bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages
Authors: Liu Xin , Li Zhenke , Sun Jinxing , Zhang Zhijie , Li Weiguo 
Published: March 2023

AbstractPurposeThe combined application of immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapy has shown synergistic effects on glioblastoma (GBM). As important resources of PD-L1 in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have significant impact of the efficiency of ICIs. However, the effects of anti-angiogenesis agents on immune checkpoints expression are not fully understood.MethodGBM-educated macrophages were generated from circulating monocytes of healthy controls and GBM patients under the education of GBM cell line. Surface expression of PD-L1 and VEGFR1 on GBM-educated macrophages was analyzed. VEGFR1 NAb and soluble VEGFR1 (sVEGFR1) were added and their effects on PD-L1 expression on TAMs was investigated. Serum soluble PD-L1 (sPD-L1) and sVEGFR1 levels in GBM patients were measured and their correlation was analyzed.ResultThe expression intensity of PD-L1 on GBM-educated macrophages was higher and its up-regulation partially depends on VEGFR1 signaling pathway. GBM-educated macrophages secreted less levels of soluble VEGFR1 (sVEGFR1), and exogenous sVEGFR1 down-regulated PD-L1 expression intensity. PD-L1 blockade promoted the secretion of sVEGFR1. Finally, sVEGFR1 and sPD-L1 in serum of GBM patients were overexpressed, and a positive correlation was found.ConclusionThese findings reveal the interaction between PD-L1 and VEGFR1 signaling pathway in GBM-educated macrophages. VEGFR1 is involved with PD-L1 overexpression, which can be impeded by autocrine regulation of sVEGFR1. sVEGFR1 secretion by GBM-educated macrophages can be promoted by PD-L1 blockade. Taken together, these findings provide evidences for the combined application of ICIs and anti-angiogenesis therapies in the treatment of GBM.
Aberrant lncRNA expression in patients with proliferative diabetic retinopathy: preliminary results from a single-center observational study
Authors: Zeng Lan , Zhou Minwen , Wang Xiaocong , Long Xiaofeng , Ye Meng , Yuan Yuan , Tan Wei 
Published: March 2023

Abstract
Background
Diabetic retinopathy (DR) is a leading cause of blindness. Vision threat is particularly severe in patients with retinal neovascularization. However, little is known about the role of long noncoding RNAs (lncRNAs) in proliferative diabetic retinopathy (PDR). The goal of this study was to identify lncRNAs involved in PDR.

Methods
We compared lncRNA expression profiles in the vitreous between patients with PDR and those with idiopathic macular hole (IMH) and between patients with PDR who had received anti-vascular endothelial growth factor (VEGF) therapy and those who had not. Vitreous samples from patients with PDR and IMH were screened for lncRNAs using microarray-based analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the microarray results. Bioinformatic analysis was also performed. Moreover, the effect of anti-VEGF therapy was investigated in vitreous samples of patients with PDR treated with anti-VEGF therapy and those who were not.

Results
A total of 1067 differentially expressed noncoding RNA transcripts were found during screening in the vitreous humor of patients with PDR than in those with IMH. Five lncRNAs were subjected to qRT-PCR. RP11-573 J24.1, RP11-787B4.2, RP11-654G14.1, RP11-2A4.3, and RP11-502I4.3 were significantly downregulated; this was validated by the comparison using the microarray data. In addition, 835 differentially expressed noncoding RNA transcripts were found during screening in the vitreous humor of patients with PDR treated with anti-VEGF therapy compared with untreated PDR patients. RP4-631H13.2 was significantly upregulated, which is consistent with the trend of the microarray analysis.

Conclusions
There were systemic expression differences in the vitreous at the microarray level between patients with PDR and those with IMH and between patients with PDR after anti-VEGF treatment and those that did not receive anti-VEGF treatment. LncRNAs identified in the vitreous humor may be a novel research field for PDR.
Diabetic retinopathy screenings in West Virginia: an assessment of teleophthalmology implementation
Authors: Schofield Travis , Patel Ami , Palko Joel , Ghorayeb Ghassan , Laxson L. Carol 
Published: March 2023

Abstract
Background
The prevalence of diabetes in the state of West Virginia (WV) is amongst the highest in the United States, making diabetic retinopathy (DR) and diabetic macular edema (DME) a major epidemiological concern within the state. Several challenges exist regarding access to eye care specialists for DR screening in this rural population. A statewide teleophthalmology program has been implemented. We analyzed real-world data acquired via these systems to explore the concordance between image findings and subsequent comprehensive eye exams and explore the impact of age on image gradeability and patient distance from the West Virginia University (WVU) Eye Institute on follow-up.

