bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADT-11. PROTON BEAM THERAPY (PBT) FOR CENTRAL NERVOUS SYSTEM (CNS) TUMOURS IN CHILDREN: A CANADIAN PEDIATRIC BRAIN TUMOUR CONSORTIUM STUDY
Authors: Wong Kendrew S K , Patel Samir , Lafay-Cousin Lucie , Logie Natalie , D’Alessandro Paul , Magimairajan Vanan , Cacciotti Chantel , Perreault Sebastien , Alves Melanie , Galopin Marie , Poirier Éloise , Skamene Sonia , Bergeron-Gravel Samuel , Lagacé Simon , Charpentier Anne-Marie , Erker Craig , Crooks Bruce , Rutledge Rob , Sandhu Ash , Brooks Beth , Lo Andrea C , Tsang Derek S , Cheng Sylvia 
Published: June 2024

Abstract

BACKGROUND
Radiotherapy is important for treating pediatric CNS tumours. The main modalities include photon therapy and PBT. PBT offers potential advantages over photon therapy in children since its precise dose control can limit long-term side effects. However, Canadian patients needing PBT are referred to the United States (US) because PBT is unavailable in Canada. We aimed to describe PBT use and outcomes over time for Canadian pediatric patients with CNS tumours.

METHODS
Patient demographics, treatment characteristics, and outcomes were extracted from medical records of patients from 10/13 Canadian provinces/territories. Patients diagnosed with a CNS tumour at ≤20 years old between 2001-2021 who received curative-intent PBT were included. PBT plans were compared using Fisher’s exact or Kruskal-Wallis rank sum tests. Overall survival (OS) was estimated using the Kaplan-Meier method.

RESULTS
Of 195 patients (59.0% male) included in the study, majority were from Alberta (28.7%), Quebec (26.7%), British Columbia (22.6%), and Ontario (20.5%). Median age at diagnosis was 8.0 years. Most tumours (77.9%) were non-metastatic. Medulloblastoma was the most common diagnosis (30.8%). Provinces/territories referred patients to proton centres in the same geographical regions, except Alberta (74.5% referred to Florida). Referral numbers have increased ~180%/year since 2011. Median time from diagnosis to PBT was 126 days [11-5236] for all patients, and 36 days [21-1313] for medulloblastoma. Radiation doses, irradiation site, therapy duration, and time to treatment were not different (p≥0.2) across all PBT facilities for medulloblastoma. 5-year OS were 86.8% and 73.0% for the PBT study population and the Cancer in Young People-Canada reference population, respectively, in those aged &lt;15 years.

CONCLUSIONS
Given the unavailability of PBT in Canada, pediatric CNS tumour patients were referred to US PBT facilities close in proximity. Further studies are needed to better understand provincial referral patterns and barriers to equitable PBT access across Canada.
STEM-04. BIOBANKING PATIENT-DERIVED MODELS OFFERS A PRECISE SPATIAL AND EPIGENETIC APPROACH TO UNRAVEL THE INITIATION, PROGRESSION, AND THERAPEUTIC RESISTANCE OF PEDIATRIC BRAIN TUMORS
Authors: Deschuyter Marlene , Salmanli Chinar , Wolf Thibaut , Lhermitte Benoit , Reita Damien , Fuchs Quentin , Hubsch Clémence , Foppolo Sophie , Dontenwill Monique , Martin Sophie , Entz-Werlé Natacha 
Published: June 2024

Abstract

BACKGROUND
Aggressive brain cancers represent the most lethal forms of tumors in pediatric population. Their molecular drivers and co-alterations are currently guiding therapeutic strategies. Due to heterogeneous nature of these tumors, they are quickly developing resistance to treatment. Recognizing intrinsic and extrinsic mechanisms underlying therapeutic resistance, international scientific community has recognized an urgent need to create precise models of brain tumors capable of predicting therapeutic responses. So far, patient-derived cell lines (PDCL) remain the most reliable model to estimate and mimic evolving scenarios. The primary challenges lie in derivation methods and in cellular and spatial validation.

METHODS
In the context of the PEDIAMODECAN program, we collected 105 fresh brain tumor samples, including 34 LGG, 24 HGG, 19 ependymomas, 19 medulloblastomas, and 9 other rare entities, to concurrently generate PDCLs and patient-derived xenografts (PDX).

