piston pump without changing the relative motion relationship of the interfaces. Considering the lubricant oil film thickness as the main measurement parameter, the attitude of the slipper under the conditions of different load pressure, rotation speed and charge pressure are studied experimentally. After the test, the wear state of the swash plate is observed. According to the friction trace on the surface of the swash plate, the prediction for the attitude of the slipper and the zone easy to wear are verified.
Functionalized Folate-Modified Graphene Oxide/PEI siRNA Nanocomplexes for Targeted Ovarian Cancer Gene Therapy
Authors: Wang Yunfei , Sun Guoping , Gong Yingying , Zhang Yuying , Liang Xiaofei , Yang Linqing
Published: March 2020

Gene therapy is emerging as a valid method for the treatment of ovarian cancer, including small interfering RNA (siRNA). Although it is so powerful, few targeting efficient gene delivery systems seriously hindered the development of gene therapy. In this study, we synthesized a novel gene vector PEG-GO-PEI-FA by functionalized graphene oxide (GO), in which folic acid (FA) can specifically bind to the folate receptor (FR), which is overexpressed in ovarian cancer. Characterizations of the nanocomplexes were evaluated by dynamic light scattering (DLS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). The siRNA condensation ability and stability were assessed by agarose gel electrophoresis. Cellular uptake efficiency and lysosomal escape ability in ovarian cancer cells were investigated by confocal laser scanning microscopy. Furthermore, cellular biosafety of the system and inhibitory of the siRNA tolerability were evaluated by CCK-8 assay. The size of the PEG-GO-PEI-FA nanocomplexes was 216.1 ± 2.457 nm, exhibiting mild cytotoxicity in ovarian cancer cells. With high uptake efficiency, PEG-GO-PEI-FA can escape from the lysosome rapidly and release the gene. Moreover, PEG-GO-PEI-FA/siRNA can effectively inhibit the growth of ovarian cancer cells. By and large, the PEG-GO-PEI-FA/siRNA may offer a promising strategy for siRNA delivery in the treatment of FR-positive ovarian carcinoma or similar tumors.
CNV Radar: an improved method for somatic copy number alteration characterization in oncology
Authors: Soong David , Stratford Jeran , Avet-Loiseau Herve , Bahlis Nizar , Davies Faith , Dispenzieri Angela , Sasser A. Kate , Schecter Jordan M. , Qi Ming , Brown Chad , Jones Wendell , Keats Jonathan J. , Auclair Daniel , Chiu Christopher , Powers Jason , Schaffer Michael
Published: March 2020

Background

Cancer associated copy number variation (CNV) events provide important information for identifying patient subgroups and suggesting treatment strategies. Technical and logistical issues, however, make it challenging to accurately detect abnormal copy number events in a cost-effective manner in clinical studies.

Results

Here we present CNV Radar, a software tool that utilizes next-generation sequencing read depth information and variant allele frequency patterns, to infer the true copy number status of genes and genomic regions from whole exome sequencing data. Evaluation of CNV Radar in a public multiple myeloma dataset demonstrated that CNV Radar was able to detect a variety of CNVs associated with risk of progression, and we observed > 70% concordance with fluorescence in situ hybridization (FISH) results. Compared to other CNV callers, CNV Radar showed high sensitivity and specificity. Similar results were observed when comparing CNV Radar calls to single nucleotide polymorphism array results from acute myeloid leukemia and prostate cancer datasets available on TCGA. More importantly, CNV Radar demonstrated its utility in the clinical trial setting: in POLLUX and CASTOR, two phase 3 studies in patients with relapsed or refractory multiple myeloma, we observed a high concordance rate with FISH for del17p, a risk defining CNV event (88% in POLLUX and 90% in CASTOR), therefore allowing for efficacy assessments in clinically relevant disease subgroups. Our case studies also showed that CNV Radar is capable of detecting abnormalities such as copy-neutral loss of heterozygosity that elude other approaches.

Conclusions

We demonstrated that CNV Radar is more sensitive than other CNV detection methods, accurately detects clinically important cytogenetic events, and allows for further interrogation of novel disease biology. Overall, CNV Radar exhibited high concordance with standard methods such as FISH, and its success in the POLLUX and CASTOR clinical trials demonstrated its potential utility for informing clinical and therapeutic decisions.
Evidence for a novel overlapping coding sequence in POLG initiated at a CUG start codon
Authors: Khan Yousuf A. , Jungreis Irwin , Wright James C. , Mudge Jonathan M. , Choudhary Jyoti S. , Firth Andrew E. , Kellis Manolis
Published: March 2020

Background

POLG, located on nuclear chromosome 15, encodes the DNA polymerase γ(Pol γ). Pol γ is responsible for the replication and repair of mitochondrial DNA (mtDNA). Pol γ is the only DNA polymerase found in mitochondria for most animal cells. Mutations in POLG are the most common single-gene cause of diseases of mitochondria and have been mapped over the coding region of the POLG ORF.

