bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic analysis on expression quantitative trait loci identifies a novel regulatory variant in ring finger and WD repeat domain 3 associated with prognosis of pancreatic cancer
Authors: Zhu Ying , Peng Xiating , Wang Xiaoyang , Ying Pingting , Wang Haoxue , Li Bin , Li Yue , Zhang Ming , Cai Yimin , Lu Zequn , Niu Siyuan , Yang Nan , Zhong Rong , Tian Jianbo , Chang Jiang , Miao Xiaoping 
Published: July 2022

Abstract

Background:
Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.

Methods:
Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.

Results:
A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 (RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process.

Conclusions:

RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.
Cardiorespiratory Insufficiency and Performance Fatigability in Women With Systemic Lupus Erythematosus
Authors: Wooten Liana C. , Hasni Sarfaraz , Mikdashi Jamal A. , Keyser Randall E. 
Published: July 2022

Purpose:Patients with systemic lupus erythematosus (SLE) experience excessive, debilitating fatigue with previously reported evidence of etiologically mediated cardiorespiratory impairments. Performance fatigability provides a precise characterization of fatigue as it can be quantified objectively as a function of time, frequency, and/or duration. Nevertheless, little consideration has been given to understanding performance fatigability and its physiological determinants in those with SLE. The purpose of this study was to characterize performance fatigability in patients with SLE, using measures surrounding the anaerobic threshold, with emphasis on cardiorespiratory impairment as a potential mediating factor.Methods:This was a case–control study design. 44 physically inactive women, 26 with SLE and 18 controls, completed a treadmill cardiopulmonary exercise test to volitional exhaustion.Results:There were no significant differences in age (SLE 34.8(9.0) versus control 36.9(7.3) years;P= .422) between groups. Body mass index (SLE 27.1(5.4) versus control 23.8(5.2) kg/m2;P= .045) was significantly higher in the SLE versus control group. Resting heart rate (SLE 68(16) versus control 78(15) bpm;P= .040) was significantly lower in the SLE compared with the control group. The VO2corresponding to the anaerobic threshold (AT-VO2), used to identify the onset of exercise-induced fatigue, was significantly lower in women with SLE than in controls (SLE 12.4(3.1) versus control 16.4(2.2) ml/kg/min;P< .001), as was AT-stage (SLE 2.5(0.90) versus control 3.4(0.78);P= .002). In addition, the Fatigue Severity Scale (FSS) score was highly and inversely correlated with AT-VO2(rho = −0.615;P< .001), and FSS was highly correlated with the functional aerobic impairment index (rho = 0.663;P< .001).Conclusions:This study underscores severe performance fatigability in patients with SLE and its link to cardiorespiratory insufficiency. Physiological presentation of performance fatigability was observed during very low intensities of exercise, emphasizing the negative impact it may have on physical function in this population.
Pediatric Enterococcal Bacteremia: A 12-Year Retrospective Study in a French Pediatric Center
Authors: Bizot Etienne , Truong Jeanne , Mariani-Kurkdjian Patricia , Bonacorsi Stephane , Faye Albert , Caseris Marion 
Published: July 2022

Background:
Enterococcal bloodstream infections (EBSIs) are rare infections in children associated with 5%–10% of mortality in previous studies. The recent evolution of antimicrobial resistance and therapies require updated data.

Methods:
We conducted an observational retrospective study between January 2008 and December 2019 describing the characteristics of children with EBSI in a French pediatric hospital. All positive Enterococcus spp. blood cultures associated with sepsis symptoms were analyzed. We also compared characteristics of healthcare-associated infections (HAIs) and community-acquired infections (CAIs) and described antimicrobial resistance evolution during this period.