RESULTS
Regarding the derivation process itself, we successfully maintained 80% of samples in 2D and 54% in PDX models. As anticipated, the LGG group showed the higher percentage of PDX failure (90%). Nevertheless, for high-grade subtypes, PDX generation rate increased to 85,7%. No correlation was found between derivation success and a shorter interval between surgical removal and dissociation processes. Histological analysis of PDXs models confirmed the similar microscopic features to those of primary tumors. Next-Generation Sequencing (NGS), methylome assays and spatial transcriptomic analyses of derived models matched those of the original patient tumors. Epigenetic approaches were proved to be the most effective methods for validating models, in addition to spatial transcriptomic analyses that highlighted similar inter-tumor heterogeneity between PDX models and primary tumor counterparts.

CONCLUSIONS
Establishing a systematic PDCL/PDX biobank for all pediatric brain tumors represents one of the most effective approaches to develop models capable of accurately reproducing tumoral heterogeneity, histological and molecular diversity, and facilitating the design predictive screenings for targeted therapies combined with irradiation.
STEM-08. ANGIOGENESIS IN PEDIATRIC CHOROID PLEXUS PAPILLOMAS
Authors: Sulaiman Nurfarhanah Bte Syed , Merchant Khurshid Z , Seow Wan Tew , Ng Lee Ping , Low Sharon Y Y 
Published: June 2024

Abstract

BACKGROUND
Choroid plexus papillomas (CPP) are rare brain tumors that tend to occur in very young children. Although most of them are curative with surgical resection, a subset of them has propensity for tumor recurrence, progression, and metastasis. Moreover, surgery can be technically difficult due to their deep locations and high vascularity. In-depth mechanisms of their biology remain poorly understood. Separately, the process of angiogenesis has been implicated in several cancers. To date, there has been no previous study focused on CPP and angiogenesis. This study aims to explore and ascertain the existence of angiogenesis in CPP.

METHODS
This is a study approved by the hospital ethics review board. Cerebrospinal fluid (CSF) and CPP tumor samples are collected at the time of surgery. A multiplex immunoassay panel is used to measure cytokine concentrations in the CSF samples. Identified cytokines of interest are input into online platforms to assess for protein-protein interaction pathways. Concurrently, patient-derived primary cell cultures and their supernatants are derived from CPP samples. A targeted proteome blot array and HUVEC tubule formation assays are used to validate clinical and in silico findings.

RESULT
CSF profiling showed higher expression of MCP-1, MMP-1, IL-2, TNF-ɑ, TRAIL and CD40-L in CPP patient samples versus non-tumor controls. Next, in silico assessment via STRING and BioGRID platforms report that these cytokines are associated with endothelial cell regulation. This is clinically relevant as we are aware that the endothelium has important functions in the regulation of angiogenesis. Using an angiogenesis-focused approach, CPP-derived cell lines and supernatants showed congruently higher expression of MCP-1, MMP-1 and TNF-ɑ. Next, tubule formation was observed in HUVEC cultures where conditioned CPP cell culture media was added.

CONCLUSIONS
Based on our preliminary findings, this proof-of-concept study demonstrates potential to explore the role of angiogenesis in CPP for better disease understanding.
Plasma Microbial Cell-free DNA Next-generation Sequencing Can Be a Useful Diagnostic Tool in Patients With Osteoarticular Infections
Authors: Petri Francesco , Mahmoud Omar K , Ranganath Nischal , El Zein Said , Abu Saleh Omar , Berbari Elie F , Fida Madiha 
Published: June 2024

Abstract

Background
Recent advances in shotgun metagenomic sequencing (sMGS) for detecting microbial cell-free DNA (mcfDNA) in peripheral blood have shown promise across various patient populations. This study evaluates the application of sMGS for diagnosing osteoarticular infections (OAIs), a condition with significant diagnostic challenges.

Methods
We conducted a retrospective analysis on 73 patients suspected of OAIs at the Mayo Clinic from 2019 to 2023, incorporating mcfDNA sMGS (Karius test [KT]) into their diagnostic evaluation. We categorized the clinical impact of KT on OAI diagnoses and management into 4 distinct outcomes. (1) KT was able to confirm an established diagnosis, (2) KT supported noninfectious diseases diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information.