Results

Using PhyloCSF to survey alternative reading frames, we found a conserved coding signature in an alternative frame in exons 2 and 3 of POLG, herein referred to as ORF-Y that arose de novo in placental mammals. Using the synplot2 program, synonymous site conservation was found among mammals in the region of the POLG ORF that is overlapped by ORF-Y. Ribosome profiling data revealed that ORF-Y is translated and that initiation likely occurs at a CUG codon. Inspection of an alignment of mammalian sequences containing ORF-Y revealed that the CUG codon has a strong initiation context and that a well-conserved predicted RNA stem-loop begins 14 nucleotides downstream. Such features are associated with enhanced initiation at near-cognate non-AUG codons. Reanalysis of the Kim et al. (2014) draft human proteome dataset yielded two unique peptides that map unambiguously to ORF-Y. An additional conserved uORF, herein referred to as ORF-Z, was also found in exon 2 of POLG. Lastly, we surveyed Clinvar variants that are synonymous with respect to the POLG ORF and found that most of these variants cause amino acid changes in ORF-Y or ORF-Z.

Conclusions

We provide evidence for a novel coding sequence, ORF-Y, that overlaps the POLG ORF. Ribosome profiling and mass spectrometry data show that ORF-Y is expressed. PhyloCSF and synplot2 analysis show that ORF-Y is subject to strong purifying selection. An abundance of disease-correlated mutations that map to exons 2 and 3 of POLG but also affect ORF-Y provides potential clinical significance to this finding.
Genome-wide identification and expression analysis of PUB genes in cotton
Authors: Lu Xuke , Shu Na , Wang Delong , Wang Junjuan , Chen Xiugui , Zhang Binglei , Wang Shuai , Guo Lixue , Chen Chao , Ye Wuwei
Published: March 2020

Background

The U-box gene encodes a ubiquitin ligase that contain U-box domain. The plant U-box gene (PUB) plays an important role in the response to stresses, but few reports about PUBs in cotton were available. Therefore research on PUBs is of great importance and a necessity when studying the mechanisms of stress- tolerance in cotton.

Results

In this study, we identified 93, 96, 185 and 208 PUBs from four sequenced cotton species G. raimondii (D5), G. arboreum (A2), G. hirsutum (AD1) and G. barbadense (AD2), respectively. Prediction analysis of subcellular localization showed that the PUBs in cotton were widely localized in cells, but primarily in the nucleus. The PUBs in cotton were classified into six subfamilies (A-F) on the basis of phylogenetic analysis, which was testified by the analysis of conserved motifs and exon-intron structures. Chromosomal localization analysis showed that cotton PUBs were unevenly anchored on all chromosomes, varying from 1 to 14 per chromosome. Through multiple sequence alignment analysis, 3 tandem duplications and 28 segmental duplications in cotton genome D5, 2 tandem duplications and 25 segmental duplications in A2, and 143 homologous gene pairs in A2 and D5 were found; however no tandem duplications in A2 or D5 were found. Additionally, 105, 14 and 17 homologous gene pairs were found in the intra-subgenome of At and Dt, At sub-genome and Dt sub-genome of G. hirsutum, respectively. Functional analysis of GhPUB85A and GhPUB45D showed that these genes positively responded to abiotic stresses, but the expression patterns were different. In addition, although the expression levels of these two homologous genes were similar, their contributions were different when responding to stresses, specifically showing different responses to abiotic stresses and functional differences between the two subgenomes of G. hirsutum.

Conclusions

This study reported the genome-wide identification, structure, evolution and expression analysis of PUBs in cotton, and the results showed that the PUBs were highly conserved throughout the evolutionary history of cotton. All PUB genes were involved in the response to abiotic stresses (including salt, drought, hot and cold) to varying degrees.
Correction to: Wnt3a induces exosome secretion from primary cultured rat microglia
Authors: Hooper Claudie , Sainz-Fuertes Ricardo , Lynham Steven , Hye Abdul , Killick Richard , Warley Alice , Bolondi Cecilia , Pocock Jennifer , Lovestone Simon
Published: March 2020

Following the publication of this article [1], it has been noted by the authors that an image of the same cell nuclei has been used in error twice, in Fig. 8, parts A and B. These images are redundant in this figure as the images in parts D and E show Wnt3a treated and control cells stained with both Hoechst 33342 (as in parts A and B) and fluorescein diacetate. The data from multiple repetitions of the Hoechst 33342 stain experiment are presented in graph C. Thus, the duplicated images (in Fig. 8A and B) add no additional data and do not change the results or conclusions reached in the article. The authors apologize for any confusion this may have caused.
Nitrogen addition increases sexual reproduction and improves seedling growth in the perennial rhizomatous grass Leymus chinensis
Authors: Gao Song , Wang Junfeng , Knops Johannes M. H. , Wang Jiao
Published: March 2020

