bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Value of the Modified Model for End-Stage Liver Disease (MELD) Score Including albumin in acute heart failure
Authors: Liao Shengen , Lu Xinyi , Cheang Iokfai , Zhu Xu , Yin Ting , Yao Wenming , Zhang Haifeng , Li Xinli 
Published: December 2020

Abstract
Background: Liver and renal function evaluated by the model for end-stage liver disease (MELD) score, the MELD excluding the international normalized ratio (MELD_XI) score and the MELD including sodium (MELD_sodium) score have been considered predictors of adverse events for patients with acute heart failure (AHF). However, the prognostic value of the MELD including albumin (MELD_albumin) score in patients with AHF has not been assessed. Methods: A total of 466 patients with AHF were prospectively evaluated. We compared the accuracy of the 4 MELD score formulas using the time-dependent receiver operating characteristic (ROC) curve and corresponding areas under the curve (AUC). Results: During a median follow-up period of 34 months, 196 deaths occurred. In the fully adjusted Cox regression model, standardized hazard ratios with 95% confidence interval expressing the risk of all-cause mortality were 1.22 (1.06–1.40), 1.20 (1.04–1.39), 1.21 (1.05-1.41) and 1.23 (1.06–1.42) for MELD, MELD_XI, MELD_albumin and MELD_sodium scores, respectively. The MELD_albumin score showed the best prognostic accuracy (AUC = 0.658) for the prediction of long-term all-cause mortality, followed by the MELD_sodium score (AUC = 0.590), the MELD score (AUC = 0.580), and the MELD_XI score (AUC = 0.544). Conclusions: The MELD_albumin score performs more accurately than the MELD score and the other modified MELD scores for predicting the risk of all-cause mortality in patients with acute heart failure.
Enhanced specificity of high sensitivity somatic variant profiling in cell-free DNA via paired normal sequencing: design, validation, and clinical experience of the MSK-ACCESS liquid biopsy assay
Authors: Brannon Angela Rose , Jayakumaran Gowtham , Diosdado Monica , Patel Juber , Razumova Anna , Hu Yu , Meng Fanli , Haque Mohammad , Sadowska Justyna , Murphy Brian , Baldi Tessara , Johnson Ian , Ptashkin Ryan , Hasan Maysun , Sriniva Preethi , Rema Anoop Balakrishnan , Rijo Ivelise , Agarunov Aaron , Won Helen , Perera Dilmi , Brown David , Samoila Aliaksandra , Jing Xiaohong , Gedvilaite Erika , Yang Julie , Stephens Dennis , Dix Jenna-Marie , DeGroat Nicole , Nafa Khedoudja , Syed Aijazuddin , Li Alan , Lebow Emily , Bowman Anita , Ferguson Donna , Liu Ying , Mata Douglas , Sharma Rohit , Yang Soo-Ryum , Bale Tejus , Benhamida Jamal , Chang Jason , Dogan Snjezana , Hameed Meera , Hechtman Jaclyn , Moung Christine , Ross Dara , Vakiani Efsevia , Vanderbilt Chad , Yao JinJuan , Razavi Pedram , Smyth Lillian , Chandarlapaty Sarat , Iyer Gopa , Abida Wassim , Harding James , Krantz Benjamin , O'Reilly Eileen , Yu Helena , Li Bob , Rudin Charles , Diaz Luis , Solit David , Arcila Maria , Ladanyi Marc , Houck-Loomis Brian , Tsui Dana , Berger Michael , Zehir Ahmet , Benayed Ryma 
Published: December 2020