Results
In our cohort, KT was performed in 73 patients. Among the infected individuals, KT yielded positive results in 22 of 43 (51.2%) cases. Of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, whereas in 5 (22.7%) cases, the KT established an unsuspected diagnosis. Native vertebral osteomyelitis diagnosis (P &lt; .001) or OAIs with concomitant presence of endocarditis or endovascular infection (P = .005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result.

Conclusions
In complex OAIs, KT enhanced diagnostic accuracy by 11.6%, proving especially beneficial in diagnosing native vertebral osteomyelitis and infections with concurrent endocarditis or endovascular complications. Our findings underscore the utility of KT in the diagnostic workflow for challenging OAI cases, potentially altering clinical management for a significant subset of patients.
Innovations in Survey Research
Authors: Cooksey Elizabeth , Herrera Lucia , Hoffman Jenifer , Rusnak Laura 
Published: June 2024

Abstract
A survey panel is a group of people who have been recruited by various means, provided some basic demographic profile data, and agreed to share their opinions when asked to take part in specific surveys. This chapter highlights various panels used by researchers over the past couple of decades to draw samples for their own study surveys. Probability and non-probability samples are distinguished and pros and cons of each are outlined. The American Population Panel (APP) is then described and used to illustrate mechanics underlying panel initiation, growth and maintenance, along with problems encountered in the process (for example, fraud among potential respondents). The ways in which the APP can serve specific research needs such as questionnaire pilot testing, finding specific population subgroups, and following the same respondents over time are discussed.
Tacrolimus personalized therapy based on CYP3A5 genotype in Chinese patients with idiopathic inflammatory myopathies
Authors: Tian Xueke , Liu Lijun , Liu Shengyun , Yang Jing 
Published: June 2024

Abstract

Objective
Idiopathic inflammatory myopathies (IIM) are a heterogeneous and life-threatening group of diseases; in particular, anti-melanoma differentiation-associated gene 5 antibody positive DM (MDA5+ DM) is reportedly strongly associated with high mortality rate. Tacrolimus (TAC) provides an excellent therapeutic option, but the trough concentration (Cmin)–outcome relationship remains unexplored. This study was undertaken to identify optimal Cmin and individualized dose based on CYP3A5 genotype for IIM patients.

Methods
A total of 134 IIM patients with 467 Cmin were enrolled. We examined the relationship between TAC Cmin and relapses. The receiver operating characteristic analysis was used to confirm the optimal Cmin. Analyses of factors influencing Cmin were conducted. The dose requirement based on CYP3A5 genotype was confirmed.

Results
TAC Cmin is strongly associated with relapses. The optimal cutoff values were 5.30, 5.85, 4.85 and 5.35 ng/ml for acute, subacute, chronic and all-phase IIM patients (P = 0.001, 0.013, 0.002 and &lt;0.001, respectively), as well as 5.35, 5.85, 5.55 and 5.85 ng/ml for acute, subacute, chronic and all-phase MDA5+ DM patients (P = 0.007, 0.001, 0.036 and &lt;0.001, respectively). CYP3A5 genotype was one of the significant factors influencing TAC Cmin. CYP3A5 expressers required 0.059 mg/kg/day to attain the target Cmin, while nonexpressers required 0.046 mg/kg/day (P = 0.019).

Conclusion
TAC treatment may elicit favorable outcome in patients with IIM and MDA5+ DM when Cmin exceeded 5.35 and 5.85 ng/ml, which is crucial to a lower relapse rate. The individualized dose based on the CYP3A5 genotype provides a reference for TAC personalized therapy in IIM.
The Effort of Repairing a Misperceived Word Can Impair Perception of Following Words, Especially for Listeners With Cochlear Implants
Authors: Winn Matthew B. 
Published: June 2024

Objectives:
In clinical and laboratory settings, speech recognition is typically assessed in a way that cannot distinguish accurate auditory perception from misperception that was mentally repaired or inferred from context. Previous work showed that the process of repairing misperceptions elicits greater listening effort, and that this elevated effort lingers well after the sentence is heard. That result suggests that cognitive repair strategies might appear successful when testing a single utterance but fail for everyday continuous conversational speech. The present study tested the hypothesis that the effort of repairing misperceptions has the consequence of carrying over to interfere with perception of later words after the sentence.