Background

The Eurasian steppe is an important vegetation type characterized by cold, arid and nitrogen poor conditions. At the Eastern edge, including in the Songnen grassland, the vegetation is dominated by Leymus chinensis (henceforth L. chinensis) and is increasing threatened by elevated anthropogenic nitrogen deposition. L. chinensis is a perennial grass that mainly reproduces vegetatively and its sexual reproduction is limited. However, sexual reproduction plays an important role influencing colonization after large disturbances. To develop an understanding of how elevated nitrogen deposition changes the plant community structure and functioning we need a better understanding how sexual reproduction of L. chinensis changes with nitrogen enrichment. Here we report on a field experiment where we added 10 g N m− 2 yr− 1 and examined changes in seed traits, seed germination and early seedling growth.

Results

Nitrogen addition increased seed production by 79%, contributing to this seed increases were a 28% increase in flowering plant density, a 40% increase in seed number per plant and a 11% increase in seed weight. Seed size increased with a 42% increase in large seeds and a 49% decrease in the smallest seed size category. Seed germination success improved by 10% for small seeds and 18% for large seeds. Combined, the increased in seed production and improved seed quality doubled the potential seed germination. Subsequent seedling above and below-ground biomass also significantly increased.

Conclusions

All aspects of L. chinensis sexual reproduction increased with nitrogen addition. Thus, L. chinensis competitive ability may increase when atmospheric nitrogen deposition increases, which may further reduce overall plant diversity in the low diversity Songnen grasslands.
Invasive intestinal mucormycosis in a 40-year old immunocompetent patient - a rarely reported clinical phenomenon: a case report
Authors: Wotiye Abdi Bati , KS Poornachandra , Ayele Biniyam Alemayehu
Published: March 2020

Background

Mucormycosis is rare, life-threatening fungal infection. Frequently observed in those patients having underlying immunosuppression such as, diabetes, organ transplantation, Human immunodeficiency virus (HIV) infection, and elevated serum iron. However, invasive intestinal mucormycosis occurring in immunocompetent individuals without the traditional risk factors is extremely rare clinical phenomenon.

Case presentation

We report a 40-year-old male patient who presented with 1 week history of diffuse abdominal pain and high grade fever, associated with vomiting and frequent loose stools. Has history of chronic alcohol ingestion. Otherwise, no past history of chronic medical illness, nor he had contact with individuals with similar illness. He was in a septic shock with multiple organ failure up on presentation to emergency room. Physical examination revealed icterus sclera with abdominal tenderness. He was immediately resuscitated using crystalloids, supported with inotrope, and antibiotics. Histopathological examination of tissue sample from colonic ulcer biopsy revealed invasive intestinal mucormycosis. Patient showed full clinical and histopathological resolution after course of parenteral Liposomal Amphotercin B.

Conclusion

This case highlights the fact that, despite its life-threatening nature, it’s possible to treat patients with invasive intestinal mucormycosis with aggressive antifungal and supportive care without surgical intervention, provided that all the necessary supportive care were initiated early and the disease was diagnosed early and appropriate medical management was initiated timely. In addition, it’s important to consider intestinal mucormycosis even in patients who are immunocompetent without traditional risk factors.
Interventions for women who report domestic violence during and after pregnancy in low- and middle-income countries: a systematic literature review
Authors: Daley Diandra , McCauley Mary , van den Broek Nynke
Published: March 2020

Background

Domestic violence is a leading cause of social morbidity and may increase during and after pregnancy. In high-income countries screening, referral and management interventions are available as part of standard maternity care. Such practice is not routine in low- and middle-income countries (LMIC) where the burden of social morbidity is high.

Methods

We systematically reviewed available evidence describing the types of interventions, and/or the effectiveness of such interventions for women who report domestic violence during and/or after pregnancy, living in LMIC. Published and grey literature describing interventions for, and/or effectiveness of such interventions for women who report domestic violence during and/or after pregnancy, living in LMIC was reviewed. Outcomes assessed were (i) reduction in the frequency and/or severity of domestic violence, and/or (ii) improved physical, psychological and/or social health. Narrative analysis was conducted.

Results

After screening 4818 articles, six studies were identified for inclusion. All included studies assessed women (n = 894) during pregnancy. Five studies reported on supportive counselling; one study implemented an intervention consisting of routine screening for domestic violence and supported referrals for women who required this. Two studies evaluated the effectiveness of the interventions on domestic violence with statistically significant decreases in the occurrence of domestic violence following counselling interventions (488 women included). There was a statistically significant increase in family support following counselling in one study (72 women included). There was some evidence of improvement in quality of life, increased use of safety behaviours, improved family and social support, increased access to community resources, increased use of referral services and reduced maternal depression. Overall evidence was of low to moderate quality.

