bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocytes in sarcoidosis are potent tumour necrosis factor producers and predict disease outcome
Authors: Lepzien Rico , Liu Sang , Czarnewski Paulo , Nie Mu , Österberg Björn , Baharom Faezzah , Pourazar Jamshid , Rankin Gregory , Eklund Anders , Bottai Matteo , Kullberg Susanna , Blomberg Anders , Grunewald Johan , Smed-Sörensen Anna 
Published: January 2021

BackgroundPulmonary sarcoidosis is an inflammatory disease characterised by granuloma formation and heterogeneous clinical outcome. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine contributing to granuloma formation and high levels of TNF have been shown to associate with progressive disease. Mononuclear phagocytes (MNPs) are potent producers of TNF and highly responsive to inflammation. In sarcoidosis, alveolar macrophages have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells, which are poorly studied in sarcoidosis, despite their central role in inflammation.ObjectiveTo determine the role of pulmonary monocyte-derived cells and dendritic cells during sarcoidosis.MethodsWe performed in-depth phenotypic, functional and transcriptomic analysis of MNP subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls. We followed the clinical development of patients and assessed how the repertoire and function of MNP subsets at diagnosis correlated with 2-year disease outcome.ResultsMonocytes/monocyte-derived cells were increased in blood and BAL of sarcoidosis patients compared to healthy controls. Interestingly, high frequencies of blood intermediate monocytes at time of diagnosis associated with chronic disease development. RNA sequencing analysis showed highly inflammatory MNPs in BAL of sarcoidosis patients. Furthermore, frequencies of BAL monocytes/monocyte-derived cells producing TNF without exogenous stimulation at time of diagnosis increased in patients that were followed longitudinally. In contrast to alveolar macrophages, the frequency of TNF-producing BAL monocytes/monocyte-derived cells at time of diagnosis was highest in sarcoidosis patients that developed progressive disease.ConclusionOur data show that pulmonary monocytes/monocyte-derived cells are highly inflammatory and can be used as a predictor of disease outcome in sarcoidosis patients.
Blood eosinophils on hospital admission for COPD exacerbation do not predict the recurrence of moderate and severe relapses
Authors: Csoma Balázs , Bikov András , Tóth Ferenc , Losonczy György , Müller Veronika , Lázár Zsófia 
Published: January 2021

Background and objectiveThe relationship between hospitalisation with an eosinophilic acute exacerbation of COPD (AE-COPD) and future relapses is unclear. We aimed to explore this association by following 152 patients for 12 months after hospital discharge or until their first moderate or severe flare-up.MethodsPatients hospitalised with AE-COPD were divided into eosinophilic and non-eosinophilic groups based on full blood count results on admission. All patients were treated with a course of systemic corticosteroid. The Cox proportional hazards model was used to study the association with the time to first re-exacerbation; a generalised linear regression model was applied to identify clinical variables related to the recurrence of relapses.ResultsWe did not find a difference in the time to the next moderate or severe exacerbation between the eosinophilic (≥2% of total leukocytes and/or ≥200 eosinophils·µL−1, n=51, median (interquartile range): 21 (10–36) weeks) and non-eosinophilic groups (n=101, 17 (9–36) weeks, log-rank test: p=0.63). No association was found when other cut-off values (≥3% of total leukocytes and/or ≥300 eosinophils·µL−1) were used for the eosinophilic phenotype. However, the higher number of past severe exacerbations, a lower forced expiratory volume in 1 s (FEV1) at discharge and higher pack-years were related to shorter exacerbation-free time. According to a subgroup analysis (n=73), 48.1% of patients with initial eosinophilic exacerbations had non-eosinophilic relapses on readmission.ConclusionsOur data do not support an increased risk of earlier recurring moderate or severe relapses in patients hospitalised with eosinophilic exacerbations of COPD. Eosinophilic severe exacerbations present a variable phenotype.
Association between body mass index and mortality in hospitalised patients with community-acquired pneumonia
Authors: Kim Richard Y. , Glick Connor , Furmanek Stephen , Ramirez Julio A. , Cavallazzi Rodrigo 
Published: January 2021