Design:
Stimuli were open-set coherent sentences that were presented intact or with a word early in the sentence replaced with noise, forcing the listener to use later context to mentally repair the missing word. Sentences were immediately followed by digit triplets, which served to probe carryover effort from the sentence. Control conditions allowed for the comparison to intact sentences that did not demand mental repair, as well as to listening conditions that removed the need to attend to the post-sentence stimuli, or removed the post-sentence digits altogether. Intelligibility scores for the sentences and digits were accompanied by time-series measurements of pupil dilation to assess cognitive load during the task, as well as subjective rating of effort. Participants included adults with cochlear implants (CIs), as well as an age-matched group and a younger group of listeners with typical hearing for comparison.

Results:
For the CI group, needing to repair a missing word during a sentence resulted in more errors on the digits after the sentence, especially when the repair process did not result in a coherent sensible perception. Sentences that needed repair also contained more errors on the words that were unmasked. All groups showed substantial increase of pupil dilation when sentences required repair, even when the repair was successful. Younger typical hearing listeners showed clear differences in moment-to-moment allocation of effort in the different conditions, while the other groups did not.

Conclusions:
For CI listeners, the effort of needing to repair misperceptions in a sentence can last long enough to interfere with words that follow the sentence. This pattern could pose a serious problem for regular communication but would go overlooked in typical testing with single utterances, where a listener has a chance to repair misperceptions before responding. Carryover effort was not predictable by basic intelligibility scores, but can be revealed in behavioral data when sentences are followed immediately by extra probe words such as digits.
Impact of Spinal Surgery on Intrathecal Nusinersen Injections in Pediatric Spinal Muscular Atrophy
Authors: Aksoy Taha , Ramazanov Rafik , Öz Yildiz Sibel , Demirkiran Gökhan , Haliloğlu Göknur , Yazici Muharrem 
Published: June 2024

Background:
Complex spinal deformities necessitate surgical interventions that may intervene with intrathecal injections in patients with spinal muscular atrophy (SMA). This study aimed to determine the effect of spinal deformity correction surgery on nusinersen administration.

Methods:
Pediatric patients with SMA, operated by a single surgeon, either via magnetically controlled growing rod (MCGR) or definitive fusion (DF) with skip instrumentation, were evaluated retrospectively in terms of safety and feasibility of intrathecal injections. Patients’ and their parents’ perspectives were evaluated through a questionnaire regarding any shift in the setting of injections.

Results:
Fourteen patients with 15 spinal surgeries (10 MCGR and 5 DF) were included. Eleven patients received intrathecal treatment both before and after the surgery. Preoperative (n=3) and postoperative (n=9) fluoroscopic guidance was required leading to a shift in the application settings in 6 patients. Of 106 preoperative injections, 15% required fluoroscopy and 2% required anesthesia. Postoperatively, of 88 injections, 73% required fluoroscopy and 26% required anesthesia. No patients discontinued intrathecal injections due to technical difficulties associated with the spinal surgery.

Conclusions:
This study demonstrates that spinal surgery does not prevent safe and successful intrathecal nusinersen injections. In the DF group, the skip instrumentation technique provided access to interlaminal space for intrathecal injections. In either surgical group, no further auxillary approach was required. Modifications in the injection technique require an institutional approach, and concerns of patients and their families should be addressed accordingly.

Level of Evidence:
IV
The Impact of Donor History of Sleep Apnea on Corneal Tissue Evaluation Parameters
Authors: Ramini Abhishek , Zhang Nancy , Lee Megan , Vadakkepattath Indu , Sawant Onkar B. , Bouchard Charles S. 
Published: June 2024

Purpose:
The goal of this study was to explore whether the donor history of sleep apnea affects corneal tissue evaluation parameters.

Methods:
This was a retrospective study assessing the impact of donor history of sleep apnea in a dataset obtained from the Eversight Eye Bank. Comparative analysis and multivariate regression were used to assess differences in key parameters including endothelial cell density (ECD) and central corneal thickness.

Results:
Data analyzed consisted of 50,170 tissues from 25,399 donors with no history of sleep apnea and 5473 tissues from 2774 donors with a history of sleep apnea. Tissue from donors with a history of sleep apnea showed lower ECD than those from donors with no history of sleep apnea (−51 cells/mm2, P < 0.001). Multivariate linear regression demonstrated that history of sleep apnea was a predictor of lower ECD by 13.72 cells/mm2 (P = 0.0264). Secondary analysis demonstrated that underweight and obese body mass indexes were significant predictors of increased ECD in donors with no history of sleep apnea (P < 0.0001, P = 0.025, respectively). Body mass index category was not a significant predictor of ECD in donors with a history of sleep apnea. In a smaller subset of 10,756 tissues, sleep apnea was not a significant predictor of central corneal thickness.

