bluuebunny/crossref_metadata_2025_split huggingface dataset:
Esomeprazole attenuates inflammatory and fibrotic response in lung cells through the MAPK/Nrf2/HO1 pathway
Authors: Ebrahimpour Afshin , Wang Min , Li Li , Jegga Anil G. , Bonnen Mark D. , Eissa N. Tony , Raghu Ganesh , Jyothula Soma , Kheradmand Farrah , Hanania Nicola A. , Rosas Ivan O. , Ghebre Yohannes T. 
Published: May 2021

Abstract
Introduction
Idiopathic pulmonary fibrosis (IPF) is an orphan disease characterized by progressive loss of lung function resulting in shortness of breath and often death within 3–4 years of diagnosis. Repetitive lung injury in susceptible individuals is believed to promote chronic oxidative stress, inflammation, and uncontrolled collagen deposition. Several preclinical and retrospective clinical studies in IPF have reported beneficial outcomes associated with the use of proton pump inhibitors (PPIs) such as esomeprazole. Accordingly, we sought to investigate molecular mechanism(s) by which PPIs favorably regulate the disease process.

Methods
We stimulated oxidative stress, pro-inflammatory and profibrotic phenotypes in primary human lung epithelial cells and fibroblasts upon treatment with bleomycin or transforming growth factor β (TGFβ) and assessed the effect of a prototype PPI, esomeprazole, in regulating these processes.

Results
Our study shows that esomeprazole controls pro-inflammatory and profibrotic molecules through nuclear translocation of the transcription factor nuclear factor-like 2 (Nrf2) and induction of the cytoprotective molecule heme oxygenase 1 (HO1). Genetic deletion of Nrf2 or pharmacological inhibition of HO1 impaired esomeprazole-mediated regulation of proinflammatory and profibrotic molecules. Additional studies indicate that activation of Mitogen Activated Protein Kinase (MAPK) pathway is involved in the process. Our experimental data was corroborated by bioinformatics studies of an NIH chemical library which hosts gene expression profiles of IPF lung fibroblasts treated with over 20,000 compounds including esomeprazole. Intriguingly, we found 45 genes that are upregulated in IPF but downregulated by esomeprazole. Pathway analysis showed that these genes are enriched for profibrotic processes. Unbiased high throughput RNA-seq study supported antifibrotic effect of esomeprazole and revealed several novel targets.

Conclusions
Taken together, PPIs may play antifibrotic role in IPF through direct regulation of the MAPK/Nrf2/HO1 pathway to favorably influence the disease process in IPF.
Prevalence and risk factors of thrombotic events on patients with COVID-19: a systematic review and meta‐analysis
Authors: Xiong Xiaoming , Chi Jianhua , Gao Qinglei 
Published: May 2021

AbstractBackgroundCoagulation abnormalities in COVID-19 patients accompanied with poor prognosis. This study aimed to determine the prevalence and risk factors of thrombotic events on COVID-19 patients.Methods.We systematically reviewed all the studies about thrombotic events on COVID-19 patients in PubMed, Embase, Web of Science, MedRxiv, bioRxiv, from Dec 1, 2019 to July 5, 2020. The weighted mean difference (MD) or odds ratio (OR) or relative risk (RR) with 95 % confidence intervals (CI) for clinical data in COVID-19 patients with or without thrombotic events was calculated.Results12 articles contained 1083 patients were included for meta-analysis. The prevalence of thrombosis was 22 % (95 % CI 0.08–0.40) in COVID-19 patients and increased to 43 % (95 % CI 0.29–0.65) after admission to the intensive care unit (ICU). Compared with non-thrombotic patients, thrombotic patients had higher levels of D-dimer (MD = 2.79 μg/ml, 95 % CI 2.27–3.31 μg/ml), lactate dehydrogenase (LDH) (MD = 112.71 U/L, 95 % CI 62.40–163.02 U/L), and white blood cells (WBC) (MD = 1.14 *109/L, 95 % CI 0.47–1.81*109/L) while decreased lymphocytes (MD= -0.20*109/L, 95 % CI -0.38 – -0.02*109/L). Age, platelet counts, and male sex tended to be risks while diabetes tended to be a protection for thrombosis for COVID-19 patients, although no statistical difference was achieved. Finally, patients with thrombosis were at a higher risk of death (OR = 2.39, 95 % CI 1.36–4.20).ConclusionsPrevalence of thrombosis in COVID-19 patients was high, especially in ICU, though pharmacologic thromboembolism prophylaxis was applied. Therefore, higher levels of D-dimer, LDH, WBC, and decreased lymphocytes needed to be paid close attention to in patients with COVID-19.
Exclusivity of breastfeeding and body composition: learnings from the Baby-bod study
Authors: Jayasinghe Sisitha , Herath Manoja P. , Beckett Jeffrey M. , Ahuja Kiran D. K. , Byrne Nuala M. , Hills Andrew P. 
Published: May 2021

Abstract
Background
This report evaluated the breastfeeding status in a Tasmanian cohort and its effects on infant and maternal anthropometry and body composition.