Results:
In total 74 EBSI were included. Enterococcus faecalis was the most common pathogen (n = 60/74, 81%) followed by Enterococcus faecium (n = 18, 24%), including 4 enterococcal coinfections. EBSIs were mainly associated with central-line associated infection (38%), surgical site infection (14%) or urinary tract infection (11%). An underlying disease was present in 95.9%. However, 4 patients died in the month following the EBSI resulting in a 5.4%, 30-day mortality. All were HAI. HAI (84% of EBSI) was associated with longer bacteremia [31% persistent bacteremia (more than 3 days) versus 0% for CAI; P = 0.029] and more antimicrobial resistance. Amoxicillin resistance is increasing since 2013 in E. faecium (63% in 2013–2019), although high-level gentamicin resistance is stable (19%). Only 1 EBSI due to vancomycin-resistant Enterococcus was described in our cohort, who died.

Conclusions:
EBSIs are rare infections in children mostly described in children with underlying disease. Healthcare-associated bacteremia is associated with higher rates of resistance and poorer prognosis, requiring the involvement of pediatric infectious disease specialists to improve management.
Etiology and Risk Factors for Admission to the Pediatric Intensive Care Unit in Children With Encephalitis in a Developing Country
Authors: Guerrero María P. , Romero Andrés F. , Luengas Miguel , Dávalos Diana M. , Mesa-Monsalve Juan Gonzalo , Vivas-Trochez Rosalba , Camacho-Moreno German , Trujillo-Valencia Mónica , Giraldo Juan P. Calle , Mejía Luis F. , Rojas-Hernández Juan P. , Vinasco Nathaly , Racines Andrea Ruiz , Meléndez Alejandro , Beltrán Claudia P. , López Pio , Chaucanez Yamile , Patiño Jaime , Rodríguez Wilfrido Coronell , Salgado Doris , Martínez Marly , Restrepo Andrea , Márquez Kelly , Galvis Diego , Benavidez Iván , Rojas Christian A. , Cantor Erika , López Medina Eduardo 
Published: July 2022

Objective:
To describe a cohort of pediatric patients with encephalitis and their risk factors for admission to the pediatric intensive care unit (PICU).

Study Design:
Children (<18 years old), with encephalitis evaluated by conventional microbiology and syndromic, multiplex test in cerebrospinal fluid (CSF) between July 2017 and July 2020, were recruited from 14 hospitals that comprise the Colombian Network of Encephalitis in Pediatrics. Multivariate analyses were used to evaluate risk factors associated with the need for PICU admission.

Results:
Two hundred two children were included, of which 134 (66.3%) were male. The median age was 23 months (IQR 5.7–73.2). The main etiologies were bacteria (n = 55, 27%), unspecified viral encephalitis (n = 44, 22%) and enteroviruses (n = 27, 13%), with variations according to age group. Seventy-eight patients (38.6%) required management in the PICU. In multivariate analysis, factors associated with admission to the PICU were the presence of generalized seizures (OR 2.73; 95% CI: 1.82–4.11), status epilepticus (OR 3.28; 95% CI: 2.32–4.62) and low leukocyte counts in the CSF (OR 2.86; 95% CI: 1.47–5.57). Compared with enterovirus, bacterial etiology (OR 7.50; 95% CI: 1.0–56.72), herpes simplex encephalitis (OR 11.81; 95% CI: 1.44–96.64), autoimmune encephalitis (OR 22.55; 95% CI: 3.68–138.16) and other viral infections (OR 5.83; 95% CI: 1.09–31.20) increased the risk of PICU admission.

Conclusions:
Data from this national collaborative network of pediatric patients with encephalitis allow early identification of children at risk of needing advanced care and can guide the risk stratification of admission to the PICU.
Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease
Authors: Dipasquale Valeria , Pellegrino Salvatore , Ventimiglia Marco , Cucinotta Ugo , Citrano Michele , Graziano Francesco , Cappello Maria , Busacca Anita , Orlando Ambrogio , Accomando Salvatore , Romano Claudio ,   Sicilian Network for Inflammatory Bowel Disease
Published: July 2022

Objective
To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD).

Methods
A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes.

Results
Eighty-seven patients [Crohn’s disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations (P = 0.018) and in those who were nonnaïve to anti-TNF-α (P = 0.027).

