bluuebunny/crossref_metadata_2025_split huggingface dataset:
The characteristics, management and outcomes of high- and low-grade renal injuries in paediatric trauma patients at a major trauma centre
Authors: Bird Ruth , De Los Reyes Thomas , Beno Suzanne , Siddiqui Asad 
Published: March 2022

Introduction Children, given anatomical variations, are at increased risk of renal injury following trauma. The management of paediatric renal injuries has, similar to other solid organ injuries, largely shifted towards conservative management; however, hemodynamically unstable patients may still warrant surgical exploration or interventional techniques. The aim of this study is to describe the local incidence, demographics, morbidity and outcomes associated with high- and low-grade renal injury in a paediatric major trauma population. Method This was a 5-year retrospective review of trauma registry data and chart analysis of all paediatric renal injuries from major trauma at a North American level 1 paediatric trauma centre between January 2016–31 December 2020. Data was analysed using SPSS v27 with p < 0.05 considered significant. Results Of 1334 major trauma patients, 45 suffered a kidney injury (20 high-grade and 25 low-grade injuries), of which 93.3% underwent conservative management with no difference in outcomes between groups. 80% of patients had concurrent injuries (a quarter requiring surgery for these), with a trend towards higher rates of chest injuries in high-grade renal injury patients ( p = 0.08). Bicycle injuries were statistically more likely to cause high-grade renal injury ( p = 0.02). Angiography was utilized infrequently (3/45 patients, 6.6%), and no patients underwent embolization in our study population. Overall mortality (4.4%) and length of stay were unaffected by grade of injury. Conclusion Paediatric renal injury is an uncommon injury in major trauma patients (3.4%). Most cases can be managed conservatively regardless of the grade of injury. Renal injury patients are likely to have concurrent injuries, often requiring surgery. Further studies are needed to measure the success and utilization of interventional radiology techniques for management in children.
The effects of e-stories on preschoolers’ narrative comprehension, retelling and reading attitudes among poor and good comprehenders
Authors: Altun Dilek 
Published: March 2022

Previous studies have presented discrepant findings of e-stories’ contribution to children’s narrative comprehension, which can be attributed to not only the variation of multimedia features among studies but also to learner and text features. The main goal of the present study was to expand understanding of the effect of e-stories on children’s narrative skills and reading attitudes for poor and good story comprehenders. A quasi-experimental factorial design was employed to explore the effect of book type and group level on children’s narrative skills and reading attitudes. The participating children were pre-readers. The printed version of The Red Winged Owl was read aloud to small groups of 4–5 children. Participants included 41 good and 40 poor comprehenders (age range 59–68 months) who were identified based on narrative comprehension scores. The experimental group was exposed to four e-stories on an iPad, while the control group listened to readings of the printed versions of the same storybooks. Data were collected by administering pre- and post-tests and the preschool reading attitudes scale and by asking narrative comprehension questions. Children’s retellings were audio-recorded. The findings revealed that (a) the poor and good comprehender groups had higher narrative comprehension in the short text e-story condition, (b) there was a significant interaction effect for the narrative comprehension of poor and good comprehenders in longer texts and (c) children’s post-reading attitude scores did not differ by group level.
How do factors of sociodemographic, health literacy and dementia experience influence carers’ knowledge of dementia?
Authors: Crawley Sophie , Moore Kirsten , Vickerstaff Victoria , Fisher Emily , Cooper Claudia , Sampson Elizabeth L 
Published: March 2022

Background Dementia is a life limiting disease following a progressive trajectory. As carers often become key decision makers, their knowledge of dementia will have health implications for the person living with dementia as well as carer’s psychological wellbeing. Aim To explore how sociodemographic factors, health literacy and dementia experience influence family carers knowledge about dementia. Method In this cross-sectional, mixed methods study, we interviewed 150 family carers and assessed their dementia knowledge using the Dementia Knowledge Assessment Scale (DKAS). Linear regression analyses were used to examine whether health literacy, previous experiences of dementia, support group attendance and sociodemographic characteristics predicted knowledge. Sixteen carers also completed qualitative interviews which explored unmet information needs. Transcripts and field notes were thematically analysed. Results Most participants were partners (47%) or adult children (48%) and cared for someone with severe (32%) or moderate (43%) dementia. Mean DKAS scores were 34.8/50 (SD = 7.0, range = 17–48) reflecting 8/25 incorrect answers. Backwards elimination regression found greater dementia knowledge was associated with greater health literacy for appraising information (coef 3.48, 95% CI (1.38, 5.58); p = 0.001) and more years of education (coef 0.39, 95% CI (0.12, 0.65); p = 0.004). Although not significant, knowledge was slightly lower in those who attended a support group, and a trend was found between ability to understand health information and knowledge. Only 39% accurately identified dementia as life shortening, indicating notable gaps in knowledge. Four qualitative themes were identified; arm yourself with information, ability to steer through information, other experience of dementia can be helpful and the importance of relationships with health care professionals. Conclusions In an information age, vast amounts of information are available, but this can bring difficulties. Carers with more years of education and higher health literacy knew more about dementia. Professionals should consider how carers with lower health literacy can be supported through provision of timely, relevant information.
Accounting for the rarity of the disease when designing clinical trials with a focus on pediatric cancers
Authors: Mauguen Audrey 
Published: March 2022