The obesity paradox postulates that increased body mass index (BMI) is protective in certain patient populations. We aimed to investigate the association of BMI and different weight classes with outcomes in hospitalised patients with community-acquired pneumonia (CAP).This cohort study is a secondary data analysis of the University of Louisville Pneumonia Study database, a prospective study of hospitalised adult patients with CAP from June, 2014, to May, 2016, in Louisville, KY, USA. BMI as a predictor was assessed both as a continuous and categorical variable. Patients were categorised as weight classes based on World Health Organization definitions: BMI of <18.5 kg·m−2(underweight), BMI of 18.5 to <25 kg·m−2(normal weight), BMI of 25.0 to <30 kg·m−2(overweight), BMI of 30 to <35 kg·m−2(obesity class I), BMI of 35 to <40 kg·m−2(obesity class II), and BMI of ≥40 kg·m−2(obesity class III). Study outcomes, including time to clinical stability, length of stay, clinical failure and mortality, were assessed in hospital, at 30 days, at 6 months and at 1 year. Clinical failure was defined as the need for noninvasive ventilation, invasive ventilation or vasopressors within 1 week of admission. Patient characteristics and crude outcomes were stratified by BMI categories, and generalised additive binomial regression models were performed to analyse the impact of BMI as a continuous variable on study outcomes adjusting for possible confounding variables.7449 patients were included in the study. Median time to clinical stability was 2 days for every BMI group. There was no association between BMI as a continuous predictor and length of stay <5 days (chi-squared=1.83, estimated degrees of freedom (EDF)=2.74, p=0.608). Clinical failure was highest in the class III obesity group, and higher BMI as a continuous predictor was associated with higher odds of clinical failure. BMI as a continuous predictor was significantly associated with 30-day (chi-squared=39.97, EDF=3.07, p<0.001), 6-month (chi-squared=89.42, EDF=3.44, p<0.001) and 1-year (chi-squared=83.97, EDF=2.89, p<0.001) mortalities. BMI ≤24.14 kg·m−2was a risk factor whereas BMI ≥26.97 kg·m−2was protective for mortality at 1-year. The incremental benefit of increasing BMI plateaued at 35 kg·m−2.We found a protective benefit of obesity on mortality in CAP patients. However, we uniquely demonstrate that the association between BMI and mortality is not linear, and no incremental benefit of increasing BMI levels is observed in those with obesity classes II and III.
A toolkit for studying Varroa genomics and transcriptomics: preservation, extraction, and sequencing library preparation
Authors: Hasegawa Nonno , Techer Maeva , Mikheyev Alexander S. 
Published: January 2021

Abstract
Background
The honey bee parasite, Varroa destructor, is a leading cause of honey bee population declines. In addition to being an obligate ectoparasitic mite, Varroa carries several viruses that infect honey bees and act as the proximal cause of colony collapses. Nevertheless, until recently, studies of Varroa have been limited by the paucity of genomic tools. Lab- and field-based methods exploiting such methods are still nascent. This study developed a set of methods for preserving Varroa DNA and RNA from the field to the lab and processing them into sequencing libraries. We performed preservation experiments in which Varroa mites were immersed in TRIzol, RNAlater, and absolute ethanol for preservation periods up to 21 days post-treatment to assess DNA and RNA integrity.

Results
For both DNA and RNA, mites preserved in TRIzol and RNAlater at room temperature degraded within 10 days post-treatment. Mites preserved in ethanol at room temperature and 4 °C remained intact through 21 days. Varroa mite DNA and RNA libraries were created and sequenced for ethanol preserved samples, 15 and 21 days post-treatment. All DNA sequences mapped to the V. destructor genome at above 95% on average, while RNA sequences mapped to V. destructor, but also sometimes to high levels of the deformed-wing virus and to various organisms.

