bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the role of cytokinesis-block micronucleus assay as a biomarker for oxidative stress-inducing DNA damage in type 2 diabetes mellitus patients
Authors: Vishakh R. , Suchetha Kumari N. , Bhandary Adithi , Shetty Shilpa S. , Bhandary Prajna , Tamizh Selvan G. 
Published: June 2023

Abstract
Background
Type 2 Diabetes Miletus (T2DM) is a common metabolic and lifestyle disorder leading to increased oxidative stress and DNA damage. The present study aims to evaluate the feasibility of utilizing the cytokinesis-block micronucleus assay (CBMN) as a biomarker for assessing the DNA damage induced due to variations in oxidative stress.

Methodology
The study group includes diabetic (n = 50) and non-diabetic (n = 50) subjects. The assays for the diabetes-like fasting blood sugar, postprandial glucose and hemoglobin A1c (HbA1c), lipid profiling, and serum ferritin level along with c-reactive protein (CRP) were applied. Further, the CBMN assay was performed to evaluate the micronuclei present in the lymphocytes of control and T2DM groups.

Results
Significant imbalance in the glycaemic index, dyslipidemia, increased ferritin levels, and CRP levels, with a significant increase of micronucleus frequency, was found in T2DM patients compared with the control group. Results suggest a trend of positive correlation between HbA1c and the micronuclei, indicating the assay’s potential importance as a biomarker for T2DM-induced risk assessment.

Conclusion
From the observed results, it can be suggested that the CBMN assay could be used to assess the risk of oxidative stress-induced DNA damage in high glycaemic index diabetic patients.
Treating negative symptoms of schizophrenia: current approaches and future perspectives
Authors: Howes Oliver , Fusar-Poli Paolo , Osugo Martin 
Published: June 2023

SummaryNegative symptoms are core symptoms of schizophrenia which are common throughout the course of the illness. We outline their functional impact, before reviewing the latest research and guidelines on their assessment and treatment. Finally, we discuss conceptual issues related to measurement of negative symptoms and approaches to address these.
Intensity at the end of life in pediatric neuro-oncology patients: The case for pediatric palliative care.
Authors: Udemgba Chinwe , Hoehn Karen Sarah , Darlington Wendy Shannon , Palama Brett 
Published: June 2023

10021 Background: Although pediatric cancer is rare, it is the leading cause of death by disease after infancy for children and adolescents in the United States. Children exist in the context of a family; hence, excellent care for a child must also include attention to the needs of the family. Palliative care aims to enhance quality-of-life for these children living with life threatening illnesses and their families. Among pediatric cancers, brain tumors have high disease-related mortality rates; therefore, early introduction of palliative care to these patients is critical. This study aims to evaluate the association of palliative care during the terminal admissions of pediatric neuro-oncology patients and intensity of care provided at the end of life. Methods: Pediatric patients with brain tumors were identified using the Pediatric Health Information System (PHIS). Inclusion criteria were age <18, diagnosis of brain tumor as defined by ICD-10 codes, discharged as deceased, and hospital admission between 1/1/2017 and 12/31/2021. Intensity of care measures included: pediatric intensive care unit (PICU) admission, mechanical ventilation, total parenteral nutrition (TPN), and extracorporeal membrane oxygenation (ECMO). Results: 567 patients met the inclusion criteria. 359/567 (63%) patients had an inpatient palliative care consultation during their terminal hospital stay. Patients receiving a palliative care consultation had a lower percentage of PICU admission (64.9 vs 83.2, p=<0.001), mechanical ventilation use (51.0 vs 76.0, p=<0.001), and TPN use (18.1 vs 25.5, p=0.027). There were no significant differences in length of stay (22.07 vs 22.25 days, p=0.181) and ECMO use (0.28% vs 1.92%, p=0.450). Conclusions: Pediatric patients receiving palliative care consultations during their terminal admission received less intense care while having comparable lengths of stay. Palliative care should be offered to all families, even with aggressive goals, to help incorporate quality of life and comfort in the treatment plan and to ensure bereavement support is available if needed. Similar to data in the adult palliative care literature, this data demonstrates reduced resource utilization among pediatric patients receiving palliative care. Palliative care has been shown to be a supportive service that has the potential to improve the quality of life of patients. The first step toward equitable healthcare is to ensure that all children with a potentially terminal cancer diagnosis have access to full supportive services, including palliative care.
Comprehensive genomic profiling and individual therapeutic planning in high-risk/refractory pediatric solid tumors: A single-center real-world study.
Authors: Slaby Ondrej , Pokorna Petra , Pálová Hana , Kyr Michal , Múdry Peter , Sterba Jaroslav 
Published: June 2023