Methods
An observational-cohort analysis of self-reported feeding data from 175 Tasmanian mother-baby dyads (recruited via in-person contact between September 2017 and October 2019), was executed. Only mothers who were ≥ 18 years of age, who had a singleton pregnancy and were able to speak and understand English, were included in the study. Infants outside a gestational age range between 37+ 0 and 41+ 6 weeks were excluded. Infant (using Air Displacement Plethysmography) and maternal body composition was assessed at 0, 3 and 6 months. Analysis of variance with relevant statistical corrections were utilised for cross-sectional and longitudinal comparisons between non-exclusively breastfed (neBF) and exclusively breastfed (eBF) groups.

Results
Fat-free mass was significantly higher [t = 2.27, df = 98, P = 0.03, confidence interval (CI) 0.03, 0.48] in neBF infants at 6 months (5.59 ± 0.59 vs 5.33 ± 0.50 kg) despite a higher mean fat-free mass in eBF infants at birth (2.89 ± 0.34 vs 3.01 ± 0.35 kg). Weak evidence for different fat mass index trajectories was observed for eBF and neBF infants in the first 6 months of life (ANOVA, F = 2.42, df = 1.9, P = 0.09) with an inversion in fat mass index levels between 3 and 6 months. Body Mass Index (BMI) trajectories were significantly different in eBF and neBF mothers through pregnancy and the first 6 months postpartum (ANOVA, F = 5.56, df = 30.14, P = 0.01). Compared with eBF mothers, neBF mothers retained significantly less weight (t = − 2.754, df = 158, P = 0.02, CI -6.64, − 1.09) at 3 months (0.68 ± 11.69 vs 4.55 ± 6.08 kg) postpartum. Prevalence for neBF was incrementally higher in mothers with a normal BMI compared to mothers with obesity, and mothers who underwent surgical or medical intervention during birth were less likely to exclusively breastfeed.

Conclusions
Infants with different feeding patterns may display varying growth patterns in early life and sustained breastfeeding can contribute to greater postpartum maternal weight loss.
An optimized sporulation method for the wheat fungal pathogen Pyrenophora tritici-repentis
Authors: Jacques Silke , Lenzo Leon , Stevens Kofi , Lawrence Julie , Tan Kar-Chun 
Published: May 2021

Abstract
Background
The necrotrophic fungal pathogen Pyrenophora tritici-repentis (Ptr) causes tan (syn. yellow) spot of wheat and accounts for significant yield losses worldwide. Understanding the molecular mechanisms of this economically important crop disease is crucial to counteract the yield and quality losses of wheat globally. Substantial progress has been made to comprehend the race structure of this phytopathogen based on its production of necrotrophic effectors and genomic resources of Ptr. However, one limitation for studying Ptr in a laboratory environment is the difficulty to isolate high spore numbers from vegetative growth with mycelial contamination common. These limitations reduce the experimental tractability of Ptr.

Results
Here, we optimized a multitude of parameters and report a sporulation method for Ptr that yields robust, high quality and pure spores. Our methodology encompasses simple and reproducible plugging and harvesting techniques, resulting in spore yields up to 1500 fold more than the current sporulation methods and was tested on multiple isolates and races of Ptr as well as an additional seven modern Australian Ptr isolates. Moreover, this method also increased purity and spore harvest numbers for two closely related fungal pathogens (Pyrenophora teres f. maculata and f. teres) that cause net blotch diseases in barley (Hordeum vulgare), highlighting the usability of this optimized sporulation protocol for the wider research community.

