bluuebunny/crossref_metadata_2025_split huggingface dataset:
LMIC-03. BRAINSTEM RADIATION NECROSIS IN A PATIENT WITH RECURRENT MEDULLOBLASTOMA. SUCCESFULL TREATMENT OF A HIGHLY FEARED COMPLICATION
Authors: Leal-Cavazos Carlos A , Arenas-Ruiz Jose A , Piñeiro-Retif Rafael , Vidal-Gutierrez Oscar 
Published: June 2024

Abstract

BACKGROUND
Medulloblastoma is the most common malignant brain tumor in pediatric population. Standard treatment combines surgery, risk-adapted craniospinal irradiation and chemotherapy. Given the well-known cognitive sequelae in young children associated to radiation, strategies in infants try to avoid upfront radiation. A significant number of patients treated during infancy will ultimately relapse. Re-irradition in relapse setting has proven to be effective in disease control (survival depending on several factors) although there is a concern in exceeding radiation tolerance and risk of toxicity.

METHODS
Herein, we describe the case of male patient that presented at 1 year of age with a non-metastatic anaplastic medulloblastoma that was completely resected. He received 3 cycles of adjuvant chemotherapy (as per Head Start II), local relapse was detected in tumor bed during evaluation and was completely resected, afterwards he received myeloablative chemotherapy with stem cell rescue and posterior fossa radiation therapy (54 Gy). At 8 months off therapy patient developed spinal relapse in imaging with negative cytology, then treated with spinal irradiation 36Gy without adjuvant chemotherapy. He remained disease free during 12 months, then tumor recur at the right cerebellopontine angle, surgery was complete and there was no evidence of distant disease. Patient received adjuvant local radiation with 30.6Gy followed by chemotherapy (bi weekly bevacizumab + irinotecan). Cumulative maximal dose to brainstem was 84Gy. 2 months after radiation patient presented with extreme sleepiness and imaging findings compatible with brainstem radiation necrosis, symptoms resolved promptly after scheduled bevacizumab. Patient is currently 6-year-old and remains free of disease after 3 years off therapy.

CONCLUSION
Medulloblastoma treatment in infants is challenging because survival is not the only goal. Future clinical trials will help to better tailored treatment based on molecular biology. Re-irradiation in medulloblastoma has been described as well tolerated but clinician should be aware of its complications and management.
LMIC-05. THE ROLE OF CENTRALIZATION IN PEDIATRIC NEURO-ONCOLOGY: EVIDENCE FROM A DEVELOPING COUNTRY
Authors: Hoveyan Julieta , Asatryan Eduard , Hovhannisyan Saten , Papyan Ruzanna , Lazaryan Armine , Mkhitharyan Armen , Matinyan Narek , Arzumanyan Niko , Minasyan Mariam , Melnichenko Irina , Minasyan Elya , Salman Zeena , Qaddoumi Ibrahim , Iskanyan Samvel , Hakobyan Lusine , Sargsyan Lilit , Danielyan Samvel , Tamamyan Gevorg , Bardakhchyan Samvel , Bailey Simon , Amayiri Nisreen 
Published: June 2024

Abstract

BACKGROUND
Several studies from developed countries showed that centralization of pediatric cancer care is associated with survival benefits. The role of centralization might be crucial in pediatric neuro-oncology where multidisciplinary approach is essential. The aim of this study is to evaluate the impact of centralization in neuro-oncology in a developing country.

METHODS
In 2019, the consolidation of three pre-existing pediatric oncology units in Armenia resulted in the centralization of pediatric cancer care. After 2019 all patients undergo chemotherapy and follow up at the Pediatric Cancer and Blood Disorders Center of Armenia. This analysis compares demographic data, tumor characteristics and management of 54 patients diagnosed before centralization (2009-2018) and 66 patients diagnosed after centralization (2019-2023).

