bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global scientific trends on aflatoxin research during 1998–2017: a bibliometric and visualized study
Authors: Zyoud Sa’ed H. 
Published: November 2019

Abstract
Background
Aflatoxins are fungal metabolites associated with contaminated food products. Intake of aflatoxin-contaminated food results in serious health hazards and even death. Therefore, the aim of this study is to evaluate the global scientific output of research of aflatoxin by using bibliometric techniques.

Methods
This bibliometric study was conducted using Scopus database and classified the retrieved publications were classified from different aspects, including the countries/region of focus, journals, authors, institutes, citations, and content analysis to discover any hot and emerging topics. In addition, the bibliometric analysis of the international collaborative network and hot research topics were generated by VOSviewer© software version 1.6.10. The publication period was restricted in the search for two decades (1998–2017).

Results
The search engine of the Scopus database found 9845 documents published in the field of aflatoxin. The USA is the top publishing source in the world (22.85%), followed by China (11.85%), India (9.32%), and Italy (5.25%). In earlier years, researchers focused on terms related to the topics of “sources and biosynthesis of aflatoxin”, “health effects by aflatoxin”, and “detoxification and treatment of aflatoxin”. However, in recent years, researchers pay more attention to the topic of detection and quantification of aflatoxin.

Conclusions
The quantity of research in global aflatoxin has substantially increased over the past two decades. The evaluation of the historical status and development trend in aflatoxin scientific research can guide future research, and ultimately provide the basis for improving management procedures for governmental decisions, healthcare, industries, and educational institutions.
Building capacity: a cross-sectional evaluation of the US Training Institute for Dissemination and Implementation Research in Health
Authors: Vinson Cynthia A. , Clyne Mindy , Cardoza Nina , Emmons Karen M. 
Published: November 2019

Abstract
Background
In 2011, the National Institute of Health (NIH) initiated the Training in Dissemination and Implementation Research in Health (TIDIRH) program. Over its first 5 years, TIDIRH provided an in-person, week-long training to 197 investigators who were new to the dissemination and implementation (D&I) field. This paper evaluates the long-term impact of TIDIRH on trainees’ use of D&I methods, collaborations, and research funding.

Methods
Trainees were selected to participate through a competitive process. We compared the 197 trainees to 125 unselected applicants (UAs) whose application score was within one standard deviation of the mean for all trainees’ scores for the same application year. A portfolio analysis examined electronic applications for NIH peer-reviewed funding submitted by trainees and UAs between 2011 and 2019. A survey of trainees and UAs was conducted in 2016, as was a faculty survey among the 87 individuals who served as TIDIRH instructors.

Results
A major goal of TIDIRH was to build the field, at least in part through networking and collaboration. Thirty-eight percent of trainees indicated they had extensive contact with faculty following the training, and an additional 38% indicated they had at least limited contact. Twenty-four percent of trainees had extensive collaboration with other fellows post-TIDIRH, and 43% had at least limited contact. Collaborative activities included the full range of academic activities, including manuscript development, grant writing, and consultation/collaboration on research studies.
The portfolio analysis combining grant mechanisms showed that overall, TIDIRH trainees submitted more peer-reviewed NIH grants per person than UA and had significantly better funding outcomes (25% vs 19% funded, respectively). The greatest difference was for large research project, program/center, and cooperative agreement grants mechanisms.

Conclusions
Overall, this evaluation found that TIDIRH is achieving its three primary goals: (1) building a pipeline of D&I investigators, (2) creating a network of scholars to build the field, and (3) improving funding outcomes for D&I grants.
In silico comparison of the dosimetric impacts of a greater omentum spacer for abdominal and pelvic tumors in carbon-ion, proton and photon radiotherapy
Authors: Yamada Masayoshi , Sato Hiraku , Ieko Yoshiro , Miyasaka Yuya , Kanai Takayuki , Yano Natsuko , Ono Takashi , Akamatsu Hiroko , Harada Mayumi , Ichikawa Mayumi , Teranishi Yasushi , Kikuchi Yasuhiro , Nemoto Kenji 
Published: November 2019