Abstract
Circulating cell-free DNA (cfDNA) from blood plasma of cancer patients can be used to interrogate somatic tumor alterations non-invasively or when adequate tissue is unavailable. We have developed and clinically implemented MSK-ACCESS (Analysis of Circulating cfDNA to Evaluate Somatic Status), an NGS assay for detection of very low frequency somatic alterations in select exons and introns of 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance and utility of MSK-ACCESS, we report results from the first 681 prospective blood samples (617 patients) that underwent clinical analysis to guide patient management. Somatic mutations, copy number, and/or structural variants were detected in 73% of the samples, and 56% of these circulating-tumor DNA (ctDNA) positive samples had clinically actionable alterations. The utilization of matched white blood cell sequencing allowed retention of somatic alterations while filtering out over 10,000 germline and clonal hematopoiesis variants, thereby greatly enhancing the specificity of the assay. Taken together, our experience illustrates the importance of analyzing a matched normal sample when interpreting cfDNA results and highlights the potential of cfDNA profiling to guide treatment selection, monitor treatment response, and identify mechanisms of treatment resistance.
Effectiveness of Joint 3+1 Malaria Strategy Along China-Myanmar Cross Border Areas
Authors: Lin Zu-rui , Li Shi-gang , Sun Xiao-dong , Guo Xiang-rui , Zheng Zhi , Yang Jie , Pian Hong-ru , Tian Peng , Chen Qi-yan , Sun Xiao-ying , Ding Chun-li , Duan Kai-xia , Chen Hong-wei , Bee Dakhidam Yaw , Zhou Hong-ning 
Published: December 2020

Abstract
Background: Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised the national malaria elimination goal. A pilot project on 3+1 strategy of joint cross-border malaria prevention and control was carried out in building border malaria buffer area in the both sides since 2017; Here, 3 was the three preventive lines in Yingjiang County to strengthen targeted measures of elimination malaria in China and +1 was a defined border area in Laiza City to adopt the integrated measures of malaria control in Myanmar.Methods: A retrospective analysis from 2015 to 2019 was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence in +1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An.Minimus were statistically significant indictors to assess the effect of the joint interventions.Results: In +1 area of Myanmar from 2015 to 2019, the average of annual parasite incidence was (59.11±40.73) / 1000 and plasmodium vivax accounted for 96.27 % of total confirmed cases. After the pilot project, the annual parasite incidence, microscopic parasite prevalence rate and density of An. Minimus reduced by 89%,100% and 93.93% respectively, but the submicroscopic parasite prevalence rate was no significant difference between the two surveys (p =0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The average of annual importation rate from 2015 to 2019 was (0.47±0.15)/1000. After the pilot project, it reduced by 53% of whole county, 67% of the first preventive line, 52% of the second preventive line and 36% of the third preventive line respectively. The density of An. Minimus in the first preventive line reduced by 94.51% and did not have significant difference between that of+1 area of Myanmar (Z value=-1.18，p value=0.24). Conclusion: The pilot project on 3+1 strategy has made remarkable effectiveness and a buffer area of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China. The combined use and expanded coverage of indoor residual spraying and long-lasting insecticidal nets (LLINs) was more effective than only use of LLINs in reducing the transmission of plasmodium vivax caused by An. Minimus. It is necessary to adopt submicroscopic infection interventions to eliminate potential sources of infection in Laiza City of Myanmar.
The effectiveness of E-learning in continuing medical education for Tuberculosis health workers: a quasi-experiment from China
Authors: Wang Ziyue , Zhang Lijie , Liu Yuhong , Jiang Weixi , Tang Shenglan , Liu Xiaoyun 
Published: December 2020