Conclusions

Screening, referral and supportive counselling is likely to benefit women living in LMIC who experience domestic violence. Larger-scale, high-quality research is, however, required to provide further evidence for the effectiveness of interventions. Improved availability with evaluation of interventions that are likely to be effective is necessary to inform policy, programme decisions and resource allocation for maternal healthcare in LMIC.

Trial registration

Systematic review registration number: PROSPERO CRD42018087713.
Clinicopathological variables influencing overall survival, recurrence and post-recurrence survival in resected stage I non-small-cell lung cancer
Authors: Wang Chengdi , Wu Yuxuan , Shao Jun , Liu Dan , Li Weimin
Published: March 2020

Background

To investigate clinicopathological variables influencing overall survival, overall recurrence, and post-recurrence survival (PRS) in patients who experienced curative-intent surgical resection of stage I non-small-cell lung cancer (NSCLC).

Methods

We investigated a series of 1387 patients with stage I NSCLC who underwent surgical resection from 2008 to 2015. The effect clinicopathological factors on death, recurrence, and PRS were evaluated by Kaplan-Meier estimates and cox regression analysis.

Results

Among the 1387 stage I patients, 301 (21.7%) experienced recurrence. The 5-year cumulative incidence of recurrence (CIR) for all patients was 20.2% and median PRS was 25.5 months. The older age (P = 0.036), p-stage IB (P = 0.001), sublobar resection(P<0.001), histology subtype (P<0.001), and lymphovascular invasion (LVI) (P = 0.042) were significantly associated with worse overall survival. Among 301 recurrent patients, univariable analysis indicated that p-stage IB (versus IA) (P<0.001), LVI (P<0.001) and visceral pleural invasion (VPI) (P<0.001) were remarkably correlated with the higher incidence of recurrence. Taking the effect of clinicopathological variables on PRS into consideration, smoking history (P = 0.043), non-adenocarcinoma (P = 0.013), high architectural grade of LUAD (P = 0.019), EGFR wild status (P = 0.002), bone metastasis (P =0.040) and brain metastasis (P = 0.042) were substantially related with poorer PRS. Multivariate analysis demonstrated that high architectural grade of LUAD (P = 0.008), brain metastasis (P = 0.010) and bone metastasis (P = 0.043) were independently associated with PRS.

Conclusion

In patients with resected stage I NSCLC, the older age, p-stage IB (versus IA), sublobar resection, histology subtype, and LVI were significantly associated with worse overall survival. P-stage IB (versus IA), LVI, and VPI were significantly correlated with the higher incidence of recurrence. High architectural grade of LUAD, brain metastasis and bone metastasis were independent risk factors with PRS.
A retrospective analysis on metastatic rate of the internal mammary lymph node and its clinical significance in adjuvant radiotherapy of breast cancer patients
Authors: Li Li , Zhang Hongyan , Wang Linwei , Xie Conghua , Zhou Yunfeng , Zhong Yahua
Published: March 2020

Background

There is a discrepancy about the metastatic rate of internal mammary lymph nodes (IMNs) between clinical and pathologic findings. We aimed to investigate the metastatic rate of IMNs and to provide recommendations on target volume delineation of IMNs for adjuvant radiotherapy in breast cancer patients.

Methods

We retrospectively analyzed data from 114 breast cancer patients treated with surgery without adjuvant radiotherapy who developed local and/or regional lymph node recurrence/metastasis at our institute from January 2015 to January 2019. Patients with widely lung or pleural metastases were excluded. We first analyzed the recurrence rate with the chest wall, the metastatic rate of internal mammary/anterior mediastinal, ipsilateral axillary and supraclavicular lymph nodes, and then investigated the distribution of the IMNs.

Results

Among the 114 included patients, the recurrence rate with the chest wall, metastatic rate of IMNs, IMNs/anterior mediastinal lymph nodes, ipsilateral axillary lymph nodes, and the ipsilateral supraclavicular lymph nodes was 43, 37.7, 59.6, 12.3, and 22.8%, respectively. The metastatic IMNs were mainly located from the first to the second intercostal space. However, metastatic lymph nodes could also be observed above the upper edge of the first rib.

Conclusions

The metastatic rate is high in the IMNs and irradiation of the internal mammary lymphatic chain is required. It is suggested that the upper bound of the internal mammary lymphatic chain should be up to the subclavian vein with a 5-mm margin, thus connecting to the caudal border of supraclavicular clinical target volume in breast cancer patients at high risk of recurrence.
Primary malignant pericardial tumour in Lynch syndrome
Authors: Paolisso Pasquale , Saturi Giulia , Foà Alberto , Saponara Maristella , Nannini Margherita , Pantaleo Maria Abbondanza , Leone Ornella , Turchetti Daniela , Calistri Daniele , Savini Carlo , Pacini Davide , Pizzi Carmine , Galiè Nazzareno
Published: March 2020

Background

This case represents the first report of malignant primary cardiac tumour in a patient with Lynch Syndrome associated with MSH2 pathogenic variant.