Methods
Nonmydriatic fundus images of diabetic eyes acquired at primary care clinics throughout WV were reviewed by retina specialists at the WVU Eye Institute. Analysis included the concordance between image interpretations and dilated examination findings, hemoglobin A1c (HbA1c) levels and DR presence, image gradeability and patient age, and distance from the WVU Eye Institute and follow-up compliance.

Results
From the 5,512 fundus images attempted, we found that 4,267 (77.41%) were deemed gradable. Out of the 289 patients whose image results suggested DR, 152 patients (52.6%) followed up with comprehensive eye exams—finding 101 of these patients to truly have DR/DME and allowing us to determine a positive predictive value of 66.4%. Patients within the HbA1c range of 9.1-14.0% demonstrated significantly greater prevalence of DR/DME (p < 0.01). We also found a statistically significant decrease in image gradeability with increased age. When considering distance from the WVU Eye Institute, it was found that patients who resided within 25 miles demonstrated significantly greater compliance to follow-up (60% versus 43%, p < 0.01).

Conclusions
The statewide implementation of a telemedicine program intended to tackle the growing burden of DR in WV appears to successfully bring concerning patient cases to the forefront of provider attention. Teleophthalmology addresses the unique rural challenges of WV, but there is suboptimal compliance to essential follow-up with comprehensive eye exams. Obstacles remain to be addressed if these systems are to effectively improve outcomes in DR/DME patients and diabetic patients at risk of developing these sight-threatening pathologies.
Effects of atropine and tropicamide on ocular biological parameters in children: a prospective observational study
Authors: Tao Yulin , Li Mohan , Tan Jian , Huang Jing , Cheng Xiaokang , Xie Ping , Liu Xiansheng , Zhou Qiong , Ouyang Jun 
Published: March 2023

Abstract
Background
The effectiveness of cycloplegia in delaying the progression of myopia and its application in refractive examination in children have been extensively studied, but there are still few studies on the effects of atropine/tropicamide on ocular biological parameters. Therefore, the purpose of this study was to explore the effects of atropine/tropicamide on children's ocular biological parameters in different age groups and the differences between them.

Methods
This was a prospective observational study in which all school children were examined for dioptres and ocular biological parameters in the outpatient clinic, and 1% atropine or tropicamide was used for treatment. After examination, we enrolled the patients grouped by age (age from 2 to 12 years treated by atropine, 55 cases; age from 2 to 10 years treated by tropicamide, 70 cases; age from 14 to 17 years treated by tropicamide, 70 cases). The ocular biological parameters of each patient before and after cycloplegia were measured, and the difference and its absolute value were calculated for statistical analysis using an independent-samples t test.

Results
We compared the value and the absolute value of the differences in ocular biological parameters before and after cycloplegia in the same age group, and we found that the differences were not statistically significant (P > 0.05). There were significant differences in the corresponding values of AL, K1 and ACD among the different age groups (P < 0.05). Before cycloplegia, there were significant differences in AL, K, K1, K2 and ACD in different age groups (P < 0.05). However, the differences in AL, K, K1, K2 and ACD among different age groups disappeared after cycloplegia (P > 0.05).

Conclusions
This study demonstrated that atropine/tropicamide have different effects on cycloplegia in children of different ages. The effects of atropine/tropicamide on ocular biological parameters should be fully considered when evaluating the refractive state before refractive surgery or mydriasis optometry for children of different ages.
A physical sign of pathological myopia: myopic scleral pit
Authors: Zhang Wenhua , Zhang Yaping , Xu Jingxuan , Dan Handong , Li Xiaoli , Song Zongming 
Published: March 2023

Abstract
Purpose
Myopic scleral pit (MSP) is a rare physical sign of pathological myopia (PM). The aim of this study was to summarize the clinical characteristics of MSP and analyze its correlation with PM.

