bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Newly Established Pralatrexate-resistant Cell Lines and the Mechanisms of Resistance
Authors: Hosono Naoko , Oiwa Kana , Nishi Rie , Scott Luigi , O’Connor Owen A. , Yamauchi Takahiro 
Published: September 2020

Abstract
Background
Pralatrexate (PDX) is a novel antifolate approved for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma. However, some patients exhibit intrinsic resistance or develop acquired resistance to PDX. Here, we evaluated the mechanisms underlying acquired drug resistance and identified strategies to prevent resistance.
Methods
We established two PDX-resistant T-lymphoblastic leukemia cell lines (CEM and MOLT4) through repeated escalating exposure to PDX. Gene expression analysis and methylation profiling were performed to identify the mechanisms of resistance. We then explored rational drug:drug combinations to prevent resistance.
Results
PDX-resistant cells exhibited a 30-fold increase in half-maximal inhibitory concentration values compared with those of their parental cells. Induction of apoptosis by PDX was significantly decreased in both PDX-resistant cell lines. Intracellular uptake of [14C]-PDX decreased in PDX-resistant CEM cells, and dihydrofolate reductase (DHFR) expression was increased in PDX-resistant MOLT4 cells. Gene expression array analysis revealed that DNA-methyltransferase 3β expression was significantly elevated in both cell lines. Moreover, decitabine plus PDX showed synergistic effects in drug-resistant cell lines compared with parental lines. In addition, both PDX-resistant cell lines showed sensitivity to nucleoside analogs, i.e., cytarabine and forodesine.
Conclusions
This is the first study to explore the specific mechanisms of PDX resistance in T-cell lymphoma. The resistance mechanisms were associated with reduced cellular uptake of PDX and overexpression of DHFR. Epigenetic alterations were also considered to play a role in the resistance mechanism. The cells exhibited increased sensitivity to nucleoside analogs. These results could facilitate rational combinations to improve the clinical efficacy of PDX.
A Feasibility Study of the Mistletoe and Breast Cancer (MAB) Trial: A Protocol for a Randomised Double-blind Controlled Trial
Authors: Bryant Susan , Duncan Lorna , Feder Gene , Huntley Alyson 
Published: September 2020

Abstract
Background: A Cochrane review of mistletoe therapy concludes that there is some evidence that mistletoe extracts may offer benefits on measures of quality of life during chemotherapy for breast cancer, but these results need replication. Our aim was to test the feasibility of a placebo controlled, double blind randomised controlled trial of mistletoe therapy in patients with breast cancer undergoing chemotherapy with or without radiotherapy. Methods/design: A placebo controlled, double blind randomised controlled trial of mistletoe therapy in patients with breast cancer. There will be three arms (groups) in the trial: Iscador M, Iscador P, with physiological saline as the placebo. The aim is to recruit 45 adult patients with a new diagnosis of early or locally advanced breast cancer, up to 12 weeks following definitive breast surgery whose standard treatment plan includes chemotherapy with or without radiotherapy. They will be taught to administer the MAB therapies subcutaneously and will titrate up to their optimal dose. MAB therapy will continue throughout their standard chemotherapy and radiotherapy and one month beyond. The main outcome of the MAB study is the feasibility of conducting such a trial within the NHS in order to inform a future fully powered investigative trial. Feasibility will be measured through recruitment, retention and patient experience using clinical research forms, patient diaries, cancer-related questionnaires and qualitative interviews conducted with both patients and oncology staff.Discussion: This trial is the first of its kind in the UK. Currently mistletoe therapy is mostly available through private practice in the UK. Completion of this feasibility study will support applications for further funding for a fully powered randomised controlled trial which will measure effectiveness and cost-effectiveness of this herbal therapy.
Lifecycle Management of Insecticides Used for Disease Vector Control: A Global Survey
Authors: Berg Henk van den , Bezerra Haroldo Sergio da Silva , Chanda Emmanuel , Al-Eryani Samira , Nagpal Bhupender Nath , Gasimov Elkhan , Velayudhan Raman , Yadav Rajpal Singh 
Published: September 2020