Case presentation

A 57-year-old woman with previous ovarian cystadenocarcinoma was admitted to the emergency room for hematic pericardial effusion. Multimodal diagnostic imaging revealed two solid pericardial vascularized masses. After pericardiectomy, the final histological diagnosis was poorly differentiated pleomorphic sarcomatoid carcinoma. During follow-up she developed an ampulla of Vater adenocarcinoma. Genetic analysis identified an MSH2 pathogenic variant.

Conclusion

This case contributes to expand the tumour spectrum of Lynch syndrome, suggesting that MSH2 pathogenic variants cause a more complex multi-tumour cancer syndrome than the classic Lynch Syndrome. In MSH2 variant carriers, symptoms such as dyspnoea and chest discomfort might alert for rare tumours and a focused cardiac evaluation should be considered.
An unusual hematopoietic stem cell transplantation for donor acute lymphoblastic leukemia: a case report
Authors: Zhou Di , Xie Ting , Chen Suning , Ling Yipeng , Xu Yueyi , Chen Bing , Ouyang Jian , Yang Yonggong
Published: March 2020

Background

Donor acute lymphoblastic leukemia with recipient intact is a rare condition. We report a case of donor developing acute lymphoblastic leukemia 8 yrs after donating both bone marrow and peripheral blood hematopoietic stem cells.

Case presentation

This case report describes a 51-year old female diagnosed with acute lymphoblastic leukemia who donated both bone marrow and peripheral blood stem cells 8 yrs ago for her brother with severe aplastic anemia. Whole exome sequencing revealed leukemic genetic lesions (SF3B1 and BRAF mutation) only appeared in the donor sister, not the recipient, and an unusual type of hematopoietic stem cell transplantation with the recipient’s peripheral blood stem cells was done. The patient remained in remission for 3 months before disease relapsed. CD19 CAR-T therapy followed by HLA-identical unrelated hematopoietic stem cell transplantation was applied and the patient remains in remission for 7 months till now.

Conclusions

This donor leukemia report supports the hypothesis that genetic lesions happen randomly in leukemogenesis. SF3B1 combined with BRAF mutation might contribute to the development of acute lymphoblastic leukemia.
Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study
Authors: Takayama Hiroomi , Ohta Masayuki , Iwashita Yukio , Uchida Hiroki , Shitomi Yuki , Yada Kazuhiro , Inomata Masafumi
Published: March 2020

Background

Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented. However, few reports have investigated the association between dedifferentiation and glycosylation. Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation.

Methods

We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule. Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.

Results

Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans. Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones. Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components. Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.

Conclusion

Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans. MGAT1 may play a role in the dedifferentiation of HCC.
Different transcriptome profiles between human retinoblastoma Y79 cells and an etoposide-resistant subline reveal a chemoresistance mechanism
Authors: Song Wen-ping , Zheng Si , Yao Hong-juan , Zhou Xiao-fei , Li Rui , Zhang Cheng-yue , Zhao Jun-yang , Wang Lie-wei , Shao Rong-guang , Li Liang
Published: March 2020

Background

Retinoblastoma (RB) is the most frequent pediatric retinal tumor. In the present study, to elucidate chemoresistance mechanisms and identify potential biomarkers in RB, we utilized RNA sequencing (RNAseq) technological platforms to reveal transcriptome profiles and identify any differentially expressed genes (DEGs) between an etoposide drug-resistant subline (Y79/EDR) and parental Y79 cells.

Methods

To test whether Y79/EDR cells showed resistance to antineoplastic agents for RB, we treated the cells with etoposide, carboplatin and vincristine and analyzed them with a Cell Counting Kit-8 (CCK-8). Y79/EDR and parental Y79 cells were used for RNAseq and bioinformatics analysis to enable a genome-wide review of DEGs between the two lines using the DESeq R package (1.10.1). Then, DEG enrichment in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was analyzed with KOBAS software. Next, real-time quantitative reverse transcription polymerase chain reaction (real time QRT-PCR) and cytotoxicity assays were performed to experimentally and functionally validate the identified candidate biomarkers.

Results

Y79/EDR cells showed resistance to etoposide, carboplatin and vincristine at different concentrations. In total, 524 transcripts were differentially expressed in Y79/EDR cells based on analysis of fragments per kilobase of transcript per million fragments mapped (FPKM); among these, 57 genes were downregulated and 467 genes were upregulated in Y79/EDR cells compared to parental Y79 cells. We selected candidate DEGs, includingARHGAP9,HIST1H4H,RELN,DDIT4,HK2,STC1andPFKFB4,for mRNA expression validation with real time QRT-PCR assays and found that the expression levels determined by real time QRT-PCR were consistent with the RNAseq data. Further studies involving downregulation ofARHGAP9with a specific siRNA showed thatARHGAP9altered the cellular sensitivity of Y79 cells to etoposide and carboplatin.