Background Clinical trials are challenging in rare diseases like pediatric cancers, where the accrual is limited. In these trials, inference assumptions are the same as in common diseases, that is the sample comes from a quasi-infinite population. This leads to overestimating the variance of the mean treatment effect. The finite-population correction factor correcting this bias is often used in surveys, but not in clinical trials. With few assumptions, the use of this correction factor can improve trials efficiency, showing that the power of those trials is sometimes higher than it appears. Methods First, a simulation study assesses the standard error of the mean treatment effect and coverage of the 95% confidence interval with and without the correction. Second, the analytical power of a z-test with and without the correction is given. Finally, the impact on the sample size calculation is investigated. The impact of assuming a finite population is assessed for varying treatment effect, sample size and population size. Results The simulation results confirm the overestimation of the standard error without the correction factor. When using the correction factor, the gain in power reaches up to 10.1%, 15.3% and 12.3% to detect a difference in treatment effect of 10%, 15% and 20%, respectively. The gain is negligible for n = 30, in scenarios with high power (>95%), and for large populations. This gain in power translates into a decrease in sample size: if the conventional calculation leads to a sample size 10% of the population size, then the sample size can be divided by 1.1; if the conventional calculation leads to a sample size 20% of the population size, then the sample size can be divided by 1.2, in order to reach the planned type I error and power. Conclusion When dealing with rare diseases like pediatric cancers, the power of clinical trials might be higher than it appears if using conventional sample sizes. When correcting the variance of the mean using the population size, a gain in efficiency is observed with reasonable sample sizes and treatment differences for very small population sizes, showing that this approach can be useful for some pediatric cancer clinical trials.
Direct to angiography suite approaches for the triage of suspected acute stroke patients: a systematic review and meta-analysis
Authors: Brehm Alex , Tsogkas Ioannis , Ospel Johanna M. , Appenzeller-Herzog Christian , Aoki Junya , Kimura Kazumi , Pfaff Johannes A.R. , Möhlenbruch Markus A. , Requena Manuel , Ribo Marc J. , Sarraj Amrou , Spiotta Alejandro M. , Sporns Peter , Psychogios Marios-Nikos 
Published: March 2022

Background: Increasing evidence suggests improved time metrics leading to better clinical outcomes when stroke patients with suspected large vessel occlusion (LVO) are transferred directly to the angiography suite (DTAS) compared with cross-sectional imaging followed by transfer to the angiography suite. We performed a systematic review and meta-analysis on the efficacy and safety of DTAS approaches. Methods: We searched Embase, Medline, Scopus, and clinicaltrials.gov for studies comparing outcomes of DTAS and conventional triage. Eligible studies were assessed for risk of bias. We performed a random-effects meta-analysis on the differences of median door-to-groin and door-to-reperfusion times between intervention and control group. Secondary outcomes included good outcome at 90 days (modified Rankin Scale ⩽ 2) rate of symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. Results: Eight studies (one randomized, one cluster-randomized trial and six observational studies) with 1938 patients were included. Door-to-groin and door-to-reperfusion times in the intervention group were on median 29.0 min [95% confidence interval (CI): 14.3–43.6; p < 0.001] and 32.1 min (95% CI: 15.1–49.1; p < 0.001) shorter compared with controls. Prespecified subgroup analyses for transfer ( n = 1753) and mothership patients ( n = 185) showed similar reductions of the door-to-groin and door-to-reperfusion times in response to the intervention. The odds of good outcome did not differ significantly between both groups but were numerically higher in the intervention group (odds ratio: 1.38, 95% CI: 0.97–1.95; p = 0.07). There was no significant difference for mortality and sICH between the groups. Conclusion: DTAS approaches for the triage of suspected LVO patients led to a significant reduction in door-to-groin and door-to-reperfusion times but an effect on functional outcome was not detected. The subgroup analysis showed similar results for transfer and mothership patients. Registration﻿: This study was registered in PROSPERO (CRD42020213621).
First-line immunotherapy or angiogenesis inhibitor plus chemotherapy for HER2-altered NSCLC: a retrospective real-world POLISH study
Authors: Yang Guangjian , Yang Yaning , Liu Runze , Li Weihua , Xu Haiyan , Hao Xuezhi , Li Junling , Xing Puyuan , Zhang Shuyang , Ai Xin , Xu Fei , Wang Yan 
Published: March 2022

