bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance chemotherapy using S-1 following definitive chemoradiotherapy in patients with N3 nasopharyngeal carcinoma
Authors: Zong Jingfeng , Xu Hanchuan , Chen Bijuan , Guo Qiaojuan , Xu Yun , Chen Chuanben , Weng Youliang , Zheng Wei , Pan Jianji , Lin Shaojun 
Published: October 2019

Abstract

Background
Patients with N3 stage nasopharyngeal carcinoma (NPC) are at high risk for treatment failure. This study aims to assess the efficacy of maintenance chemotherapy (MC) using S-1 (MC-S1), a novel oral fluoropyrimidine agent, following definitive chemoradiotherapy (CRT) using intensity-modulated radiotherapy (IMRT) in patients with N3 nasopharyngeal carcinoma (N3-NPC).

Methods
A retrospective review was conducted for all N3-NPC treated with CRT with MC (CRT-MC) or without MC (CRT-non-MC) during 2014–2016. Toxicities with MC were recorded. Overall survival (OS), locoregional failure-free survival (LFFS) and distant metastasis free survival (DMFS) were compared between CRT-MC vs. CRT-non-MC cohorts.

Results
A total of 130 N3 patients were identified, of whom 21 (16.2%) were treated with CRT-MC, and 109 (83.8%) with CRT-non-MC. Patient characteristics did not significantly differ between the CRT-MC and CRT-non-MC groups, with the exception of the number of cycles of neoadjuvant chemotherapy. Following IMRT 69 patients achieved a complete response (CR) (CRT-MC: 10; CRT-non-MC: 59), 61 had a partial response (PR) (11 vs. 50), and none maintained stable disease (SD) or developed progression of disease (PD). After a median follow-up of 41 months for surviving patients, a significant differences in OS (76.3% vs. 95.2%, p = 0.046) and DMFS (70.3% vs. 90.5%, p = 0.043) but not LFFS (84.9% vs. 100%, p = 0.091) at 3 years were observed between the CRT-non-MC and CRT-MC groups. Skin hyperpigmentation, leucopenia, fatigue, neutropenia, anorexia and nausea were the common but not severe (grade 1–2) toxicities of MC.

Conclusions
Using MC-S1 in N3-NPC patients following IMRT achieved superior survival to the CRT-non-MC patients. The toxicities of MC-S1 were mild and tolerable. Further clinical trials are required to evaluate the efficacy of MC-S1 in N3-NPC patients.
Hybrid procedure for treating adult congenital heart disease with valvular heart disease in two patients
Authors: Li Chun-sheng , Lu Zhong , Song Xiao-rong , Yan Zhong-ya 
Published: October 2019

Abstract

Background
The traditional approach for adult congenital heart disease combined with valvular disease is surgical treatment under cardiopulmonary bypass (CPB). This approach has a high incidence of postoperative complications, especially in patients with pulmonary hypertension and old age. We present two patients in whom the hybrid procedure was used to treat congenital malformations, followed by valve formation and replacement surgery.

Case presentation
A 63-year-old man had a muscular ventricular septal defect complicated by mitral regurgitation and a 57-year-old man had patent ductus arteriosus complicated by aortic stenosis. In both of the patients, the congenital malformation was successfully treated by the hybrid procedure, followed by valve repair or replacement. Both patients had no complications. A post-procedure echocardiogram showed no residual shunt across the duct.

Conclusions
Our findings suggest that the hybrid procedure is a useful alternative for treating adult congenital heart disease with valvular heart disease. This procedure reduces the surgical incision and difficulty of surgery, shortens the CPB time, avoids residual leakage after surgery, and reduces recovery and hospitalization times.
Controlling the laxative abuse of anorexia nervosa patients with the Serigaya Methamphetamine Relapse Prevention Program workbook: a case report
Authors: Toyoshima Kuniyoshi , Kusumi Ichiro 
Published: October 2019

Abstract

Background
There is no consensus on effective treatment for laxative abuse in patients with eating disorders. Here, we report the case of a patient with laxative abuse who showed some improvement through an intervention based on the Matrix model.

