bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions
Authors: Akahane Toshiaki , Kanomata Naoki , Harada Oi , Yamashita Tetsumasa , Kurebayashi Junichi , Tanimoto Akihide , Moriya Takuya 
Published: September 2020

Abstract
Background: Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.Methods: Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results: Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.Conclusions: The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.
Identification of major depressive disorder disease-related genes and functional pathways based on system dynamic changes of network connectivity
Authors: Geng Ruijie , Huang Xiao 
Published: September 2020

Abstract
Objective: Major depressive disorder (MDD) is a leading psychiatric disorder that involves complex abnormal biological functions and neural networks. This study aimed to compare the changes in the network connectivity of different brain tissues under different pathological conditions, analyzed the biological pathways and genes that are significantly related to disease progression, and further predicted the potential therapeutic drug targets.Methods: Expression of differentially expressed genes (DEGs) were analyzed with postmortem cingulate cortex (ACC) and prefrontal cortex (PFC) mRNA expression profile datasets downloaded from the Gene Expression Omnibus (GEO) database, including 76 MDD patients and 76 healthy subjects in ACC and 63 MDD patients and 63 healthy subjects in PFC. The co-expression network construction was based on system network analysis. The function of the genes was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Human Protein Reference Database (HPRD, http://www.hprd.org/) was used for gene interaction relationship mapping.Results: We filtered 586 DEGs in ACC and 616 DEGs in PFC for further analysis. By constructing the Co-expression network, we found that the gene connectivity was significantly reduced under disease conditions (P=0.04 in PFC and P=1.227e-09 in ACC). Crosstalk analysis showed that CD19, PTDSS2 and NDST2 were significantly differentially expressed in ACC and PFC of MDD patients. Among them, CD19 and PTDSS2 have been targeted by several drugs in the Drugbank database. KEGG pathway analysis demonstrated that the function of CD19 and PTDSS2 were enriched with the pathway of Glycerophospholipid metabolism and T cell receptor signaling pathway. Conclusion: Co-expression network and tissue comparing analysis can identify signaling pathways and cross talk genes related to MDD, which may provide novel insight for understanding the molecular mechanisms of MDD.
The misdiagnosis of prolonged disorders of consciousness by a clinical consensus compared with repeated Coma-Recovery Scale-Revised assessment
Authors: Wang Jing , Hu Xiaohua , Hu Zhouyao , Sun Ziwei , Laureys Steven , Di Haibo 
Published: September 2020

Abstract
Background: Previous studies have shown that a single Coma-Recovery Scale-Revision (CRS-R) assessment can identify high rates of misdiagnosis by clinical consensus. The aim of this study was to investigate the proportion of misdiagnosis by clinical consensus compared to repeated behavior-scale assessments in patients with prolonged disorders of consciousness (DOC).Methods: Patients with prolonged DOC during hospitalization were screened by clinicians, and the clinicians formed a clinical-consensus diagnosis. Trained professionals used the CRS-R to evaluate the consciousness levels of the enrolled patients repeatedly (≥5 times) within a week. Based on the repeated evaluation results, the enrolled patients with prolonged DOC were divided into unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and emergence from MCS (EMCS). Finally, the relationship between the results of the CRS-R and the clinical consensus were analyzed.Results: In this study, 137 patients with a clinical-consensus diagnosis of prolonged DOC were enrolled. It was found that 24.7% of patients with clinical UWS were actually in MCS after a single CRS-R behavior evaluation, while the repeated CRS-R evaluation results showed that the proportion of misdiagnosis of MCS was 38.2%. A total of 16.7% of EMCS patients were misdiagnosed with clinical MCS, and 1.1% of EMCS patients were misdiagnosed with clinical UWS. Conclusions: The rate of the misdiagnosis by clinical consensus is still relatively high. Therefore, clinicians should be aware of the importance of the bedside CRS-R behavior assessment and should apply the CRS-R tool in daily procedures. Keywords: Coma-Recovery Scale-Revised, Disorders of consciousness, Unresponsive wakefulness syndrome, Minimally conscious state, MisdiagnosisTrial registration: ClinicalTrials.gov ID: NCT04139239; Registered 24 October 2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04139239
New vectors in northern Sarawak, Malaysian Borneo, for the zoonotic malaria parasite, Plasmodium knowlesi
Authors: De Ang Joshua Xin , Kadir Khamisah Abdul , Mohamad Dayang Shuaisah Awang , Matusop Asmad , Divis Paul Cliff Simon , Yaman Khatijah , Singh Balbir 
Published: September 2020