Conclusion

Our initial findings provided a genomic view of the transcription profiles of etoposide-induced acquired resistance in RB. Follow-up studies indicated thatARHGAP9might be a chemoresistance biomarker in RB, providing insight into potential therapeutic targets for overcoming acquired chemoresistance in RB. These findings can aid in understanding and overcoming chemoresistance during treatment of RB in the clinic.
Association of macular thickness with parapapillary atrophy in myopic eyes
Authors: Piao Helong , Guo Yue , Ha Jun Young , Sung Mi Sun , Park Sang Woo
Published: March 2020

Background

To investigate whether macular structure could be affected by axial elongation and to determine the association between macular intraretinal thickness and the microstructure of β-zone parapapillary atrophy (PPA) in myopic eyes.

Methods

The study recruited 113 healthy myopic subjects (113 eyes). Images of the macula, subfoveal choroid, and optic nerve head were acquired using spectral-domain optical coherence tomography (SD-OCT). An automatic segmentation algorithm was used to segment the macular images into 7 intraretinal layers. PPA widths with and without Bruch’s membrane (PPA+BMand PPA-BM, respectively) were evaluated. Linear regression analysis was performed to evaluate the association between macular intraretinal thickness and axial length and the microstructure of PPA.

Results

An increase in axial length was associated with a decrease in whole macular thickness of the peripheral region and an increase in whole macular thickness of the central region. Thickness alterations of the macular intraretinal layers were most apparent in the peripheral region. A significant correlation was found between PPA-BMwidth and macular intraretinal layer thickness, whereas no significant correlation was found between PPA+BMwidth and macular intraretinal layer thickness. Moreover, both PPA+BMand PPA-BMwidths significantly correlated with subfoveal choroidal thickness.

Conclusions

Macular intraretinal layer thickness may be affected by PPA-BMwidth. These findings indicate that the microstructure of PPA should be considered when evaluating the macula in patient with myopia and glaucoma.
Hypoglycemia in patients with congenital muscle disease
Authors: Hayes Leslie H. , Yun Pomi , Mohassel Payam , Norato Gina , Donkervoort Sandra , Leach Meganne E. , Alvarez Rachel , Rutkowski Anne , Shaw Natalie D. , Foley A. Reghan , Bönnemann Carsten G.
Published: March 2020

Background

Only a few small studies have previously reported episodes of hypoglycemia in children with neuromuscular diseases; however, there has been no broader investigation into the occurrence of hypoglycemia in children with congenital muscle disease (CMD).

Methods

Pediatric patients enrolled in the CMD International Registry (CMDIR) with a history of hypoglycemia were included in this retrospective review. Hypoglycemic episodes and associated clinical and biochemical characteristics were characterized.

Results

Ten patients with CMD (5 with LAMA2-related muscular dystrophy) reported at least one episode of hypoglycemia beginning at an average age of 3.5 years. Predominant symptoms included altered mental status and nausea/vomiting, and laboratory studies demonstrated metabolic acidosis and ketonuria, consistent with ketotic hypoglycemia.

Conclusion

Patients with CMD may have an increased risk of hypoglycemia during fasting, illness, or stress due to their relatively low muscle mass and hence, paucity of gluconeogenic substrate. Clinicians should therefore maintain a high index of suspicion for hypoglycemia in this high-risk patient population and caregivers should routinely be trained to recognize and treat hypoglycemia.
Ménétrier’s disease in childhood: a case report from China
Authors: Zhang Jiewei , Wang Yizhong , Liu Haifeng , Xiao Yongmei , Zhang Ting
Published: March 2020

Background

Ménétrier’s disease (MD) is a protein-losing gastropathy characterized by gastric hypertrophy, foveolar hyperplasia and hypoalbuminemia. MD is uncommon in childhood with nonspecific clinical symptoms, and the exact cause of pediatric MD is still unclear.

Case presentation

Here, we reported a 4 year and 10-month boy presenting with MD from China. The patient was suffered with vomiting, abdominal pain, hypoproteinemia and edema. Laboratory tests showed that the boy was infected with Clostridium difficile (CD). Gastrointestinal endoscopy revealed giant gastric folds, and histological gastric biopsies showed foveolar hyperplasia with glandular atrophy, infiltration of eosinophils in the lamina propria of the patient. Finally, the boy was recovered after supportive therapy with intravenous albumin and CD eradication.