AbstractPurposeThe purpose of this study was to compare carbon-ion (C-ion), proton and photon radiotherapy (RT) plans with regard to dose reduction of the gastrointestinal (GI) tract by using a greater omentum spacer (GO spacer).MethodsWe retrospectively retrieved data for ten patients who received the GO spacer as surgical spacer placement for abdominal and pelvic tumors. Simulation plans were created on pre-spacer Computed Tomography (CT) and post-spacer CT for C-ion RT, proton RT and photon RT to compare the dose of the GI tract. The plans were normalized so that at least 95% of the planning target volume (PTV) received 70 Gy (relative biological effectiveness equivalent) delivered in 35 fractions. All plans were created with the lowest possible dose to the GI tract under conditions that meet the dose constraints for the PTV and spinal cord (maximum dose < 45 Gy). The part of the GI tract to be evaluated was defined as that most adjacent to the PTV. C-ion RT plans and proton RT plans were calculated by a spot scanning technique, and photon RT plans were calculated employing by fixed-field intensity-modulated radiation therapy.ResultsD2 cc and V10–70 of the GI tract were significantly lower on post-spacer plans than on pre-spacer plans for all three RT modalities. Regarding post-spacer plans, D2 cc of the GI tract was significantly lower on C-ion RT plans and proton RT plans than on photon RT plans (C-ion vs photonp = 0.001, proton vs photonp = 0.002). However, there was no significant difference between C-ion RT plans and proton RT plans for D2 cc of the GI tract (C-ion vs protonp = 0.992). In the photon RT plan for one patient, D2 cc of the GI tract did not meet < 50 Gy.ConclusionsThe GO spacer shows a significant dose reduction effect on the GI tract.
Infiltration tendency of internal mammary lymph nodes involvement in patients with breast cancer: anatomical characteristics and implications for target delineation
Authors: Wang Yujie , Qi Weixiang , Xu Haoping , Zhang Miao , Han Yimin , Chen Jiayi , Xu Cheng 
Published: November 2019

Abstract
Background
Despite increasing clinical data suggest that internal mammary node (IMN) irradiation would improve local-regional control and overall survival in breast cancer, its role remains controversial due to increased risk of cardiac and pulmonary toxicity. The current study aims to determine the high risk areas of IMN metastases by collecting and analyzing the axial imaging of IMN involvement, in order to optimize IMN delineation for breast cancer.

Methods
Breast cancer patients with IMN involvement were retrospectively identified from single-center database. All available imaging modalities including thoracic CT, breast MRI, ultrasound and PET/CT were used to diagnose IMN metastases. Anatomical characteristics from axial imaging, including distribution of involved ribs and distance from the internal mammary vessels (IMV), were collected for each metastatic IMN. What’s more,the natural infiltration tendency of IMNs from IMV was calculated in this study.

Results
In total, 83 metastatic IMNs from 70 breast cancer patients (initial diagnosed:34 and recurrence: 36) were located from axial CT image in this study. The second intercostal space was the most likely involved in patients with single(n = 35, 53.0%) and multiple intercostal space (n = 31, 47.0%) involvement. The percentage of including IMN with a 5 mm, 6 mm and 7 mm medial/lateral distance to the IMV were 75.9% (63/83), 89.2.6% (74/83) and 92.3% (77/83) respectively. While in maximal dorsal/ventral distance, nearly 95% of the nodes were encompassed into 6 mm depth to the IMV. Over 65% of IMN adenopathy (32/49,65.3%) were found to have a growth direction close to the sternum. By retrospective reviewing diagnostic reports, MRI demonstrated a high diagnostic performance in diagnosis of IMN disease (90.3%, 28/31), while CT had a higher misdiagnosis rate (22/63, 34.9%). The diagnostic efficiency of IMN could be improved if different methods were combined.

Conclusions
For patients with indications of prophylactic IMN irradiation, a 7 mm medial and 6 mm dorsal distance to the IMV on axial CT would be optimal to cover the clinical volume of IMN; and it would be reasonable to extend clinical tumor volume (CTV) coverage towards sternum for patients with evident IMN disease. Multi-imaging modalities are recommended to improve the diagnostic specificity and sensitivity of IMN metastases.
Chronic hepatitis B: dynamic change in Traditional Chinese Medicine syndrome by dynamic network biomarkers
Authors: Lu Yiyu , Fang Zhaoyuan , Zeng Tao , Li Meiyi , Chen Qilong , Zhang Hui , Zhou Qianmei , Hu Yiyang , Chen Luonan , Su Shibing 
Published: November 2019

Abstract
Background
In traditional Chinese medicine (TCM) clinical practice, TCM syndromes help to understand human homeostasis and guide individualized treatment. However, the TCM syndrome changes with disease progression, of which the scientific basis and mechanism remain unclear.