Abstract
Background: Vector control plays a critical role in the prevention, control and elimination of vector-borne diseases, and interventions of vector control continue to depend largely on the action of chemical insecticides. A global survey was conducted on the lifecycle management practices of vector control insecticides at country level to identify gaps to inform future strategies to improve efficacy of interventions and reduce the side effects of chemicals used on health and the environment.Methods: A survey by questionnaire was disseminated among all WHO Member States on the lifecycle management practices of vector control insecticides at country level. Data were analysed using descriptive statistics.Results: Responses were received from 94 countries, indicating a response rate of 48%. Capacity for insecticide resistance monitoring has been established in part of the countries, often with external support; however, this capacity was lacking from other countries. Procurement of vector control insecticides was often taking place at decentralized levels, over which the central authorities lacked control, for example, to select the product or assure quality of the product. Moreover, some countries experienced problems with estimating the correct amounts for procurement, especially for emergency purposes. Countries across regions showed shortcomings in worker safety, pesticide storage practices, and pesticide waste disposal. Shortcomings were most pronounced in countries of the European & Others Group, most of which have long been relatively free from mosquito-borne diseases but have recently faced challenges of re-emerging vector-borne diseases.Conclusions: Critical shortcomings in the management of vector control insecticides are common in countries across regions, with risks of adverse pesticide effects on health and the environment. Advocacy and resource mobilization are needed at regional and country level to address these challenges.
Paternity in male kidney transplant recipients: A French national survey, the PATeRNAL study.
Authors: Boyer Annabel , Lobbedez Thierry , Ouethrani Mohamed , Lecouf Angélique Thuillier , Bouvier Nicolas , Châtelet Valérie , de Ligny Bruno Hurault 
Published: September 2020

Abstract
Background: There is concern about the impact of immunosuppressive agents taken by male kidney transplant (KT) recipients on the risk of foetal malformations. The aim of our survey was to estimate the paternity rate and the outcomes of pregnancies fathered by kidney transplanted males. Methods: This survey analysed 1332 male KT recipients older than 18 years, followed in 13 centres in France. A self-reported questionnaire was used to collect data on the patients, treatments at the time of conception and the pregnancy outcomes.Results: The study included data on 349 children from 404 pregnancies fathered by 232 male KT recipients. The paternity rate was 17% (95% CI [15–20]). There were 37 (9%, 95% CI [7–12]) spontaneous abortions, 12 (3%, 95% CI [2–5]) therapeutic abortions, 2 (0.5%, 95% CI [0.1–1]) still births, and 13 (4%, 95% CI [2–6]) malformations reported. Compared to the general population, there was no difference in the proportion of congenital malformations nor unwanted outcomes whether the father was exposed or not to immunosuppressive agents.Conclusions: This survey does not provide any warning signal that pregnancies fathered by male patients exposed to immunosuppressive agents, notably the debated MMF/MPA, have more complications than pregnancies in the general population.
Molecular Detection of Equid Herpesvirus Type 2 (Ehv-2) and Type 5 (Ehv-5) in Bronchoalveolar Lavage Fluid From Asymptomatic Thoroughbred Horses in Southern Brazil
Authors: Finger Mariane Angélica , Biava Janaina Socolovski , Dornbusch Peterson Triches , Perotta João Henque , Ullmann Leila Sabrina , Serpa Priscila Beatriz da Silva , Santos Andrea Pires dos , BIONDO ALEXANDER WELKER , Leutenegger Christian M. , Filho Ivan Roque de Barros 
Published: September 2020