Conclusion

For the nonspecific clinical symptoms of MD, gastrointestinal endoscopic evaluations with gastric tissue biopsies are required to establish the diagnosis of MD in children with unexplained hypoalbuminemia.
Complex biomechanical properties of non-augmented and augmented pedicle screws in human vertebrae with reduced bone density
Authors: Schulze Martin , Riesenbeck Oliver , Vordemvenne Thomas , Raschke Michael J. , Evers Julia , Hartensuer René , Gehweiler Dominic
Published: March 2020

Background

In osteoporotic bone, the quality of the bone-to-implant interface is decreased, which may lead to early implant failure. Screw anchorage can be improved by augmentation. This effect is mainly investigated with a pull-out test. To our knowledge, the effect of cement augmentation in an in vivo physiological setup focusing on screw movement has not been investigated to date. The aim of this work was to investigate and compare augmented and native screw behavior in a physiologically related setup.

Methods

Twelve fresh-frozen human lumbar vertebrae were divided into two groups. Each vertebra was bilaterally instrumented with either non-augmented or augmented pedicle screw systems and loaded in a recently developed test setup that provided cyclic conditions comparable to a physiological gait. The cyclic loading should test the primary implant stability, comparable to the postoperative period of two months in a worst-case scenario in the absence of osseous remodeling. Screws were tracked optically, and screw movement and failure patterns were observed.

Results

Mutual influence between the left and right sides resulted in a successive, rather than simultaneous, failure. Augmentation of the screws in vertebrae with poor bone quality reduced screw subsidence and thus improved the rigidity of the screw-to-implant interface by up to six-fold. The non-augmented condition was significantly related to early screw failure.

Conclusions

Pedicle screw system failure involves a complex bilateral-coupled mechanism. The cyclic loading based on physiological conditions during walking has allowed the postoperative conditions and clinical failure mechanisms to be simulated in vitro and clarified. Future implant systems should be investigated with a physiologically related setup.
The inhibition by human MSCs-derived miRNA-124a overexpression exosomes in the proliferation and migration of rheumatoid arthritis-related fibroblast-like synoviocyte cell
Authors: Meng Hong-Yan , Chen Li-Qing , Chen Li-Hui
Published: March 2020

Background

Rheumatoid arthritis is a long-term, progressive autoimmune disease. It is characterized by synovial hyperplasia leading to swelling, stiffness, and joint deformity in more than one joint. Fibroblast-like synoviocytes are the major cell types that make up the synovial intima structure, which is one of the decisive factors in the development and course of rheumatoid arthritis.

Methods

The potential therapeutic effects of MSCs-derived miRNA-124a overexpression exosomes were evaluated in vitro by the method including MTT assay and cell cycle test for cell proliferation, scratch wound closure and transwell for cell migration, flow cytometry and western for the apoptosis detection.

Results

Exosomes derived from human MSCs that overexpression miRNA-124a were prepared and characterized. We found that the pretreatment of this exosome was able to inhibit the proliferation and migration of fibroblast-like synoviocyte cell line and promote the apoptosis of this cell during the co-incubation.

Conclusions

Exosomes derived from MSCs were proved to be a suitable vector for the delivery of therapeutic miRNA-124a, and such miRNA-124a overexpression exosomes were expected to provide a new medicine and strategy for the treatment of rheumatoid arthritis.
Distinct severity of phenotype in Hajdu-Cheney syndrome: a case report and literature review
Authors: Zeng Chunhua , Lin Yunting , Lu Zhikun , Chen Zhen , Jiang Xiaoling , Mao Xiaojian , Liu Zongcai , Lu Xinshuo , Zhang Kangdi , Yu Qiaoli , Wang Xiaoya , Huang Yonglan , Liu Li
Published: March 2020

Background

Hajdu-Cheney syndrome (HCS) is a rare inherited skeletal disorder caused by pathogenic mutations in exon 34 of NOTCH2. Its highly variable phenotypes make early diagnosis challenging. In this paper, we report a case of early-onset HCS with severe phenotypic manifestations but delayed diagnosis.

Case presentation

The patient was born to non-consanguineous, healthy parents of Chinese origin. She presented facial anomalies, micrognathia and skull malformations at birth, and was found hearing impairment, congenital heart disease and developmental delay during her first year of life. Her first visit to our center was at 1 year of age due to cardiovascular repair surgery for patent ductus arteriosus (PDA) and ventricular septal defect (VSD). Skull X-ray showed wormian bones. She returned at 7 years old after she developed progressive skeletal anomalies with fractures. She presented with multiple wormian bones, acro-osteolysis, severe osteoporosis, bowed fibulae and a renal cyst. Positive genetic test of a de novo heterozygous frameshift mutation in exon 34 of NOTCH2 (c.6426dupT) supported the clinical diagnosis of HCS.