10035 Background: Despite major improvements in the survival of pediatric cancer patients that were achieved through the intensification of chemotherapy and the perfection of supportive care in the past decades, treatment outcomes for high-risk, relapsed, and refractory solid cancers remain unsatisfactory. Accelerating the progress of pediatric oncology requires both therapeutic advances and attention to reducing the long-term cytotoxic treatment-related side effects. This could be achieved by targeting specific molecular changes that drive pediatric malignancies. Methods: From September 2016 to August 2020, a total of 192 patients with pediatric high-risk solid tumors successfully underwent comprehensive genomic profiling. Since more than thirty patients had two or more biopsies from recurrent relapses, the total number of samples examined was 295. In the cohort, there were 78 cases of central nervous system tumors, 68 sarcomas, 14 neuroblastomas, 10 lymphomas, and 22 tumors of other histology. Whole-exome sequencing was performed in all patients, fusion gene analysis in 96% of patients, whole-transcriptome profiling in 84% of patients, and CNV analysis in 63% of patients. Results: The diagnostic yield of therapeutically actionable findings was 40%, with single-nucleotide variants and small insertions/deletions being the most common actionable alteration types. In 23% of patients, a clinically relevant gene fusion was identified. The majority of the identified fusions were of diagnostic significance, and 18% of those were therapeutically targetable gene fusions involving BRAF, RAF1, ALK, FGFR1, or NTRK2. Four patients were eligible for immunotherapy based on high tumor mutational burden ( > 10 mut/Mb). Lymphomas and CNS tumors showed the highest rate of patients with therapeutically actionable findings (60% and 56%, respectively), followed by neuroblastomas (36%), sarcomas (25%), and other solid tumors (23%). All results and individual treatment plans were discussed and approved at multidisciplinary molecular tumor boards. Conclusions: Precision medicine in pediatric oncology has rapidly developed over the last decade and resulted in new therapeutic options based on molecular biomarkers and increased our understanding of the complexity of pediatric malignancies. Supported by the Ministry of Health of the Czech Republic, grant nr. NU20-03-00240 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU.
Outcomes of childhood, adolescent, and young adult cancer survivors (CAYACS) with solid organ transplants: A population-based study.
Authors: Gupta Sumit , Lau Cindy , Ng Vicky , Miserachs Mar , Teoh Chia Wei , Solomon Melinda , Nathan Paul C. 
Published: June 2023