Conclusion
This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.
Did Age at Surgery Influence Outcome in Patients With Hirschsprung Disease? A Nationwide Cohort Study in the Netherlands
Authors: Roorda Daniëlle , Verkuijl Sanne J. , Derikx Joep P. M. , Trzpis Monika , Meinds Rob J. , Sloots Cornelius E. J. , Witvliet Marieke J. , de Blaauw Ivo , van Gemert Wim G. , van Heurn Lodewijk W. E. , Broens Paul M. A. 
Published: July 2022

Objectives:
Hirschsprung disease (HD) requires surgical resection of affected bowel, but the current evidence is inconclusive regarding the optimal age for resection. The aim of this study was to assess whether age at resection of the aganglionic segment is a determinant for surgical outcomes.

Methods:
A cross-sectional cohort study was done including all consecutive patients with HD between 1957 and 2015, aged 8 years or older (n = 830), who were treated in 1 of the 6 pediatric surgical centers in the Netherlands. Outcome measures were mortality, postoperative complications, stoma rate and redo surgery rate, retrieved from the medical records. Additionally, constipation and fecal incontinence rate in long term were assessed with the Defecation and Continence Questionnaire (DeFeC and P-DeFeC).

Results:
The medical records of 830 patients were reviewed, and 346 of the 619 eligible patients responded to the follow-up questionnaires (56%). There was a small increase in the risk of a permanent stoma [odds ratio (OR) 1.01 (95% confidence interval {CI}: 1.00–1.02); P = 0.019] and a temporary stoma [OR 1.01 (95% CI: 1.00–1.01); P = 0.022] with increasing age at surgery, regardless of the length of the aganglionic segment and operation technique. Both adjusted and unadjusted for operation technique, length of disease, and temporary stoma, age at surgery was not associated with the probability and the severity of constipation and fecal incontinence in long term.

Conclusions:
In this study, we found no evidence that the age at surgery influences surgical outcomes, thus no optimal timing for surgery for HD could be determined.
Muscle Strength, Agility, and Body Composition in Children With Intestinal Failure on Parenteral Nutrition
Authors: So Stephanie , Patterson Catherine , Betts Zachary , Belza Christina , Courtney-Martin Glenda , Avitzur Yaron , Wales Paul W. 
Published: July 2022

Objectives:With increasing number of children with intestinal failure (IF) on long-term parenteral nutrition (PN), this study assesses the impact of IF on muscle strength, speed, and agility and body composition (BC), identifying clinical factors that may predict impairment.Methods:Cross-sectional study in children 5–18 years with IF on PN. Assessments included Bruininks-Oseretsky Test of Motor Proficiency-2 strength and agility subtest (BOT-2), and grip strength. BC data from dual-energy x-ray absorptiometry (DXA) measurements and clinical variables were collected by chart abstraction. Data were compared to age and sex matched controls and population norms.Results:Twenty-one children with IF (14 males), median age 8.33 (IQR: 6.96–11.04) years and 33 controls (20 males), 8.25 (6.67–10.79) years were included. Strength and agility (P< 0.001) and grip strength (P= 0.001) differed between groups. Nine of 21 (43%) of children with IF scored >1 standard deviation (SD) below mean on BOT-2 and 13 of 21 (62%) had grip strength >1 SD below mean. DXA measurements showed 10 of 18 (56%) of children had lower fat-free mass (FFM)% and higher fat mass (FM)% than reference norms. Decreased FFM% was associated with lower BOT-2 scores (r= 0.479;P= 0.044) and grip strength scores >1 SD below mean (P= 0.047). Additional clinical factors significantly impacting strength and agility included prematurity, height, hospitalizations, sepsis, and small bowel length.Conclusions:Children with IF are at risk of decreased muscle strength and agility, along with altered BC. Ongoing medical, nutritional, and rehabilitation intervention is vital to optimize outcomes.
Effect of the COVID-19 Pandemic on Chlamydial Infection Treatment in Women Discharged From an Urban Safety-Net Emergency Unit
Authors: Park Eunsol , Alvarez Kristin S. , Harms Michael , Johnson Courtney , Griffith William 
Published: July 2022

Background
Chlamydia is the most frequently reported sexually transmitted infection. COVID-19 exacerbated the challenges in treating and preventing new Chlamydia trachomatis (CT) infections. This study examined the impact of COVID-19 on treating CT-positive patients discharged from a safety-net women's emergency unit.