RESULTS
After centralization the incidence of recorded newly diagnosed CNS tumors in Armenia has dramatically increased (2.4 times). Six cases of CNS tumors diagnosed before 2019 were first registered after centralization. Assessment for metastatic status in embryonal tumors after centralization improved (20% vs 93.75%, p=0.0001). In addition, increased molecular testing was achieved (5.56% vs 31.8%, p=0.001). The number of patients getting access to multidisciplinary care and discussions via teleconference increased dramatically (5.56% versus 86.4%, p=0.0001). A trend toward a shorter median time from first symptoms to diagnosis was found (1.75-month vs 1-month, p=0.85). In addition, significant changes in the underlying pathology were recorded. Before and after centralization embryonal tumors, low-grade gliomas and high-grade gliomas accounted 37% vs 24.25%, 22.2% vs 31.8% and 11.1% vs 15.15% of CNS tumors, respectively. The availability of follow-up information marginally increased after centralization (83.3% vs 87.8%, p=0.48).

CONCLUSIONS
CNS tumors especially low-grade gliomas were frequently not registered before centralization. The current study proves that centralization helps to improve CNS tumors registration, diagnosis, and evaluation as well as facilitating multidisciplinary care. Further research is needed for evaluating the survival benefits of centralization.
LMIC-26. DEVELOPMENT OF THE ST. JUDE GLOBAL VIRTUAL PEDIATRIC NEURO-ONCOLOGY FELLOWSHIP (VPNOF): INCREASING PEDIATRIC NEURO-ONCOLOGY CAPACITY IN LOW- AND MIDDLE- INCOME COUNTRIES (LMIC)
Authors: Salman Zeena , Moreira Daniel , Resendiz Alma Benito , Hoveyan Julieta , Rahmartani Ludi , Ain Rahat Ul , Zhang Anan , Amayiri Nisreen , Bailey Simon , Bouffet Eric , Chan Godfrey Chi-Fung , Liu Anthony P Y , La Madrid Andres Morales , Mushtaq Naureen , Tsui Karen , Bhat Vasudeva , Cirt Ramona , Ngcana Thandeka , Salazar Mauricio Sanchez , Somathilaka Mahendra , Yang Peiyi , Chinnaswamy Girish , Dhall Girish , Gupta Tejpal , Jalali Rakesh , Lassaletta Alvaro , Osorio Diana S , Shatara Margaret , Upadhyaya Santhosh , Uppuluri Ramya , Rodriguez-Galindo Carlos , Qaddoumi Ibrahim 
Published: June 2024

Abstract

BACKGROUND
Most children with central nervous system (CNS) tumors reside in LMICs, yet their complex management is limited by the availability of trained pediatric neuro-oncologists (PNO). The St. Jude Global VPNOF was designed to train pediatric oncologists (PO) in LMICs as CNS tumor experts while remaining in their home countries.

METHODS
The VPNOF structure was initially developed through semi-structured interviews of physicians who had served as global mentors or mentees in pediatric oncology. Employing a modified Delphi method, we identified the key components necessary to virtually train POs in LMICs to become PNOs.

RESULTS
A two-year fellowship program was designed with a curriculum tailored for POs in LMICs. Two main components were identified as critical to the objective of building PNO capacity: mentorship and clinical training. Mentorship involves a triad with one global and one loco-regional mentor per fellow, aiding in the fellow’s career and institutional goal setting to advance PNO care. Clinical training includes regularly scheduled virtual tumor boards and didactics, and ad-hoc case discussions with mentors while managing patients at their home institution. Additionally, fellows travel to their mentors’ institution twice for a four-week clinical rotation. In 2022, five fellows from Armenia, China, Indonesia, Mexico, and Pakistan were selected. In 2023, an additional six fellows were selected from China, Costa Rica, India, Romania, South Africa, and Sri Lanka. To date, 18 months of the two-year fellowship have resulted in the establishment of multi-disciplinary approaches, increased patient volume, increased evidence-based practices, and publication by the first cohort of 21 abstracts and two journal publications to date.

