bluuebunny/crossref_metadata_2025_split huggingface dataset:
International High-Risk Clones Among Extended-Spectrum β-Lactamase–Producing Escherichia coli in Dhaka, Bangladesh
Authors: Mazumder Razib , Hussain Arif , Abdullah Ahmed , Islam Md. Nazrul , Sadique Md. Tuhin , Muniruzzaman S. M. , Tabassum Anika , Halim Farhana , Akter Nasrin , Ahmed Dilruba , Mondal Dinesh 
Published: October 2021

Background:Escherichia coli is a major extended-spectrum β-lactamase (ESBL)–producing organism responsible for the rapid spread of antimicrobial resistance (AMR) that has compromised our ability to treat infections. Baseline data on population structure, virulence, and resistance mechanisms in E. coli lineages from developing countries such as Bangladesh are lacking.Methods: Whole-genome sequencing was performed for 46 ESBL–E. coli isolates cultured from patient samples at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)-Dhaka. Sequence data were analyzed to glean details of AMR, virulence, and phylogenetic and molecular markers of E. coli lineages.Results: Genome comparison revealed presence of all major high-risk clones including sequence type 131 (ST131) (46%), ST405 (13%), ST648 (7%), ST410 (4.3%), ST38 (2%), ST73 (2%), and ST1193 (2%). The predominant ESBL gene and plasmid combination were blaCTX–M–15 and FII-FIA-FIB detected in diverse E. coli phylogroups and STs. The blaNDM–5 (9%) gene was present in prominent E. coli STs. One (2%) mcr-1–positive ST1011 E. coli, coharboring blaCTXM–55 gene, was detected. The extraintestinal pathogenic E. coli genotype was associated with specific E. coli lineages. The single nucleotide polymorphism (SNP)-based genome phylogeny largely showed correlation with phylogroups, serogroups, and fimH types. Majority of these isolates were susceptible to amikacin (93%), imipenem (93%), and nitrofurantoin (83%).Conclusion: Our study reveals a high diversity of E. coli lineages among ESBL-producing E. coli from Dhaka. This study suggests ongoing circulation of ST131 and all major non-ST131 high-risk clones that are strongly associated with cephalosporin resistance and virulence genes. These findings warrant prospective monitoring of high-risk clones, which would otherwise worsen the AMR crises.
Changes of Health-Related Quality of Life Within the 1st Year After Stroke–Results From a Prospective Stroke Cohort Study
Authors: Kainz Anabelle , Meisinger Christa , Linseisen Jakob , Kirchberger Inge , Zickler Philipp , Naumann Markus , Ertl Michael 
Published: October 2021

Introduction: As prospective data on long-term patient-reported outcome measures (PROMs) to assess Health related Quality of Life (HRQoL) after stroke are still scarce, this study examined the long-term course of PROMs and investigated influential factors such as recanalization therapies.Materials and Methods: A total of 945 (mean age 69 years; 56% male) stroke patients were enrolled with a personal interview and chart review performed at index event. One hundred forty (15%) patients received thrombolysis (IVT) and 53 (5%) patients received endovascular therapy (ET) or both treatments as bridging therapy (BT). After 3 and 12 months, a follow-up was conducted using a postal questionnaire including subjective quality of life EQ-5D-5L (European Quality of Life 5 Dimensions). At all time-points, Modified Rankin Scale (mRS) was additionally used to quantify functional stroke severity. Differences between therapy groups were identified using post-hoc-tests. Linear and logistic regression analyses were used to identify predictors of outcomes.Results: Recanalization therapies were associated with significant improvements of NIHSS (National Institutes of Health Stroke Scale [regression coefficient IVT 1.21 (p = 0.01) and ET/BT 7.6; p = 0.001] and mRS (modified Rankin Scale) [regression coefficient IVT 0.83; p = 0.001 and ET/BT 2.0; p = 0.001] between admission and discharge compared to patients with stroke unit therapy only, with a trend toward improvement of EQ-5D after 12 months [regression coefficient 4.67 (p = 0.17)] with IVT. HRQoL was considerably impaired by stroke and increased steadily in 3- and 12-months follow-up in patients with (mean EQ-5D from 56 to 68) and without recanalization therapy (mean EQ-5D from 62 to 68). In severe strokes a major and significant improvement was only detected during period of 3 to 12 months (p = 0.03 in patients with and p = 0.005 in patients without recanalization therapy).Conclusions: Despite significant and continuous improvements after stroke the HRQoL after 12 months remained below the age-matched general population, but was still unexpectedly high in view of the accumulation of permanent disabilities in up to 30% of the patients. Especially in severe strokes, it is important to evaluate HRQoL beyond a 3-months follow-up as improvements became significant only between 3 months and 1 year.
Analysis of the Distribution of Urine Color and Its Relationship With Urine Dry Chemical Parameters Among College Students in Beijing, China – A Cross-Sectional Study
Authors: Liu Jingnan , Zhang Zijuan , Pang Xiaohan , Cheng Yaxing , Man Da , He Xinyi , Zhao Huihui , Zhao Ruizhen , Wang Wei 
Published: October 2021