Case presentation
A woman diagnosed with anorexia nervosa-binge eating/purging type (AN-BP) steadfastly denied laxative abuse and would not admit to suffering from an eating disorder. This led to low motivation for undergoing conventional psychotherapy, psychoeducation, and cognitive behavioral therapy. These were ineffective and followed by repeated cycles of hospitalization and discharge. The patient’s general condition, as depicted by her laboratory and clinical parameters, deteriorated due to the medical complications resulting from laxative abuse.
Focusing on laxative abuse, we considered an intervention for drug addiction. Because the patient could maintain a diet diary and acknowledged laxative abuse as a drug addiction, we introduced the Serigaya Methamphetamine Relapse Prevention Program (SMARPP) workbook as a self-administered treatment. The patient meticulously completed the treatment and experienced a gradual improvement in laxative abuse. She has not been re-hospitalized in 4 years, currently performs household chores, and demonstrates improved social function.

Conclusions
In patients with AN-BP, the SMARPP workbook may be effective in treating laxative abuse.
RUNX1 mutations promote leukemogenesis of myeloid malignancies in ASXL1-mutated leukemia
Authors: Bera Rabindranath , Chiu Ming-Chun , Huang Ying-Jung , Lin Tung-Huei , Kuo Ming-Chung , Shih Lee-Yung 
Published: October 2019

Abstract

Background
Additional sex combs-like 1 (ASXL1) mutations have been described in all forms of myeloid neoplasms including chronic myelomonocytic leukemia (CMML) and associated with inferior outcomes, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) remains poorly understood. Transformation of CMML to secondary AML (sAML) is one of the leading causes of death in CMML patients. Previously, we observed that transcription factor RUNX1 mutations (RUNX1-MT) coexisted with ASXL1-MT in CMML and at myeloid blast phase of chronic myeloid leukemia. The contribution of RUNX1 mutations in the pathogenesis of myeloid transformation in ASXL1-mutated leukemia, however, remains unclear.

Methods
To evaluate the leukemogenic role of RUNX1-MT in ASXL1-mutated cells, we co-expressed RUNX1-MT (R135T) and ASXL1-MT (R693X) in different cell lines and performed immunoblot, co-immunoprecipitation, gene expression microarray, quantitative RT-PCR, cell proliferation, differentiation, and clonogenic assays for in vitro functional analyses. The in vivo effect was investigated using the C57BL/6 mouse bone marrow transplantation (BMT) model.

Results
Co-expression of two mutant genes increased myeloid stem cells in animal model, suggesting that cooperation of RUNX1 and ASXL1 mutations played a critical role in leukemia transformation. The expression of RUNX1 mutant in ASXL1-mutated myeloid cells augmented proliferation, blocked differentiation, and increased self-renewal activity. At 9 months post-BMT, mice harboring combined RUNX1 and ASXL1 mutations developed disease characterized by marked splenomegaly, hepatomegaly, and leukocytosis with a shorter latency. Mice transduced with both ASXL1 and RUNX1 mutations enhanced inhibitor of DNA binding 1 (ID1) expression in the spleen, liver, and bone marrow cells. Bone marrow samples from CMML showed that ID1 overexpressed in coexisted mutations of RUNX1 and ASXL1 compared to normal control and either RUNX1-MT or ASXL1-MT samples. Moreover, the RUNX1 mutant protein was more stable than WT and increased HIF1-α and its target ID1 gene expression in ASXL1 mutant cells.

Conclusion
The present study demonstrated the biological and functional evidence for the critical role of RUNX1-MT in ASXL1-mutated leukemia in the pathogenesis of myeloid malignancies.
Galectin-1 promotes hepatocellular carcinoma and the combined therapeutic effect of OTX008 galectin-1 inhibitor and sorafenib in tumor cells
Authors: Leung Zoe , Ko Frankie Chi Fat , Tey Sze Keong , Kwong Ernest Man Lok , Mao Xiaowen , Liu Bonnie Hei Man , Ma Angel Po Yee , Fung Yi Man Eva , Che Chi-Ming , Wong Danny Ka Ho , Lai Ching Lung , Ng Irene Oi-Lin , Yam Judy Wai Ping 
Published: October 2019