Conclusions
Ethanolic preservation of field-collected mites is inexpensive and simple, and allows them to be shipped and processed successfully in the lab for a wide variety of sequencing applications. It appears to preserve RNA from both Varroa and at least some of the viruses it vectors.
Comparison of hypoxemia, intubation procedure, and complications for non-invasive ventilation against high-flow nasal cannula oxygen therapy for patients with acute hypoxemic respiratory failure: a non-randomized retrospective analysis for effectiveness and safety (NIVaHIC-aHRF)
Authors: Zhang Chao , Ou Min 
Published: January 2021

Abstract
Background
Optimization of preoxygenation procedure can help to secure the method of intubation by reducing the risks of severe hypoxemia and other problems. There is confusion for efficacy of non-invasive ventilation compared to high-flow oxygen therapy regarding occurrence of severe hypoxemia during the intubation procedure. The purpose of the study was to compare the difference between noninvasive ventilation and high flow oxygen therapy to prevent desaturation during laryngoscopy.

Methods
Patients underwent high-flow nasal cannula oxygen therapy (HCO cohort, n = 161) or non-invasive ventilation procedure (NIV cohort, n = 154) for oxygenation and ventilation due to acute hypoxemic respiratory failure in the intensive care unit. Data before preoxygenation, preoxygenation, intubation, laryngoscopy, and complications of patients due to tracheal intubation were retrospectively collected and analyzed.

Results
There was no difference between both cohorts for the demographical and clinical conditions of the patients before preoxygenation (p > 0.05 for all parameters), numbers of patients with severe hypoxia during the intubation procedure (35 vs. 45, p = 0.303), the time duration of laryngoscopy (p = 0.847), number of laryngoscopies attempts (p = 0.804), and immediate and late complications during the intubation procedure. The values of pulse oximetry were reported higher for patients of NIV cohort than those of HCO cohort during preoxygenation. Fewer numbers of patients were reported with severe hypoxia among patients of the NIV cohort than those of the HCO cohort (24 vs., 40, p = 0.042) who have moderate-to-severe hypoxemia (partial pressure of arterial oxygen to fraction of inspired oxygen ratio ≤ 200 mmHg) before preoxygenation. The most common complications were hypertension, pulmonary aspiration, and increased 30-day mortality.

Conclusions
When compared, there was no difference between non-invasive ventilation technique and high-flow oxygen therapy to minimize severe hypoxia prior to laryngoscopy and endotracheal intubation in patients with acute respiratory failure.
Steps towards implementing evidence-based screening in family medicine in Ukraine: SWOT-analysis of an approach of multidimensional empowerment
Authors: Kolesnyk Pavlo , Frese Thomas , Vinker Shlomo , Shushman Ivanna , Zharkova Albina , Messaadi Nassir , Kolesnyk Andriy , Bayen Sabine 
Published: January 2021

Abstract
Background
The purpose of this study is to forward the implementation of an operational evidence-based state screening program of common diseases in Ukraine, where currently no state-based and evidence-based screening (EBS) exists. EBS should be performed by Family Doctors in a primary care setting and concern prevalent diseases in adults, such as: obesity (BMI), hypertension (BP measurement), diabetes (glycaemia), dyslipidemia (cholesterol/lipids), colon cancer (FOBT/colonoscopy), breast cancer (mammography), STIs (chlamydia, syphilis), HIV, HBV, HCV (i.e. serology or other rapid tests), HPV (swabs), cervical cancer (test Pap). depression (i.e., PHQ-9), and smoking (i.e., Fagerstrom).

Methods
Four needs-based research actions were led among citizens and healthcare professionals, based on multidimensional empowerment. Internal Strengths and Weaknesses of the ongoing implementation process were identified through these studies, whereas external Opportunities and Threats were determined by the present socio-cultural and political context. This SWOT analysis is likely to guide future state-based initiatives to accomplish EBS implementation in Ukraine.

Results
Internal Strengths are the bottom-up multidimensional empowerment approach, teaching of EBS and the development of an internet-based platform “Screening adviser” to assist shared decision making for person-centred EBS programs. Internal Weaknesses identified for the Family Doctors are a heterogeneous screening and the risk of decreasing motivation to screen. External Opportunities include the ongoing PHC reform, the existent WONCA and WHO support, and the existence of EBS programs in Europe. External Threats are the lack of national guidelines, not fully introduced gate keeping system, the vulnerable socio-economic situation, the war situation in the East of Ukraine and the Covid-19 pandemic.