Conclusions
Large-scale spore infection and virulence assays are essential for the screening of wheat and barley cultivars and combined with the genetic mapping of these populations allows pinpointing and exploiting sources of host genetic resistance. We anticipate that improvements in spore numbers and purity will further advance research to increase our understanding of the pathogenicity mechanisms of these important fungal pathogens.
Ultrasound-guided surgery for lateral snapping hip: a novel ultraminimally invasive surgical technique
Authors: Villanueva Manuel , Iborra Álvaro , Sanz-Ruiz Pablo , Noriega Concepción 
Published: May 2021

Abstract
Background
Greater trochanteric pain syndrome encompasses a range of causes of lateral hip pain including greater trochanteric bursitis, tendinopathy and tears of the gluteus minimus and medius, and lateral snapping hip (LSH).
Surgical options for LSH range from open surgery to endoscopic surgery, including a diamond-shaped cut or a simple transversal release to gluteus maximus tendon release.
Resection of an area of proximal iliotibial band (ITB) and step-cut or z-plasty lengthening have not proven superior to transverse release of the ITB. Therefore, making a complete and effective transverse cut guided by ultrasound may represent a potential advance over endoscopic surgery.

Purpose
In this case series study, we describe how to perform proximal release of the ITB guided by ultrasound.

Methods
The surgical technique—either z-plasty or transverse section of the ITB—was first validated on 10 cadaver specimens and then used in clinical practice. Fourteen patients (5 males and 9 females) were operated from 2014 to 2018. Mean age was 43 years (29–62).

Results
The snap resolved in all patients, as verified actively during the surgical procedure as the patient has only local anesthesia. The VAS score for sports activity improved from 7 (5–9) before surgery to 0 (0–2) after 1 year. The HSS score improved from 58 points (47–72) to 96 at 1–2 years. There were no complications other than minor hematomas nor recurrences.

Conclusion
Ultrasound-guided release of the LSH is a novel surgical option with encouraging results in patients for whom conservative protocols have failed. It can be performed under local anesthesia in an outpatient setting with minimal aggressiveness. It is relatively easy, quick, and painless; no stitches are required. Weight bearing is immediate, and patients usually need crutches for only 2–3 days. Although complete recovery may take 3 months, the rehabilitation protocol is fast and painless.
Lymphoproliferative malignancies in patients with neurofibromatosis 1
Authors: Bergqvist Christina , Hemery François , Jannic Arnaud , Ferkal Salah , Wolkenstein Pierre 
Published: May 2021

AbstractNeurofibromatosis 1 (NF1) is an inherited, autosomal-dominant, tumor predisposition syndrome with a birth incidence as high as 1:2000. A patient with NF1 is four to five times more likely to develop a malignancy as compared to the general population. The number of epidemiologic studies on lymphoproliferative malignancies in patients with NF1 is limited. The aim of this study was to determine the incidence rate of lymphoproliferative malignancies (lymphoma and leukemia) in NF1 patients followed in our referral center for neurofibromatoses. We used the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital’s electronic health records. We performed a keyword search on clinical notes generated between Jan/01/2014 and May/11/2020 for patients aged 18 years or older. A total of 1507 patients with confirmed NF1 patients aged 18 years and above were identified (mean age 39.2 years; 57% women). The total number of person-years in follow-up was 57,736 (men, 24,327 years; women, 33,409 years). Mean length of follow-up was 38.3 years (median, 36 years). A total of 13 patients had a medical history of either lymphoma or leukemia, yielding an overall incidence rate of 22.5 per 100,000 (0.000225, 95% confidence interval (CI) 0.000223–0.000227). This incidence is similar to that of the general population in France (standardized incidence ratio 1.07, 95% CI 0.60–1.79). Four patients had a medical history leukemia and 9 patients had a medical history of lymphoma of which 7 had non-Hodgkin lymphoma, and 2 had Hodgkin lymphoma. Our results show that adults with NF1 do not have an increased tendency to develop lymphoproliferative malignancies, in contrast to the general increased risk of malignancy. While our results are consistent with the recent population-based study in Finland, they are in contrast with the larger population-based study in England whereby NF1 individuals were found to be 3 times more likely to develop both non-Hodgkin lymphoma and lymphocytic leukemia. Large-scale epidemiological studies based on nationwide data sets are thus needed to confirm our findings.
Cytogenetic and mutational analysis and outcome assessment of a cohort of 284 children with de novo acute myeloid leukemia reveal complex karyotype as an adverse risk factor for inferior survival
Authors: Chen Xi , Wang Xingjuan , Dou Hu , Yang Zhenzhen , Bi Junqin , Huang Yi , Lu Ling , Yu Jie , Bao Liming 
Published: May 2021

Abstract
Background
Acute myeloid leukemia (AML) is rare in children. Although complex karyotype (CK) defined as ≥ 3 cytogenetic abnormalities is an adverse risk factor in adult AML, its prognostic impact on childhood AML remains to be determined.