Abstract
Background: Respiratory conditions are the leading cause of training disruption in racing horses. Molecular approaches to diagnose respiratory viruses have provided an opportunity for early and subclinical pathogen detection, particularly in samples from the upper respiratory tract. Gammaherpesvius (EHV-2 and EHV-5) have variable presentations in horses. However, the infection can be asymptomatic and act as a co-factor for the development of other diseases. In this descriptive observational study, 10 healthy, young horses at regular training in Southern Brazil underwent clinical examination, videoendoscopy of the respiratory system, cytological evaluation of TA (tracheal aspirate) and BALF (bronchoalveolar lavage fluid), along with qPCR, in order to evaluate the presence of EHV-2 and EHV-5 in lower respiratory tract samples and compare with correspondent cytological and endoscopical findings. Results: At least one abnormality per horse during endoscopy examination was observed, including, but not limited to, mucous secretion in the airways and pharyngeal lymphoid hyperplasia. The presence of EHV-2 and EHV-5 was detected by qPCR in three out of ten animals. One horse was positive for EHV-2 alone, one for EHV-5 alone, and one was positive for both viruses. No videoendoscopic finding correlated with each other neither predicts gammaherpesvirus status (positive or negative test). Additionally, there was no relationship between the percentage of cells in both TA and BALF and the probability to test positive for herpesvirus.Conclusions: To the authors’ knowledge, this is the first molecular detection of EHV-2 and 5 in Brazilian Thoroughbred horses. These findings may provide new insights into the epidemiological situation of EHV-2 and 5 in Brazilian athletic young horses, evidencing the importance of the molecular investigation, early detection, and prevention of respiratory diseases.
“No Thanks, I Don’t Want to See Snakes Again”: A Qualitative Study of Pain Management Versus Preservation of Cognition in Palliative Care Patients
Authors: Wegier Pete , Varenbut Jaymie , Bernstein Mark , Lawlor Peter G , Isenberg Sarina R 
Published: September 2020

Abstract
BackgroundTowards the end of life, use of opioid analgesics becomes more common in patients to control pain and improve quality of life. While pain medication may help manage pain, unwanted cognitive side effects are frequently noted. This balancing act presents a trade-off for patients between pain relief and adverse effects, where the desire to relieve pain must be evaluated against the desire to maintain cognitive clarity and may represent a difficult decision for patients receiving palliative care. Our goal was to understand how patients’ decision making about pain medications balances the pain relief from those medications against the cognitive decline often associated with them.MethodsWe conducted qualitative semi-structured interviews with patients receiving home-based palliative care from a program in Toronto, Canada. Interview recordings were transcribed and analyzed using thematic analysis.ResultsThirty-one interviews were conducted. Some patients preferred cognitive preservation over pain management because of a sense that cognition is central to their identity, the desire to maintain lucidity, a desire to continue participating in work or hobbies, and fear of addiction. Conversely, some patients preferred pain management over cognitive preservation because of a desire to avoid suffering, an inability to sleep without medications, or an acceptance of some cognitive compromise. A few patients attempted to find balance through tapering drugs, limiting their use of breakthrough analgesic doses, or using alternative strategies. ConclusionsDecision making around pain and pain management is a highly preference-sensitive process—with no clear right or wrong decisions, only the preferences of each patient. The findings from this study may influence the design of future patient-facing decision aids around pain management. Future studies should pilot interventions to better assist patients with this decision.
A Cross-sectional Investigation of Latrine and Pure Water Coverage and Related Factors Among Residence of Negele town, Arsi zone, Southeast Ethiopia
Authors: Dagaga Diriba Temesgen , Geleta Girma Deboch 
Published: September 2020