AbstractBackgroundGalectins are beta-galactose specific binding proteins. In human cancers, including hepatocellular carcinoma (HCC), galectin-1 (Gal-1) is often found to be overexpressed. In order to combat the dismal diagnosis and death rates of HCC, gene silencing and targeted inhibition of Gal-1 was investigated for its improved therapeutic potential.MethodsCellular and secretory Gal-1 levels were analyzed using HCC clinical samples. The study of Gal-1 was carried by both knockdown and overexpression approaches. The stable clones were tested by in vitro assays and in vivo experiments. Mass spectrometry was used to identify downstream targets of Gal-1. The upstream regulator of Gal-1, microRNA-22 (miR-22) was characterized by functional assays. The therapeutic effect of inhibiting Gal-1 was also analyzed.ResultsGal-1 overexpression was observed in HCC and correlated with aggressive clinicopathological features and poorer survival. The loss of Gal-1 resulted in hindered cell migration, invasion and anchorage independent growth. This was also observed in the animal models, in that when Gal-1 was knocked down, there were fewer lung metastases. Proteomic profiling of control and Gal-1 knockdown cells identified that the level of retention in endoplasmic reticulum 1 (RER1) was suppressed when Gal-1 level was reduced. The cell motility of Gal-1 knockdown cells was enhanced upon the rescue of RER1 expression. In HCC tissues, Gal-1 and RER1 expressions displayed a significant positive correlation. The upstream regulator of Gal-1, miR-22 was observed to be underexpressed in HCC tissues and negatively correlated with Gal-1. Silencing of miR-22 resulted in the upregulation of Gal-1 and enhanced cell growth, migration and invasion. However, such enhancement was abolished in cells treated with OTX008, an inhibitor of Gal-1. Combinational treatment of OTX008 and sorafenib significantly reduced tumor growth and size.ConclusionsGal-1 overexpression was detected in HCC and this played a role in promoting tumorigenic processes and metastasis. The function of Gal-1 was found to be mediated through RER1. The correlations between miR-22, Gal-1 and RER1 expressions demonstrated the importance of miR-22 regulation on Gal-1/RER1 oncogenic activity. Lastly, the combinational treatment of OTX008 and sorafenib proved to be an improved therapeutic option compared to when administering sorafenib alone.
Metformin overcomes resistance to cisplatin in triple-negative breast cancer (TNBC) cells by targeting RAD51
Authors: Lee Jung Ok , Kang Min Ju , Byun Won Seok , Kim Shin Ae , Seo Il Hyeok , Han Jeong Ah. , Moon Ji Wook , Kim Ji Hae , Kim Su Jin , Lee Eun Jung , In Park Serk , Park Sun Hwa , Kim Hyeon Soo 
Published: October 2019

Abstract

Background
Chemotherapy is a standard therapeutic regimen to treat triple-negative breast cancer (TNBC); however, chemotherapy alone does not result in significant improvement and often leads to drug resistance in patients. In contrast, combination therapy has proven to be an effective strategy for TNBC treatment. Whether metformin enhances the anticancer effects of cisplatin and prevents cisplatin resistance in TNBC cells has not been reported.

Methods
Cell viability, wounding healing, and invasion assays were performed on Hs 578T and MDA-MB-231 human TNBC cell lines to demonstrate the anticancer effects of combined cisplatin and metformin treatment compared to treatment with cisplatin alone. Western blotting and immunofluorescence were used to determine the expression of RAD51 and gamma-H2AX. In an in vivo 4T1 murine breast cancer model, a synergistic anticancer effect of metformin and cisplatin was observed.

Results
Cisplatin combined with metformin decreased cell viability and metastatic effect more than cisplatin alone. Metformin suppressed cisplatin-mediated RAD51 upregulation by decreasing RAD51 protein stability and increasing its ubiquitination. In contrast, cisplatin increased RAD51 expression in an ERK-dependent manner. In addition, metformin also increased cisplatin-induced phosphorylation of γ-H2AX. Overexpression of RAD51 blocked the metformin-induced inhibition of cell migration and invasion, while RAD51 knockdown enhanced cisplatin activity. Moreover, the combination of metformin and cisplatin exhibited a synergistic anticancer effect in an orthotopic murine model of 4T1 breast cancer in vivo.