Methods
Eight cases with PM and MSP were enrolled in this study. Comprehensive ophthalmic examinations, including subjective refraction, slit-lamp biomicroscope, intraocular pressure, fundus photographs, A- and B-scan ultrasonography and spectral-domain optical coherence tomography, were performed.

Results
All the patients had a long history of PM with visual impairment, long axial length, and myopia-related fundus degeneration. Mean axial length was 31.48 ± 2.17 mm. Mean size of MSP was 0.69 ± 0.29 optic disc diameter (PD). Mean logMAR BCVA was 1.21 ± 0.88 logMAR. Spearman correlation analysis showed that the logMAR BCVA had no correlation with the size of pits (P = 0.34). Fundus examination revealed a focal pale concave located in the sclera exposed area of retinal choroid atrophy was found in all cases. OCT showed a deep scleral pit where the retinal choroid was thin or absent, without retinal sensory detachment or sensory defect.

Conclusions
This study identified a rare scleral lesion in all eight individuals with PM, which was termed “myopic scleral pit”. This phenomenon is different from focal choroidal excavation and posterior staphyloma.
Vernal keratoconjunctivitis in Down syndrome: a case report
Authors: Artesani Maria Cristina , Esposito Mariacristina , Valentini Diletta , Villani Alberto , Fiocchi Alessandro Giovanni , Buzzonetti Luca 
Published: March 2023

Abstract
Background
Down syndrome (DS) or Trisomy 21 is the most common chromosomal disease and is characterized by possible heart defects, cognitive impairment and visual disorders.

Case presentation
We describe for the first time a 17-year-old Caucasian girl suffering from Down syndrome associated with vernal keratoconjunctivitis (VKC), a rare disorder of the anterior segment of the eye, characterized by intense photophobia, redness, watering eyes and itching due to an inflammatory-allergic reaction of the cornea and conjunctiva. On slit-lamp examination, the girl showed conjunctival hyperemia, papillary hypertrophy, giant papillae and corneal leukoma in right eye as a result of a previous corneal ulcer. A successful topical immunosuppressant therapy with cyclosporin 1% was started.

Conclusion
So far, to our knowledge, this is the first description of VKC in a patient with DS. Finding an inflammatory-allergic disease such as VKC in DS is unusual but it must be taken into account because keratoconus, one of the most frequent eye pathologies in DS, can be secondary to an unrecognized VKC.
Evaluation of a new digital pediatric malnutrition risk screening tool for hospitalized children with congenital heart disease
Authors: Zhang Yajie , Lu Lina , Yang Ling , Yan Weihui , Yu Qun , Sheng Jinye , Mao Xiaomeng , Feng Yi , Tang Qingya , Cai Wei , Wang Ying 
Published: March 2023

Abstract
Background
In a cohort of hospitalized children with congenital heart disease (CHD), a new digital pediatric malnutrition screening tool as a mobile application was validated, and its effectiveness and clinical value were determined as a prospective study.

Methods and results
Children with CHD (n = 1125) were screened for malnutrition risk. The incidence of risk and the differences among various age groups and types of CHD were characterized. The optimal threshold for the tool to determine if there is a risk of malnutrition is score 2, while the Youden index was 79.1%, and the sensitivity and specificity were 91.2% and 87.9%, respectively. Based on such criterion, 351 children were at risk of malnutrition accounting for 31.20% of the total. Compared with the non-malnutritional risk group, the median age for the group at risk for malnutrition was younger (8.641 months [4.8, 23.1] vs. 31.589 months [12.4, 54.3], P < 0.01), and the length of stay was longer (12.000 [8.0, 17.0] vs. (8.420 [5.0, 12.0], P < 0.01]. There were significant differences in malnutrition risk among different age groups (χ2 = 144.933, P < 0.01), and children under one year of age exhibited the highest risk for malnutrition and more extended hospital stay (H = 78.085, P < 0.01). The risk of malnutrition among children with cyanotic CHD was higher than in those with non-cyanotic CHD (χ2 = 104.384, P < 0.01).