Methods
To demonstrate the underlying mechanism of dynamic changes in the TCM syndrome, we applied a dynamic network biomarker (DNB) algorithm to obtain the DNBs of changes in the TCM syndrome, based on the transcriptomic data of patients with chronic hepatitis B and typical TCM syndromes, including healthy controls and patients with liver-gallbladder dampness-heat syndrome (LGDHS), liver-depression spleen-deficiency syndrome (LDSDS), and liver-kidney yin-deficiency syndrome (LKYDS). The DNB model exploits collective fluctuations and correlations of the observed genes, then diagnoses the critical state.

Results
Our results showed that the DNBs of TCM syndromes were comprised of 52 genes and the tipping point occurred at the LDSDS stage. Meanwhile, there were numerous differentially expressed genes between LGDHS and LKYDS, which highlighted the drastic changes before and after the tipping point, implying the 52 DNBs could serve as early-warning signals of the upcoming change in the TCM syndrome. Next, we validated DNBs by cytokine profiling and isobaric tags for relative and absolute quantitation (iTRAQ). The results showed that PLG (plasminogen) and coagulation factor XII (F12) were significantly expressed during the progression of TCM syndrome from LGDHS to LKYDS.

Conclusions
This study provides a scientific understanding of changes in the TCM syndrome. During this process, the cytokine system was involved all the time. The DNBs PLG and F12 were confirmed to significantly change during TCM-syndrome progression and indicated a potential value of DNBs in auxiliary diagnosis of TCM syndrome in CHB.
Trial registration Identifier: NCT03189992. Registered on June 4, 2017. Retrospectively registered (http://www.clinicaltrials.gov)
Biliary tract large cell neuroendocrine carcinoma: current evidence
Authors: Raiker Riva , Chauhan Aman , Hasanein Hassan , Burkeen Grant , Horn Millicent , Veedu Janeesh , Vela Cory , Arnold Susanne , Kolesar Jill , Anthony Lowell , Evers B. Mark , Cavnar Michael 
Published: November 2019

Abstract
Background
Primary neuroendocrine carcinomas of the gallbladder and biliary tract are rare, with pure large cell neuroendocrine carcinomas (LCNEC) being exceedingly rare and with a particularly poor prognosis.

Methods
We performed a review of published data on biliary tract large cell neuroendocrine carcinomas in PubMed.

Results
Preliminary search revealed over 2000 results but we found only 12 cases of pure large cell neuroendocrine carcinomas of biliary tract noted in literature to date. Because it commonly presents with non-specific symptoms of abdominal pain and jaundice, diagnosis is made after resection with histo-pathological and immunohistochemical analysis. These cancers are particularly aggressive with high recurrence rates, most often presenting with metastasis to regional lymph nodes and/or the liver resulting in a poor prognosis. Overall, complete surgical excision with systemic chemotherapy is the treatment mainstay. If the cancer is unresectable due to multiple metastases, medical management with systemic chemotherapy is the primary treatment modality.

Conclusion
The prognosis of hepatobiliary LCNEC remains poor with median survival of only 11 months from initial diagnosis. Studies focusing on high grade neuroendocrine carcinoma are needed to enhance our understanding of biology and therapeutics in this rare but aggressive cancer.
Biallelic ERBB3 loss-of-function variants are associated with a novel multisystem syndrome without congenital contracture
Authors: Li Niu , Xu Yufei , Zhang Yi , Li Guoqiang , Yu Tingting , Yao Ruen , Zhou YunFang , Shen Yiping , Yin Lei , Wang Xiumin , Wang Jian 
Published: November 2019