Conclusions
We started EBS implementation through research actions, based on a multidimensional empowerment of citizens, HCP and in EBS pathways involved stakeholder teams, to foster a sustainable operational human resource to get involved in that new EBS pathway to implement. The presented SWOT-analysis of this ongoing implementation process allows to plan and optimize future steps towards a state based and supports EBS program in Ukraine.
Prognostic value of low microRNA-34a expression in human gastrointestinal cancer: a systematic review and meta-analysis
Authors: Chen Yan-Ling , Liu Xiao-Lin , Li Ling 
Published: January 2021

Abstract
Background
Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs).

Methods
All eligible studies were found by searching PubMed, Web of Science and EMBASE, and survival results were extracted. Then, the hazard ratio (HR) with the corresponding 95% confidence interval (CI) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratios (ORs) and 95% CIs.

Results
A total of 20 studies were included in this meta-analysis. For overall survival (OS), lower miR-34a expression could probably predict poorer outcome in GICs, with a pooled HR of 1.86 (95% CI: 1.52–2.28, P < 0.01). For disease-free survival (DFS), progression-free survival (PFS), and recurrence-free survival (RFS), lower miR-34a expression was related to worse DFS/PFS/RFS with a pooled HR of 1.86 (95% CI: 1.31–2.63, P  <  0.01). A significant relation of differentiation/TNM stage/lymphatic metastasis and the expression level of miR-34a was identified.

Conclusion
This meta-analysis revealed that lower miR-34a expression is significantly connected with worse OS and DFS/PFS/RFS in GIC patients. In addition, the miR-34a expression level is relatively lower in patients with lymph node metastasis than in patients without lymph node metastasis, and decreased miR-34a expression levels are linked to poor tumour differentiation and late TNM stage. MiR-34a may become a new factor for the prognosis prediction and progression of GICs.
Patients with low nicotinamide N-methyltransferase expression benefit significantly from bevacizumab treatment in ovarian cancer
Authors: Li Jun , Yue Huiran , Yu Hailin , Lu Xin , Xue Xiaohong 
Published: January 2021

Abstract
Background
The role of nicotinamide N-methyltransferase (NNMT) in ovarian cancer is still elusive. Our aim is to explore the expression of NNMT in ovarian cancer and to assess its association with patient prognosis and treatment response.

Methods
We first analyzed the differential expression of NNMT among fallopian tube epithelium, primary ovarian cancers, metastatic ovarian cancers, and recurrent ovarian cancers using Gene Expression Ominus (GEO) database (GSE10971, GSE30587, GSE44104 and TCGA datasets). Then, we assessed the association of NNMT expression with clinical and molecular parameters using CSIOVDB database and GSE28739 dataset. Next, we evaluate the association of NNMT expression with the prognosis of ovarian cancer patients in both GSE9891 dataset and TCGA dataset. Finally, GSE140082 dataset was used to explore the association of NNMT expression with bevacizumab response.

Results
NNMT expression was significantly elevated in lymphovascular space invasion (LVSI)-positive ovarian cancers compared with that in LVSI-negative ovarian cancers (TCGA dataset, P < 0.05), Moreover, increased expression of NNMT was associated with increased tumor stage, grade, and mesenchymal molecular subtype (CSIOVDB database). Survival analysis indicated that increased expression of NNMT was associated with a reduced OS in both GSE9891 dataset (HR: 2.28, 95%CI: 1.51–3.43, Log-rank P < 0.001) and TCGA dataset (HR: 1.55, 95%CI: 1.02–2.36, Log-rank P = 0.039). Multivariate analysis further confirmed the negative impact of NNMT expression on OS in ovarian cancer patients in those two datasets. Furthermore, the NNMT-related nomogram showed that NNMT shared a larger contribution to OS, compared with debulking status. More interestingly, bevacizumab conferred significant improvements in OS for patients with low NNMT expression (HR: 0.56, 95%CI: 0.31–0.99, Log-rank P = 0.049). In contrast, patients with high NNMT expression didn’t benefit from bevacizumab treatment significantly (HR: 0.85, 95%CI: 0.48–1.49, Log-rank P = 0.561). NNMT expression was positively correlated with the expression of genes, LDHA and PGAM1, involved in Warburg effect.