Conclusions
The new digital pediatric malnutrition screening tool showed high sensitivity and specificity in children with CHD. The tool indicated that the malnutrition risk for young children and children with cyanotic or Bethesda moderate and complex CHD was higher, and the hospitalization time was longer than in the non-risk group. The tool provides a rational approach to targeted nutrition intervention and support and may improve clinical outcomes.
Co-occurrence of neurofibromatosis type 1 and pseudoachondroplasia – a first case report
Authors: Pálla Sára , Anker Pálma , Farkas Klára , Plázár Dóra , Kiss Sándor , Marschalkó Péter , Szalai Zsuzsanna , Bene Judit , Hadzsiev Kinga , Maróti Zoltán , Kalmár Tibor , Medvecz Márta 
Published: March 2023

AbstractBackgroundNeurofibromatosis type 1 and pseudoachondroplasia are both rare autosomal dominant disorders, caused by pathogenic mutations inNF1andCOMPgenes, respectively. Both neurofibromin 1 and cartilage oligomeric matrix protein (COMP) play a role in the development of the skeleton. Carrying both germline mutations has not been previously reported; however, it can affect the developing phenotype.Case presentationThe index patient, an 8-year-old female presented with several skeletal and dermatologic anomalies resembling the coexistence of multiple syndromes. Her mother had dermatologic symptoms characteristic for neurofibromatosis type 1, and her father presented with distinct skeletal anomalies. NGS-based analysis revealed a heterozygous pathogenic mutation in genesNF1andCOMPin the index patient. A previously unreported heterozygous variant was detected for theNF1gene. The sequencing of theCOMPgene revealed a previously reported, pathogenic heterozygous variant that is responsible for the development of the pseudoachondroplasia phenotype.ConclusionsHere, we present the case of a young female carrying pathogenicNF1andCOMPmutations, diagnosed with two distinct heritable disorders, neurofibromatosis type 1 and pseudoachondroplasia. The coincidence of two monogenic autosomal dominant disorders is rare and can pose a differential diagnostic challenge. To the best of our knowledge, this is the first reported co-occurrence of these syndromes.
Child physical abuse screening in a pediatric ED; Does TRAIN(ing) Help?
Authors: Heyming Theodore , Knudsen-Robbins Chloe , Sharma Supriya , Thackeray Jonathan , Schomberg John , Lara Bryan , Wickens Maxwell , Wong Daphne 
Published: March 2023

Abstract
Background
Child maltreatment is distressingly prevalent yet remains under-recognized by healthcare providers. In 2015 the Ohio Children's Hospital Association developed the Timely Recognition of Abusive INjuries (TRAIN) collaborative in an effort to promote child physical abuse (CPA) screening. Our institution implemented the TRAIN initiative in 2019. The objective of this study was to examine the effects of the TRAIN initiative at this institution.

Methods
In this retrospective chart review we recorded the incidence of sentinel injuries (SIS) in children presenting to the Emergency Department (ED) of an independent level 2 pediatric trauma center. SIS were defined and identified by a diagnosis of ecchymosis, contusion, fracture, head injury, intracranial hemorrhage, abdominal trauma, open wound, laceration, abrasion, oropharyngeal injury, genital injury, intoxication, or burn in a child < 6.01 months of age. Patients were stratified into pre-TRAIN (PRE), 1/2017–9/2018, or post-TRAIN (POST), 10/2019–7/2020, periods. Repeat injury was defined as a subsequent visit for any of the previously mentioned diagnoses within 12 months of the initial visit. Demographics/visit characteristics were analyzed using Chi square analysis, Fischer’s exact test, and student’s paired t-test.

Results
In the PRE period, 12,812 ED visits were made by children < 6.01 months old; 2.8% of these visits were made by patients with SIS. In the POST period there were 5,372 ED visits, 2.6% involved SIS (p = .4). The rate of skeletal surveys performed on patients with SIS increased from 17.1% in the PRE period to 27.2% in the POST period (p = .01). The positivity rate of skeletal surveys in the PRE versus POST period was 18.9% and 26.3% respectively (p = .45). Repeat injury rates did not differ significantly in patients with SIS pre- versus post-TRAIN (p = .44).