Abstract
ObjectiveTo evaluate the effectiveness of E-learning in continuing medical education (CME) programs for Tuberculosis (TB) health workers in terms of knowledge improvement and behaviour change, and provide policy recommendations based on the evidence from programs implemented in China.MethodsTB health professionals survey and in-depth interviews were conducted at provincial, prefectural, county, and primary care levels in the three project provinces. Difference-in-difference (DID) and multivariate linear regression models was employed to capture the effectiveness of knowledge improvement. Behaviour change was analysed using both qualitative and quantitative data.ResultsFor clinicians, pre-post data showed no significant difference in knowledge increases between pilot and non-pilot areas (pilot areas: +17 points vs. non-pilot areas: +18 points, p = 0.066). However, clinicians who attended the synchronous E-learning had an average score 7.3 points higher (p = 0.026) and an average knowledge score increase of 0.3 points (p = 0.028) for each event attended. Asynchronous E-learning did not have a significant impact among clinical doctors. For public health physicians, E-learning intervention had no significant effect on their knowledge score (DID model: pilot: +4 points vs. non-pilot: +9 points, p= 0.389, multivariate linear regression model: p = 0.161). For primary care workers, pre-post data showed a significantly higher score increase in the pilot areas (+10 points) than the non-pilot areas (+4 points, p = 0.005). Primary care workers who attended the E-learning activities had an average score 10.9 points higher (p<0.001) and an average increase of 1.8 points per training module attended (p = 0.002). More than half of participants (56.0% - 57.3%) agreed that they could apply what they learned to their practice, especially among well-educated health personnel from provincial level institutions. Traditional face-to-face training has no significant impact on all types of medical staff.ConclusionsE-learning interventions for TB clinical and primary care health workers were associated with higher TB knowledge level, and some participants have already started applying what they learned in their practice. However, public health physicians didn’t get much benefits from E-learning activities, probably due to the mismatch of training supply of & demand for training and environmental factors.
Urinary tract infections in culled sows from Greek herds: prevalence and associations between findings of histopathology, bacteriology and urinalysis
Authors: Cernat Mihaela , Skampardonis Vasilis , Papadopoulos Georgios A. , Kroustallas Fotios , Chalvatzi Sofia , Petridou Euanthia , Psychas Vassilios , Marouda Christina , Fortomaris Paschalis , Leontides Leonidas 
Published: December 2020

Abstract
Background
Urinary tract infections (UTI) of sows which include cystitis, which may progress to ureteritis and pyelonephritis affect their productivity, longevity and welfare. In this study we determined the prevalence of UTI by histopathology and bacteriology and investigated possible associations between histologically confirmed cystitis and the results of urinalysis and urine cultures in culled sows from three Greek farrow-to-finish herds.
Materials and methods
Routinely culled sows were included in the study. Their urinary bladders were collected from abattoirs and examined histopathologically. Furthermore, urinalysis and urine cultures were performed on urine samples aseptically collected from the bladders.
Results
Histologically confirmed cystitis was evident in 85/185 (45.94%) culled sows. Among those, 44 (51.76%) suffered from acute and 41 (48.24%) from chronic inflammation. The majority of the positive urine cultures were due to colonization of the urinary tract with E.coli, which was responsible for 55.81% of the total cases, followed by Staphylococcus spp. which caused 18.60% of the infections detected. Evidence of cystitis was associated with bacteriuria and sows with bacteriuria were 2.30 (p = 0.03, 95% CI: 1.10–4.83) times more likely to have histologically confirmed cystitis compared to sows with negative urine cultures. Bacteriuria was associated with proteinuria (p < 0.01), urine pH (p < 0.01) and presence of sediment (p < 0.01) in urine. Sows with proteinuria had 9.72 (2.63–35.88) times higher odds of bacteriuria than those without. Histologically defined cystitis was associated with proteinuria (p < 0.01) and increased urine pH (p < 0.01). Sows with proteinuria were 5.18 times (2.03–13.2) more likely to have histological lesions consistent with cystitis, than those without.
Conclusions
In the studied herds, UTI affected almost one out of two culled sows. Bacteriuria, which was more common among sows with UTI than those without, was mainly ascribed to members of the intestinal and environmental microbiota. Proteinuria and the existence of urine sediment which were associated with UTI may be proposed as likely on-farm predictors of UTI in live sows.
Evaluation of Methotrexate Toxicity and its Relationship with ABCB1 Genetic Polymorphism in Pediatric with Acute Lymphoblastic Leukemia
Authors: Moradveisi Borhan , Mohammadi Ebrahim , Ghaderi Ebrahim , Zamani Fatemeh , Zakaryaei Farima 
Published: December 2020

