bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of putative drug resistant biomarkers in Plasmodium falciparum isolated from Ghanaian blood donors
Authors: Aninagyei Enoch , Duedu Kwabena Obeng , Rufai Tanko , Tetteh Comfort Dede , Chandi Margaretta Gloria , Ampomah Paulina , Acheampong Desmond Omane 
Published: July 2020

Abstract
Background
Plasmodium falciparum parasites, which could harbour anti-malaria drug resistance genes, are commonly detected in blood donors in malaria-endemic areas. Notwithstanding, anti-malaria drug resistant biomarkers have not been characterized in blood donors with asymptomatic P. falciparum infection.

Methods
A total of 771 blood donors were selected from five districts in the Greater Accra Region, Ghana. Each donor sample was screened with malaria rapid diagnostic test (RDT) kit and parasitaemia quantified microscopically. Dried blood spots from malaria positive samples were genotyped for P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum multi-drug resistance (Pfmdr1), P. falciparum dihydropteroate-synthetase (Pfdhps), P. falciparum dihydrofolate-reductase (Pfdhfr) and Kelch 13 propeller domain on chromosome 13 (Kelch 13) genes.

Results
Of the 771 blood donors, 91 (11.8%) were positive by RDT. Analysis of sequence reads indicated successful genotyping of Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes in 84.6, 81.3, 86.8, 86.9 and 92.3% of the isolates respectively. Overall, 21 different mutant haplotypes were identified in 69 isolates (75.8%). In Pfcrt, CVIET haplotype was observed in 11.6% samples while in Pfmdr1, triple mutation (resulting in YFN haplotype) was detected in 8.1% of isolates. In Pfdhfr gene, triple mutation resulting in IRNI haplotype and in Pfdhps gene, quintuple mutation resulting in AGESS haplotype was identified in 17.7% parasite isolates. Finally, five non-synonymous Kelch 13 alleles were detected; C580Y (3.6%), P615L (4.8%), A578S (4.8%), I543V (2.4%) and A676S (1.2%) were detected.

Conclusion
Results obtained in this study indicated various frequencies of mutant alleles in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes from P. falciparum infected blood donors. These alleles could reduce the efficacy of standard malaria treatment in transfusion-transmitted malaria cases. Incorporating malaria screening into donor screening protocol to defer infected donors is therefore recommended.
An improved deep learning approach and its applications on colonic polyp images detection
Authors: Wang Wei , Tian Jinge , Zhang Chengwen , Luo Yanhong , Wang Xin , Li Ji 
Published: July 2020

Abstract
Background
Colonic polyps are more likely to be cancerous, especially those with large diameter, large number and atypical hyperplasia. If colonic polyps cannot be treated in early stage, they are likely to develop into colon cancer. Colonoscopy is easily limited by the operator’s experience, and factors such as inexperience and visual fatigue will directly affect the accuracy of diagnosis. Cooperating with Hunan children’s hospital, we proposed and improved a deep learning approach with global average pooling (GAP) in colonoscopy for assisted diagnosis. Our approach for assisted diagnosis in colonoscopy can prompt endoscopists to pay attention to polyps that may be ignored in real time, improve the detection rate, reduce missed diagnosis, and improve the efficiency of medical diagnosis.

Methods
We selected colonoscopy images from the gastrointestinal endoscopy room of Hunan children’s hospital to form the colonic polyp datasets. And we applied the image classification method based on Deep Learning to the classification of Colonic Polyps. The classic networks we used are VGGNets and ResNets. By using global average pooling, we proposed the improved approaches: VGGNets-GAP and ResNets-GAP.

Results
The accuracies of all models in datasets exceed 98%. The TPR and TNR are above 96 and 98% respectively. In addition, VGGNets-GAP networks not only have high classification accuracies, but also have much fewer parameters than those of VGGNets.