Conclusion
Implementation of TRAIN at this institution appears to be associated with increased skeletal survey rates.
Unusual circumstance for craniopharyngioma discovery on meningoencephalitis: a pediatric case report
Authors: Oozeerally Jihann , Berthomieu Lionel , Bertozzi Anne-Isabelle , Estublier Bastien , Oliver Isabelle , Siegfried Aurore , Antherieu Pierre , Thene Emilie , Jamme Thibaut , Levade Thierry , Sevely Annick , Brehin Camille , Baudou Eloïse 
Published: March 2023

Abstract
Background
Craniopharyngioma is a rare condition in children, but it is the most frequent tumor that occurs in the hypothalamic pituitary region. Chemical meningitis has been described as an uncommon postoperative complication, but no chemical meningitis due to a spontaneous rupture leading to craniopharyngioma diagnosis in children has been reported.

Case presentation
This is a case of a 13-year-old boy presenting with fever, vomiting and headache for two days. The CT scan revealed a suprasellar lesion, and lumbar puncture showed aseptic meningitis. The cerebral MRI suggested a craniopharyngioma and the cerebrospinal fluid cholesterol concentration was abnormally high. A thorough medical history indicated some visual disturbance, which improved at the onset of meningitis, and an inflection of the growth curve. The anatomopathological analysis of the tumor confirmed the diagnosis of craniopharyngioma.

Conclusions
This case is the first to report the discovery of a craniopharyngioma with meningoencephalitis caused by the rupture of a craniopharyngioma cyst in a child.
Diagnosis was facilitated by determining the cholesterol level in the cerebrospinal fluid, as well as fine anamnesis to identify visual and growth disturbances.
The burden of childhood and adolescent cancers in North Africa and the Middle East (NAME) region: findings from the Global Burden of Disease study 2019
Authors: Karimi Amirali , Saeedi Moghaddam Sahar , Azadnajafabad Sina , Esfahani Zahra , Sharifnejad Tehrani Yeganeh , Abbasi-Kangevari Mohsen , Shobeiri Parnian , Ghamari Seyyed-Hadi , Masinaei Masoud , Rezaei Nazila , Shahin Sarvenaz , Rayzan Elham , Rezaei Negar , Larijani Bagher , Kompani Farzad 
Published: March 2023

Abstract
Introduction
Despite the significant burden of childhood and adolescent cancers, no specific studies recently discussed the burden of cancer in this group in the North Africa and the Middle East (NAME) region. Therefore, we aimed to study the burden of cancers in this group in this region.

Materials and methods
We retrieved the Global Burden of Disease (GBD) data for children and adolescent cancers (0–19 years old) in the NAME region from 1990 to 2019. 21 types of neoplasms were grouped as “neoplasms”, comprising 19 specific cancer groups as well as “other malignant neoplasms” and “other neoplasms”. Three significant parameters of incidence, deaths, and Disability-Adjusted Life Years (DALYs) were studied. The data are presented with 95% uncertainty intervals (UI), and reported rates per 100,000.

Results
In 2019, almost 6 million (95% UI: 4.166 M–8.405 M) new cases and 11,560(9770-13,578) deaths due to neoplasms occurred in the NAME region. Incidence was higher in females (3.4 M), while deaths (6226 of overall 11,560) and DALYs (501,118 of overall 933,885) were estimated as higher in males. Incidence rates did not significantly change since 1990, while deaths and DALYs rates declined significantly. After excluding “other malignant neoplasms” and “other neoplasms”, leukemia was responsible for the highest number of incidence and deaths (incidence: 10,629(8237-13,081), deaths: 4053(3135-5013), followed by brain and central nervous system cancers (incidence: 5897(4192-7134), deaths: 2446(1761-2960)), and non-Hodgkin lymphoma (incidence: 2741 (2237-3392), deaths: 790(645–962)). Incidence rates of neoplasms were similar for most countries, but countries varied more in terms of death rates. Afghanistan 8.9(6.5–11.9), Sudan 6.4(4.5–8.6), and the Syrian Arab Republic 5.6(4.3–8.3) had the highest overall death rates.

Conclusion
The NAME region is observing relatively constant incidence rates and a decreasing pattern in the deaths and DALYs. Despite this success, several countries are lagging behind in development. Different issues such as economic problems, armed conflicts and political instabilities, lack of equipment or experienced staff or poor distribution, stigmatization and disbelief in the healthcare systems account for unfavorable numbers in some countries. Such problems require urgent solutions as new sophisticated and personalized cares raise the alarm for even more inequalities between high and low-income countries.