Abstract
Background: Acute lymphoblastic leukemia(ALL) is the most common type of hematologic malignancy in children. Based on COG protocol, one of the treatments for these children is methotrexate. Methotrexate has many complications in Pediatrics. Nowadays, the relationship between gene mutations and complications of each drug are discussed. This study aimed to evaluate the pharmacogenetics of methotrexate with emphasis on ABCB1 gene and its implications for the treatment of ALL children in Kurdistan province.Methods: Blood samples were obtained from children with ALL, and then DNA extraction and polymerase chain reaction (PCR) were performed with approximately 300μMol / μL of each direct primer in the final volume of 50µL. The PCR method was used to amplify the ABCB1 gene and the reaction products were identified by 0.5% agarose gel electrophoresis. The length of the PCR fragments was confirmed by observation by UV-Trans-illuminator. Moreover, blood and liver toxicity in all patients treated with methotrexate were measured by measuring leukocyte counts, platelets, neutrophil percentages, hemoglobin, alanine transaminase activity, and aspartate trans Aminase was evaluated.Results: 81 children with ALL, 45 males (55.5%) and 36 females with a mean age of 6.32 + 3.08 (y/o) were evaluated in this study. ABCB1 3435 C->T gene mutation frequency was 70.4% and the frequency of ABCB1 1199 G->A gene mutation was 4.9%.Frequency of gastrointestinal toxicity, leukopenia, anemia, thrombocytopenia, hepatotoxicity, neutropenia and renal toxicity were higher in patients with heterozygous and homozygous ABCB1 3435 C->T mutant polymorphisms than in patients with normal polymorphism, but the frequency of toxicity in patients with heterozygous and homozygous ABCB1 1199 G->A mutant polymorphisms were lower than patients with normal homozygous polymorphism, but these difference were not statistically significant.Conclusion: According to the results of our study, it can be concluded that methotrexate drug toxicity was higher in patients with ABCB1 3435 C->T gene mutation, but there was no significant correlation because of the low sample size. Furthermore it can be concluded that ABCB1 1199 G->A gene mutation may have a protective effect against the side effects of methotrexate, therefore it is recommended this hypothesis be tested in future studies.
Cancer-Associated Mutations Reveal a Novel Role for EpCAM as an Inhibitor of Cathepsin-L and Tumor Cell Invasion
Authors: Sankpal Narendra , Brown Taylor C. , Fleming Timothy P. , Herndon John M. , Amaravati Anusha A. , Loynd Allison N , Gillanders William E. 
Published: December 2020

Abstract
BackgroundEpithelial cell adhesion molecule (EpCAM) is a 40-kD type-I transmembrane protein that is frequently overexpressed in human epithelial cancers. Recent evidence implicates EpCAM in the regulation of oncogenic signaling pathways and epithelial-mesenchymal transition. Of note, multiple proteins with thyroglobulin-type-1 (TY-1) domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor invasion and metastasis.MethodsHuman cancer sequencing studies reveal that somatic EpCAM mutations are present in up to 5.1% of tested tumors form public database search. To determine how EpCAM mutations affect cancer biology we studied C66Y, a damaging TY-1 domain mutation identified in liver cancer, as well as 13 other cancer-associated EpCAM mutations. Using in-vitro and in-vivo models, immunoprecipitations and localizations we demonstrate EpCAM inhibits CTSL activity based mutations and thereby its localization.ResultsWe demonstrate that wild type (WT) EpCAM, but not C66Y EpCAM, inhibits CTSL activity in vitro, and the TY-1 domain of EpCAM is responsible for this inhibition. WT EpCAM, but not C66Y EpCAM, inhibits tumor cell invasion in vitro and lung metastasis in vivo. In an extended panel of human cancer cell lines, EpCAM expression is inversely correlated with CTSL activity. Previous studies have demonstrated that EpCAM germline mutations can prevent EpCAM from being expressed at the cell surface. We demonstrate that C66Y and multiple other EpCAM cancer-associated mutations prevent surface expression of EpCAM. Cancer-associated mutations that prevent EpCAM cell surface expression abrogate the ability of EpCAM to inhibit CTSL activity and tumor cell invasion. ConclusionsThese studies reveal a novel role for EpCAM as a CTSL inhibitor, confirm the functional relevance of multiple cancer-associated EpCAM mutations, and suggest a therapeutic vulnerability in cancers harboring EpCAM mutations.
Opposite Effects of the Triple Target (DNA-PK/PI3K/mTOR) Inhibitor PI-103 on the Radiation Sensitivity of Glioblastoma Cell Lines MO59K and MO59J Differing in DNA-PK and ATM Status
Authors: Djuzenova Cholpon S. , Fischer Thomas , Katzer Astrid , Sisario Dmitri , Korsa Tessa , Steussloff Gudrun , Sukhorukov Vladimir L. , Flentje Michael 
Published: December 2020