Conclusion

This is the second reported HCS case caused by the mutation c.6426dupT in NOTCH2, but presenting much earlier and severer clinical expression. Physicians should be aware of variable phenotypes so that early diagnosis and management may be achieved.
Cranberry extract initiates intrinsic apoptosis in HL-60 cells by increasing BAD activity through inhibition of AKT phosphorylation
Authors: Mansouri Rasha A. , Percival Susan S.
Published: March 2020

Background

Cranberry has been studied as a potential anticancer agent as it is capable of inducing apoptosis within cancer cells. The aim of this study was to better define the mechanism by which cranberry triggers apoptosis in HL-60 cells.

Methods

The study was carried on cranberry extracts (CB). Anti-apoptotic B-cell lymphoma-2 (BCL-2) and pro-apoptotic BCL-2-associated death promoter death (BAD) proteins in cell lysates were detected through Western blotting techniques. Equivalent protein loading was confirmed through anti-α-tubulin antibody.

Results

The results showed that treatment of HL-60 cells with CB causes a significant increase in the levels of caspase-9 and caspases-3/7 and increased mitochondrial outer membrane permeability, leading to the release of cytochrome C and Smac. These apoptotic events were associated with a significant decrease in protein kinase B (AKT) phosphorylation, which caused significant increase in BAD de-phosphorylation and promoted a sequence of events that led to intrinsic apoptosis.

Conclusion

The study findings have described a molecular framework for CB-initiated apoptosis in HL-60 cells and suggested a direction for future in vivo studies investigating the anticancer effect of cranberry.
How does video case-based learning influence clinical decision-making by midwifery students? An exploratory study
Authors: Nunohara Kana , Imafuku Rintaro , Saiki Takuya , Bridges Susan M. , Kawakami Chihiro , Tsunekawa Koji , Niwa Masayuki , Fujisaki Kazuhiko , Suzuki Yasuyuki
Published: March 2020

Background

Clinical decision-making skills are essential for providing high-quality patient care. To enhance these skills, many institutions worldwide use case-based learning (CBL) as an educational strategy of pre-clinical training. However, to date, the influence of different learning modalities on students’ clinical decision-making processes has not been fully explored. This study aims to explore the influence of video and paper case modalities on the clinical decision-making process of midwifery students during CBL.

Methods

CBL involving a normal pregnant woman was provided for 45 midwifery students. They were divided into 12 groups; six groups received the video modality, and six groups received the paper modality. Group discussions were video-recorded, and focus groups were conducted after the CBL. Transcripts of the group discussions were analysed in terms of their interaction patterns, and focus groups were thematically analysed based on the three-stage model of clinical decision-making, which includes cue acquisition, interpretation, and evaluation/decision-making.

Results

The students in the video groups paid more attention to psychosocial than biomedical aspects and discussed tailored care for the woman and her family members. They refrained from vaginal examinations and electric fetal heart monitoring. Conversely, the students in the paper groups paid more attention to biomedical than psychosocial aspects and discussed when to perform vaginal examinations and electric fetal heart monitoring.

Conclusion

This study clarified that video and paper case modalities have different influences on learners’ clinical decision-making processes. Video case learning encourages midwifery students to have a woman- and family-centred holistic perspective of labour and birth care, which leads to careful consideration of the psychosocial aspects. Paper case learning encourages midwifery students to have a healthcare provider-centred biomedical perspective of labour and childbirth care, which leads to thorough biomedical assessment.
Evaluating a young-onset dementia service from two sides of the coin: staff and service user perspectives
Authors: Giebel Clarissa , Eastham Cassie , Cannon Jacqueline , Wilson John , Wilson Janet , Pearson Anna
Published: March 2020

Background

People with young-onset dementia (YOD) can often struggle getting the right treatment. This is because of their frequently different characteristics and needs compared to people with late-onset dementia. The aim of this project was to assess a memory service for its adaptation to the needs and wishes of people with YOD and their carers.

Methods

This project evaluated a memory service in the North West of England by performing two focus groups with clinical staff and six semi-structured interviews with people with YOD and carers. The focus groups took place on site and lasted one hour each. People with YOD and their carers were identified via the memory clinics caseload and via the local Alzheimer’s Society charity organisation. Both focus groups and interviews were audio-recorded and transcribed, and data were analysed using thematic analysis. The public (a person living with YOD and his carer) were involved from the design stages of the project through to the analysis and dissemination.

Results

Eleven members of staff with different clinical backgrounds participated in the focus groups and six interviews were held with people with YOD and their carers. Both indicated that whilst the diagnostic process is relatively well conducted at the service, the post-diagnostic service has many gaps. These include limited post-diagnostic support by the service, better enabling peer support, as well as providing meaningful activities, as some activities provided might be more suitable to older adults with dementia.

Conclusions

Post-diagnostic services and support for people with YOD and their carers need to be improved. The next step will be to implement the findings from this service evaluation in practice and improve service satisfaction and relevance to people with YOD.