Objectives: The objective of this study was to provide a new classification method by analyzing the relationship between urine color (Ucol) distribution and urine dry chemical parameters based on image digital processing. Furthermore, this study aimed to assess the reliability of Ucol to evaluate the states of body hydration and health.Methods: A cross-sectional study among 525 college students, aged 17–23 years old, of which 59 were men and 466 were women, was conducted. Urine samples were obtained during physical examinations and 524 of them were considered valid, including 87 normal samples and 437 abnormal dry chemistry parameters samples. The urinalysis included both micro- and macro-levels, in which the CIE L*a*b* values and routine urine chemical examination were performed through digital imaging colorimetry and a urine chemical analyzer, respectively.Results: The results showed that L* (53.49 vs. 56.69) in the abnormal urine dry chemistry group was lower than the normal group, while b* (37.39 vs. 33.80) was greater. Urine color can be initially classified based on shade by grouping b*. Abnormal urine dry chemical parameter samples were distributed more in the dark-colored group. Urine dry chemical parameters were closely related to Ucol. Urine specific gravity (USG), protein, urobilinogen, bilirubin, occult blood, ketone body, pH, and the number of abnormal dry chemical parameters were all correlated with Ucol CIE L*a*b*; according to a stepwise regression analysis, it was determined that more than 50% of the variation in the three-color space values came from the urine dry chemical parameters, and the b* value was most affected by USG (standardized coefficient β = 0.734, p &lt; 0.05). Based on a receiver operating characteristic curve (ROC) analysis, Ucol ≥ 4 provided moderate sensitivity and good specificity (AUC = 0.892) for the detection of USG ≥ 1.020.Conclusions: Our findings on the Ucol analysis showed that grouping Ucol based on b* value is an objective, simple, and practical method. At the same time, the results suggested that digital imaging colorimetry for Ucol quantification is a potential method for evaluating body hydration and, potentially, health.
Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling
Authors: Qin Tao , Li Jie , Xiao Ying , Wang Xueni , Gong Mengyuan , Wang Qiqi , Zhu Zeen , Zhang Simei , Zhang Wunai , Cao Fang , Han Liang , Wang Zheng , Ma Qingyong , Sha Huanchen 
Published: October 2021

BackgroundPerineural invasion (PNI) is an important pathologic feature of pancreatic cancer, and the incidence of PNI in pancreatic cancer is 70%-100%. PNI is associated with poor outcome, metastasis, and recurrence in pancreatic cancer patients. There are very few treatments for PNI in pancreatic cancer. Honokiol (HNK) is a natural product that is mainly obtained from Magnolia species and has been indicated to have anticancer activity. HNK also has potent neurotrophic activity and may be effective for suppressing PNI. However, the potential role of HNK in the treatment of PNI in pancreatic cancer has not been elucidated.MethodsIn our study, pancreatic cancer cells were treated with vehicle or HNK, and the invasion and migration capacities were assessed by wound scratch assays and Transwell assays. A cancer cell-dorsal root ganglion coculture model was established to evaluate the effect of HNK on the PNI of pancreatic cancer. Western blotting was used to detect markers of EMT and neurotrophic factors in pancreatic tissue. Recombinant TGF-β1 was used to activate SMAD2/3 to verify the effect of HNK on SMAD2/3 and neurotrophic factors. The subcutaneous tumor model and the sciatic nerve invasion model, which were established in transgenic engineered mice harboring spontaneous pancreatic cancer, were used to investigate the mechanism by which HNK inhibits EMT and PNI in vivo.ResultsWe found that HNK can inhibit the invasion and migration of pancreatic cancer cells. More importantly, HNK can inhibit the PNI of pancreatic cancer. The HNK-mediated suppression of pancreatic cancer PNI was partially mediated by inhibition of SMAD2/3 phosphorylation. In addition, the inhibitory effect of HNK on PNI can be reversed by activating SMAD2/3. In vivo, we found that HNK can suppress EMT in pancreatic cancer. HNK can also inhibit cancer cell migration along the nerve, reduce the damage to the sciatic nerve caused by tumor cells and protect the function of the sciatic nerve.ConclusionOur results demonstrate that HNK can inhibit the invasion, migration, and PNI of pancreatic cancer by blocking SMAD2/3 phosphorylation, and we conclude that HNK may be a new strategy for suppressing PNI in pancreatic cancer.
Comparison of PET/CT and MRI in the Diagnosis of Bone Metastasis in Prostate Cancer Patients: A Network Analysis of Diagnostic Studies
Authors: Liu Fanxiao , Dong Jinlei , Shen Yelong , Yun Canhua , Wang Ruixiao , Wang Ganggang , Tan Jiyang , Wang Tao , Yao Qun , Wang Bomin , Li Lianxin , Mi Jingyi , Zhou Dongsheng , Xiong Fei 
Published: October 2021