Abstract
BackgroundAccess to safe water and improved sanitation contributes to the human heath and socio-economic development of a country. This study was conducted to assess the latrine and pure water coverage and related factors among dwellers of Negele town, Arsi zone, southeast EthiopiaMethodTwo kebeles (administrative units) were randomly selected from each zone of the town to collect data via questionnaires from randomly selected households (380), via interview from purposely selected key informants (40) and via personal observation employing a cross-sectional survey design from April-May 2018. Data were analyzed using microsoft Excel program and the results were expressed using table as frequencie and percentages . ResultLatrine coverage of the town was low (45%) mainly due to shortage of land and fund. Among the available latrines, 75% were closer than recommended distance (6m) to kitchens, 52.3% lacked roofs, 53% lacked doors, and 100% lacked hole cover and water to clean. Latrine lacking households defecate in various sites of the environment with problems on environmental sanitation, personal safety and health issues. Similarly, pure water coverage was very low (7.6%) as a result of deficient water sources and non-functioning pipe lines forcing the people to use unprotected water source or expend much time in fetching water from private taps.Conclusion Latrine and pure water coverage of Negele town was far less than the national Millennium Development Goal (MDG) which targetted 100% improved hygiene and sanitation coverage by 2015. The big gap demonstrated by this study may intiate the admistration of the town to provide land, arrange loan or search for aids for the construction of standardized private and public toilets. Searching additional water sources like underground water and maintaining non-functional and/or constructing new pipe lines may also be promoted as a result of this study to improve the pure water coverage of the town. Public participatory plans may also be designed to solve shortage of latrine and water coverage of the town via continuous awareness creation.
Relationship of common variants in Krüppel-like factor 7 gene with susceptibility and prognosis of oral squamous cell carcinoma
Authors: Wang Lili , Song Hongguang , Yang Shiming 
Published: September 2020

Abstract
Background

The aim of this study was to assess the prognostic value of Krüppel-like factor 7 (KLF7) for patients with oral squamous cell carcinoma(OSCC).
Methods

The expression of KLF7 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in pairs of tumor tissues and adjacent non-tumor tissues of OSCC. Chi-square (χ2) test was applied to evaluate the association of KLF7 expression with clinicopathological characteristics of OSCC patients. Overall survival was estimated using the Kaplan-Meier method with log rank test. The cox proportional hazards model was used for univariate and multivariate analyses.
Results

The expression of KLF7 was remarkably increased in OSCC tissues compared with adjacent non-tumor tissues (P < 0.001). KLF7 expression was related to TNM stage (P = 0.006), tumor size (P = 0.010), smoking (P = 0.006) and drinking (P = 0.000). Kaplan-Meier analysis showed that OSCC patients with high KLF7 expression had a poorer overall survival than those with low expression (log rank test, P = 0.018). Moreover, multivariate analyses showed that KLF7 was an independent prognostic factor for OSCC (P = 0.002 HR = 2.645 95%CI: 1.426–4.906).
Conclusion

Decreased expression of KLF7 may be a potential unfavorable prognostic factor for patients with OSCC.
Petal Color-Transition in Lonicera japonica is Mainly Associated with Increase of the Carotenoid Content and Carotenoid Biosynthetic Gene Expression
Authors: Xia Yan , Chen Weiwei , Xiang Weibo , Wang Dan , Xue Baogui , Liu Xinya , Xing Lehua , Wu Di , Wang Shuming , Guo Qigao , Liang Guolu 
Published: September 2020

Abstract
Background: Plants have remarkable diversity in petal color through the biosynthesis and accumulation of various pigments. To better understand the mechanisms regulating the petal pigmentation, we used multiple approaches to investigate the changes of carotenoids, gene expression dynamics and endogenous hormones in Lonicera japonica during petal color transitions, i.e. green bud petal (GB_Pe), white flower petal (WF_Pe) and yellow flower petal (YF_Pe). Results: Metabolome analysis showed that YF_Pe had a much higher content of carotenoids than white petals, with violaxanthin identified as the major carotenoid compound in YF_Pe. Comparative transcriptome analysis revealed that the key differentially expressed genes (DEGs) involved in carotenoid biosynthesis, such as phytoene synthase, phytoene desaturase and ζ-carotene desaturase, were significantly up-regulated in YF_Pe. However, expression levels of the carotenoid degradation-related genes, including abscisic-aldehyde oxidase 3 and carotenoid cleavage dioxygenase 4, were significantly down-regulated in YF_Pe. The results indicated that upregulated carotenoids concentrations and carotenoids biosynthesis-related genes promote the color transition. Furthermore, enrichment analysis of DEGs was mainly associated with the metabolic pathways of hormone signal transduction during petal color transitions. The DEGs were mainly involved in the auxin, cytokinin, gibberellin (GA), brassinosteroid (BR), jasmonic acid and abscisic acid (ABA) signal pathways. Accordingly, analyses of changes in indoleacetic acid, zeatin riboside, GA, BR, methyl jasmonate and ABA levels indicated that the color transitions are regulated by endogenous hormones. Conclusion: Our results provide new insight into the regulatory mechanisms underlying the petal color transitions during flower development process in L. japonica.
Clinical Manifestations of Liver and Renal Impairments in Asymptomatic, Moderate and Severe COVID-19 Patients of Madinah City of Saudi Arabia: A Retrospective Analysis
Authors: beigh Firdous , Syeed Nidda , Saeed Walaa , Alahmadey Ziab , Seedi Ibrahim 
Published: September 2020