Abstract
Background: Plasmodium knowlesi is a significant cause of human malaria in Sarawak, Malaysian Borneo. Only one study has been previously undertaken in Sarawak to identify vectors of P. knowlesi, where Anopheles latens was incriminated as the vector in Kapit, central Sarawak. A study was therefore undertaken to identify malaria vectors in a different location in Sarawak.Methods: Mosquitoes found landing on humans and resting on leaves over a 5-day period at two sites in the Lawas District of northern Sarawak were collected and identified. DNA samples extracted from salivary glands of Anopheles mosquitoes were subjected to nested PCR malaria-detection assays. The small subunit ribosomal RNA (SSU rRNA) gene of Plasmodium was sequenced, and the internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the mosquitoes were sequenced from the Plasmodium-positive samples for phylogenetic analysis.Results: Totals of 65 anophelines and 127 culicines were collected. By PCR, 6 An. balabacensis and 5 An. donaldi were found to have single P. knowlesi infections while 3 other An. balabacensis had either single, double or triple infections with P. inui, P. fieldi, P. cynomolgi and P. knowlesi. Phylogenetic analysis of the Plasmodium SSU rRNA gene confirmed 3 An. donaldi and 3 An. balabacensis with single P. knowlesi infections, while 3 other An. balabacensis had two or more Plasmodium species of P. inui, P. knowlesi, P. cynomolgi and some species of Plasmodium that could not be conclusively identified. Phylogenies inferred from the ITS2 and/or cox1 sequences of An. balabacensis and An. donaldi indicate that they are genetically indistinguishable from An. balabacensis and An. donaldi, respectively, found in Sabah, Malaysian Borneo. Conclusions: Previously An. latens was identified as the vector for P. knowlesi in Kapit, central Sarawak, Malaysian Borneo, and now An. balabacensis and An. donaldi have been incriminated as vectors for zoonotic malaria in Lawas, northern Sarawak.
Predictors of Poor Postoperative Outcomes in Pediatric Surgery Patients in Rural Ghana
Authors: Peiffer Sarah , Ssentongo Anna E. , Keeney Laura , Amponsah-Manu Forster , Yeboako Richard , Ofosu-Akromah Richard , Arkorful Temitope Ebenezer , Agyemang Eric , Tsai Anthony , Oh John , Ssentongo Paddy 
Published: September 2020

Abstract
Background/Purpose: Perioperative complications cause significant pediatric morbidity and mortality in low- and lower middle -income countries. This study investigates factors associated with prolonged length of stay, 90-day readmission and in-hospital mortality among pediatric patients at Eastern Regional Hospital (ERH) in Ghana. Methods: This is a retrospective review of perioperative morbidity and mortality in children <18 years at ERH in Koforidua, Ghana. All pediatric surgeries performed between January 2015 and December 2017 were included in this study. Univariate analysis was performed using Pearson’s chi-square tests or Fisher’s exact tests. Variables that were significant on univariate analysis were included in multivariable logistic regression models adjusted for age and gender.Results: We analyzed 468 patients <18 years of age with a median length of stay (LOS) of 3 days. The 90-day readmission and in-hospital mortality rates were 138 and 17 per 1000 patients, respectively. The most common procedures were herniorrhaphy (19%) and appendectomy (15%). Gastrointestinal surgery, surgical trauma, surgical infection and lack of insurance were significantly associated with prolonged LOS. Young age and female gender were significantly associated with in-hospital mortality. Malaria was significantly associated with 90-day readmission. Conclusions: Malaria infection is a significant risk factor for readmission, which should be investigated and treated in pediatric surgical patients in rural Ghana. Ensuring that all patients have insurance may result in shorter hospital stays. Provision of laparoscopic equipment may reduce hospital stays for patients undergoing gastrointestinal surgery. Expansion of the surgical work force, particularly pediatric surgeons, could improve perioperative survival in the very young population.
Effects of environmental distractors on nurse emergency triage accuracy: a pilot study protocol
Authors: delmas philippe , fiorentino Assunta , antonini matteo , Vuilleumier severine , Stotzer guy , Kollbrunner Aurélien , Jaccard Dominique , Hulaas Jarle , Rutschmann Olivier , simon josette , Hugli Olivier , de Keranflec’h Charlotte Gilart , pasquier jerome 
Published: September 2020

