bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of risk factors for urinary colonization in patients with the double J catheter
Authors: Saouli Amine , Karmouni Tarik , El Khader Khalid , Koutani Abdellatif , Andaloussi Ahmed Iben Attya 
Published: February 2021

Abstract
Background
The aim of this study is to evaluate the prevalence of urinary colonization in patients with the JJ stent and to define the predictive factors associated with this colonization.

Methods
This is a monocentric prospective study (between January 2013 and April 2017), conducted in the department of Urology B of Ibn Sina Hospital in Rabat. One hundred and forty-five double ureteral stents carried by 120 patients, 25 of which had bilateral double ureteral stent, were examined. The bacteriological profile of the urine of our patients was followed by the completion of an initial urine examination and another at the time of the removal of the JJ. The comparison of the means was made by the Student's test and the Mann–Whitney test for continuous variables and by the KHI-2 test and Fisher's test for qualitative variables. The threshold of significance is set at 0.05.

Results
The rate of colonization of JJ stent was 35.8% (43 out of 120). The urinary colonization rate was 31.7% (38 out of 120). Average time of indwelling of JJ stent was 90 days.
On double ureteral stent culture, we identified Escherichia Coli as the most predominant colonizing pathogen (47.3% of probes) followed by Enterococcus faecalis and Klebsiella pneumoniae (18.4% and 15.8%, respectively). 11.5% of colonized patients developed infectious complications (5 out of 43) and have been treated successfully except a patient who died from septic shock.

In univariate analysis, diabetes mellitus (p = 0.007, OR = 4.1, CI = 1.46–11.48), urgent establishment of JJ (p = 0.03, OR = 4.61; IC = 1.08–19.6) and time of indwelling of the JJ (p = 0.05, OR = 1.89, CI = 0.95–3.77) were the predictive factors for urinary colonization in patients with JJ. In multivariate analysis, these three factors were statistically associated with this risk: diabetes mellitus (p = 0.005, OR = 0.23, CI = 0.08–0.64), the urgent establishment of JJ (p = 0.05, OR = 0.26, CI = 0, 06–1.04) and time of indwelling of the JJ more than 30 days (p = 0.007, OR = 4.29, CI = 1.49–12.37).

Conclusion
The prevalence of urinary colonization in patients with the double J stent was 31.7%. Diabetes mellitus, time of indwelling of the JJ more than 30 days and urgent JJ ​​ establishment are associated with a higher risk of these urinary colonizations.
Strict monitoring is therefore recommended in patients with these risk factors. These results should be confirmed by multicenter and randomized studies to analyze the development of urinary tract infections in colonized patients.
The saga of the peer review process: author’s perspective
Authors: Agrawal Mayank , Suhani Suhani 
Published: February 2021

AbstractPeer review system is the cornerstone of scientific publishing. The indented process is not as tedious as it has become, mainly due to the time delay, unavailability of expert reviewers, and the callous attitude of some. While there have been articles explaining the whole process and expressing the editor’s viewpoints on the peer review system, we wish to present the author’s perspective on this system.
Sparse data embedding and prediction by tropical matrix factorization
Authors: Omanović Amra , Kazan Hilal , Oblak Polona , Curk Tomaž 
Published: February 2021

AbstractBackgroundMatrix factorization methods are linear models, with limited capability to model complex relations. In our work, we use tropical semiring to introduce non-linearity into matrix factorization models. We propose a method calledSparse Tropical Matrix Factorization() for the estimation of missing (unknown) values in sparse data.ResultsWe evaluate the efficiency of the method on both synthetic data and biological data in the form of gene expression measurements downloaded from The Cancer Genome Atlas (TCGA) database. Tests on unique synthetic data showed that approximation achieves a higher correlation than non-negative matrix factorization (), which is unable to recover patterns effectively. On real data, outperforms on six out of nine gene expression datasets. While assumes normal distribution and tends toward the mean value, can better fit to extreme values and distributions.Conclusionis the first work that uses tropical semiring on sparse data. We show that in certain cases semirings are useful because they consider the structure, which is different and simpler to understand than it is with standard linear algebra.
A base measure of precision for protein stability predictors: structural sensitivity
Authors: Caldararu Octav , Blundell Tom L. , Kepp Kasper P. 
Published: February 2021

Abstract
Background
Prediction of the change in fold stability (ΔΔG) of a protein upon mutation is of major importance to protein engineering and screening of disease-causing variants. Many prediction methods can use 3D structural information to predict ΔΔG. While the performance of these methods has been extensively studied, a new problem has arisen due to the abundance of crystal structures: How precise are these methods in terms of structure input used, which structure should be used, and how much does it matter? Thus, there is a need to quantify the structural sensitivity of protein stability prediction methods.