10056 Background: Organ toxicity requiring solid organ transplant (SOT) is a rare but serious effect of cancer treatment. Given restricted donor organ supply, teams must assess CAYACS requiring SOT in relation to potential recipients with non-malignant indications; decisions are limited by scant long-term outcome data. We compared long-term outcomes for CAYACS requiring SOT with other SOT recipients. Methods: All Ontario, Canada children < 18 years at cancer diagnosed 1986-2021 at pediatric centres, and AYA aged 15-21 diagnosed at adult centres for acute leukemia, lymphoma, sarcoma, or testicular cancer between 1992-2012 were identified using population-based clinical databases. Patients with SOT prior to their primary cancer diagnosis were excluded. SOT was identified through linkage to healthcare databases; patients were matched 1:2 to non-malignant SOT recipients by sex, SOT year and type, and birth year. Post-SOT outcomes including overall survival (OS) and post SOT cancers were compared between CAYACS and SOT controls. Results: Among 16,533 CAYA with cancer, 85 received SOT: 46 liver, 18 kidney, 11 lung, and 10 heart. Among liver recipients, 33 (71.7%) were for primary cancer treatment (e.g. hepatoblastoma) vs. 13 (28.3%) for organ toxicity. Median age at original cancer diagnosis was 4 years [interquartile range (IQR) 1-13] and at SOT was 13 (IQR 3-20). CAYACS with SOT as treatment for long-term toxicity (liver subset plus all renal, lung, heart, N = 52) had a median time from cancer diagnosis to SOT of 9 years (IQR 4-16) and experienced lower 10-year OS from time of SOT [67.7%, 95th confidence interval (95CI) 50.8-79.9] vs. SOT matched controls [86.0% (74.8-92.5); hazard ratio (HR) 3.9; 95CI 1.6-9.7; p = 0.003]. When stratified by SOT type, similar trends were seen but were only statistically significant among lung SOT recipients (Table). The 5-year cumulative incidence of primary cancer relapse from time of SOT among those who received liver SOT for primary cancer therapy was 15.9% (95CI 5.6-30.8). Among CAYACS who require SOT following organ toxicity, 10-year cumulative incidence of second cancers was 8.6%±4.2%; this was similar to the incidence of first cancer among SOT controls (6.4%±2.6%; HR 1.6, 95CI 0.6-4.0; p = 0.34). Conclusions: Though CAYACS requiring SOT have inferior survival compared to other SOT patients, the majority achieve long-term cancer-free survival. These data can inform discussions on the suitability of CAYACS for SOT. [Table: see text]
Outcomes among survivors of childhood cancer in low- and middle-income countries: A systematic review.
Authors: Denburg Avram , Wong Kevin Alexander , Moskalewicz Alexandra , Gupta Sumit 
Published: June 2023

10057 Background: Low- and middle-income countries (LMICs) account for most of the global childhood cancer burden. Though cure rates lag behind those in high-income countries (HICs), a substantial proportion of LMIC children do survive. Long-term side effects of cancer or cancer therapy (late effects) are well-documented among childhood cancer survivors (CCS) in HICs, but whether prevalence and risk factors of late effects are comparable in LMICs is unclear. We thus conducted a systematic review to assess LMIC CCS outcomes. Methods: Five major health sciences databases were searched from inception to November 2022 in all languages. We included observational studies conducted in LMICs (World Bank 2021 classification) that evaluated outcomes in CCSs diagnosed with any malignancy. Mean or median length of follow-up must have been ≥ 5 years from original cancer diagnosis. Meta-analyses were precluded by cohort and outcome heterogeneity. Results: Of 1,994 studies identified, 113 underwent full-text review and 21 met inclusion criteria (16 full articles and 5 conference abstracts). Studies were conducted in lower-middle income (N = 12, 57%) or upper-middle income (N = 9, 43%) countries; no low-income country data were found. Study regions were mainly South and East Asia (N = 10, 48%) and the Americas (N = 8, 38%). Almost half (N = 9, 43%) of studies were conducted in India and only one African study from Cameroon was identified. Over half (N = 12, 57%) of studies were cross-sectional in design. Only five (24%) cohorts were comprised entirely of 5-year survivors. CCS of all childhood cancer types were evaluated in 12 (57%) cohorts, and 9 (43%) were specific to one cancer type. Ten (48%) studies were conducted in a survivorship clinic. Second cancers, followed by endocrine, reproductive, and cardiovascular late effects were most frequently assessed. Second cancers were reported in 1%–11% of CCS cohorts (N = 10 studies). The prevalence of hypothyroidism and metabolic syndrome ranged from 2%-49% (N = 6 studies) and 4%-17% (N = 5 studies), respectively. Gonadal dysfunction ranged from 2%-82% (N = 6 studies). Cardiac dysfunction and hypertension ranged from 1%-16% (N = 3 studies) and 5-19% (N = 3 studies), respectively. Late effects of the musculoskeletal (N = 4 studies) and urinary (N = 4 studies) systems were least investigated. Conclusions: Substantial knowledge gaps exist in LMIC childhood cancer survivorship. Few LMIC-based studies were identified, with no low-income country data available. In middle-income countries, variability existed in how late effects were defined and assessed; data was also limited by selection bias and small sample sizes. Additional systematically collected data on LMIC CCS cohorts are urgently needed.
Influence of genetic predisposition and lifestyle on modifiable cardiovascular risk factors among survivors of childhood cancer.
Authors: Wilson Carmen L , Dhaduk Rikeenkumar , Zhou Xin , Matt Gavriel , Yasui Yutaka , Im Cindy , Armstrong Gregory T. , Dixon Stephanie B , Sapkota Yadav , Wang Zhaoming , Hudson Melissa M. , Robison Leslie L. , Ness Kirsten K. 
Published: June 2023