Abstract
Background: Radiotherapy is routinely used to combat glioblastoma multiforme (GBM). However, the treatment efficacy is often limited by the radioresistance of GBM cells.Methods: Two isogenic GBM lines MO59K and MO59J, differing in intrinsic radiosensitivity and mutational status of DNA-PK and ATM, were analyzed regarding their response to DNA-PK/PI3K/mTOR inhibition by PI-103 in combination with radiation. To this end we assessed colony-forming ability, induction and repair of DNA damage by γH2AX, expression of marker proteins, including those belonging to NHEJ and HR repair pathways, degree of apoptosis, autophagy, and cell cycle alterations.Results: We found that PI-103 radiosensitized MO59K cells but, surprisingly, it induced radiation resistance in MO59J cells. In MO59K cells, combined PI-103 and radiation treatment induced much higher γH2AX expression measured by Western blot as compared to MO59J. Another cell line-specific difference includes diminished expression of p53 in MO59J cells, which was further reduced by PI-103. Additionally, PI-103-treated MO59K cells exhibited an increased expression of the apoptosis marker cleaved PARP. In contrast, PI-103-treated MO59J cells showed an increased level of LC3BII, indicative of cytoprotective autophagy. Moreover, irradiation induced a strong G2 arrest in MO59J cells (~80% vs. ~50% in MO59K), which was, however, partially abolished by PI-103 thus allowing cell-cycle progression of a fraction of cells. In contrast, treatment with PI-103 increased the G2 fraction in irradiated MO59K cells.Conclusions: The triple-target inhibitor PI-103 exerted radiosensitization on MO59K cells, but, unexpectedly, caused radioresistance in the MO59J line, lacking DNA-PK. The difference is most likely due to low expression of the DNA-PK substrate p53 in MO59J cells, which was further reduced by PI-103. This led to less apoptosis as compared to drug-free MO59J cells and enhanced survival via partially abolished cell-cycle arrest. The findings suggest that the lack of DNA-PK-dependent NHEJ in MO59J line might be compensated by DNA-PK independent DSB repair via a yet unknown mechanism. Future research on an extended cell panel should focus on finding ways to enhance the radiosensitivity of cell lines with deficiencies in DNA-PK and ATM, the key proteins involved in the DNA damage response.
Reduction of Initial Dose of Enzalutamide does not Decrease the Incidence and Severity of Adverse Events in Castration-Resistant Prostate Cancer
Authors: Tsuzuki Shunsuke , Nakanishi Shotaro , Tamaki Mitsuyoshi , Oshiro Takuma , Miki Jun , Yamada Hiroki , Shimomura Tatsuya , Kimura Takahiro , Furuta Nozomu , Saito Seiichi , Egawa Shin 
Published: December 2020

Abstract
Background: There was no clear evidence whether the initial dose of enzalutamide affects the incidence of adverse events (AEs), and oncological outcome in patients with castration-resistant prostate cancer (CRPC). Methods: The clinical chart of 233 CRPC patients treated with enzalutamide was reviewed retrospectively. After 1:3 propensity score matching (PSM), 124 patients were classified to whom introduced with full dose of enzalutamide or whom with reduced dose and the oncological outcomes were compared. To investigate the independent predictive factors with progression-free survival (PFS) and overall survival (OS), univariate and multivariate Cox regression analyses were performed.Results: Of total, 190 CRPC patients initiated with full dose enzalutamide were younger and better performance status compared with 43 patients beginning with reduced dose. After PSM, the baseline characteristics were not different between full and reduced dose group. The incidence rate of patients with prostate specific antigen (PSA) decline of >90% in reduced dose group was significantly lower than that in full dose group (34.8% vs46.2%) (p-value 0.03). The incidence rates of AEs were not statistically different between reduced dose group (22.6%) and full dose group (34.4%) (p-value 0.24). On multivariate analyses, initial enzalutamide dose was not a predictive factor of PFS and OS. Conclusion: Initiating with reduced dose of enzalutamide did not significantly decrease the incidence rate of AEs, and it showed less PSA response rate. There is no clear rationale of treating with initial reduction of enzalutamide resulted in overcome incidence of AEs.