bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria
Authors: Henrici Ryan C. , Sautter Casey L. , Bond Caitlin , Opoka Robert O. , Namazzi Ruth , Datta Dibyadyuti , Ware Russell E. , Conroy Andrea L. , John Chandy C. 
Published: September 2021

Abstract
Plasmodium falciparum malaria causes morbidity and mortality in African children with sickle cell anemia (SCA), but comparisons of host responses to P falciparum between children with SCA (homozygous sickle cell disease/hemoglobin SS [HbSS]) and normal hemoglobin genotype/hemoglobin AA (HbAA) are limited. We assessed parasite biomass and plasma markers of inflammation and endothelial activation in children with HbAA (n = 208) or HbSS (n = 22) who presented with severe anemia and P falciparum parasitemia to Mulago Hospital in Kampala, Uganda. Genotyping was performed at study completion. No child had known SCA at enrollment. Children with HbSS did not differ from children with HbAA in peripheral parasite density, but had significantly lower sequestered parasite biomass. Children with HbSS had greater leukocytosis but significantly lower concentrations of several plasma inflammatory cytokines, including tumor necrosis factor α (TNF-α). In contrast, children with HbSS had threefold greater concentrations of angiopoietin-2 (Angpt-2), a marker of endothelial dysregulation associated with mortality in severe malaria. Lower TNF-α concentrations were associated with increased risk of postdischarge mortality or readmission, whereas higher Angpt-2 concentrations were associated with increased risk of recurrent clinical malaria. Children with SCA have decreased parasite sequestration and inflammation but increased endothelial dysregulation during severe anemia with P falciparum parasitemia, which may ameliorate acute infectious complications but predispose to harmful long-term sequelae.
A close association of freedom from pain, migraine-related functional disability, and other outcomes: results of a post hoc analysis of randomized lasmiditan studies SAMURAI and SPARTAN
Authors: Lipton Richard B. , Baygani Simin K. , Tepper Stewart J. , Krege John H. , Vasudeva Raghavendra , Pearlman Eric M. , Hauck Paula M. , Loo Li Shen 
Published: August 2021

Abstract
Background
While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing.

Methods
Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom.

Results
Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time.

Conclusions
This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint.

Trial Registration
SAMURAI (NCT02439320); SPARTAN (NCT02605174).
The COVID-19 pandemic: the effect on airway Management in non-COVID emergency patients
Authors: Ruangsomboon Onlak , Boonmee Phetsinee , Nimmannit Akarin 
Published: August 2021

Abstract
Background
During the COVID-19 outbreak, healthcare providers might have avoided droplet/aerosol-generating procedures, such as non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) due to the concern of themselves being infected. We hypothesized that this change of practice could have also occurred to other non-COVID-infected patients in the Emergency Department (ED).

Methods
A retrospective analytic study was conducted in the ED of Siriraj Hospital, Bangkok, Thailand, including adult patients presenting with signs and symptoms of respiratory distress between 1 March and 30 April 2020 (the COVID period). A comparison group using the same inclusion criteria was retrieved from 1 March to 30 April 2019 (the pre-COVID period). The primary outcome was rate of NIV and HFNC use. The secondary outcomes were rate of intubation, failure of NIV and HFNC, complications, and mortality.

Results
A total of 360 and 333 patients were included during the pre-COVID and COVID periods, respectively. After adjusting for baseline differences, patients in the COVID period were less likely to receive either NIV or HFNC than the pre-COVID period (adjusted OR 0.52 [95%CI 0.29–0.92]). Overall, intubation rate was similar between the two study periods. However, patients in respiratory distress with pulmonary edema had a relatively higher intubation rate in the COVID period. There were higher failure rates of NIV and HFNC, more infectious complications, and a higher rate of mortality in the pre-COVID period.