Conclusions
Metformin enhances anticancer effect of cisplatin by downregulating RAD51 expression, which represents a novel therapeutic target in TNBC management.
Retrotransposon gag-like 1 (RTL1) and the molecular evolution of self-targeting imprinted microRNAs
Authors: Mainieri Avantika , Haig David 
Published: October 2019

AbstractBackgroundTranscription of the antisense strand ofRTL1produces a sense mRNA that is targeted for degradation by antisense microRNAs transcribed from the sense strand. Translation of the mRNA produces a retrotransposon-derived protein that is implicated in placental development. The sense and antisense transcripts are oppositely imprinted: sense mRNAs are expressed from the paternally-derived chromosome, antisense microRNAs from the maternally-derived chromosome.ResultsTwo microRNAs at theRTL1locus, miR-431 and the rodent-specific miR-434, are derived from within tandem repeats. We present an evolutionary model for the establishment of a new self-targeting microRNA derived from within a tandem repeat that inhibits production of RTL1 protein when maternally-derived in heterozygotes but not when paternally-derived.ConclusionsThe interaction of sense and antisense transcripts can be interpreted as a form of communication between maternally-derived and paternally-derivedRTL1alleles that possesses many of the features of a greenbeard effect. This interaction is evolutionary stable, unlike a typical greenbeard effect, because of the necessary complementarity between microRNAs and mRNA transcribed from opposite strands of the same double helix. We conjecture that microRNAs and mRNA cooperate to reduce demands on mothers when an allele is paired with itself in homozygous offspring.ReviewersThis article was reviewed by Eugene Berezikov and Bernard Crespi.
Multi-center screening of the Pathogen Box collection for schistosomiasis drug discovery
Authors: Maccesi Martina , Aguiar Pedro H. N. , Pasche Valérian , Padilla Melody , Suzuki Brian M. , Montefusco Sandro , Abagyan Ruben , Keiser Jennifer , Mourão Marina M. , Caffrey Conor R. 
Published: October 2019

Abstract

Background
Over the past five years, as a public service to encourage and accelerate drug discovery for diseases of poverty, the Medicines for Malaria Venture (MMV) has released box sets of 400 compounds named the Malaria, Pathogen and Stasis Boxes. Here, we screened the Pathogen Box against the post-infective larvae (schistosomula) of Schistosoma mansoni using assays particular to the three contributing institutions, namely, the University of California San Diego (UCSD) in the USA, the Swiss Tropical and Public Health Institute (Swiss TPH) in Switzerland, and the Fundação Oswaldo Cruz (FIOCRUZ) in Brazil. With the same set of compounds, the goal was to determine the degree of inter-assay variability and identify a core set of active compounds common to all three assays. New drugs for schistosomiasis would be welcome given that current treatment and control strategies rely on chemotherapy with just one drug, praziquantel.

Methods
Both the UCSD and Swiss TPH assays utilize daily observational scoring methodologies over 72 h, whereas the FIOCRUZ assay employs XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) at 72 h to measure viability as a function of NAD+/NADH redox state. Raw and transformed data arising from each assay were assembled for comparative analysis.

Results
For the UCSD and Swiss TPH assays, there was strong concordance of at least 87% in identifying active and inactive compounds on one or more of the three days. When all three assays were compared at 72 h, concordance remained a robust 74%. Further, robust Pearsonʼs correlations (0.48–0.68) were measured between the assays. Of those actives at 72 h, the UCSD, Swiss TPH and FIOCRUZ assays identified 86, 103 and 66 compounds, respectively, of which 35 were common. Assay idiosyncrasies included the identification of unique compounds, the differential ability to identify known antischistosomal compounds and the concept that compounds of interest might include those that increase metabolic activity above baseline.

Conclusions
The inter-assay data generated were in good agreement, including with previously reported data. A common set of antischistosomal molecules for further exploration has been identified.
From the feces to the genome: a guideline for the isolation and preservation of Strongyloides stercoralis in the field for genetic and genomic analysis of individual worms
Authors: Zhou Siyu , Harbecke Dorothee , Streit Adrian 
Published: October 2019