CONCLUSIONS
The VPNOF is an innovative approach to leveraging global mentorship to train PO in resource-limited settings to become PNOs. Virtual mentorship and training have led to implementation of new practices aimed at improving quality of care for children with CNS tumors in LMICs.
MODL-01. IN VITRO MODELING OF AND AUTOMATED DRUG SCREENING IN EMBRYONAL BRAIN TUMORS USING TUMOR-BRAIN ORGANOIDS
Authors: Riedel Nicole C , Walter Carolin , Aust Paula , de Faria Flavia , Altendorf Lea , Göbel Carolin , Verma Archana , Roy Rajanya , Thomas Christian , Schüller Ulrich , Bruder Jan M , Kerl Kornelius 
Published: June 2024

Abstract

BACKGROUND
Embryonal brain tumors (EBTs) such as medulloblastoma, atypical teratoid rhabdoid tumor (AT/RT), and embryonal tumor with multilayered rosettes (ETMR) uniquely arise in the developing brain. Traditional 2D models often fall short in capturing the tumoral microenvironment (TME) and intratumoral heterogeneity, which may limit their translational potential.

METHODS
To address this, we co-aggregated EBT cells from AT/RT (Chla02 and SHH310) and ETMR (BT183 and murine GEMM cells) with forebrain organoids derived from human induced pluripotent stem cells and developed an automated, screening-ready in vitro model (EBT-FBO). We used immunohistochemistry, whole-mount immunostaining, and single-cell RNA sequencing to characterize our model and compared it with a developmental forebrain atlas. We further used our model for cell type-specific drug screening and validated the results in vivo.

RESULTS
Our EBT-FBO model mimicked the differentiation states of a mid-gestational fetal forebrain, providing a natural immature neuronal environment for supratentorial EBT cells. This environment allowed the EBT cells from both AT/RT and ETMR to mimic in vivo tumor cell states and avoided the cycling cell selection common in other models. We screened over 160 drugs in ETMR-FBO and identified antracyclines and Triptolide as having anti-tumor, yet non-neurotoxic effects. Our in-depth transcriptomic analysis identified new therapeutic targets, including PDGFR-signaling for ETMR. Building on this insight, we disrupted tumor-TME interactions and observed significant anti-tumor effects both in vitro and in vivo.

CONCLUSIONS
EBT-FBO provide embryonal brain tumors like ETMR or AT/RT with their intrinsic, immature neuronal microenvironment essential for recapitulating natural tumor heterogeneity. This marks a significant advancement towards targeted therapy and patient-specific models in precision medicine.
MODL-03. THERAPEUTIC EFFICACY OF IMIPIRIDONES IN LYNCH SYNDROME-ASSOCIATED GLIOMAS
Authors: Chong Wai Chin , Putnam Ethan , Subramaniam Bavani , Woldegerima Ayda , Mizoguchi Sean , Cerna Steve , Yadavilli Sridevi , Bornhorst Miriam , Packer Roger , Nazarian Javad 
Published: June 2024

Abstract

INTRODUCTION
Lynch Syndrome, a hereditary cancer syndrome linked to DNA mismatch repair gene mutations (MMRD), predisposes individuals to various cancers, including high grade gliomas (Lynch-HGG). Effective treatments for Lynch-HGGs are scarce, and suitable pre-clinical models are needed to identify novel therapeutic combinations.

METHODS
In this study, we generated patient-derived cell line models of Lynch-HGGs (n=3), characterized them through Western blot analysis for MMRD gene markers, and conducted genome and transcriptomic analyses. Murine models were then generated via intracranial injection of cultured cells expressing mCherry-luciferase reporter genes. Drug screening based on transcriptomic analysis was performed to identify potential therapeutic agents.