Conclusion
During the COVID-19 pandemic, the overall usage of NIV and HFNC in emergency non-COVID patients decreased. Although not affecting the overall intubation rate, this change of practice could have affected some groups of patients. Therefore, treatment decisions based on a balance between the benefits to the patients and the safety of healthcare providers should be made.
Assessment of COVID-19 progression on day 5 from symptoms onset
Authors: Gentilotti Elisa , Savoldi Alessia , Compri Monica , Górska Anna , De Nardo Pasquale , Visentin Alessandro , Be Giorgia , Razzaboni Elisa , Soriolo Nicola , Meneghin Dario , Girelli Domenico , Micheletto Claudio , Mehrabi Sara , Righi Elda , Tacconelli Evelina 
Published: August 2021

Abstract
Background
A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19.

Methods
Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO2/FiO2 ratio < 200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age > 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values.

Results
A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66–0.81) for predicting disease progression by day-11.

Conclusion
An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians’ decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.
Overexpression of UTX promotes tumor progression in Oral tongue squamous cell carcinoma patients receiving surgical resection: a case control study
Authors: Chen Yen-Hao , Chen Chang-Han , Chien Chih-Yen , Su Yan-Ye , Luo Sheng-Dean , Li Shau-Hsuan 
Published: September 2021

Abstract
Background
Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) has been identified as a histone 3 lysine 27 (H3K27) demethylase and acted as a tumor suppressor gene or oncogenic function. The current study was to explore the significance of UTX in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection.

Methods
A total of 148 OTSCC patients who underwent surgical resection were identified, including 64 patients (43%) with overexpression of UTX and 84 patients (57%) harboring low expression of UTX. We also used two OTSCC cell lines, SAS and Cal 27, to determine the modulation of cancer. Chi-square test was used to investigate the difference of categorical variables between the groups; survival outcome was analyzed using the Kaplan–Meier method in univariate analysis, and a Cox regression model was performed for multivariate analyses.

Results
Univariate and multivariate analyses showed overexpression of UTX were significantly related to worse disease-free survival (P = 0.028) and overall survival (P = 0.029). The two OTSCC cell lines were treated with GSK-J4, a potent inhibitor of UTX, and transwell migration and invasion assays showed an inhibitory effect with a dose-dependent manner. In addition, western blot analyses also revealed the inhibition of cell cycle and epithelial-mesenchymal transition.

Conclusion
Our study suggests that UTX plays an important role in the process of OTSCC and overexpression of UTX may predict poor prognosis in OTSCC patients who received surgical resection.
Simulated weightbearing computed tomography for verification of radiographic staging of varus ankle osteoarthritis: a cross-sectional study
Authors: Tomiwa Kiyonori , Tanaka Yasuhito , Kurokawa Hiroaki , Kadono Kunihiko , Taniguchi Akira , Maliwankul Korakot 
Published: August 2021

Abstract
Background
Varus ankle osteoarthritis is classified using only weightbearing anteroposterior ankle radiographs; however, sagittal ankle alignment may also affect the position and extent of joint space obliteration. We hypothesized that the sagittal alignment of the ankle may also affect the position and extent of joint space obliteration visible on the coronal section; therefore, we identified the sites of joint space obliteration in patients with stage 3 varus ankle osteoarthritis for comparison with the sites observed on simulated weightbearing computed tomography and investigated the effects of anterior and posterior ankle subluxation.

Methods
Simulated weightbearing computed tomography scans of 83 ft with varus ankle osteoarthritis (26 stage 3a, 57 stage 3b) were performed to check for joint space obliteration in the ankle. Further classification as exhibiting either anterior, posterior, or no subluxation on weightbearing lateral radiographs was performed.

Results
Anterior, posterior, and no subluxation was seen in 5, 9, and 12 ankles among the 26 classified as stage 3a, respectively, and in 22, 12, and 23 ankles among the 57 classified as stage 3b, respectively. The mean tibial lateral surface angle on weightbearing lateral radiographs in stage 3a ankles was 75.6, 83.3, and 80.3 degrees in the anterior, posterior, and no subluxation groups, respectively; and 75.5, 86.6, and 82.7 degrees in stage 3b ankles (p < .05). In stage 3b ankles, widespread joint space obliteration was observed at the anterior distal articular surface of the tibia in all 22 ankles with anterior subluxation and at the posterior distal articular surface of the tibia in all 12 ankles with posterior subluxation.