Conclusions
The experimental results show that the proposed approach has good effect on the automatic detection of colonic polyps. The innovations of our method are in two aspects: (1) the detection accuracy of colonic polyps has been improved. (2) our approach reduces the memory consumption and makes the model lightweight. Compared with the original VGG networks, the parameters of our VGG19-GAP networks are greatly reduced.
Severe syndromic ID and skewed X-inactivation in a girl with NAA10 dysfunction and a novel heterozygous de novo NAA10 p.(His16Pro) variant - a case report
Authors: Bader Ingrid , McTiernan Nina , Darbakk Christine , Boltshauser Eugen , Ree Rasmus , Ebner Sabine , Mayr Johannes A. , Arnesen Thomas 
Published: July 2020

Abstract
Background
NAA10 is the catalytic subunit of the major N-terminal acetyltransferase complex NatA which acetylates almost half the human proteome. Over the past decade, many NAA10 missense variants have been reported as causative of genetic disease in humans. Individuals harboring NAA10 variants often display variable degrees of intellectual disability (ID), developmental delay, and cardiac anomalies. Initially, carrier females appeared to be oligo- or asymptomatic with X-inactivation pattern skewed towards the wild type allele. However, recently it has been shown that NAA10 variants can cause syndromic or non-syndromic intellectual disability in females as well. The impact of specific NAA10 variants and the X-inactivation pattern on the individual phenotype in females remains to be elucidated.

Case presentation
Here we present a novel de novo NAA10 (NM_003491.3) c.[47A > C];[=] (p.[His16Pro];[=]) variant identified in a young female. The 10-year-old girl has severely delayed motor and language development, disturbed behavior with hyperactivity and restlessness, moderate dilatation of the ventricular system and extracerebral CSF spaces. Her blood leukocyte X-inactivation pattern was skewed (95/5) towards the maternally inherited X-chromosome. Our functional study indicates that NAA10 p.(H16P) impairs NatA complex formation and NatA catalytic activity, while monomeric NAA10 catalytic activity appears to be intact. Furthermore, cycloheximide experiments show that the NAA10 H16P variant does not affect the cellular stability of NAA10.

Discussion and conclusions
We demonstrate that NAA10 p.(His16Pro) causes a severe form of syndromic ID in a girl most likely through impaired NatA-mediated Nt-acetylation of cellular proteins. X-inactivation analyses showed a skewed X-inactivation pattern in DNA from blood of the patient with the maternally inherited allele being preferentially methylated/inactivated.
Risk of chronic kidney disease in patients with kidney stones—a nationwide cohort study
Authors: Chuang Tzung-Fang , Hung Hung-Chang , Li Shu-Fen , Lee Mei-Wen , Pai Jar-Yuan , Hung Chin-Tun 
Published: July 2020

Abstract
Background
Chronic kidney disease (CKD) and kidney stones are common in Taiwan; in particular, CKD has a high prevalence but low self-awareness rate. CKD-related risk factors such as diabetes, hypertension, and nephrotoxic drugs are well-known and uncontested; however, kidney stones are relatively less studied and easily overlooked as a risk factor. The objective of this study was to investigate whether kidney stones are a risk factor for CKD.

Methods
We conducted a nationwide population-based matched cohort study to assess the risk of incident CKD in people with kidney stones. Data on incident stones formers in the year 2001—excluding those with a history of CKD—were obtained from Taiwan’s National Health Insurance database. Stone formers were matched (1:4) to control subjects according to sex, age, and index date. The total observation period of the study was 10 years, and the primary end-point was the occurrence of CKD. Student’s t-test and Chi-squared test were used to compare continuous and categorical data, respectively. Logistic regression was used to calculate the odds ratio of kidney stone patients with incident CKD relative to the control group. Cox proportional hazard regression model was used to obtain the hazard ratio for development of incident CKD among patients with kidney stones.

Results
The incidence of CKD in the kidney stone cohort was 11.2%, which was significantly higher than that of the control group (P < .001). Survival analysis showed that the stones cohort was 1.82 times more likely to experience CKD than the controls. Age, sex, hypertension, diabetes mellitus, and hyperlipidemia increased the risk of CKD incidence (1.04, 1.27, 1.55, 3.31, and 1.25 times, respectively).

Conclusion
Kidney stones are a definite risk factor for CKD; therefore, patients with stones are suggested to undergo regular renal function monitoring and receive appropriate treatment to avoid CKD.
Efficacy of different urinary uric acid indicators in patients with chronic kidney disease
Authors: Guan Haochen , Zheng Yuqi , Zhou Xun , Xu Ying , Fu Chensheng , Xiao Jing , Ye Zhibin 
Published: July 2020

Abstract
Background
Mounting studies have shown that hyperuricemia is related to kidney diseases through multiple ways. However, the application of urinary uric acid indicators in patients with reduced renal function is not clear. In this study, we aim to determine the effects of renal function on various indicators reflecting uric acid levels in patients with chronic kidney disease (CKD).