AbstractBackgroundGain-of-function pathogenic variants of the Erb-B2 receptor tyrosine kinase 3 (ERBB3) gene contribute to the occurrence and development of a variety of human carcinomas through activation of phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK) signaling. ERBB3 gene homozygous germline variants, whose loss of function may cause autosomal recessive congenital contractural syndrome, were recently identified. This study aims to identify the disease-causing gene in a Chinese pedigree with variable phenotypes involving multiple systems, including developmental delay, postnatal growth retardation, transient lower limb asymmetry, facial malformations, atrioventricular canal malformation, bilateral nystagmus and amblyopia, feeding difficulties, immunodeficiency, anemia, and liver damage, but without congenital contracture.MethodsTrio-whole exome sequencing (WES) was performed to identify the disease-causing gene in a 24-month-old Chinese female patient. The pathogenicity of the identified variants was evaluated using in silico tools and in vitro functional studies.ResultsTrio-WES revealed compound heterozygous variants of c.1253 T > C (p.I418T) and c.3182dupA (p.N1061Kfs*16) in theERBB3gene. Functional studies showed that p.I418T resulted in normal expression of ERBB3, which was capable of interacting with ERBB2. However, the variant impaired ERBB3 phosphorylation, consequently blocking ERBB2 phosphorylation and AKT and ERK activation. The truncated protein resulting from the c.3182dupA variant also lacked the capacity to activate downstream signaling pathways.ConclusionsWe report the first patient with a novel multisystem syndrome disorder without congenital contracture resulting from biallelic loss-of-function variants ofERBB3.
Comparison of zebrafish and mice knockouts for Megalencephalic Leukoencephalopathy proteins indicates that GlialCAM/MLC1 forms a functional unit
Authors: Pérez-Rius Carla , Folgueira Mónica , Elorza-Vidal Xabier , Alia A. , Hoegg-Beiler Maja B. , Eeza Muhamed N. H. , Díaz María Luz , Nunes Virginia , Barrallo-Gimeno Alejandro , Estévez Raúl 
Published: November 2019

Abstract
Background
Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC) is a rare type of leukodystrophy characterized by astrocyte and myelin vacuolization, epilepsy and early-onset macrocephaly. MLC is caused by mutations in MLC1 or GLIALCAM, coding for two membrane proteins with an unknown function that form a complex specifically expressed in astrocytes at cell-cell junctions. Recent studies in Mlc1−/− or Glialcam−/− mice and mlc1−/− zebrafish have shown that MLC1 regulates glial surface levels of GlialCAM in vivo and that GlialCAM is also required for MLC1 expression and localization at cell-cell junctions.

Methods
We have generated and analysed glialcama−/− zebrafish. We also generated zebrafish glialcama−/−mlc1−/− and mice double KO for both genes and performed magnetic resonance imaging, histological studies and biochemical analyses.

Results
glialcama−/− shows megalencephaly and increased fluid accumulation. In both zebrafish and mice, this phenotype is not aggravated by additional elimination of mlc1. Unlike mice, mlc1 protein expression and localization are unaltered in glialcama−/− zebrafish, possibly because there is an up-regulation of mlc1 mRNA. In line with these results, MLC1 overexpressed in Glialcam−/− mouse primary astrocytes is located at cell-cell junctions.

Conclusions
This work indicates that the two proteins involved in the pathogenesis of MLC, GlialCAM and MLC1, form a functional unit, and thus, that loss-of-function mutations in these genes cause leukodystrophy through a common pathway.
Phylogeny and polymorphism in the E6 and E7 of human papillomavirus: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44) in women from Shanghai
Authors: Zhao Junwei , Zhan Qin , Guo Junhan , Liu Min , Ruan Yetian , Zhu Tailin , Han Lingfei , Li Fang 
Published: November 2019

Abstract
Background
Persistent infection with human papillomaviruses (HPVs) has been associated with cervical intraepithelial neoplasia (CIN) and cervical cancer. However, why only a fraction of HPV cases progress to cancer is still unclear.

Methods
We focused on the heterogeneity, classification, evolution and dispersal of variants for 14 common HPV types in 262 HPV-positive patients with cervical lesions. The E6 and E7 genes of HPV were sequenced and compared with the HPV reference for sequence analysis. Phylogenetic trees were constructed using the neighbour-joining tree method with MEGA 7.0.