Abstract
Background: The clinical decisions of emergency department triage nurses need to be of the highest accuracy. However, studies have found repeatedly that these nurses over- or underestimate the severity of patient health conditions. This has major consequences for patient safety and patient flow management. Workplace distractors such as noise and task interruptions have been pointed to as factors that might explain this inaccuracy. The use of a serious game reproducing the work environment during triage affords the opportunity to explore the impact of these distractors on nurse emergency triage accuracy, in a safe setting. Methods/Design: A pilot study with a factorial design will be carried out to test the acceptability and feasibility of a serious game developed specifically to simulate the triage process in emergency departments and to explore the primary effects of distractors on nurse emergency triage accuracy. Eighty emergency nurses will be randomized into four groups: three groups exposed to different distractors (A: noise, B: task interruptions, C: noise and task interruptions) and one control group. All nurses will have to complete 20 clinical vignettes within two hours. For each vignette, a gold standard assessment will be determined by experts. Pre-tests will be conducted with clinicians and certified emergency nurses to evaluate the appeal of the serious game. Discussion: Study results will inform the design of large-scale investigations and will help identify teaching, training and research areas that require further development.
The effect of the Presence of Children on Adult Smoking Behaviour: Empirical Evidence Based on China Family Panel Studies
Authors: LIN Haoxiang , Chang Chun , LIU Zhao , Tan huaqing 
Published: September 2020

Abstract
Background: Despite a number of studies linking family and marriage factors with health behaviour, the effects of children on the health behaviour of parents are still understudied. This study explored the association between the presence of children and adults’ smoking behaviours. Methods: This study used panel data from the China Family Panel Studies 2010 and 2012, and the data set included 23157 households and 45513 adults. Logistic regression was performed to analyse the association of the presence of children on adults’ smoking behaviours. Subgroup regression was used to examine heterogeneous effects. Results: Full sample regressions showed that the number of children was significantly inversely associated with smoking behaviour (OR=0.93; 95% 0.90-0.96). Further subsample regression finds that such effect is only significant among the high-education group (OR= 0.92; 95% 0.87-0.97), high-skill workers (OR= 0.89; 95% 0.80-0.99) and couples who had an age gap greater than 2 years (OR=0.91; 95% 0.88-0.95). Conclusions: Our findings confirm the existence of the upward intergenerational effect of the presence of children on adults’ smoking behaviour in China. However, such effects are not equal across all demographic characteristics. Future research could explore other parts of the upward mechanism and possible pathways for a stronger effect. In resource-poor areas, targeting cessation activities at those who have children at an early age may be an effective strategy.
Recent epidemiology of patients with Gastro-Entero-Pancreatic Neuroendocrine Neoplasms (GEP-NEN) in Japan: a population-based study
Authors: Masui Toshihiko , Ito Tetsuhide , Komoto Izumi , Uemoto Shinji 
Published: September 2020

