bluuebunny/crossref_metadata_2025_split huggingface dataset:
The GPCR adaptor protein norbin suppresses the neutrophil-mediated immunity of mice to pneumococcal infection
Authors: Pantarelli Chiara , Pan Dingxin , Chetwynd Stephen , Stark Anne-Katrien , Hornigold Kirsti , Machin Polly , Crossland Laraine , Cleary Simon J. , Baker Martin J. , Hampson Elizabeth , Mandel Anna , Segonds-Pichon Anne , Walker Rachael , van ’t Veer Cornelis , Riffo-Vasquez Yanira , Okkenhaug Klaus , Pitchford Simon , Welch Heidi C.E. 
Published: August 2021

AbstractStreptococcal pneumonia is a worldwide health problem that kills ∼2 million people each year, particularly young children, the elderly, and immunosuppressed individuals. Alveolar macrophages and neutrophils provide the early innate immune response to clear pneumococcus from infected lungs. However, the level of neutrophil involvement is context dependent, both in humans and in mouse models of the disease, influenced by factors such as bacterial load, age, and coinfections. Here, we show that the G protein–coupled receptor (GPCR) adaptor protein norbin (neurochondrin, NCDN), which was hitherto known as a regulator of neuronal function, is a suppressor of neutrophil-mediated innate immunity. Myeloid norbin deficiency improved the immunity of mice to pneumococcal infection by increasing the involvement of neutrophils in clearing the bacteria, without affecting neutrophil recruitment or causing autoinflammation. It also improved immunity during Escherichia coli–induced septic peritonitis. It increased the responsiveness of neutrophils to a range of stimuli, promoting their ability to kill bacteria in a reactive oxygen species–dependent manner, enhancing degranulation, phagocytosis, and the production of reactive oxygen species and neutrophil extracellular traps, raising the cell surface levels of selected GPCRs, and increasing GPCR-dependent Rac and Erk signaling. The Rac guanine-nucleotide exchange factor Prex1, a known effector of norbin, was dispensable for most of these effects, which suggested that norbin controls additional downstream targets. We identified the Rac guanine-nucleotide exchange factor Vav as one of these effectors. In summary, our study presents the GPCR adaptor protein norbin as an immune suppressor that limits the ability of neutrophils to clear bacterial infections.
Long-term effect of hematopoietic cell transplantation on systemic inflammation in patients with mucopolysaccharidoses
Authors: van den Broek Brigitte T.A. , Lindemans Caroline A. , Boelens Jaap Jan , Delemarre Eveline M. , Drylewicz Julia , Verhoeven-Duif Nanda , van Hasselt Peter M. , Nierkens Stefan 
Published: August 2021

Abstract
Mucopolysaccharidoses (MPS) are devastating inherited diseases treated with hematopoietic cell transplantation (HCT). However, disease progression, especially skeletal, still occurs in all patients. Secondary inflammation has been hypothesized to be a cause. To investigate whether systemic inflammation is present in untreated patients and to evaluate the effect of HCT on systemic inflammation, dried blood spots (n = 66) of patients with MPS (n = 33) treated with HCT between 2003 and 2019 were included. Time points consisted of pre-HCT and, for patients with MPS type I (MPS I), also at 1, 3, and 10 years of follow-up. Ninety-two markers of the OLINK inflammation panel were measured and compared with those of age-matched control subjects (n = 31) by using principal component analysis and Wilcoxon rank sum tests with correction. Median age at transplantation was 1.3 years (range, 0.2-4.8 years), and median time of pre-HCT sample to transplantation was 0.1 year. Normal leukocyte enzyme activity levels were achieved in 93% of patients post-HCT. Pretransplant samples showed clear separation of patients and control subjects. Markers that differentiated pre-HCT between control subjects and patients were mainly pro-inflammatory (50%) or related to bone homeostasis and extracellular matrix degradation (33%). After 10 years’ follow-up, only 5 markers (receptor activator of nuclear factor kappa-Β ligand, osteoprotegerin, axis inhibition protein 1 [AXIN1], stem cell factor, and Fms-related tyrosine kinase 3 ligand) remained significantly increased, with a large fold change difference between patients with MPS I and control subjects. In conclusion, systemic inflammation is present in untreated MPS patients and is reduced upon treatment with HCT. Markers related to bone homeostasis remain elevated up to 10 years after HCT and possibly reflect the ongoing skeletal disease, making them potential biomarkers for the evaluation of new therapies.
Bayesian Hodges-Lehmann tests for statistical equivalence in the two-sample setting: Power analysis, type I error rates and equivalence boundary selection in biomedical research
Authors: Kelter Riko 
Published: August 2021