Methods
Anthropometric and biochemical examinations were performed in 625 patients with CKD recruited from Dept of Nephrology of Huadong hospital affiliated to Fudan University. Multiple regression analyses were used to study correlations of the estimated glomerular filtration rate (eGFR) with serum uric acid (SUA) and renal handling of uric acid. For further study, smooth curve plots and threshold effect analyses were applied to clarify associations between renal function and uric acid levels.

Results
The nonlinear relationships were observed between eGFR and urinary uric acid indicators. The obvious inflection points were observed in smooth curve fitting of eGFR and fractional excretion of uric acid (FEur), excretion of uric acid per volume of glomerular filtration (EurGF). In subsequent analyses where levels of eGFR< 15 mL/min/1.73m2 were dichotomized (CKD5a/CKD5b), patients in the CKD5a showed higher levels of FEur and EurGF while lower levels of urinary uric acid excretion (UUA), clearance of uric acid (Cur) and glomerular filtration load of uric acid (FLur) compared with CKD5b group (all P < 0.05). And there was no significant difference of SUA levels between two groups. On the other hand, when eGFR< 109.9 ml/min/1.73 m2 and 89.1 ml/min/1.73 m2, the resultant curves exhibited approximately linear associations of eGFR with Cur and FLur respectively.

Conclusion
FEur and EurGF showed significantly compensatory increases with decreased renal function. And extra-renal uric acid excretion may play a compensatory role in patients with severe renal impairment to maintain SUA levels. Moreover, Cur and FLur may be more reliable indicators of classification for hyperuricemia in CKD patients.
RETRACTED ARTICLE: Invasion inhibition in pancreatic cancer using the oral iron chelating agent deferasirox
Authors: Amano Shogo , Kaino Seiji , Shinoda Shuhei , Harima Hirofumi , Matsumoto Toshihiko , Fujisawa Koichi , Takami Taro , Yamamoto Naoki , Yamasaki Takahiro , Sakaida Isao 
Published: July 2020

Abstract
Background
Iron is required for cellular metabolism, and rapidly proliferating cancer cells require more of this essential nutrient. Therefore, iron regulation may well represent a new avenue for cancer therapy. We have reported, through in vitro and in vivo research involving pancreatic cancer cell lines, that the internal-use, next-generation iron chelator deferasirox (DFX) exhibits concentration-dependent tumour-suppressive effects, among other effects. After performing a microarray analysis on the tumour grafts used in that research, we found that DFX may be able to suppress the cellular movement pathways of pancreatic cancer cells. In this study, we conducted in vitro analyses to evaluate the effects of DFX on the invasive and migratory abilities of pancreatic cancer cells.

Methods
We used pancreatic cancer cell lines (BxPC-3, Panc-1, and HPAF II) to examine the efficacy of DFX in preventing invasion in vitro, evaluated using scratch assays and Boyden chamber assays. In an effort to understand the mechanism of action whereby DFX suppresses tumour invasion and migration, we performed G-LISA to examine the activation of Cdc42 and Rac1 which are known for their involvement in cellular movement pathways.

Results
In our scratch assays, we observed that DFX-treated cells had significantly reduced invasive ability compared with that of control cells. Similarly, in our Boyden chamber assays, we observed that DFX-treated cells had significantly reduced migratory ability. After analysis of the Rho family of proteins, we observed a significant reduction in the activation of Cdc42 and Rac1 in DFX-treated cells.
Conclusions: DFX can suppress the motility of cancer cells by reducing Cdc42 and Rac1 activation. Pancreatic cancers often have metastatic lesions, which means that use of DFX will suppress not only tumour proliferation but also tumour invasion, and we expect that this will lead to improved prognoses.
Efficacy and safety of nivolumab for advanced gastric cancer patients with poor performance statuses
Authors: Matsumoto Toshihiko , Yamamoto Yosuke , Kuriona Yusuke , Okazaki Ukyo , Kimura Shogo , Miura Kou , Tsuduki Takao , Watanabe Takanori , Mastumoto Yusuke , Takatani Masahiro 
Published: July 2020

Abstract
Background
Nivolumab has changed the treatment of advanced gastric cancer (AGC). Nivolumab shows better outcomes compared to best supportive care among AGC patients who received at least two prior regimens. However, there are no reliable data regarding AGC patients with poor performance status (PS) who received nivolumab. We investigated the efficacy and safety of nivolumab among AGC patients with poor PS.