Methods
This was a preretrospective and postretrospective cohort study. Chlamydia trachomatis–positive female patients seen in the women's emergency unit were evaluated. Patients discharged in 2019, the “pre–COVID-19” group, and those discharged in 2020, the “COVID-19” group, were compared. The primary outcome was CT treatment within 30 days, and secondary outcomes included prescription dispensation, repeat tests taken, and expedited partner treatment. A subgroup of patients discharged before treatment who entered a nurse-led follow-up program was also evaluated.

Results
Of the 1357 cases included, there were no differences in successful 30-day treatment (709 of 789 [89.9%] vs. 568 of 511 [89.9%], P = 0.969) or repeat positive CT test (74 of 333 [22.2%] vs. 46 of 211 [21.8%]), P = 0.36) between pre–COVID-19 and COVID-19. However, the patients who picked up their prescription (196 of 249 [78.7%] vs. 180 of 206 [87.4%], P = 0.021) and those who were prescribed expedited partner therapy (156 of 674 [23.1%] vs. 292 of 460 [63.5%], P < 0.001) increased. Findings in the subgroup of patients who entered the follow-up program were consistent with those in the full cohort.

Conclusions
The COVID-19 pandemic did not change treatment patterns of CT-positive patients in this safety-net women's emergency unit. However, patients were more likely to pick up their medications during COVID-19. Despite the perseverance of these programs through the pandemic, most patients are discharged before positive results, and a fair amount remain untreated.
Clinical Challenges in Pediatric Ventilation Liberation: A Meta-Narrative Review
Authors: van Dijk Jefta , Blokpoel Robert G. T. , Abu-Sultaneh Samer , Newth Christopher J. L. , Khemani Robinder G. , Kneyber Martin C. J. 
Published: July 2022

OBJECTIVES:
To map the evidence for ventilation liberation practices in pediatric respiratory failure using the Realist And MEta-narrative Evidence Syntheses: Evolving Standards publication standards.

DATA SOURCES:
CINAHL, MEDLINE, COCHRANE, and EMBASE. Trial registers included the following: ClinicalTrials.gov, European Union clinical trials register, International Standardized Randomized Controlled Trial Number register.

STUDY SELECTION:
Abstracts were screened followed by review of full text. Articles published in English language incorporating a heterogeneous population of both infants and older children were assessed.

DATA EXTRACTION:
None.

DATA SYNTHESIS:
Weaning can be considered as the process by which positive pressure is decreased and the patient becomes increasingly responsible for generating the energy necessary for effective gas exchange. With the growing use of noninvasive respiratory support, extubation can lie in the middle of the weaning process if some additional positive pressure is used after extubation, while for some extubation may constitute the end of weaning. Testing for extubation readiness is a key component of the weaning process as it allows the critical care practitioner to assess the capability and endurance of the patient’s respiratory system to resume unassisted ventilation. Spontaneous breathing trials (SBTs) are often seen as extubation readiness testing (ERT), but the SBT is used to determine if the patient can maintain adequate spontaneous ventilation with minimal ventilatory support, whereas ERT implies the patient is ready for extubation.

CONCLUSIONS:
Current literature suggests using a structured approach that includes a daily assessment of patient’s readiness to extubate may reduce total ventilation time. Increasing evidence indicates that such daily assessments needs to include SBTs without added pressure support. Measures of elevated load as well as measures of impaired respiratory muscle capacity are independently associated with extubation failure in children, indicating that these should also be assessed as part of ERT.
Radiomic Analysis of Pulmonary Nodules for Distinguishing Malignancy From Benignancy: The Value of Using Iodine Maps From Dual-Energy Computed Tomography
Authors: Zhong Yan , Xu Hai , Zhang Wei , Li Hai , Yu Tong-Fu , Yuan Mei 
Published: July 2022

Objective
The aim of the study is to investigate the diagnostic accuracy of radiomics on iodine maps from dual-energy computed tomography (DECT) in distinguishing lung cancer from benign pulmonary nodules.