AbstractBackgroundNull hypothesis significance testing (NHST) is among the most frequently employed methods in the biomedical sciences. However, the problems of NHST andp-values have been discussed widely and various Bayesian alternatives have been proposed. Some proposals focus on equivalence testing, which aims at testing an interval hypothesis instead of a precise hypothesis. An interval hypothesis includes a small range of parameter values instead of a single null value and the idea goes back to Hodges and Lehmann. As researchers can always expect to observe some (although often negligibly small) effect size, interval hypotheses are more realistic for biomedical research. However, the selection of an equivalence region (the interval boundaries) often seems arbitrary and several Bayesian approaches to equivalence testing coexist.MethodsA new proposal is made how to determine the equivalence region for Bayesian equivalence tests based on objective criteria like type I error rate and power. Existing approaches to Bayesian equivalence testing in the two-sample setting are discussed with a focus on the Bayes factor and the region of practical equivalence (ROPE). A simulation study derives the necessary results to make use of the new method in the two-sample setting, which is among the most frequently carried out procedures in biomedical research.ResultsBayesian Hodges-Lehmann tests for statistical equivalence differ in their sensitivity to the prior modeling, power, and the associated type I error rates. The relationship between type I error rates, power and sample sizes for existing Bayesian equivalence tests is identified in the two-sample setting. Results allow to determine the equivalence region based on the new method by incorporating such objective criteria. Importantly, results show that not only can prior selection influence the type I error rate and power, but the relationship is even reverse for the Bayes factor and ROPE based equivalence tests.ConclusionBased on the results, researchers can select between the existing Bayesian Hodges-Lehmann tests for statistical equivalence and determine the equivalence region based on objective criteria, thus improving the reproducibility of biomedical research.
Two-stage sampling in the estimation of growth parameters and percentile norms: sample weights versus auxiliary variable estimation
Authors: Vamvakas George , Norbury Courtenay , Pickles Andrew 
Published: August 2021

AbstractBackgroundThe use of auxiliary variables with maximum likelihood parameter estimation for surveys that miss data by design is not a widespread approach, despite its documented improved efficiency over traditional approaches that deploy sampling weights. Although efficiency gains from the use of Normally distributed auxiliary variables in a model have been recorded in the literature, little is known about the effects of non-Normal auxiliary variables in the parameter estimation.MethodsWe simulate growth data to mimic SCALES, a two-stage survey of language development with a screening phase (stage one) for which data are observed for the whole sample and an intensive assessments phase (stage two), for which data are observed for a sub-sample, selected using stratified random sampling. In the simulation, we allow a fully observed Poisson distributed stratification criterion to be correlated with the partially observed model responses and develop five generalised structural equation growth models that host the auxiliary information from this criterion. We compare these models with each other and with a weighted growth model in terms of bias, efficiency, and coverage. We finally apply our best performing model to SCALES data and show how to obtain growth parameters and population norms.ResultsParameter estimation from a model that incorporates a non-Normal auxiliary variable is unbiased and more efficient than its weighted counterpart. The auxiliary variable method is capable of producing efficient population percentile norms and velocities.ConclusionsThe deployment of a fully observed variable that dominates the selection of the sample and correlates strongly with the incomplete variable of interest appears beneficial for the estimation process.
Modeling of atrophy size trajectories: variable transformation, prediction and age-of-onset estimation
Authors: Behning Charlotte , Fleckenstein Monika , Pfau Maximilian , Adrion Christine , Goerdt Lukas , Lindner Moritz , Schmitz-Valckenberg Steffen , Holz Frank G , Schmid Matthias 
Published: August 2021