Results
We computed the structural sensitivity of six widely-used prediction methods by use of saturated computational mutagenesis on a diverse set of 87 structures of 25 proteins. Our results show that structural sensitivity varies massively and surprisingly falls into two very distinct groups, with methods that take detailed account of the local environment showing a sensitivity of ~ 0.6 to 0.8 kcal/mol, whereas machine-learning methods display much lower sensitivity (~ 0.1 kcal/mol). We also observe that the precision correlates with the accuracy for mutation-type-balanced data sets but not generally reported accuracy of the methods, indicating the importance of mutation-type balance in both contexts.

Conclusions
The structural sensitivity of stability prediction methods varies greatly and is caused mainly by the models and less by the actual protein structural differences. As a new recommended standard, we therefore suggest that ΔΔG values are evaluated on three protein structures when available and the associated standard deviation reported, to emphasize not just the accuracy but also the precision of the method in a specific study. Our observation that machine-learning methods deemphasize structure may indicate that folded wild-type structures alone, without the folded mutant and unfolded structures, only add modest value for assessing protein stability effects, and that side-chain-sensitive methods overstate the significance of the folded wild-type structure.
Identification and elimination of genomic regions irrelevant for magnetosome biosynthesis by large-scale deletion in Magnetospirillum gryphiswaldense
Authors: Zwiener Theresa , Mickoleit Frank , Dziuba Marina , Rückert Christian , Busche Tobias , Kalinowski Jörn , Faivre Damien , Uebe René , Schüler Dirk 
Published: February 2021

Abstract
Background
Magnetosome formation in the alphaproteobacterium Magnetospirillum gryphiswaldense is controlled by more than 30 known mam and mms genes clustered within a large genomic region, the ‘magnetosome island’ (MAI), which also harbors numerous mobile genetic elements, repeats, and genetic junk. Because of the inherent genetic instability of the MAI caused by neighboring gene content, the elimination of these regions and their substitution by a compact, minimal magnetosome expression cassette would be important for future analysis and engineering. In addition, the role of the MAI boundaries and adjacent regions are still unclear, and recent studies indicated that further auxiliary determinants for magnetosome biosynthesis are encoded outside the MAI. However, techniques for large-scale genome editing of magnetic bacteria are still limited, and the full complement of genes controlling magnetosome formation has remained uncertain.

Results
Here we demonstrate that an allelic replacement method based on homologous recombination can be applied for large-scale genome editing in M. gryphiswaldense. By analysis of 24 deletion mutants covering about 167 kb of non-redundant genome content, we identified genes and regions inside and outside the MAI irrelevant for magnetosome biosynthesis. A contiguous stretch of ~ 100 kb, including the scattered mam and mms6 operons, could be functionally substituted by a compact and contiguous ~ 38 kb cassette comprising all essential biosynthetic gene clusters, but devoid of interspersing irrelevant or problematic gene content.

Conclusions
Our results further delineate the genetic complement for magnetosome biosynthesis and will be useful for future large-scale genome editing and genetic engineering of magnetosome biosynthesis.
The relationship between seasonality, latitude and tuberculosis notifications in Pakistan
Authors: Butt Mohsin F. , Younis Sidra , Wu Zhenqiang , Hadi Syed H. , Latif Abdullah , Martineau Adrian R. 
Published: February 2021