BackgroundAccurate diagnosis of bone metastasis status of prostate cancer (PCa) is becoming increasingly more important in guiding local and systemic treatment. Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) have increasingly been utilized globally to assess the bone metastases in PCa. Our meta-analysis was a high-volume series in which the utility of PET/CT with different radioligands was compared to MRI with different parameters in this setting.Materials and MethodsThree databases, including Medline, Embase, and Cochrane Library, were searched to retrieve original trials from their inception to August 31, 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The methodological quality of the included studies was assessed by two independent investigators utilizing Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). A Bayesian network meta-analysis was performed using an arm-based model. Absolute sensitivity and specificity, relative sensitivity and specificity, diagnostic odds ratio (DOR), and superiority index, and their associated 95% confidence intervals (CI) were used to assess the diagnostic value.ResultsForty-five studies with 2,843 patients and 4,263 lesions were identified. Network meta-analysis reveals that 68Ga-labeled prostate membrane antigen (68Ga-PSMA) PET/CT has the highest superiority index (7.30) with the sensitivity of 0.91 and specificity of 0.99, followed by 18F-NaF, 11C-choline, 18F-choline, 18F-fludeoxyglucose (FDG), and 18F-fluciclovine PET/CT. The use of high magnetic field strength, multisequence, diffusion-weighted imaging (DWI), and more imaging planes will increase the diagnostic value of MRI for the detection of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT was performed in the detection of bone metastasis on patient-based level (sensitivity, 0.94 vs. 0.91; specificity, 0.94 vs. 0.96; superiority index, 4.43 vs. 4.56).Conclusions68Ga-PSMA PET/CT is recommended for the diagnosis of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT should be performed in the detection of bone metastasis.
The Clinical Implications and Molecular Mechanism of CX3CL1 Expression in Urothelial Bladder Cancer
Authors: Jiang Guangliang , Wang Hui , Huang Da , Wu Yishuo , Ding Weihong , Zhou Qidong , Ding Qiang , Zhang Ning , Na Rong , Xu Ke 
Published: October 2021

BackgroundCX3CL1 is a chemokine that may play important roles in cancer immune regulation. Its mechanism in bladder cancer (BCa) is poorly understood. The objective of the current study was to evaluate the association between CX3CL1 and BCa and the related biological mechanisms.MethodsA total of 277 patients with BCa were enrolled in the present study. The association between CX3CL1 expression and disease outcome was evaluated. In vitro and in vivo experiments were performed using the TCCSUP cell line to investigate the function of CX3CL1 in BCa.ResultsCompared with low expression, high expression of CX3CL1 was significantly associated with poorer progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.26-3.27, P=0.006), cancer-specific survival (HR=2.16, 95% CI: 1.59-2.93, P&lt;0.001), and overall survival (HR=1.55, 95% CI: 1.08-2.24, P=0.039). Multivariable Cox regression analysis suggested that CX3CL1 was an independent prognostic factor for BCa outcomes. In vitro and in vivo experiments indicated that high expression of CX3CL1 was significantly associated with cell proliferation (P&lt;0.001) and invasion (P&lt;0.001). Gene expression profiling results showed that after CX3CL1 knockdown, CDH1 was significantly upregulated, while ETS1, RAF1, and EIF4E were significantly downregulated. Pathway enrichment analysis suggested that the ERK/MAPK signaling pathway was significantly inhibited (P&lt;0.001).ConclusionsCX3CL1 is an independent predictor of a poor prognosis in BCa and can promote the proliferation and invasion of BCa cells.
The Association of Real-World CA 19-9 Level Monitoring Patterns and Clinical Outcomes Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma
Authors: George Ben , Kent Matthew , Surinach Andy , Lamarre Neil , Cockrum Paul 
Published: October 2021