Methods
We retrospectively collected clinicopathologic data from patients with AGC who underwent nivolumab monotherapy at our institution from October 2017 to June 2019.

Results
Forty-nine AGC patients who received nivolumab were assessed. Twenty-seven patients had PS 0 or 1 (Good group) and 22 had PS 2 or 3 (Poor group). The median progression-free survival and overall survival durations were 2.0 and 6.0 months in the Good group, respectively, and 1.2 and 2.8 months in the Poor group, respectively. The overall survival was significantly shorter in the Poor group (6.0 vs 2.8 months, p = 0.0255). The disease control rates were 23 and 9% in the Good and Poor groups, respectively. Thirty-three percent of patients experienced immune-related adverse events in the Good group, and 18% in the Poor group.

Conclusion
Nivolumab is feasible but insufficient as third- or later-line treatment for AGC patients with poor PS.
Intrinsic patient factors predictive of inpatient rehabilitation facility discharge following primary total knee arthroplasty: a systematic review and meta-analysis
Authors: Sattler Larissa , Hing Wayne , Rathbone Evelyne , Vertullo Christopher 
Published: July 2020

Abstract
Background
Total Knee Arthroplasty (TKA) reduces pain and improves function in those suffering from severe osteoarthritis. A significant cost of TKA is post-acute care, however, current evidence suggests that discharge to an Inpatient Rehabilitation Facility (IRF) has inferior outcomes to home discharge, with no greater benefit in physical function. Only individual studies have investigated TKA patient characteristics predictive of discharge destination, therefore, the aim is to systematically review the literature and meta-analyse intrinsic patient factors predictive of IRF discharge. If predictive factors are known, then early discharge planning and intervention strategies could be implemented.

Methods
Databases PubMed, CINAHL, Embase, Cochrane, and Pedro were searched up to October 2019 for all studies investigating pre-operative intrinsic patient factors predictive of IRF discharge. For assessing the methodological quality of included studies, the Quality In Prognosis Studies (QUIPS) tool was used. Statistical analysis and graphical reporting were conducted in R statistical software. To assess the effect of predictors of discharge destination, odds ratios with the corresponding 95%CI were extracted from the results of univariate and multivariable analyses.

Results
A total of 9 articles published between 2011 to 2018 with 218,151 TKA patients were included. Of the 13 intrinsic patient factors reported, 6 met the criteria for synthesised review: age, obesity, comorbidity, gender, SF-12/VR-12 survey, and smoking. Due to the heterogeneity of statistical analysis and reporting 2 variables could undergo meta-analysis, gender and smoking. Female gender increased the likelihood of IRF discharge by 78% (OR = 1.78; 95%CI = 1.43–2.20; I2 = 33.3%), however, the relationship between smoking status and discharge destination was less certain (OR = 0.80; 95%CI = 0.42–1.50; I2 = 68.5%).

Conclusion
In this systematic literature review and meta-analysis female gender was shown to be predictive of IRF discharge after total knee arthroplasty. There was also a trend for those of older age and increased comorbidity, as measured by the Charlson Comorbidity Index, or the severely obese to have an increased likelihood of IRF discharge. The marked heterogeneity of statistical methods and reporting in existing literature made pooled analysis challenging for intrinsic patient factors predictive of IRF discharge after TKA. Further, high quality studies of prospective design on predictive factors are warranted, to enable early discharge planning and optimise resource allocation on post-acute care following TKA.

Trial registration
This review was registered with PROSPERO (CRD42019134422).
Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study
Authors: Aasbrenn Martin , Lydersen Stian , Farup Per G 
Published: July 2020

Abstract
Background
Zonulin is a biomarker of impaired intestinal permeability, which has been associated with various disorders. The primary aim was to study serum zonulin (s-zonulin) in individuals with morbid obesity before and after a conservative weight loss intervention followed by bariatric surgery. The secondary aims were to explore predictors of s-zonulin, and the associations between the changes of the predictors and changes in s-zonulin, and to compare the associations in the two treatment periods.