RESULTS
Our findings showed loss of MMRD protein consistent with the primary mutation, and a constant loss of P53, a tumor suppressor protein. One cell line, 7316-3058, exhibited an absence of NF1 expression, another critical tumor suppressor protein. Transcriptomic analysis unveiled upregulation in cell cycle processes and SUMOylation of DNA damage response and repair proteins. In vitro treatment with imipiridone compounds (ONC201 and ONC206) demonstrated varying degrees of drug response, with 7316-3058 displaying high sensitivity to the targeted inhibitor. Unfortunately, this therapeutic efficacy did not translate to the in vivo murine model, suggesting underlying mechanisms that impede drug efficiency.

CONCLUSION
In summary, we developed effective pre-clinical models of Lynch-HGG that can be used to screen different drug combinations targeted to treat these tumors. Furthermore, despite promising in-vitro data, we demonstrated the limited efficacy of imipiridones in treating Lynch-HGG in vivo, emphasizing the challenges in translating in vitro findings to in vivo contexts. This study contributes valuable insights to the development of effective therapeutic strategies for Lynch Syndrome-associated gliomas.
RADT-10. LITHIUM TREATMENT PROTECTS MICROGLIA AND NEWLY GENERATED NEURONAL POPULATIONS IN A MOUSE MODEL OF CRANIAL RADIOTHERAPY
Authors: Rodrigues Carlos F D , Preka Efthalia , Lastra-Romero Alejandro , Zisiadis Georgios Alkis , Ruchiy Yana , Fragkopoulou Adamantia , Blomgren Klas 
Published: June 2024

Abstract

BACKGROUND
Radiotherapy remains a cornerstone of the treatment of high-grade brain tumors. However, while lifesaving, it results in long-term complications in 50-96 % of the treated individuals, where cognitive deficits are particularly debilitating. Currently, no treatments or preventive strategies are available to avert these deficits. Lithium (Li), long used to treat bipolar affective disorder, has been shown to reduce radiation-induced cognitive deficits in rodent models by preventing apoptosis of the neuronal stem and progenitor cells in the hippocampus and stimulating their proliferation. This work aimed to further elucidate the mechanisms behind the protective and pro-regenerative actions of Li in the irradiated young brain.

METHODS
Postnatal day (PD) 21, C57BL6/J mice were injected intraperitoneally with Li chloride (4 mmol/kg) and kept on a Li carbonate-containing diet for 4 weeks. Control animals were injected with saline and administered an equivalent control diet. On PD 25, the animals were administered a single-dose whole-brain radiation of 8 Gy and were subsequently sacrificed at different time points, spanning from 2 weeks to 1 year. At sacrifice, the hippocampi were harvested for single-cell RNA sequencing using a novel, 2-step protocol to harvest viable cells of all types, including neurons.

RESULTS
The results showed that radiation triggered the expression of senescence-related genes in the hippocampal microglia (e.g., Cdkn1a, Ccl12), which Li has prevented through the activation of the Bcl2 family of genes. Moreover, they corroborate the protective effect of Li on newly generated hippocampal neurons, which undergo remodeling over time, leading to the emergence of new subpopulations.

CONCLUSIONS
This work represents another advancement towards understanding the action of Li in the irradiated brain and confirms its potential to become the first pharmacological treatment for radiation-induced complications.
Long-term Outcomes of Adjunctive Lung Resection for Nontuberculous Mycobacteria Pulmonary Disease
Authors: Kang Noeul , Jhun Byung Woo 
Published: June 2024

Abstract

Background
Adjunctive lung resection is recommended for select patients with nontuberculous mycobacteria (NTM) pulmonary disease (PD). However, data are limited on long-term recurrence rates in patients infected with major pathogens, including Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABC).

Methods
In this prospective observational study, we retrospectively analyzed data from 125 patients with MAC-PD (n = 90) or MABC-PD (n = 35) who underwent adjunctive lung resection. We evaluated microbiological response, postoperative complications, recurrence, and all-cause mortality over a median 80-month follow-up.