AbstractBackgroundPakistan ranks amongst the top 20 highest burden tuberculosis (TB) countries in the world. Approximately 369,548 cases of TB (all forms) were notified in 2018, with an estimated incidence of 265 per 100,000 people per year. In other settings, TB has been shown to demonstrate seasonal variation, with higher incidence in the spring/summer months and lower incidence in the autumn/winter; the amplitude of seasonal variation has also been reported to be higher with increasing distance from the equator.MethodsNotifications of newly-diagnosed pulmonary and extrapulmonary TB cases were obtained for 139 districts in Pakistan from 2011 to 2017. Data were provided by the Pakistan National TB Control Programme, Islamabad, Pakistan. Statistical analyses were performed to determine whether there was seasonal variation in TB notifications in Pakistan; whether the amplitude of seasonal variation in TB notifications varied according to latitude; whether the amplitude of seasonal variation of TB in Pakistan differed between extrapulmonary TB vs. pulmonary TB. To assess the quarterly seasonality of TB, we used the X-13-ARIMA-SEATS seasonal adjustment programme from the United States Census Bureau. The mean difference and corresponding 95% confidence intervals of seasonal amplitudes between different latitudes and clinical phenotype of TB were estimated using linear regression.ResultsTB notifications were highest in quarter 2, and lowest in quarter 4. The mean amplitude of seasonal variation was 25.5% (95% CI 25.0 to 25.9%). The mean seasonal amplitude of TB notifications from latitude 24.5°N- < 26.5°N was 29.5% (95% CI 29.3 to 29.7%) whilst the mean seasonal amplitude of TB notifications from latitude 34.5°N - < 36.5°N was 21.7% (95% CI 19.6 to 23.9%). The mean seasonal amplitude of TB notifications across Pakistan between latitudes 24.5°N to 36.5°N reached statistically significant difference (p < 0.001). The amplitude of seasonal variation was greater for extrapulmonary TB (mean seasonal amplitude: 32.6, 95% CI 21.4 to 21.8%) vs. smear positive pulmonary TB mean seasonal amplitude: 21.6, 95% CI 32.1 to 33.1%),p < 0.001.ConclusionTB notifications in Pakistan exhibit seasonal variation with a peak in quarter 2 (April–June) and trough in quarter 4 (October–December). The amplitude of seasonality decreases with increasing latitude, and is more pronounced for extrapulmonary than for pulmonary TB.
Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa
Authors: Obasa Adetayo Emmanuel , Ambikan Anoop T. , Gupta Soham , Neogi Ujjwal , Jacobs Graeme Brendon 
Published: February 2021

Abstract
Background
HIV-1C has been shown to have a greater risk of virological failure and reduced susceptibility towards boosted protease inhibitors (bPIs), a component of second-line combination antiretroviral therapy (cART) in South Africa. This study entailed an evaluation of HIV-1 drug resistance-associated mutations (RAMs) among minor viral populations through high-throughput sequencing genotypic resistance testing (HTS-GRT) in patients on the South African national second-line cART regimen receiving bPIs.

Methods
During 2017 and 2018, 67 patient samples were sequenced using high-throughput sequencing (HTS), of which 56 samples were included in the final analysis because the patient’s treatment regimen was available at the time of sampling. All patients were receiving bPIs as part of their cART. Viral RNA was extracted, and complete pol genes were amplified and sequenced using Illumina HiSeq2500, followed by bioinformatics analysis to quantify the RAMs according to the Stanford HIV Drug Resistance Database.

Results
Statistically significantly higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to non-nucleoside reverse transcriptase inhibitors (9%; 5/56; p = 0.042) and integrase inhibitor RAM (4%; 2/56; p = 0.002). The majority of the drug resistance mutations in the minor viral quasispecies were observed in the V82A mutation (n = 13) in protease and K65R (n = 5), K103N (n = 7) and M184V (n = 5) in reverse transcriptase.

Conclusions
HTS-GRT improved the identification of PI and reverse transcriptase inhibitor (RTI) RAMs in second-line cART patients from South Africa compared to the conventional GRT with ≥20% used in Sanger-based sequencing. Several RTI RAMs, such as K65R, M184V or K103N and PI RAM V82A, were identified in < 20% of the population. Deep sequencing could be of greater value in detecting acquired resistance mutations early.
Monitoring HIV testing and pre-exposure prophylaxis information seeking by combining digital and traditional data
Authors: Johnson Derek C. , Nobles Alicia L. , Caputi Theodore L. , Liu Michael , Leas Eric C. , Strathdee Steffanie A. , Smith Davey M. , Ayers John W. 
Published: February 2021

Abstract
Background
Public health is increasingly turning to non-traditional digital data to inform HIV prevention and control strategies. We demonstrate a parsimonious method using both traditional survey and internet search histories to provide new insights into HIV testing and pre-exposure prophylaxis (PrEP) information seeking that can be easily extended to other settings.

Method
We modeled how US internet search volumes from 2019 for HIV testing and PrEP compared against expected search volumes for HIV testing and PrEP using state HIV prevalence and socioeconomic characteristics as predictors. States with search volumes outside the upper and lower bound confidence interval were labeled as either over or under performing. State performance was evaluated by (a) Centers for Disease Control and Prevention designation as a hotspot for new HIV diagnoses (b) expanding Medicaid coverage.