Conclusions
Simulated weightbearing computed tomography revealed joint space obliteration at the anterior distal articular surface of the tibia in stage 3b ankles with anterior subluxation and at the posterior side in stage 3a and 3b ankles with posterior subluxation. In some patients with stage 3 varus ankle osteoarthritis, the obliteration of the joint space is difficult to evaluate accurately using only weightbearing anteroposterior radiographs; weightbearing lateral radiographs should also be performed.
Effects of mobile learning on writing panoramic radiograph reports: a quasi-experimental trial in dental education
Authors: Bock Anna , Elvers Dirk , Peters Florian , Kramer Chris , Kniha Kristian , Hölzle Frank , Spreckelsen Cord , Modabber Ali 
Published: September 2021

Abstract
Background
In dentistry, the reporting of panoramic radiographs is particularly challenging, as many structures are depicted in one image and pathologies need to be identified completely. To enhance the learning process for these interpretations, the advantages of the increasingly popular education method of mobile learning could be used. Therefore, this study aimed to determine the effectiveness of learning to report panoramic radiographs using an application (app) on a mobile device.

Methods
The existing e-learning programme ‘PantoDict’ was further developed into a mobile app with a new training section. Participants of a dental radiology course were divided into two groups, one of which additionally had the chance to practise reporting panoramic radiographs using the app. A test to assess the knowledge gained was conducted at the end of the semester; the course and the app were also evaluated.

Results
The group that used the app showed significantly better results in the test than the control group (p < 0.05). Although the app group approved a high satisfaction using the app as an additional supplement to the course, this did not result in a higher overall satisfaction with the course. Further, these students observed that the traditional face-to-face seminar could not be replaced by the app.

Conclusion
By using the PantoDict app, students were offered better training options for writing reports on panoramic radiographs, which resulted in significantly better test results than the results of the control group. Therefore, the mobile app is a useful supplement to classical education formats within the context of a blended learning approach.
Efficacy of Normalisation of Advance Care Planning (NACP) for people with chronic diseases in hospital and community settings: a quasi-experimental study
Authors: Jeong Sarah , Cleasby Peter , Ohr Se Ok , Barrett Tomiko , Davey Ryan , Oldmeadow Christopher 
Published: September 2021

AbstractBackgroundAdvance Care Planning (ACP) has emerged to improve end-of-life processes and experiences. However, the available evidence presents the gloomy picture of increasing number of older people living with chronic diseases and the mismatch between their preferences for and the actual place of death. The study aimed to investigate the efficacy of normalisation of an Advance Care Planning (NACP) service delivered by specially trained Registered Nurses (RNs) in hospital and community settings.MethodsA quasi-experimental study was conducted involving 16 sites (eight hospital and eight community sites) in Australia. Patients who were aged ≥18 years, who had at least one of nine chronic conditions, and who did not have an Advance Care Directive (ACD) were offered the NACP service. ACP was normalised as part of routine service on admission. The intervention, NACP, was a series of facilitated conversations about the components of ACP. The primary outcomes which included the completion of ACDs, and/or appointment of an Enduring Guardian (EG), were assessed in both intervention and control sites at pre and post intervention stages. Numbers of patients who completed an ACD or appointed an EG were described by count (percentage). ACD completion was compared between intervention and control sites using a logistic mixed effects regression model. The model includes fixed effects for treatment group, period, and their interaction, as well as random site level intercepts. Secondary model included potentially confounding variables as covariates, including age, sex and chronic diseases.ResultsThe prevalence of legally binding ACDs in intervention sites has increased from five to 85 (from 0.85% in pre to 17.6% in post), whereas it has slightly decreased from five to 2 (from 1.2% in pre and to 0.49% in post) in control sites (the difference in these changes being statistically significantp < 0.001). ACD completion rate was 3.6% (n = 4) in LHD1 and 1.2% (n = 3) in LHD2 in hospital whereas it was 53% (n = 26) in LHD1 and 80% (n = 52) in LHD2 in community.ConclusionsThe study demonstrated that NACP service delivered by ACP RNs was effective in increasing completion of ACDs (interaction odds ratio = 50) and was more effective in community than hospital settings. Involvement of various healthcare professionals are warranted to ensure concordance of care.Trial registrationThe study was retrospectively registered with the Australian New Zealand Clinical Trials Registry (Trial ID:ACTRN12618001627246) on 03/10/2018. The URL of the trial registry recordhttp://www.anzctr.org.au/trial/MyTrial.aspx
Isolated growth hormone deficiency type IA due to a novel GH1 variant: a case report
Authors: Yang Xi , Yuan Mingming , Li Zhuoguang , Ying Yanqin , Hou Ling , Luo Xiaoping 
Published: September 2021