AbstractBackgroundTo model the progression of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) by building a suitable statistical regression model for GA size measurements obtained from fundus autofluorescence imaging.MethodsBased on theoretical considerations, we develop a linear mixed-effects model for GA size progression that incorporates covariable-dependent enlargement rates as well as correlations between longitudinally collected GA size measurements. To capture nonlinear progression in a flexible way, we systematically assess Box-Cox transformations with different transformation parametersλ. Model evaluation is performed on data collected for two longitudinal, prospective multi-center cohort studies on GA size progression.ResultsA transformation parameter ofλ=0.45 yielded the best model fit regarding the Akaike information criterion (AIC). When hypertension and hypercholesterolemia were included as risk factors in the model, they showed an association with progression of GA size. The mean estimated age-of-onset in this model was 67.21±6.49 years.ConclusionsWe provide a comprehensive framework for modeling the course of uni- or bilateral GA size progression in longitudinal observational studies. Specifically, the model allows for age-of-onset estimation, identification of risk factors and prediction of future GA size. A square-root transformation of atrophy size is recommended before model fitting.
Uterine fibroids and risk of preterm birth by clinical subtypes: a prospective cohort study
Authors: Sundermann Alexandra C. , Aldridge Tiara D. , Hartmann Katherine E. , Jones Sarah H. , Torstenson Eric S. , Edwards Digna R. Velez 
Published: August 2021

Abstract
Background
Fibroids are present in approximately one in ten pregnancies and are inconsistently linked with preterm birth. We sought to determine the association between fibroids and preterm birth in a prospective cohort with standardized research ultrasounds for characterizing fibroids in early pregnancy while accounting for the clinical paths that precede preterm birth.

Methods
Participants who were pregnant or planning a pregnancy were recruited from communities in three states between 2000 and 2012. Members of this prospective cohort had a research ultrasound in the first trimester to establish pregnancy dating and to record detailed information about the presence, size, number, and location of fibroids. Baseline information from time of enrollment and a detailed first trimester interview contributed key information about candidate confounders. Birth outcomes, including clinical classification of type of preterm birth (preterm labor, preterm premature rupture of membranes, and medically indicated preterm birth) were cross-validated from participant report, labor and delivery records, and birth certificate data.

Results
Among 4,622 women with singleton pregnancies, 475 had at least one fibroid (10.3%) and 352 pregnancies resulted in preterm birth (7.6%). Prevalence of fibroids was similar for women with preterm and term births (10.2% vs. 10.3%). Fibroids were not associated with increased risk of preterm birth after taking into account confounding (risk ratio adjusted for race/ethnicity and maternal age, 0.88; 95% confidence interval, 0.62–1.24) nor any clinical subtype of preterm birth. No fibroid characteristic or combination of characteristics was associated with risk.

Conclusions
If fibroids increase risk of preterm birth, the effect is substantially smaller than previous estimates. Given lack of effect in a large population of women from the general population, rather than higher risk academic tertiary populations previously most studied, we encourage a reconsideration of the clinical impression that presence of fibroids is a major risk factor for preterm birth.
The role of complement factor H in gestational diabetes mellitus and pregnancy
Authors: Li Junxian , Shen Ying , Tian Hairong , Xie Shuting , Ji Ye , Li Ziyun , Lu Junxi , Lu Huijuan , Liu Bo , Liu Fang 
Published: August 2021