Background: There have been no comprehensive large-scale studies that have evaluated the benefits of chemotherapy-based regimens in addressing HER2-altered advanced non-small-cell lung cancer (NSCLC) in a first-line setting. Data on HER2 alteration subtypes and concomitant alterations are also limited. Accordingly, our retrospective, real-world POLISH study assesses the efficacy of first-line chemotherapy alone (C) as well as combinations with immune checkpoint inhibitors (C + I) or angiogenesis inhibitors (C + A) for HER2-altered NSCLC; molecular features are also reported. Methods: HER2-altered NSCLC patients who received a first-line treatment between November 2015 and September 2021 were screened. Patients treated with C, C + I, or C + A were included in our final efficacy analysis. Progression-free survival (PFS) was compared between the subgroups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to evaluate concomitant alterations. Results: A total of 293 patients were screened, with an identification of HER2 amplification and 37 distinct HER2 mutations, and 210 cases treated with C, C + I, or C + A were ultimately included. C + A achieved longer PFS than C (5.63 vs 4.03 months, hazard ratio: 0.64, 95% confidence interval [CI]: 0.46–0.88, p = 0.006). C + I did not improve median PFS compared to C + A or C (both p > 0.05), despite the programmed cell death ligand-1 (PD-L1) expression or tumor mutational burden. KEGG analysis revealed that concomitant upregulation of PI3 K/AKT pathway signaling was common in HER2-altered NSCLC. Conclusion: Chemotherapy plus angiogenesis inhibitors may yield a greater survival benefit than chemotherapy alone in a first-line setting for HER2-altered NSCLC, whereas an immune-based combination therapy may not be superior to a sole chemotherapy regimen. Activation of PI3 K/AKT signaling may mediate immunosuppression in HER2-altered NSCLC.
Giant Retinal Pigment Epithelium Tear Resulting in Neurosensory Retinal Detachment: An Atypical Case
Authors: Rana Harkaran S. , Cox Anthony R. , Biles Evan C. , Broderick Kevin 
Published: March 2022

Purpose: We report a rare case of neurosensory retinal detachment (RD) in the setting of a giant retinal pigment epithelium (RPE) tear. Methods: A 58-year-old man presented with a macula-involving RD in the left eye. Exam revealed a neurosensory detachment inferiorly and RPE abnormalities temporally. Optical coherence tomography showed a large RPE tear and detachment in the temporal macula contiguous with a neurosensory RD. Results: No clear etiology was identified and failure of conservative management led to vitrectomy with RD repair. Follow-up intravenous fluorescein angiography 3 months postoperatively showed a large RPE window defect. Conclusions: RPE tears are common; however, concomitant neurosensory RD is rare. A thorough workup to determine treatable causative factors is necessary; in the event of idiopathic diagnosis, close follow-up is necessary to determine the need for surgery. Pars plana vitrectomy, external drainage of subretinal fluid, endolaser, and 5000-centistoke silicone oil placement were successful in this patient.
Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19
Authors: Henderson Michael W. , Lima Franciele , Moraes Carla Roberta Peachazepi , Ilich Anton , Huber Stephany Cares , Barbosa Mayck Silva , Santos Irene , Palma Andre C. , Nunes Thyago Alves , Ulaf Raisa Gusso , Ribeiro Luciana Costa , Bernardes Ana Flavia , Bombassaro Bruna , Dertkigil Sergio San Juan , Moretti Maria Luiza , Strickland Sidney , Annichino-Bizzacchi Joyce M. , Orsi Fernanda Andrade , Mansour Eli , Velloso Licio A. , Key Nigel S. , De Paula Erich Vinicius 
Published: March 2022

Abstract
Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor–mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.
A double-blind randomised placebo-controlled trial investigating the effects of lesogaberan on the objective cough frequency and capsaicin-evoked coughs in patients with refractory chronic cough
Authors: Badri Huda , Gibbard Carmen , Denton Dimitra , Satia Imran , Al-Sheklly Bashar , Dockry Rachel J. , Holt Kimberley , McGuiness Kevin , Treadway Sam , Whorwell Peter , Houghton Lesley , Lee Augustine , Escott K. Jane , Lee Theresa , Wilkinson Greame , Holt Alison , Canning Brendan J. , Smith Jacky A. 
Published: March 2022