Results
We studied the prevalence, cytogenetic and mutational features, and outcome impact of CK in a cohort of 284 Chinese children with de novo AML. Thirty-four (12.0%) children met the criteria for CK-AML with atypical CK being more frequent than typical CK featured with -5/5q-, -7/7q-, and/or 17p aberration. Mutational prevalence was low and co-occurrence mutants were uncommon. Children with CK-AML showed shorter overall survival (OS) (5-year OS: 26.7 ± 10.6% vs. 37.5 ± 8.6%, p = 0.053) and event-free survival (EFS) (5-year EFS: 26.7 ± 10.6% vs. 38.8 ± 8.6%, p = 0.039) compared with those with intermediate-risk genetics. Typical CK tended to correlate with a decreased OS than atypical CK (5-year OS: 0 vs. 33 ± 12.7%.; p = 0.084), and CK with ≥ 5 cytogenetic aberrations was associated with an inferior survival compared with CK with ≤ 4 aberrations (5-year OS: 13.6 ± 11.7% vs. 50.0 ± 18.6%; p = 0.040; 5-year EFS: 13.6 ± 11.7% vs. 50.0 ± 18.6%; p = 0.048).

Conclusion
Our results demonstrate CK as an adverse risk factor for reduced survival in childhood AML. Our findings shed light on the cytogenetic and mutational profile of childhood CK-AML and would inform refinement of risk stratification in childhood AML to improve outcomes.
Intraoperative ultrasound-guided compared to stereotactic navigated ventriculoperitoneal shunt placement: study protocol for a randomised controlled study
Authors: Leu Severina , Halbeisen Florian , Mariani Luigi , Soleman Jehuda 
Published: May 2021

Abstract
Background
Ventriculoperitoneal shunt (VPS) placement is one of the most frequent neurosurgical procedures and the operation is performed in a highly standardised manner under maintenance of highest infection precautions. Short operation times are important since longer duration of surgery can increase the risk for VPS complications, especially infections. The position of the proximal ventricular catheter influences shunt functioning and survival. With freehand placement, rates of malpositioned VPS are still high. Several navigation techniques for improvement of shunt placement have been developed. Studies comparing these techniques are sparse. The aim of this study is to prospectively compare ultrasound (US) guided to stereotactic navigated shunt placement using optical tracking with the focus on operation time and efficiency.

Methods
In this prospective randomised, single-centre, partially-blinded study, we will include all patients undergoing VPS placement in our clinic. The patients will be randomised into two groups, one group undergoing US-guided (US-G) and the other group stereotactic navigated VPS placement using optical tracking. The primary outcome will be the surgical intervention time. This time span consists of the surgical preparation time together with the operation time and is given in minutes. Secondary outcomes will be accuracy of catheter positioning, VPS dysfunction and need for revision surgery, total operation and anaesthesia times, and amount of intraoperative ventricular puncture attempts as well as complications, any morbidity and mortality.

Discussion
To date, there is no prospective data available comparing these two navigation techniques. A randomised controlled study is urgently needed in order to provide class I evidence for the best possible surgical technique of this frequent surgery.

Trial registration
Business Administration System for Ethical Committees (BASEC) 2019-02157, registered on 21 November 2019, https://www.kofam.ch/de/studienportal/suche/88135/studie/49552; clinicalTrials.gov: NCT04450797, registered on 30 June 2020.
Prevalence of human cystic echinococcosis in the towns of Ñorquinco and Ramos Mexia in Rio Negro Province, Argentina, and direct risk factors for infection
Authors: Uchiumi Leonardo , Mujica Guillermo , Araya Daniel , Salvitti Juan Carlos , Sobrino Mariano , Moguillansky Sergio , Solari Alejandro , Blanco Patricia , Barrera Fabiana , Lamunier Janete , Arezo Marcos , Seleiman Marcos , Yadon Zaida E. , Tamarozzi Francesca , Casulli Adriano , Larrieu Edmundo 
Published: May 2021

Abstract
Background
Cystic echinococcosis (CE) is a parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus (s.l.). This study investigated the prevalence and potential risk factors associated with human CE in the towns and rural areas of Ñorquinco and Ramos Mexia, Rio Negro province, Argentina.

Methods
To detect abdominal CE cysts, we screened 892 volunteers by ultrasound and investigated potential risk factors for CE using a standardized questionnaire. Prevalence ratio (PR) with 95% confidence intervals (CI) was used to measure the association between CE and the factors investigated, applying bivariate and multivariate analyses.