Methods
This retrospective study was approved by the institutional review board, and written informed consent was waived. A total of 109 patients with 55 malignant nodules and 62 benign nodules underwent contrast-enhanced DECT. Eight iodine uptake parameters on iodine maps generated by DECT were calculated and established a predictive model. Eighty-seven radiomics features of entire tumor were extracted from iodine maps and established a radiomics model. The iodine uptake model and radiomics model were independently built based on the highly reproducible features using the least absolute shrinkage and selection operator method. The diagnostic accuracy of 2 models were assessed using receiver operating curve analysis. For external validation, 47 patients (25 benign and 22 malignant) from another hospital were assigned to testing data set.

Results
All iodine uptake features showed significant association with malignancy (P < 0.01) and 2 selected features (mean value of virtual noncontrast images and mean value of vital part on contrast-enhanced image) constituted the iodine model. The radiomics model comprised 2 features (original shape sphericity and original glszm small area high gray level emphasis), which showed good discrimination both in the training cohort (area under the curve, 0.957) and validation cohort (area under the curve, 0.800). Radiomics model showed superior performance than iodine uptake model (accuracy, 89.7% vs 80.6%).

Conclusions
Radiomics model extracted from iodine maps provided a robust diagnostic tool for discriminating pulmonary malignant nodules and had high potential in clinical application.
Role of intergenic interactions among folate cycle genes in the development of fetal growth retardation
Authors: Efremova Olesya , Ponomarenko Irina , Churnosov Mikhail 
Published: July 2022

Objective:
Metabolic disturbances in the folate cycle in mothers can lead to fetal growth retardation (FGR). This study was to analyze the role of intergenic interactions among maternal folate cycle genes in the development of FGR.

Methods:
This case-control study recruited 365 women in the third trimester of pregnancy, including 122 FGR patients and 243 controls. The women were genotyped for 5 polymorphisms of the 4 folate cycle genes: MTR (rs1805087), MTRR (rs1801394), serine hydroxymethyl transferase (SHMT1; rs1979277), and TYMS (rs699517 and rs2790). The SNP × SNP interactions in the two-, three-, and four-locus models were analyzed using the multifactor dimensionality reduction method and a modification of it (the model-based multifactor dimensionality reduction method).

Results:
Four loci of maternal folate cycle genes (rs1805087 MTR, rs2790 TYMS, rs1801394 MTRR, and rs1979277 SHMT1) were associated with FGR in 3 significant models of single nucleotide polymorphism (SNP) × SNP interactions (two-, three-, and four-locus models) (P <0.05). The highest contribution to FGR was made by polymorphic loci rs1979277 SHMT1 (1.70% of entropy), rs1805087 MTR (0.96%), and interactions between rs1979277 SHMT1 × rs1805087 MTR (-1.11%) and rs1801394 MTRR × rs1979277 SHMT1 (−0.64%). The four-locus maternal genotype combination AG rs1801394 MTRR × AA rs1805087 MTR × CT rs1979277 SHMT1 × AG rs2790 TYMS was associated with an increased risk of FGR (β = 2.69, P = 0.012). FGR-associated SNPs were correlated with the expression of 16 genes (MTR, MTRR, SHMT1, ALKBH5, CTD-2303H24.2, ENOSF1, FAM106A, FOXO3B, LGALS9C, LLGL1, MIEF2, NOS2P2, RP11-806L2.6, SMCR8, TOP3A, and USP32P2) in various tissues and organs related to FGR pathophysiology.

Conclusion:
SNP × SNP interactions of maternal folate cycle genes (MTR, MTRR, SHMT1, and TYMS) are associated with the development of FGR.