ObjectiveBaclofen is a centrally acting γ-aminobutyric acid type B (GABAB) receptor agonist which reduces gastro-oesophageal reflux and suppresses the cough reflex; however, central nervous system side-effects limit its use. Lesogaberan is a novel peripherally acting GABABagonist, but its effects on refractory chronic cough are unknown.DesignWe performed a single-centre, placebo-controlled, double-blind randomised crossover study in patients with chronic cough, refractory to the treatment of underlying conditions. Patients were randomised to treatment with lesogaberan 120 mg modified release twice daily or matched placebo for 2 weeks and then crossed over to the alternative therapy after a 2-week washout. The primary end-point was 24-h cough frequency measured with an acoustic monitoring system. In addition, cough responses to capsaicin were measured, and gastro-oesophageal reflux assessed by 24-h pH/impedance at screening.Results22 patients were randomised to receive lesogaberan/placebo or placebo/lesogaberan (female (73%); mean±sdage 63.7±7.2 years; median (interquartile range) cough duration 10.5 (5.8–17.0) years; mean (95% CI) 45 (29–67) reflux events in 24 h; two patients had abnormal oesophageal acid exposure times). Although lesogaberan reduced cough counts by 26% over placebo, this did not reach statistical significance (p=0.12). However, lesogaberan did significantly improve cough responses to capsaicin (p=0.04) and the number of cough bouts (p=0.04) compared with placebo. Lesogaberan was well tolerated in this study.ConclusionsLesogaberan improved cough hypersensitivity and the number of bouts of coughing, but not coughs per hour. This implies a possible role for peripheral GABABreceptors in refractory chronic cough.
Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis
Authors: Homayoonfal Mina , Asemi Zatollah , Yousefi Bahman 
Published: March 2022

AbstractDespite great advances, therapeutic approaches of osteosarcoma, the most prevalent class of preliminary pediatric bone tumors, as well as bone-related malignancies, continue to demonstrate insufficient adequacy. In recent years, a growing trend toward applying natural bioactive compounds, particularly phytochemicals, as novel agents for cancer treatment has been observed. Bioactive phytochemicals exert their anticancer features through two main ways: they induce cytotoxic effects against cancerous cells without having any detrimental impact on normal cell macromolecules such as DNA and enzymes, while at the same time combating the oncogenic signaling axis activated in tumor cells. Thymoquinone (TQ), the most abundant bioactive compound of Nigella sativa, has received considerable attention in cancer treatment owing to its distinctive properties, including apoptosis induction, cell cycle arrest, angiogenesis and metastasis inhibition, and reactive oxygen species (ROS) generation, along with inducing immune system responses and reducing side effects of traditional chemotherapeutic drugs. The present review is focused on the characteristics and mechanisms by which TQ exerts its cytotoxic effects on bone malignancies.
miR-152-3p impedes the malignant phenotypes of hepatocellular carcinoma by repressing roundabout guidance receptor 1
Authors: Yin Tao , Zhao Haonan 
Published: March 2022

Abstract
Background
miR-152-3p functions as a tumour suppressor in the progression of hepatic tumorigenesis. Herein, we further discussed the prognostic significance and immune infiltration of miR-152-3p and its potential gene target in hepatocellular carcinoma (HCC).

Methods
The Cancer Genome Atlas (TCGA), Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), Human Protein Atlas (HPA) and Kaplan–Meier Plotter databases were used to evaluate miR-152-3p and roundabout guidance receptor 1 (ROBO1) expression, prognosis and immune infiltration. In vitro cell experiments, including cell proliferation and apoptosis, were evaluated using Cell Counting Kit 8 (CCK8) and terminal-deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) assays.

Results
Up-regulation of ROBO1 functioned as an oncogene associated with poor prognosis, immune cell enrichment and cell proliferation in HCC. ROBO1 was significantly positively correlated with the enrichment of multiple immune cells and their biomarkers. Enrichment of type-2 T-helper (Th2) cells is an unfavourable biomarker of HCC prognosis. GSEA revealed that ROBO1 correlated with apoptosis, mitosis and carcinogenic signalling pathways. Suppression of cell proliferation and the enhancement of cell apoptosis by miR-152-3p mimics were counteracted by overexpression of ROBO1 in HCC cells.

Conclusion
ROBO1 expression is positively correlated with multiple immune checkpoint molecules, suggesting that ROBO1 may be a potential drug target to enhance the potency of immunotherapy. The miR-152-3p/ROBO1 signalling axis contributes to malignant progression and provides a prospective immunotherapeutic target for HCC.