10061 Background: We aimed to evaluate associations between polygenic risk score (PRS), and lifestyle with cardiovascular risk factors (CVRFs) assessed as continuous phenotypes (LDL, HDL, triglycerides, fasting glucose [FG], systolic [SBP] and diastolic blood pressure [DBP]) among childhood cancer survivors. Methods: Participants included 2,347 White survivors (mean age=35.5 (±9.3) years) enrolled in the St. Jude Lifetime Cohort. Phenotype-specific PRS (derived from general population) were divided into tertiles and survivors classified as being at low-, intermediate-, or high-genetic risk. Lifestyle, classified as good, intermediate, or poor, was assessed based on four factors (smoking [yes/no], physical activity [meeting CDC guidelines for physical activity], diet quality [Healthy Eating Index score >59], and obesity [BMI≥30kg/m2]). A general linear model was created for each CVRF in which the effect of lifestyle (good, intermediate, poor) was examined within genetic risk group (low, intermediate, high), adjusting for sex, age, cancer therapies and current medication use. Results: The table shows worsening CVRF profiles associated with declining lifestyle and with increasing genetic risk. For example, among survivors with poor lifestyle-high genetic risk, SBP and DBP were higher on average by 14 (95% CI = 9-18) and 9 (95% CI = 6-12) mmHg respectively, compared to survivors with good lifestyle-low genetic risk. In analyses restricted to survivors with high genetic risk, mean SBP (7, 95% CI=2-12) mmHg, DBP (4, 95% CI=1-7) mmHg, triglyceride (61, 95% CI=5-117) mg/dL, and FG (7, 95% CI=4-10) mg/dL values were higher among survivors with poor versus good lifestyle, while mean HDL was lower (-13, 95% CI= -8- -18) mg/dL. Conclusions: While the risk of CVRFs among cancer survivors are associated with high genetic risk and cancer therapies, healthy lifestyle choices may partially ameliorate perturbations in CVRFs even among those with high genetic risk. Our findings highlight the importance of developing interventions targeting modifiable behaviors in this high-risk population. [Table: see text]
Expansion of the fertility preservation program to all newly diagnosed prepubertal oncology patients at a pediatric hospital.
Authors: Leavitt Antonia Pryor , Albritton Karen H. , Cazzell Mary , Stevenson Eleanor 
Published: June 2023