Results
Abdominal CE was detected in 42/892 screened volunteers (4.7%, 95% CI 3.2–6.1), only two of whom were under 15 years of age. Thirteen (30.9%) CE cases had 25 cysts in active stages (CE1, CE2, CE3a, according to the WHO Informal Working Group on Echinococcosis [WHO-IWGE] classification). The most relevant risk factors identified in the bivariate analysis included: living in rural areas (P = 0.003), age > 40 years (P = 0.000), always drinking water from natural sources (P = 0.007), residing in rural areas during the first 5 years of life (P = 0.000) and having lived more than 20 years at the current address (P = 0.013). In the multivariate final model, the statistically significant risk factors were: frequently touching dogs (P = 0.012), residing in rural areas during the first 5 years of life (P = 0.004), smoking (P = 0.000), age > 60 years (P = 0.002) and living in rural areas (P = 0.017).

Conclusions
Our results point toward infection with CE being acquired since childhood and with constant exposure throughout life, especially in rural areas with a general environmental contamination.

Graphical Abstract
Increased risk of impaired treatment satisfaction among girls/women and young people with suboptimal HbA1c: Results of a nationwide type 1 diabetes study
Authors: Stahl-Pehe Anna , Selinski Silvia , Bächle Christina , Rosenbauer Joachim 
Published: May 2021

AbstractBackgroundThis study aims to analyze the patient-reported outcome (PRO) of treatment satisfaction in a sample of children, adolescents and young adults with long-duration type 1 diabetes and to determine potential risk factors for poor treatment satisfaction and the intraindividual changes over a 3-year period.MethodsThis study used data from two population-based questionnaire surveys conducted in 2015–2016 and 2018–2019. The participants were 11 to 27 years old and had a type 1 diabetes duration of 10 years or longer in 2015–2016 (n = 575). Factors that were potentially associated with poor treatment satisfaction (moderate, poor or very poor) compared to the reference group (very good or good treatment satisfaction) were analyzed by log binomial regression adjusted for sex and age group.ResultsIn 2015–2016 (2018–2019), 26% (33%) of the respondents rated their diabetes treatment/consultation as "very good", 53% (46%) as "good", and 20% (21%) as "poor". Based on the 2018–2019 data, girls/women had an increased risk of poor treatment satisfaction (RRgirls/women: 1.64 (1.10; 2.44), p = 0.016). In addition, people with hemoglobin A1c (HbA1c) values ≥ 7.5% had a more than twice the risk of poor treatment satisfaction than people with HbA1c values < 7.5% (RRHbA1c ≥7.5%: 2.43 (1.63; 3.63), p < 0.001). A total of 42% of people with poor treatment satisfaction in 2015–2016 also reported poor treatment satisfaction at follow-up.ConclusionsMost study participants were satisfied with their diabetes treatment. However, we identified risk groups that would benefit from targeted interventions to improve this important PRO.
Arylated gold nanoparticles have no effect on the adipogenic differentiation of MG-63 cells nor regulate any key signaling pathway during the differentiation
Authors: Abdulwahab Muhammad , Khan Amir Ali , Abdallah Sallam Hasan , Khattak Muhammad Nasir Khan , Workie Bizuneh , Chehimi Mohamed Mehdi , Mohamed Ahmed Ali 
Published: May 2021

Abstract
Objective
MG-63 cells that have osteoblastic and adipogenic differentiation potential were evaluated for internalization, and adipogenic differentiation in the presence and absence of the covalently functionalized aryl gold nanoparticles (AuNPs-C6H4-4-COOH).

Results
Inductively coupled plasma, flow cytometry and confocal microscopy analyses confirmed that gold nanoparticles were easily internalized by MG-63 cells. The MG-63 cells were differentiated into adipocytes without gold-aryl nanoparticles and with the gold-aryl nanoparticles at 5 µM concentration in both induction and maintenance media. The lipid content assay and the relative expressions of PPAR-γ, ADR1, GLUT1 and GLUT4 genes showed no significant variation with and without the gold nanoparticles treatment. Differential phosphorylation levels of 43 kinases phosphorylation sites were evaluated using the human phospho-kinase array to assess the effect of the gold nanoparticles on the signaling pathways during the differentiation. No kinase phosphorylation site was differentially phosphorylated with two or more folds after the nanoparticles treatment after the first day as well as at the end of MG-63 cells differentiation. The gold-aryl nanoparticles do not affect MG-63 cells differentiation into adipocytes neither do they affect any key signaling pathway. These properties make these gold nanoparticles suitable for future drug delivery and medical applications.