Methods
Individuals with morbid obesity were included. Data before any weight loss interventions, after a 6 months’ conservative weight loss intervention, and 6 months after bariatric surgery were used. S-zonulin was measured with an ELISA method from Immundiagnostik AB, Bensheim, Germany. Data were analysed with mixed models.

Results
The mean body mass index was 42.1 kg/m2 (SD 3.8) at inclusion and was reduced to 38.7 kg/m2 (SD 3.8) and 29.8 kg/m2 (SD 3.8) after the conservative treatment and bariatric surgery respectively. S-zonulin was 63 ng/mL (SD 32) at inclusion and was reduced with 19 ng/ml (95% CI 12 to 26, p < 0.001) after conservative treatment and 11 ng/ml (95% CI 0 to 21, p = 0.04) after bariatric surgery. At inclusion, s-zonulin was significantly associated with factors including p-glucose (B = 2.21, 95% CI 1.09 to 3.33, p < 0.001), c-reactive protein (B = 1.02, 95% CI 0.45 to 1.58, p < 0.001) and the intake of proteins (B = 0.23, 95% CI 0.08 to 0.38, p = 0.003) and non-nutritive sweeteners (B = 0.68, 95% CI 0.19 to 1.17, p = 0.007). The reduction in s-zonulin after the conservative weight loss intervention was significantly associated with improvement in diarrhoea (B = 6.6, 95% CI  1.3 to 11.8, p = 0.02), HbA1c (B = 9.7, 95% CI 1.1 to 18.3, p = 0.03), p-glucose (B = 3.5, 95% CI 1.2 to 5.9, p = 0.004) and gamma-GT (B = 0.28, 95% CI 0.09 to 0.47, p = 0.004), but not associated with the change in body mass index (B = 0.9, 95% CI − 1.5 to 3.3, p = 0.46).

Conclusions
S-zonulin was markedly reduced after the conservative weight loss intervention, and further reduced after bariatric surgery. The reduction in s-zonulin was associated with improvement of diarrhoea, markers of glucose intolerance and liver disease, but not associated with the change in body mass index.
Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population
Authors: Rivera-León Edgar Alfonso , Llamas-Covarrubias Mara Anaís , Sánchez-Enríquez Sergio , Martínez-López Erika , González-Hita Mercedes , Llamas-Covarrubias Iris Monserrat 
Published: July 2020

Abstract
Background
Type 2 diabetes mellitus (T2D) is the most frequent type of diabetes. It has a multifactorial etiology, affecting millions of people worldwide. Ghrelin gene (GHRL) encodes the ghrelin peptide, which promotes food intake, induces body weight and adipogenesis. Several single nucleotide polymorphisms (SNPs) in GHRL gene have been associated with metabolic diseases. A protective effect of the Leu72Met (rs696217) polymorphism has been described for T2D in some populations, but this effect seems to depend on the ethnicity of the patients studied.

Methods
The aim of this study was to investigate the association between the GHRL Leu72Met (rs696217) SNP with the development of T2D and serum ghrelin levels in a Western Mexican population. We performed a case-control study in which we included 284 subjects (159 with previous T2D diagnosis and 125 control subjects (CS)). Leu72Met SNP was genotyped by using PCR-RFLPs technique. Serum ghrelin levels were measured using a commercial enzyme immunoassay. Genotypic and allelic distributions were compared using Chi square test. Student T-test and Mann-Whitney U test were used to compare quantitative variables. Odds ratio (OR) was used to evaluate the association between alleles or genotypes and T2D. Multiple and logistic regression models were performed for adjustment. A two-tailed p-value ≤0.05 was considered statistically significant.

Results
Leu72Leu genotype was more frequent among T2D compared to CS (p < 0.05). After adjusting for age and body composition, there was a significant protective effect of the 72Met allele for T2D development (OR 0.40 IC 95% 0.23–0.70; p ≤ 0.001). Fasting serum ghrelin levels were lower in T2D than CS (p ≤ 0.0001) irrespective of age, body weight and BMI. No associations were found between genotypes and ghrelin serum levels in our population.

Conclusions
The GHRL 72Met allele decreases susceptibility for T2D development in a Western Mexican population. Serum ghrelin levels are lower in T2D independently of Leu72Met polymorphism genotype.