Results
Ten states over-performed in models assessing information seeking for HIV testing, while eleven states under-performed. Thirteen states over-performed in models assessing internet searches for PrEP information, while thirteen states under-performed. States that expanded Medicaid coverage were more likely to over perform in PrEP models than states that did not expand Medicaid coverage. While states that were hotspots for new HIV diagnoses were more likely to over perform on HIV testing searches.

Conclusion
Our study derived a method of measuring HIV and PrEP information seeking that is comparable across states. Several states exhibited information seeking for PrEP and HIV testing that deviated from model assessments. Statewide search volume for PrEP information was affected by a state’s decision to expand Medicaid coverage. Our research provides health officials with an innovative way to monitor statewide interest in PrEP and HIV testing using a metric for information-seeking that is comparable across states.
Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP
Authors: Santana Bárbara Brasil , Queiroz Maria Alice Freitas , Cerveira Rodrigo Arcoverde , Rodrigues Claudia Mendonça , da Silva Graça Amoras Ednelza , da Costa Carlos Araújo , de Sousa Maisa Silva , Ishak Ricardo , Goulart Luiz Ricardo , Vallinoto Antonio Carlos Rosário 
Published: February 2021

Abstract
Background
Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients.

Methods
This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA).

Results
ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000).

Conclusions
Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.
Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study
Authors: Yu Libo , Shi Qingtao , Jin Yan , Liu Zhixin , Li Jiaxin , Sun Wenzhou 
Published: February 2021

Abstract
Background
Activation of autophagy flux contributed to resistance of breast cancer (BC) cells to current chemotherapeutic drugs, which seriously limited their therapeutic efficacy and facilitated BC recurrence in clinic. However, the detailed mechanisms are still not fully understood. In the present study, we identified that inactivation of AMPK-ULK1 signaling cascade mediated protective autophagy sensitized BC cells to doxorubicin in vitro.

Methods
Cell counting kit-8 (CCK-8) assay and colony formation assay were performed to evaluate cell proliferation abilities. Trypan blue staining assay was used to examine cell viability, and Annexin V-FITC/PI double staining method was conducted to determine cell apoptosis. The autophagosomes in BC cells were observed and photographed by electronic microscope (EM). Western Blot analysis was employed to examine genes expressions at protein levels.

Results
The parental doxorubicin-sensitive BC (DS-BC) cells were exposed to increasing concentrations of doxorubicin to establish doxorubicin-resistant BC (DR-BC) cells, and the DR-BC cells were much more resistant to high-dose doxorubicin treatment compared to the DS-BC cells. Interestingly, high-dose doxorubicin specifically increased LC3B-II/I ratio, promoted autophagosomes formation and decreased p62 expression levels to facilitate autophagy in DR-BC cells, instead of DS-BC cells, and the autophagy inhibitor 3-methyladenine (3-MA) enhanced the cytotoxic effects of high-dose doxorubicin on DR-BC cells. In addition, we proved that high-dose doxorubicin triggered protective autophagy in DR-BC cells by activating AMPK-ULK1 pathway. Functionally, high-dose doxorubicin increased the expression levels of phosphorylated AMPK (p-AMPK) and ULK1 (p-ULK1) to activate AMPK-ULK1 pathway in DR-BC cells, and the inhibitors for AMPK (compound C) and ULK1 (SBI-0206965) blocked autophagy to promote cell death and slow down cell growth in DR-BC cells treated with high-dose doxorubicin.

Conclusions
Collectively, our in vitro data indicated that blockage of AMPK-ULK1 signaling cascade mediated protective autophagy might be a promising strategy to increase doxorubicin sensitivity for BC treatment.
Distribution of chimeric antigen receptor-modified T cells against CD19 in B-cell malignancies
Authors: Ying Zhitao , He Ting , Wang Xiaopei , Zheng Wen , Lin Ningjing , Tu Meifeng , Xie Yan , Ping Lingyan , Zhang Chen , Liu Weiping , Deng Lijuan , Wu Meng , Feng Feier , Leng Xin , Du Tingting , Qi Feifei , Hu Xuelian , Ding Yanping , Lu Xin-an , Song Yuqin , Zhu Jun 
Published: February 2021

Abstract
Background
The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo.

Methods
NALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry.

Results
CAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7–21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients.

Conclusions
CAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects.

Trial registration
The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421.