Abstract
Background
A case of isolated growth hormone deficiency type IA (IGHD IA) caused by novel compound heterozygous mutation in the GH1 gene was reported in this study, which aimed to provide insights that will benefit future diagnosis and treatment.

Case presentation
We analyzed and summarized the clinical data and genetic test results from a patient with IGHD admitted in March 2019 to the Department of Pediatrics Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. We described the results from a 1-year-9-months old female, whose chief complaint was “growth retardation for more than one year”. Her birth length was 49.0 cm, and her birth weight was 3.05 kg. Suboptimal intake (breastfeeding) jaundice lasted for approximately two months following birth. When evaluated at the age of 1-year-9-months old, the patient’s height was 61.0 cm (− 7.24 SD), and her weight was 6.4 kg (− 1.50 SD). The patient’s physical characteristics included yellowish hair, large and unclosed anterior fontanelles, raised forehead, and a low and flat nose. The major abnormalities observed from the auxiliary examinations included low GH (< 0.05 μg/l), low IGF-1 (16.99 μg/l), and elevated TSH (6.97 mIU/l). Genetic testing revealed two heterozygous variants: a splicing mutation (NG_011676.1(NM_022560.4): c.10 + 1G>T, inherited from her mother) in intron 1 of the GH1 gene and a deletion that encompassed the same gene (chr17: 61973811–61996255, inherited from her father). After hormone replacement therapy with L-thyroxine and recombinant human GH (rhGH), the patient’s thyroid function returned to normal, and her serum IGF-1 level significantly improved, which resulted in an accelerated increase in height.

Conclusion
This study described a case of IGHD caused by novel compound heterozygous mutations in the GH1 gene. This study suggested that closer attention should be directed to genetic testing and diagnosis based on clinical characteristics to avoid misdiagnosis.
Copy number variations of chromosome 17p11.2 region in children with development delay and in fetuses with abnormal imaging findings
Authors: Zhang Yuanyuan , Liu Xiaoliang , Gao Haiming , He Rong , Chu Guoming , Zhao Yanyan 
Published: September 2021

Abstract
Background
Deletion and duplication of the 3.7 Mb region in 17p11.2 result in two syndromes, Smith-Magenis syndrome and Potocki-Lupski syndrome, which are well-known development disorders. The purpose of this study was to determine the prevalence, genetic characteristics and clinical phenotypes of 17p11.2 deletion/duplication in Chinese children with development delay and in fetuses with potential congenital defects.

Methods
7077 children with development delay and/or intellectual disability were screened by multiplex ligation-dependent probe amplification P245 assay. 7319 fetuses with potential congenital defects were tested using next generation sequencing technique.

Results
417 of 7077 pediatric patients were determined to carry chromosome imbalance. 28 (28/7077, 0.4%) cases had imbalance at chromosome 17p11.2. Among them, 12 cases (42.9%) had heterozygous deletions and 16 cases (57.1%) had heterozygous duplications. The clinical phenotypes were variable, including neurobehavioral disorders, craniofacial/skeletal anomalies, immunologic defects, ocular problems and organ malformations. 263 of 7319 fetuses were recognized to have genomic copy number variations. Only 2 of them were found to harbor 17p11.2 imbalance. The fetus with deletion presented with ventricular septal defect and the fetus with duplication had cerebral ventricle dilation.

Conclusion
Our study highlights the phenotypic variability associated with 17p11.2 variations in China. The results further expand the phenotypic spectrum of SMS/PTLS and increase awareness of these disruptive mutations among clinicians.