10064 Background: As the majority of pediatric oncology patients survive their disease, generating a population of over 500,000 survivors in the United States, it is imperative to minimize the lifelong consequences of treatment, which includes temporary or permanent infertility caused by certain cancer treatments. Fertility preservation (FP), the opportunity to preserve one’s ability to have genetically-related children prior to damaging the reproductive system, is a young but rapidly expanding field and recent scientific advances have led to an expansion of options for prepubertal patients. A fertility consultation at diagnosis can provide patients and families with the opportunity to be informed regarding likelihood of gonadal dysfunction and to consider FP. Methods: After our pediatric hospital started to offer tissue cryopreservation, we initiated this evidence-based interventional quality improvement project. Our primary aim was to ensure that all newly diagnosed prepubertal oncology patients who met criteria for FP were correctly identified and offered an educational consultation and preservation. Inpatient admission lists and provider schedules were reviewed daily to identify patients. Treatment plans were discussed with providers to calculate infertility risk. All procedures were to be completed at the time of another procedure to increase likelihood of insurance coverage and minimize delays. Results: Between 07/15/22 and 11/30/22, 54 newly diagnosed prepubertal patients’ treatment plans were evaluated to determine treatment-related infertility risk using the Oncofertility Consortium Pediatric Initiative Network’s Risk Assessment tool. 15 patients were at a high level of significantly increased risk and were therefore eligible for consultation. 7 patients and their families received an educational consultation and 6 elected to undergo FP (3 TTCs; 3 OTCs). FP procedures did not cause a delay in starting treatment for any of these patients. 8 patients did not receive consultations. Reasons included the provider electing to proceed with treatment without consultation (4), the patient’s comorbidities (1), the inability to bundle FP with another procedure (1), and the family decision to decline consultation (1). Conclusions: Of the patients at high risk of infertility, only 46% received consultation with lack of referral prior to initiating treatment as the primary reason. Of the patients offered preservation methods, 86% elected to preserve their fertility, illustrating patient and family interest. Providers must acknowledge changes in practice and be informed on the impact that high-risk treatment protocols can have on fertility. An FP program with established policies processes can increase the likelihood that prepubertal patients at high risk for infertility are correctly identified, educated, and offered preservation.
CANKADO PRO-React eHealth support in patients with HR+ HER2- metastatic breast cancer receiving palbociclib and endocrine therapy and the affect on time to deterioration of quality of life: Primary outcome analysis of the multicenter randomized PreCycle trial.
Authors: Harbeck Nadia , Fasching Peter A. , Wuerstlein Rachel , Degenhardt Tom , Lüftner Diana , Kates Ronald E. , Schumacher Johannes , Raeth Philip , Hoffmann Oliver , Lorenz Ralf , Decker Thomas , Reinisch Mattea , Göhler Thomas , Staib Peter , Gluz Oleg , Schinkoethe Timo , Schmidt Marcus 
Published: June 2023

1008 Background: The multicenter, randomized phase IV Intergroup PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based ePRO assessment on quality of life (QoL) in HR+/HER2- locally advanced or metastatic breast cancer (MBC) patients (pts) treated with palbociclib (P) and an aromatase inhibitor or P+fulvestrant. CANKADO PRO-React, an EU- registered medical device, is an autonomous application reacting to changes in pt self- reported QoL. Methods: Between 2017 and 2021, 499 pts (median age 59y) from 71 centers were randomized (2:1, stratified by therapy line) between an active (A; CANKADO PRO-React) or an inactive arm (B; inform; limited CANKADO functionality). 412 pts (271 A; 141 B) were available for analysis of the primary endpoint, i.e. time to deterioration (TTD) of QoL (10-point drop on FACT-G), using an Aalen-Johansen estimator for cumulative incidence function of TTD DQoL with 95% pointwise confidence intervals (CI). Secondary endpoints included PFS, OS, and DQoL (QoL deterioration). Results: In all pts (ITT-ePRO), a significantly decreased risk (HR 0.6982) for the CANKADO active arm A with 95% CI [0.5059, 0.9635] regarding DQoL was observed (p=0.03). In 1stL pts (n=295), the decreased risk for arm A was 0.7162 (0.4839, 1.06; p=0.09), in 2ndL pts (n=117) 0.6614 (0.3744, 1.168; p=0.2). Absolute pt numbers declined in later visits; until about visit 30, FACT- G completion rates were 80% and higher; mean total scores were similar between arms; the change from baseline showed a linear decline and a nearly constant offset in favor of arm A, particularly in 1st L. No significant differences in clinical outcome were observed between arms: Median PFS (ITT population) was 21.4 (95% CI 19.4-23.7) (A) and 18.7 (15.1.-23.5) months (B); median OS was not reached (A) and 42.6 months (B). Conclusions: PreCycle is the first multicenter randomized eHealth trial demonstrating a significant benefit of an interactive autonomous patient empowerment application on QoL in MBC pts receiving oral tumor therapy. Clinical trial information: NCT03220178 .