Abstract
Background: The worldwide prevalence and incidence of neuroendocrine neoplasms (NEN) have been increasing recently, although few studies have analyzed data on the current situation of NENs in Japan. Here, the Japan Neuroendocrine Tumor Society (JNETS) planned to investigate the recent incidence and distribution of these tumors using data from the national cancer registry started in 2016. This study examined the incidence and distribution of primary sites as well as rate of advanced disease from this population-based registry. Methods: A retrospective, population-based study using data from the national cancer registry in Japan (NCR) was conducted to evaluate patients with gastro-entero-pancreatic NEN (GEP-NEN) in 2016. Associated population data were used to determine annual age-adjusted incidences. Results: A total of 6735 individuals were diagnosed with GEP-NEN in Japan in 2016. Annual onset incidence was 0.70/100,000 for pancreatic NEN and 2.84/100,000 for gastrointestinal NEN. NEN in the ileum accounted for only 1% of total GEP-NENs in Japan. Most NENs in the esophagus or lungs were neuroendocrine carcinomas (NECs), while the majority of those in the duodenum, ileum, appendix and rectum were grade 1 neuroendocrine tumors (NETs). Median age at initial diagnosis was in between 60 to 65. Tumors in the duodenum, appendix and rectum were mostly limited to local, while those in the esophagus, stomach and colon tended to show distant metastasis. In Japan, initial treatment for GEP-NENs was resection even if the tumor was NEC.Conclusions: This is the first report of a national registry-based incidence and distribution of GEP-NEN in Japan. These data will serve as an important first step to determining the exact etiology and trends for this pathology in Japan.
Serum lithium test requesting across three UK regions: An evaluation of adherence to monitoring guidelines
Authors: Parfitt Ceri , Duff Christopher J , Scargill Jonathan , Green Lewis , Holland David , Heald Adrian H , Fryer Anthony 
Published: September 2020

Abstract
Background: Bipolar disorder is the fourth most common mental health condition, affecting ~1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is widely recommended as a first-line treatment. We previously showed in other areas that laboratory testing patterns are variable with sub-optimal conformity to guidance. We therefore examined lithium results and requesting patterns relative to monitoring recommendations.Methods: Data on serum lithium levels and intervals between requests were extracted from Clinical Biochemistry laboratory information systems at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012-2018 (46,555 requests; 3,371 individuals). Data were examined with respect to region/source of request, age and sex.Results: Across all sites, lithium levels on many requests were outside the recommended UK therapeutic range (0.4-0.99 mmol/L); 19.2% below the range and 6.1% above the range (median [Li]: 0.60 mmol/L). A small percentage were found at the extremes (3.2% at <0.1mmol/L, 1.0% at ≥1.4mmol/L). Most requests were from general practice (56.3%) or mental health units (34.4%), though those in the toxic range (≥1.4 mmol/L) were more likely to be from secondary care (63.9%). For requesting intervals, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak at 6 months, as recommended for those aged <65 years on unchanging therapy, though re-test intervals in this age group were more likely to be longer. There was a peak at 0-7 days, reflecting those requiring closer monitoring (e.g. treatment initiation, toxicity). However, for those with initial lithium concentrations within the BNF range (0.4-0.99 mmol/L), 69.4% of tests were requested outside expected testing frequencies.Conclusions: Our data showed: (a) lithium levels are often maintained at the lower end of the recommended therapeutic range, (b) patterns of lithium results and testing frequency were comparable across three UK sites with differing models of care and, (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly, but not at 6-monthly intervals. Many tests were repeated outside expected frequencies, indicating the need for measures to minimise inappropriate testing.
SlGT11 Controls Floral Organ P atterning and F loral Determinacy in Tomato
Authors: Yang Liling , Qi Shilian , touqeer Arfa , Li Haiyang , Zhang Xiaolan , Liu XiaoFeng , wu shuang 
Published: September 2020