AbstractBackgroundComplement factor H (CFH) has been found to be associated with insulin resistance. This study assessed the correlation between CFH and other clinical parameters, and determined whether CFH played a role in gestational diabetes mellitus (GDM) and adverse pregnancy outcomes.MethodsA total of 397 pregnant women were included for analysis in this nested case-control study. Clinical parameters and serum were collected within the 11-17th gestational age at the first prenatal visit. At 24–28 weeks of gestation, a 75 g oral glucose tolerance test was performed and subjects were divided into a GDM (n = 80) and a non-GDM control group (n = 317). The delivery data were also followed. The serum CFH level was assayed by ELISA.ResultsCFH was higher in GDM than in non-GDM controls (280.02 [58.60] vs. 264.20 [68.77];P = 0.014). CFH level was moderately associated with pre-pregnancy body mass index (BMI), BMI and total triglycerides (TG), and slightly associated with gestational age, low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) in GDM and non-GDM (allP <  0.05). Moreover, CFH level was moderately correlated with alkaline phosphatase (ALP) and slightly correlated with age, uric acid (UA) and total bilirubin (TB) in non-GDM (allP <  0.05). After adjustment for clinical confounding factors, BMI, TG, gestational age, ALP, TB, age and UA were independent risk factors for log10CFH levels (allP <  0.05) in all subjects. In addition, overweight or obese pregnant women, women with hypertriglyceridemia and women in the second trimester had significantly higher CFH levels than normal weight and underweight group (P <  0.001), the non-hypertriglyceridemia group (P <  0.001) and women in the first trimester group (P < 0.05) in all pregnant women respectively. Following binary logistic regression, CFH was not independently associated with GDM and related pregnant outcomes.ConclusionsThe CFH in 11-17th weeks of gestation might be affected by many factors, including BMI, TG, gestational age, ALP, TB, age and UA. CFH was not an independent risk factor for GDM and avderse pregnancy outcomes.
Postpartum septic pelvic thrombophlebitis and ovarian vein thrombosis after caesarean section: a rare case report
Authors: Shi Qin , Gandi Deborah Shulamite , Hua Yurong , Zhu Yi , Yao Jinhan , Yang Xiaoqing , Xu Yunzhao , Zhang Yuquan 
Published: August 2021

Abstract
Background
Septic pelvic thrombophlebitis (SPT) is a well-recognized but rare puerperal complication that has two types: ovarian vein thrombophlebitis (OVT) and deep septic pelvic thrombophlebitis (DSPT). The present case report describes the clinical and imaging findings of a female patient diagnosed with right ovarian vein infectious thrombophlebitis after caesarean section (C-section).

Case presentation
A 35-year-old G3P2 female who presented with a foetal vein Galen malformation at 41 weeks of gestation underwent C-section. The patient had high fever after C-section, and anti-inflammatory treatment was not effective within 1 week. An abdominal wall incision haematoma was found, and a second surgery for the removal of the abdominal wall haematoma was performed. The patient was ultimately diagnosed with abdominal incision haematoma and right ovarian vein infectious thrombophlebitis after C-section. We used imipenem and tigecycline to strengthen the anti-inflammatory effects, simultaneously administrating low-molecular-weight heparin and warfarin as anticoagulant therapy. On the 30th day after C-section, the right ovarian vein thrombus disappeared.

Conclusion
This case illustrates the need to consider the potential relationship between abdominal incision haematoma and ovarian vein thrombophlebitis. Despite advances in the management of venous thromboembolism globally, more data on epidemiology in terms of first incidence, prevalence, recurrence and risk factors, management of bleeding complications, and increased awareness in Asian populations are necessary.
What is beyond Salmonella gastroenteritis? A case of acute pancreatitis complicating Salmonella infection in a child: a case report and literature review
Authors: Al Kaabi Salwa , Al Kaabi Aysha , Al Nuaimi Hasa 
Published: August 2021

Abstract
Background
Salmonella infection presents itself in a wide variety of ways, ranging from mild self-limited illness to severe systemic disease with multiorgan involvement. Acute pancreatitis (AP) is a very rare complication that is associated with Salmonella infection, especially among the pediatric population.

Case presentation
A five-year-old boy presented with a two-day fever and experienced vomiting, diarrhea, and abdominal pain. The boy was admitted as a case of acute gastroenteritis, and Salmonella was found in his stool culture. The severity of his abdominal pain during his hospital stay indicated the possibility of AP. A clinical examination and blood workup were performed and showed significant elevation in amylase and lipase, which confirmed the diagnosis of AP.