Conclusions:
This is the first study to demonstrate that a donor's history of sleep apnea is associated with a lower ECD in a large eye bank dataset. Future studies are needed to investigate whether history of sleep apnea affects posttransplantation outcomes.
The effects of a Teddybear Hospital project on prescool childrens’ knowledge and medical students’ professionalism: a prospective cohort study
Authors: Mildenberger Julia E. , Cámara Rafael , Muensterer Oliver J. 
Published: June 2024

Background:
The Teddybear Hospital (TH) Project is an effort to increase children’s knowledge and decrease their anxiety. It is also intended to improve medical students’ pediatric communication skills. This study evaluated the educational effects on participating preschool children and medical students.

Methods:
Preschool children were offered to bring their stuffed toys to the TH at our tertiary academic medical center. Medical students who had completed the pediatric surgery rotation staffed the TH, performed examinations, and interacted with the children. The children’s knowledge of anatomy, medical equipment, and healthy lifestyle, along with their level of anxiety towards hospitalization, was assessed using preinterventional and postinterventional validated survey tools. Preschool peers who did not participate in the TH served as controls. Participating medical students were tested on professionalism and pediatric surgical knowledge during, and 3 weeks after the intervention, and compared to their nonparticipating peers.

Results:
A total of 131 children (63 intervention, 68 control) and 48 medical students (16 intervention, 32 control) participated in the study. Children’s state anxiety decreased by 0.98 points (95% CI: −0.3 to −1.8, P<0.001), while knowledge increased significantly on ‘healthy lifestyle’ by 1.4 points (95% CI: 1.01–1.79, P<0.05), on ‘medical equipment’ by 4.5 points (95% CI: 3.8–5.2, P<0.0001), and on ‘anatomy’ by 5.05 points (95% CI: 4.73–5.73, P<0.01). No changes were detected in any of the outcome measures in the control group. Medical students’ objective professionalism increased by 4.2 points (95% CI: 1.58–6.80, P<0.01) compared to nonparticipant medical students. The tests did not show an increase in the medical students’ pediatric surgical knowledge.

Conclusions:
Preschool participation in a TH increased knowledge and decreased anxiety regarding hospitalization and medical personnel. It also helped medical students to playfully acquire medical professionalism.
Racial, ethnic, and sex disparities in the utilization and outcomes of tricuspid valve surgery
Authors: Ismayl Mahmoud , Ahmed Hasaan , Goldsweig Andrew M. , Alkhouli Mohamad , Guerrero Mayra 
Published: June 2024

Background:
Data on racial/ethnic and sex disparities in the utilization and outcomes of tricuspid valve surgery (TVS) in the United States are scarce. The authors aimed to evaluate the impact of race/ethnicity and sex on the utilization and outcomes of TVS.

Methods:
The authors analyzed the National Inpatient Sample database from 2016 to 2020 to identify hospitalizations for TVS. Racial/ethnic and sex disparities in TVS outcomes were determined using logistic regression models.

Results:
Between 2016 and 2020, 19 395 hospitalizations for TVS were identified. The utilization rate (number of surgeries/100,000 hospitalizations) was lower in Black and Hispanic patients compared with White patients for surgical tricuspid valve repair (STVr) (331 versus 493 versus 634, P<0.01) and surgical tricuspid valve replacement (STVR) (312 versus 601 versus 728, P<0.01). Similarly, the utilization rate was lower for women compared with men for STVr (1021 versus 1364, P<0.01) and STVR (930 versus 1,316, P<0.01). Compared to White men undergoing TVS, all women had lower odds of acute kidney injury [adjusted odds ratio (aOR) 0.65, 95% CI 0.55–0.78] and higher odds of blood transfusion (aOR 1.30, 95% CI 1.07–1.59), and Black men had higher odds of blood transfusion (aOR 1.59, 95% CI 1.08–2.35). In-hospital mortality and other surgical complications were similar between all groups (all P>0.05).

Conclusions:
Significant racial/ethnic and sex disparities exist in the utilization of TVS in the United States. Further studies are needed to understand the reasons for these disparities and to identify effective strategies for their mitigation.