Abstract
Background: Coronavirus disease (COVID-19) is a budding infectious disease that has affected various countries globally.The aim of this study was to analyze the effect of COVID-19 disease on liver and kidney functions and to determine their association with the severity and mortality of disease.Methods: A total of 100 confirmed COVID-19 adult patients from Madinah city of Saudi Arabia hospitalized between April 28, and June 30, 2020 were included,and categorized into asymptomatic,mild to moderate and severely ill patients.We analyzed the clinical status of liver and renal functioning in all of the three groups.Results: The majority of patients (51%) were diagnosed with mild to moderate disease, 27% of patients were severely ill and 22% of patients were asymptomatic.The liver and renal functional analysis showed that the severity of the COVID-19 patients were significantly associated with the kidney and renal impairments exhibiting higher levels of ALT, AST, Creatinine, Urea levels (P < 0.05). Furthermore, in this study, a novel association is found between high Na and Cl levels with the severely ill COVID-19 patients.Conclusion: We concluded from the present study that a significant percentage of COVID-19 patients continued to have a normal liver and renal function during the course of their disease. Nevertheless, severely ill COVID-19 patients were more prone to have abnormal liver and renal functions. During the course of treatment, the patients had a gradual normalization of their liver and kidney parameters and subsequently achieved a complete normal liver and renal functions upon discharge with no mortality.
Association between reduced preoperative serum albumin and prognosis in patients with adrenocortical carcinoma after primary resection: A retrospective study
Authors: Zhang Fuxun , Liu Zhihong , Liang Jiayu , Liu Shengzhuo , Wu Kan , Zhang Fan , Zhou Chuan , Lu Yiping , Zhu Yuchun , Wang Xianding 
Published: September 2020

Abstract
Purpose

To assess the correlation between preoperative serum albumin level and prognosis in patients with adrenocortical carcinoma after primary surgery.
Methods

We reviewed medical information of 71 included patients with diagnosis of ACC who underwent primary resection. Univariate and multivariate analysis were performed using Cox’s proportional hazards model. Survival analysis was conducted by Kaplan–Meier method with log-rank test. Receiver operating characteristic (ROC) curve and Jordan index were generated to explore cut-off value for serum albumin. Statistical significance was defined as P < 0.05.
Results

Among included patients, 33 patients (46.5%) relapsed at the end of follow-up, while 39 patients (54.9%) died. The median OS of overall included patients was 17 (range 1–104) months and median RFS was 10 (range 0–104) months. In univariate analysis, the albumin significantly associated with OS and RFS (HR:0.491, 95%CI: 0.260–0.930, P = 0.029 and HR:0.383, 95%CI: 0.192–0.766, P = 0.007, respectively). In multivariate analysis, the albumin level as an independent prognostic factor of OS was confirmed(HR:0.351, 95%CI: 0.126–0.982, P = 0.046). Meanwhile, the present
results indicates the trend that albumin might be an
independent predictor of RFS (
HR:0.423, 95%CI: 0.176–1.018, P = 0.055)
Conclusion

The preoperative serum albumin level is significantly correlated to prognosis of patients with ACC after primary resection. Reduced preoperative albumin level was proven to be a risk factor of clinical outcomes for ACC. Appropriate nutritional intervention prior to surgery may be beneficial to improve the prognosis of ACC patients.