BackgroundPancreatic cancer is expected to be the third deadliest cancer in the US in 2021. Evaluation of treatment response in patients with mPDAC necessitates scheduled clinical and radiographic assessments along with monitoring serum CA 19-9 levels. Currently available single-institution data examining the importance of CA 19-9 monitoring cannot be generalized to real-world settings. We investigated the impact of serum CA 19-9 monitoring and its association with clinical outcomes in patients with mPDAC in a population-based setting.MethodsData were extracted from the Flatiron Health electronic health record (EHR)-derived de-identified database for patients diagnosed with mPDAC between January 1, 2015, and June 30, 2020. Serum CA 19-9 levels at baseline – defined as the values obtained ≤ 60 days prior to treatment initiation - and during treatment were extracted. CA 19-9 levels &gt; 40 IU/mL were considered elevated. Survival outcomes were compared based on testing frequency, baseline CA 19-9 levels, and change in CA 19-9.Results6,118 patients with mPDAC who received treatment were included in the analysis. The median age at diagnosis was 68 years (IQR: 61-75). Patients with normal baseline CA 19-9 experienced longer median survival than patients with elevated levels [1L: 8.8 months (95% CI: 7.9 - 10) vs. 7.2 months (6.8 – 7.5), p &lt; 0.001; 2L: 7.2 months (6.1 – 9.2) vs. 5.2 months (4.9 – 5.6), p &lt; 0.001; 3L: 6.1 months (5.4 – 9.1) vs. 3.9 months (3.4 – 4.3), p &lt; 0.001]. Patients with decreasing/stable CA 19-9 during treatment experienced longer survival than patients who experienced an increase in CA 19-9 levels [1L: 10.9 months (10.5 – 11.3) vs. 5.4 months (5.1 – 5.9), p &lt; 0.0001; 2L: 8.2 months (7.7 – 8.5) vs. 4.3 months (4.1 – 4.7), p &lt; 0.001; 3L: 7.5 months (6.6 – 9.2) vs. 3.7 months (3.4 – 4.3), p &lt; 0.001].ConclusionsIn one of the largest, contemporary, real-world studies of patients with mPDAC, elevated CA 19-9 level at treatment initiation demonstrated a prognostic impact. Routine serial monitoring of CA 19-9 levels during treatment may be warranted, in addition to clinical and radiographic assessment, and may translate into better patient outcomes. Further validation studies are needed to understand the generalizability of these results.
Application of MAT Methodology in the Evaluation of Prescribing Adherence to Clinical Practice Guidelines for Secondary Prevention of Coronary Heart Disease in Post-Acute Coronary Syndrome Patients in Kuwait
Authors: Al-Taweel Dalal , Awad Abdelmoneim 
Published: October 2021

Quantification of prescribers’ adherence to evidence-based guidelines can be used as an outcome measure to assess the impact of services on the quality of medication use. Additionally, it can help in reducing inappropriate interventions and ensure that high-quality care is provided to patients. This study aimed to evaluate prescribing practices for secondary prevention of coronary heart disease (CHD) in post-acute coronary syndromes (ST-elevation myocardial infarction [STEMI] or non-ST elevation acute coronary syndrome [NSTEACS]) patients using two medication assessment tools (MATs) at secondary and tertiary health-care settings in Kuwait. Both MATs were developed and validated based on the relevant guidelines issued by the European Society of Cardiology and the American College of Cardiology/American Heart Association. A quantitative cross-sectional multicenter study was conducted on 460 patients’ medical records collected randomly from six health-care facilities in Kuwait. Application of MATSTEMI on 232 patients’ medication records (with 85.9% applicability) resulted in intermediate overall adherence (69.8%; 95% CI: 67.6–72.0). Application of MATNSTEACS on 228 patients’ medication records (with applicability 83.2%) resulted in intermediate overall adherence (73.3%; 95% CI: 70.5–76.0). There was no significant difference between the percentages of overall adherence among patients managed post-NSTEACS compared to those managed post-STEMI (p = 0.05). Multivariable logistic regression analysis revealed that the overall adherence to the MATSTEMI criteria was significantly higher among the specialized cardiac centers than among the general hospitals (OR: 1.6; 95% CI: 1.1–2.3; p = 0.02). The overall adherence to the MATNSTEACS criteria was found to be significantly lower among non-Kuwaitis than among Kuwaitis (OR: 0.6; 95% CI: 0.5–0.9; p = 0.01) and patients with a serum LDL ≥1.8 mmol/L than those with a serum LDL-C &lt; 1.8 mmol/L (OR: 0.5; 95% CI: 0.4–0.7; p &lt; 0.001). The present findings revealed that both MATs were useful tools in identifying the standard of clinical performances and highlighting areas for improvement regarding secondary prevention of CHD in post-acute coronary syndrome patients.
Anti-Photoaging and Anti-Inflammatory Effects of Ginsenoside Rk3 During Exposure to UV Irradiation
Authors: Wan Shichao , Liu Yannan , Shi Jingjing , Fan Daidi , Li Binglin 
Published: October 2021