Results
Persistent culture positivity (64%) was the most common indication for surgery, followed by hemoptysis, recurrent pneumonia, or radiologic deterioration. Postoperative complications occurred in 18 (14%) patients, with no surgery-related deaths. Treatment outcomes did not significantly differ between the MAC- and MABC-PD groups. Cure with culture conversion was achieved in 112 (90%) patients. Recurrence occurred in 37 (33%) of 112 patients, of which 18 (49%) cases were attributed to reinfection by different NTM species or subspecies. The MAC group had higher recurrence rates than the MABC group (Kaplan-Meier curve, log-rank test, P = .043) and was significantly associated with recurrence in the multivariable analysis (adjusted hazard ratio, 2.71; 95% CI, 1.23–5.99). However, mortality was higher in the MABC-PD group than the MAC-PD group (7/35 vs 4/90, P = .006).

Conclusions
Adjunctive lung resection with antibiotics helps to reduce bacterial burden and manage symptoms in patients with NTM-PD. However, it does not prevent recurrence, which is mostly caused by reinfection.
Incidence of checkpoint inhibitor-associated inflammatory arthritis, immunomodulation and mortality in cancer patients on immunotherapy: a retrospective cohort study
Authors: Bass Anne R , Xie Fenglong , Jannat-Khah Deanna , Ghosh Nilasha , Chan Karmela K , Saxena Ashish , Curtis Jeffrey R 
Published: June 2024

Abstract

Objectives
Immune checkpoint inhibitor (ICI)-associated inflammatory arthritis (ICI-IA) occurs in 4–6% of ICI-treated patients based on one observational study. We identified cases of ICI-IA using administrative claims to study its incidence and characteristics at the population level.

Methods
We used the Medicare 5% sample to identify patients initiating ICIs. Cancer patients were identified by having ≥2 ICD-9/10-CM diagnosis codes from an oncologist for lung cancer, melanoma or renal/urothelial cancer. ICI-IA was defined as having two Medicare claims ≥30 days apart with combinations of ICD-9/10-CM diagnosis codes that favoured specificity. ICI-IA was identified in patients with a musculoskeletal diagnosis after ICI initiation, who had (i) no inflammatory arthritis or inflammatory rheumatic disease before ICI initiation ever, and (ii) no musculoskeletal complaint in the one year prior to ICI. We examined DMARD utilization and visits to rheumatology in patients with ICI-IA. Landmark analysis and a time varying Cox proportional hazards model for overall survival were constructed.

Results
The incidence of ICI-IA was 7.2 (6.1–8.4) per 100 patient years. Patients with ICI-IA had a mean (s.d.) age of 73.5 (7.0) years, 48% were women and 91% were white. Median (IQR) time from ICI initiation to first ICI-IA diagnosis was 124 (56, 252) days. Only 24 (16%) received care from a rheumatologist, and 24 (16%) were prescribed a DMARD (46% by a rheumatologist). The HR for mortality in patients with ICI-IA was 0.86 (95% CI 0.59–1.26, P = 0.45).

Conclusions
The incidence of ICI-IA identified in claims data is similar to that reported in observational studies; however, few patients are treated with a DMARD or are referred to rheumatologist. There was no difference in overall survival between ICI-treated patients with and without ICI-IA.
Producerist populist attitudes and electoral support for populism in the USA and Western Europe
Authors: Ivaldi Gilles , Mazzoleni Oscar 
Published: June 2024