Conclusion
Although abdominal pain is a common presentation of Salmonella infection, the possibility of AP must be considered when the pain is severe and the characteristics of the pain are suggestive of AP. Herein, we report a case of AP complicating Salmonella infection in an immunocompetent child.
Joint trajectories of life style indicators and their links to psychopathological outcomes in the adolescence
Authors: Zhang Anhui , Fang Jiao , Wan Yuhui , Su Puyu , Tao Fangbiao , Sun Ying 
Published: August 2021

Abstract
Background
Rapid socio-economic development makes China a unique laboratory for examining how lifestyle changes affect adolescent mental health. This study aims to identify joint trajectories of modifiable lifestyle indicators during pubertal transition and its associations with psychopathological outcomes.

Methods
A cohort of 1974 children aged 7–9 years were recruited in Anhui Province, China during March 2013. The assessment of lifestyle behaviors (screen time, physical activity, sleep duration and beverage intake) and depressive symptoms were conducted from Wave 1 to Wave 4 (2018). Suicide ideation, non-suicidal self-harm (NSSI) and alcohol use were self-reported at Wave 4. Longitudinal trajectories of lifestyle patterns were defined using group-based multi-trajectory models in 2019.

Results
Four lifestyle trajectories were identified: persistent healthy (39.9%), suboptimal healthy (25.3%), unhealthy mitigation (17.2%), and persistent unhealthy (17.7%). Compared with persistent healthy group, the risk of subsequent suicide ideation [odds ratio (OR): 2.86, 95%CI: 2.15–3.81], depressive symptoms (OR: 2.16, 95%CI: 1.39–3.35), alcohol use (OR: 2.53, 95%CI: 1.78–3.61) and non-suicidal self-harm (OR: 1.35, 95%CI: 1.09–1.67) was significantly higher in persistent unhealthy group.

Conclusions
This study provided convincing evidence that unhealthy lifestyle trajectory during adolescence is associated with more than two-fold elevated odds for multiple domains of psychopathological outcomes over 5 years.
Prevalence and clinical consequences of atelectasis in SARS-CoV-2 pneumonia: a computed tomography retrospective cohort study
Authors: Mingote Álvaro , Albajar Andrea , García Benedito Paulino , Garcia-Suarez Jessica , Pelosi Paolo , Ball Lorenzo , García-Fernández Javier 
Published: August 2021

Abstract
Background
The aim of the study is to estimate the prevalence of atelectasis assessed with computer tomography (CT) in SARS-CoV-2 pneumonia and the relationship between the amount of atelectasis with oxygenation impairment, Intensive Care Unit admission rate and the length of in-hospital stay.

Patients and methods
Two-hundred thirty-seven patients admitted to the hospital with SARS-CoV-2 pneumonia diagnosed by clinical, radiology and molecular tests in the nasopharyngeal swab who underwent a chest computed tomography because of a respiratory worsening from Apr 1 to Apr 30, 2020 were included in the study. Patients were divided into three groups depending on the presence and amount of atelectasis at the computed tomography: no atelectasis, small atelectasis (< 5% of the estimated lung volume) or large atelectasis (> 5% of the estimated lung volume). In all patients, clinical severity, oxygen-therapy need, Intensive Care Unit admission rate, the length of in-hospital stay and in-hospital mortality data were collected.

Results
Thirty patients (19%) showed small atelectasis while eight patients (5%) showed large atelectasis. One hundred and seventeen patients (76%) did not show atelectasis. Patients with large atelectasis compared to patients with small atelectasis had lower SatO2/FiO2 (182 vs 411 respectively, p = 0.01), needed more days of oxygen therapy (20 vs 5 days respectively, p = 0,02), more frequently Intensive Care Unit admission (75% vs 7% respectively, p < 0.01) and a longer period of hospitalization (40 vs 14 days respectively p < 0.01).

Conclusion
In patients with SARS-CoV-2 pneumonia, atelectasis might appear in up to 24% of patients and the presence of larger amount of atelectasis is associated with worse oxygenation and clinical outcome.