Abstract
Background: Flower development directly affects fruit production in tomato. Despite the framework mediated by ABC genes have been established in Arabidopsis, the spatiotemporal precision of floral development in tomato has not been well examined.Results: Here, we analyzed a novel tomato stamenless like flower (slf) mutant in which the development of stamens and carpels is disturbed, with carpelloid structure formed in the third whorl and ectopic formation of floral and shoot apical meristem in the fourth whorl. Using bulked segregant analysis (BSA), we assigned the causal mutation to the gene Solanum lycopersicum GT11 (SlGT11) that encodes a transcription factor belonging to Trihelix gene family. SlGT11 is expressed in the early stages of the flower and the expression becomes more specific to the primordium position corresponding to stamens and carpels in later stages of the floral development. Further RNAi silencing of SlGT11 verifies the defective phenotypes of the slf mutant. The carpelloid stamen in slf mutant indicates that SlGT11 functions like as a B-type gene in the third whorl. The failed termination of floral meristem and the occurrence of floral reversion in slf indicate that SlGT11 also functions as a C-type gene in the fourth whorl. Furthermore, we find that at higher temperature, the defects of slf mutant are substantially enhanced, with petals transformed into sepals, all stamens disappeared, and the frequency of ectopic shoot/floral meristem in fourth whorl increased, indicating that SlGT11 may have the function of tomato B and E class gene in the development of second and fourth whorls.Conclusions: Together with the spatiotemporal expression pattern, we suggest that SlGT11 functions in floral organ patterning and maintenance of floral determinacy in tomato.
Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BIKER registry
Authors: Armaroli Giulia , Klein Ariane , Ganser Gerd , Ruehlmann Michael J. , Dressler Frank , Hospach Anton , Minden Kirsten , Trauzeddel Ralf , Foeldvari Ivan , Kuemmerle-Deschner Jasmin , Weller-Heinemann Frank , Urban Andreas , Horneff Gerd 
Published: September 2020

Abstract
Background: At present, etanercept represents the most commonly prescribed biologic agent for juvenile idiopathic arthritis (JIA) treatment. Children and adolescents with JIA are often treated with etanercept over long periods, sometimes even into adulthood. The objectives of this analysis were to determine the long-term safety of etanercept compared to a biologic-naïve cohort, and to assess the long-term treatment response upon continuous etanercept exposure using data from the German biologics registry (BiKeR).

Methods: JIA patients newly exposed to etanercept were documented in the BiKeR registry from January 2001 till March 2019, and baseline characteristics, effectiveness, as well as safety parameters were analysed. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), JADAS-defined minimal disease activity and remission, JIA-American College of Rheumatology (ACR) improvement criteria, as well as ACR-inactive disease definition. Safety assessments were based on adverse events (AE) reports.

Results: 2725 new etanercept users with a diagnosis of JIA were registered. Of these, etanercept was received as a first-line biologic by 95.8% and as monotherapy without concomitant methotrexate by 31.5%. After nine years on continuous treatment, 68.1% of patients presented minimal disease activity, 43.1% JADAS-defined remission on drug and 36.6% ACR-inactive disease. JIA-ACR30/50/70/90 response rates were still 82/79/71/54% after 9 years of treatment. Overall, 2053 AEs (34.3/100PY), including 226 serious AEs (SAE, 3.8/100PY), were observed upon etanercept, compared to 1345 AEs [35.6/100PY; p=0.3] and 52 SAEs (1.4/100PY; p=0.0001) in the biologic-naïve cohort. Respective exposure-adjusted rates for etanercept and biologic-naïve patients were 0.9/100PY and 0.2/100PY (p=0.0001) for serious infections, 0.4/100PY and 0.1/100PY (p=0.01) for zoster reactivation, 0.3/100PY and 0.03/100PY (p=0.015) for inflammatory bowel disease, 1.9/100PY and 1.4/100PY (p=0.09) for uveitis. Three and two malignancies were documented in the etanercept and biologic-naïve groups, as well as three and one deaths, respectively.

Conclusions: No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease. However, SAEs and serious infections, though infrequent, were more often reported on etanercept than in biologic-naïve patients. In addition, etanercept demonstrated a long-term maintenance of clinical benefits up to nine years of continuous treatment.
Keywords: Juvenile idiopathic arthritis, JIA-treatment, etanercept, TNF-inhibitors, biologics registry, drug surveillance