Abstract
This article aims to clarify the importance of producerism as a socio-economic dimension of contemporary populism. Building on the existing literature about the supply of producerism by populist politicians, we adopt a demand-side perspective to investigate whether producerism consistently manifests among the general public and how it may affect populist voting. We draw on an original set of items and a cross-national survey conducted in Western Europe and the USA to identify clusters of citizens with distinct left-wing and right-wing producerist attitudes. Our findings show that such attitudes are no longer exclusive to American politics but also found in Western Europe, albeit with country-specific modifications. Moreover, producerist citizens show distinct socio-cultural and economic attitudes and are more likely to support populist parties and candidates, particularly on the right side of the political spectrum.
Wealth, gender and sexual orientation—evidence from siblings
Authors: Dujeancourt Erwan , Boschini Anne , Nordén Anna 
Published: June 2024

AbstractUsing Swedish administrative data, this study investigates the link between wealth and sexual orientation across genders, focusing on nearly 4400 individuals who have ever been in a same-sex legal union and their siblings who had been exclusively in different-sex relationships. Employing unconditional quantile regressions and sibling fixed effects, we show that the wealth gap by gender and sexual orientation varies across the wealth distribution. Men in same-sex couples (SSCs) experience a wealth penalty below the 70th percentile but a premium above it. For women, the wealth penalty persists until the 95th percentile. Similar patterns hold for the wealth subcomponents, with men in SSCs holding more financial resources, real estate and debt at the top of the distributions, while women in SSCs hold more financial resources but less real estate and total debt. Additional analysis highlights the positive marginal effects of urban residency and years of schooling on these patterns.
Micro-CT data reveal new information on the craniomandibular and neuroanatomy of the dicynodont Gordonia (Therapsida: Anomodontia) from the late Permian of Scotland
Authors: George Hady , Kammerer Christian F , Foffa Davide , Clark Neil D L , Brusatte Stephen L 
Published: June 2024

Abstract
Dicynodontia was an abundant, globally widespread clade of Permo-Triassic synapsids on the stem lineage of mammals. Although there is an extensive body of literature on dicynodont craniomandibular anatomy, only recently has the power of computed tomographic (CT) scanning been applied to this system. CT-assisted research on dicynodonts has focused on the smallest members of the clade, while larger dicynodonts (particularly the members of the diverse, long-ranging subclade Bidentalia) have received comparatively little attention. Here, we work towards filling that gap by presenting a µCT-assisted reconstruction of ‘The Elgin Marvel’, a bidentalian specimen consisting of a complete cranium and mandible from late Permian deposits near Elgin, Scotland, which historically has been difficult to study because of its unusual preservation as void space in sandstone. This specimen can be referred to Gordonia, which is solely represented by moulds of void specimens. The µCT data reveal new information on the palate and endocranium of this taxon that could not previously be gleaned from physical moulds made from the void specimens. A phylogenetic analysis indicates that Gordonia and the Chinese Jimusaria form a clade of bidentalians characterized by narrow pterygoid medial plates, expanding our understanding of late Permian biogeography. The endocast of Gordonia is similar to that of other non-cynodont therapsids, and has a remarkably enlarged pineal body, probably related to exaggeration of the sagittal crest. Comparisons of encephalization quotients (EQ), a measure of brain size relative to body size, reveal Gordonia has a similar EQ to most other non-cynodont therapsids.
The Relationship Between Nursing Students’ Psychological Distress and Perceived Stress and the Nursing Educational Environment
Authors: Watson Mayantoinette F. , Patti Marion 
Published: June 2024

Abstract

AIM
This study aimed to identify associations between psychological distress and perceived stress and the educational environment among baccalaureate nursing students.

BACKGROUND
BSN students are a high-risk group for mental problems. High attrition rates are noted among students who screen for psychological distress.

METHOD
A quantitative descriptive design was utilized with a convenience sample of 202 students. Psychological distress was correlated with perceived stress and educational environment. Regression analysis was used to analyze the data.

RESULTS
Psychological distress was reported in 45 percent of the sample. A significant positive relationship between being married and experiencing reduced psychological distress was found. Perceived stress and educational environment were significantly correlated (p < .05).

CONCLUSION
Perceived stress from the educational environment plays a role in influential factors of psychological distress.