Conclusions
In conclusion, NNMT expression is associated with the aggressive behavior of ovarian cancer, correlates with a poor prognosis, and is predictive of sensitivity to bevacizumab treatment.
Detection of active and inactive phases of thyroid-associated ophthalmopathy using deep convolutional neural network
Authors: Lin Chenyi , Song Xuefei , Li Lunhao , Li Yinwei , Jiang Mengda , Sun Rou , Zhou Huifang , Fan Xianqun 
Published: January 2021

AbstractBackgroundThis study aimed to establish a deep learning system for detecting the active and inactive phases of thyroid-associated ophthalmopathy (TAO) using magnetic resonance imaging (MRI). This system could provide faster, more accurate, and more objective assessments across populations.MethodsA total of 160 MRI images of patients with TAO, who visited the Ophthalmology Clinic of the Ninth People’s Hospital, were retrospectively obtained for this study. Of these, 80% were used for training and validation, and 20% were used for testing. The deep learning system, based on deep convolutional neural network, was established to distinguish patients with active phase from those with inactive phase. The accuracy, precision, sensitivity, specificity, F1 score and area under the receiver operating characteristic curve were analyzed. Besides, visualization method was applied to explain the operation of the networks.ResultsNetwork A inherited from Visual Geometry Group network. The accuracy, specificity and sensitivity were 0.863±0.055, 0.896±0.042 and 0.750±0.136 respectively. Due to the recurring phenomenon of vanishing gradient during the training process of network A, we added parts of Residual Neural Network to build network B. After modification, network B improved the sensitivity (0.821±0.021) while maintaining a good accuracy (0.855±0.018) and a good specificity (0.865±0.021).ConclusionsThe deep convolutional neural network could automatically detect the activity of TAO from MRI images with strong robustness, less subjective judgment, and less measurement error. This system could standardize the diagnostic process and speed up the treatment decision making for TAO.
Growth, puberty, and bone health in children and adolescents with inflammatory bowel disease
Authors: Jin Hye-Young , Lim Jae-Sang , Lee Yena , Choi Yunha , Oh Seak-Hee , Kim Kyung-Mo , Yoo Han-Wook , Choi Jin-Ho 
Published: January 2021

AbstractBackgroundEndocrine complications such as impaired growth, delayed puberty, and low bone mineral density (BMD) can be associated with inflammatory bowel disease (IBD) in children and adolescents. This study was performed to investigate the frequency, characteristics, and outcomes of endocrine complications of IBD in children and adolescents.MethodsThis study included 127 patients with IBD diagnosed before 18 years of age [117 with Crohn disease (CD) and 10 with ulcerative colitis (UC)]. Growth profiles, pubertal status, 25-hydroxyvitamin D3[25(OH)D3] levels, and BMD were reviewed retrospectively.ResultsShort stature was observed in 14 of 127 (11.0 %) with a mean height-SDS of -2.31 ± 0.72. During a 2-year follow-up period, height-SDS did not significantly improve, while weight-SDS significantly improved. Among 109 patients who were older than 13 (girls) or 14 (boys) years of age during the study period, 11 patients (10.1 %) showed delayed puberty, which was associated with low weight-SDS. Vitamin D deficiency was documented in 81.7 % (94/115) with the average 25(OH)D3level of 14.5 ± 7.0 ng/mL. Lumbar BMD Z-score was below − 2 SDS in 25 of 119 patients (21.0 %). Height-SDS, weight-SDS, and body mass index (BMI)-SDS were lower in patients with osteoporosis than those without osteoporosis. When pediatric CD activity index scores were high (≥ 30), weight-SDS, BMI-SDS, insulin-like growth factor 1 (IGF-1)-SDS, and testosterone levels were significantly decreased.ConclusionsVitamin D deficiency and osteoporosis are common in pediatric IBD patients. As disease severity deteriorates, weight-SDS, IGF-1-SDS, and testosterone levels were decreased. Optimal pubertal development is necessary for bone health.