Ginseng is a widely cultivated perennial plant in China and Korea. Ginsenoside Rk3 is one of the major active components of ginseng and is a promising candidate to regulate skin pigments and exert anti-photoaging effects on skin physiology. Ginsenoside Rk3 was mixed with a cream (G-Rk3 cream) and smeared on the skin of mice. Then, the mice were exposed to ultraviolet (UV) A (340 nm and 40 W) and UVB (313 nm and 40 W) radiation. Special attention was given to the anti-photoaging and anti-inflammatory effects of ginsenoside Rk3 on the mouse skin. Macroscopic evaluation indicated that the mouse dorsal skin looked smooth and plump even under UV irradiation for 12 weeks. Pathological analysis indicated that there was no obvious photoaging or inflammation in the mouse skin that was treated with the G-Rk3 cream. More healthy, intact, and neat collagen fibers were observed in mice treated with the G-Rk3 cream than in untreated mice. Further analysis proved that ginsenoside Rk3 could inhibit the decrease in water and hydroxyproline levels in skin tissues and the loss of superoxide dismutase and glutathione peroxidase activities in the blood. Moreover, ginsenoside Rk3 slowed or halted increases in malondialdehyde, matrix metalloproteinase (MMP)-1, and MMP-3 levels in the blood and levels of interleukin 1, interleukin 6, and tumor necrosis factor α in skin tissues. In conclusion, ginsenoside Rk3 plays a significant role in inhibiting photoaging and inflammation to protect skin health.
Pharmacovigilance Bibliometrics: Visualizing Thematic Development in the Category of Pharmacology and Pharmacy in Web of Science
Authors: Wang Li , Feng Wanyu , Duan Jingli , Liang Jun 
Published: October 2021

Introduction: Pharmacovigilance studies include monitoring and preventing the occurrence of new, rare, or serious adverse drug reactions, making it possible to discover new safety issues without delay. Bibliometrics could assist scholars to analyze the development of pharmacovigilance.Methods: The MeSH terms of both pharmacovigilance and “adverse drug reaction reporting system” were retrieved in the Science Citation Index Expanded. The articles from 1974 to July 2021 in the pharmacology and pharmacy category were recruited. The citation reports including the publication numbers, h-index, and sum and average cited times in terms of annuals, countries, organizations, authors and journals were tabulated. The coauthorship relations in the analysis units of countries, organizations, and authors; the top 10 burst references; the document citation network; and the author’s keywords co-occurrence overlay map were visualized by bibliometric software including the website (https://bibliometric.com/), VOSviewer, CiteSpace, and CitNetExplorer.Results: From 1974 to the present, the most high-yield publication year, country, institute, author, and journal were 2020 (n = 222), France (n = 522), Netherlands Pharmacovigilance Centre Lareb (n = 82), Jean–Louis Montastruc (n = 125), Drug Safety (n = 384), respectively, in all 2,128 articles. Similarly, the United States, Institut National de la Sante et de la Recherche Medicale, and Jean–Louis Montastruc had the most coauthorship strength at the macrolevel (global), mesolevel (local), and microlevel (individual). The topics of burst references covered are the development of methodology, issues of patients reporting and under-reporting, evaluation of methods and databases, assessment of causality, and perspectives in pharmacovigilance. Eight clusters were grouped in the document citation network. “Pharmacovigilance,” “adverse drug reactions,” “pharmacoepidemiology,” “drug safety,” and “signal detection” were the research priorities, while “drug-related side effects and adverse reactions,” “VigiBase,” “disproportionality analysis,” “social media,” “FAERS,” “chemotherapy,” “patient safety,” “reporting odds ratio,” and “preventability” might be the future research hotspots.Conclusion: Positive synergies can be observed in this study by employing the multiple software tools which established the relationship between the units of analysis. The bibliometric analysis can organize the thematic development and guide the hotspots of pharmacovigilance in pharmacology and pharmacy.