Results
In this study, 233 E6 and 212 E7 sequences were successfully amplified by PCR, and these sequences were divided into 5 species groups: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44). The incidence of high-grade squamous intraepithelial lesion (HSIL) in patients infected with alpha-9 HPV was significantly increased compared with other groups (P < 0.0001), especially HPV16 (P < 0.0001). Strikingly, E7 had significantly fewer nonsynonymous variants in the HSIL compared to <HSIL groups (P = 3.17× 10− 4). The A388C (K93 N) variation in HPV58 E6 can significantly reduce the risk of HSIL (P = 0.015). However, T7220G (D32E) variation in HPV16 E6 and A7689G (N29S) in HPV16 E7 increased the incidence of HSIL compared to the <HSIL group (P = 0.036 and 0.022).

Conclusions
Strict conservation of E7 is important for HPV carcinogenicity, especially N29 of HPV16. The findings in this work provide preventative/therapeutic interventions for HPV infections and CIN.
Increased expression of protease-activated receptors 2 indicates poor prognosis in HBV related hepatocellular carcinoma
Authors: Chen Peng , Yang Na , Xu Li , Zhao Fangfang , Zhang Min 
Published: November 2019

Abstract
Objective
To investigate the potential role of protease-activated receptor 2 (PAR2) in the prognosis of hepatocellular carcinoma (HCC).

Methods
A total of 202 HCC patients who underwent liver resections were included. Tissue microarray was established with specimens of both HCC and paired adjacent liver tissues. PAR2 expression was detected by immunohistochemistry (IHC) assays.. A semi-quantification method was used to define the expression level of PAR2. The correlations between PAR2 expression and clinical features of patients with HCC was explored. The association of different PAR2 expressions with both overall survival and disease-free survival was analyzed.

Results
Results showed that the expression of PAR2 in HCC tissues was higher than that in paired para-cancerous liver tissues (4.12 ± 3.55 vs. 2.71 ± 2.56, P < 0.001). Higher expression of PAR2 was associated with poor differentiation (P < 0.001) and advanced tumor-node-metastasis stage (P = 0.015). Kaplan-Meier survival analysis indicated that HCC patients with high PAR2 expression had decreased overall survival (P = 0.033) and disease-free survival (P = 0.043) compared to patients with lower PAR2 expression. Multivariate analysis indicated that PAR2 expression (P = 0.032) was a significant independent prognostic factor for both overall survival and disease-free survival (P = 0.032; P = 0.032, respectively).

Conclusion
Our data revealed that PAR2 expression was increased in HCC. High PAR2 expression was correlated with both decreased overall survival and disease-free survival in patients with HCC. High PAR2 expression indicated a poor prognosis.
HMEJ-mediated efficient site-specific gene integration in chicken cells
Authors: Xie Long , Sun Juanjuan , Mo Lifen , Xu Tianpeng , Shahzad Qaisar , Chen Dongyang , Yang Wenhao , Liao Yuying , Lu Yangqing 
Published: November 2019

Abstract
Background
The production of transgenic chicken cells holds great promise for several diverse areas, including developmental biology and biomedical research. To this end, site-specific gene integration has been an attractive strategy for generating transgenic chicken cell lines and has been successfully adopted for inserting desired genes and regulating specific gene expression patterns. However, optimization of this method is essential for improving the efficiency of genome modification in this species.

Results
Here we compare gene knock-in methods based on homology-independent targeted integration (HITI), homology-directed repair (HDR) and homology mediated end joining (HMEJ) coupled with a clustered regularly interspaced short palindromic repeat associated protein 9 (CRISPR/Cas9) gene editing system in chicken DF-1 cells and primordial germ cells (PGCs). HMEJ was found to be a robust and efficient method for gene knock-in in chicken PGCs. Using this method, we successfully labeled the germ cell specific gene DAZL and the pluripotency-related gene Pou5f3 in chicken PGCs through the insertion of a fluorescent protein in the frame at the 3′ end of the gene, allowing us to track cell migration in the embryonic gonad. HMEJ strategy was also successfully used in Ovalbumin, which accounts for more than 60% of proteins in chicken eggs, suggested its good promise for the mass production of protein with pharmaceutical importance using the chicken oviduct system.

Conclusions
Taken together, these results demonstrate that HMEJ efficiently mediates site-specific gene integration in chicken PGCs, which holds great potential for the biopharmaceutical engineering of chicken cells.