AbstractStrongyloidiasis is a soil-borne helminthiasis, which, in spite of the up to 370 million people currently estimated to be infected with its causing agent, the nematodeStrongyloides stercoralis, is frequently overlooked. Recent molecular taxonomic studies conducted in Southeast Asia and Australia, showed that dogs can carry the same genotypes ofS. stercoralisthat also infect humans, in addition to a presumably dog-specificStrongyloidesspecies. This suggests a potential for zoonotic transmission ofS. stercoralisfrom dogs to humans. Although naturalS. stercoralisinfections have not been reported in any host other than humans, non-human primates and dogs, other as yet unidentified animal reservoirs cannot be excluded. Molecular studies also showed that humans carry rather different genotypes ofS. stercoralis. As a result, their taxonomic status and the question of whether they differ in their pathogenic potential remains open. It would therefore be very important to obtain molecular genetic/genomic information aboutS. stercoralispopulations from around the world. One way of achieving this (with little additional sampling effort) would be that people encounteringS. stercoralisin the process of their diagnostic work preserve some specimens for molecular analysis. Here we provide a guideline for the isolation, preservation, genotyping at the nuclear18SrDNA and the mitochondrialcox1 loci, and for whole genome sequencing of singleS. stercoralisworms. Since in many cases the full analysis is not possible or desired at the place and time whereS. stercoralisare found, we emphasize when and how samples can be preserved, stored and shipped for later analysis. We hope this will benefit and encourage researchers conducting field studies or diagnostics to collect and preserveS. stercoralisfor molecular genetic/genomic analyses and either analyze them themselves or make them available to others for further analysis.
Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison
Authors: Collyer Benjamin S. , Turner Hugo C. , Hollingsworth T. Déirdre , Keeling Matt J. 
Published: October 2019

AbstractBackgroundSchistosomiasis is a neglected tropical disease, targeted by the World Health Organization for reduction in morbidity by 2020. It is caused by parasitic flukes that spread through contamination of local water sources. Traditional control focuses on mass drug administration, which kills the majority of adult worms, targeted at school-aged children. However, these drugs do not confer long-term protection and there are concerns over the emergence of drug resistance. The development of a vaccine against schistosomiasis opens the potential for control methods that could generate long-lasting population-level immunity if they are cost-effective.MethodsUsing an individual-based transmission model, matched to epidemiological data, we compared the cost-effectiveness of a range of vaccination programmes against mass drug administration, across three transmission settings. Health benefit was measured by calculating the heavy-intensity infection years averted by each intervention, while vaccine costs were assessed against robust estimates for the costs of mass drug administration obtained from data. We also calculated a critical vaccination cost, a cost beyond which vaccination might not be economically favorable, by benchmarking the cost-effectiveness of potential vaccines against the cost-effectiveness of mass drug administration, and examined the effect of different vaccine protection durations.ResultsWe found that sufficiently low-priced vaccines can be more cost-effective than traditional drugs in high prevalence settings, and can lead to a greater reduction in morbidity over shorter time-scales. MDA or vaccination programmes that target the whole community generate the most health benefits, but are generally less cost-effective than those targeting children, due to lower prevalence of schistosomiasis in adults.ConclusionsThe ultimate cost-effectiveness of vaccination will be highly dependent on multiple vaccine characteristics, such as the efficacy, cost, safety and duration of protection, as well as the subset of population targeted for vaccination. However, our results indicate that if a vaccine could be developed with reasonable characteristics and for a sufficiently low cost, then vaccination programmes can be a highly cost-effective method of controlling schistosomiasis in high-transmission areas. The population-level immunity generated by vaccination will also inevitably improve the chances of interrupting transmission of the disease, which is the long-term epidemiological goal.
Factors associated with food safety practices among food handlers: facility-based cross-sectional study
Authors: Azanaw Jember , Gebrehiwot Mulat , Dagne Henok 
Published: October 2019

Abstract

Objective
The primary objective of this study was to assess factors associated with food safety practices among food handlers in Gondar city food and drinking establishments. The facility-based cross-sectional study was undertaken from March 3 to May 28, 2018, in Gondar city. Simple random sampling method was used to select both establishments and the food handlers. The data were collected through face-to-face interview using pre-tested Amharic version of the questionnaire. Data were entered and coded into Epi info version 7.0.0 and exported to SPSS version 22 for analysis.

Results
One hundred and eighty-eight (49.0%) had good food handling practice out of three hundred and eighty-four food handlers. Marital status (AOR: 0.36, 95% CI 0.05, 0.85), safety training (AOR: 4.01, 95% CI 2.71, 9.77), supervision by health professionals (AOR: 4.10, 95% CI 1.71, 9.77), routine medical checkup (AOR: 8.80, 95% CI 5.04, 15.36), and mean knowledge (AOR: 2.92, 95% CI 1.38, 4.12) were the factors significantly associated with food handling practices. The owners, managers and local health professionals should work on food safety practices improvement.