bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDKN2A deletion and radiation sensitivity in IDH-mutant astrocytomas.
Authors: Muzyka Logan , Kitagawa Yosuke , Nasser Ali Mohamed , Wetzel Ethan A , Miller Julie J. , Wakimoto Hiroaki , Cahill Daniel P. 
Published: June 2024

2041 Background: IDH-mutant astrocytomas represent the most prevalent primary tumors in younger adults (<45yo). A substantial minority of these tumors exhibit the deletion of CDKN2A (Cyclin-Dependent Kinase Inhibitor Gene 2A). Homozygous deletion of this gene– which encodes the tumor suppressor protein p16 – is associated with a malignant phenotype and poorer prognosis in IDH-mutant astrocytoma. CDKN2A deletions are primarily observed in tumors that have received radiation therapy (RT), suggesting a potential mechanistic relationship between RT and deletion. This observation gives rise to two alternative hypotheses: either RT is causing DNA damage in irradiated cells, leading to the induction of subclonal CDKN2A deletion, or a subset of cells already possesses the CDKN2A deletion and is resistant to RT, resulting in the treatment selecting for the subsequent emergence of these cells. Here, we sought to ascertain the influence of CDKN2A deletion on IDH-mutant astrocytoma cellular response to RT. Methods: The antitumor effect of RT was evaluated in vitro using patient-derived IDH-mutant astrocytoma cells, MGG152. A homozygous CDKN2A deletion was engineered in this parental line, creating a paired line to permit an isogenic comparison between CDKN2A intact versus CDKN2A deleted tumor cells. A photon irradiator was used to deliver a range of clinically-relevant RT doses spanning from 0 to 20 gray (Gy). Differences in cell viability after a predetermined incubation period were examined and relevant statistical comparisons performed. Results: Dose-response curves in response to radiation therapy, comparing CDKN2A intact and deleted cell lines, were generated (Table). Both CDKN2A intact and deleted cell lines exhibited significant reductions in viability following radiation exposure at and above 2Gy (p < 0.001). CDKN2A-deleted cells displayed a small but significantly greater sensitivity than CDKN2A-intact at 1, 2, and 5Gy (Table). Conclusions: Our findings offer evidence indicating that p16 loss does not bestow radioresistance in IDH-mutant astrocytomas. These findings align with a hypothesis that radiotherapy (RT) might promote DNA damage, and consequently, subclonal CDKN2A deletion, in irradiated IDH-mutant tumors. [Table: see text]
Can targeting TSP-1 with gabapentin enhance survival in glioblastoma? A 20-year retrospective cohort study.
Authors: Mehari Mulki , Ambati Vardhaan , Krishna Saritha , Negussie Mikias , Nava Gonzales Cesar , Dada Abraham , Kabir Aymen , Kaur Jasleen , Oten Sena , Sibih Youssef , Daniel Andy , de Groot John Frederick , Odia Yazmin , Hervey-Jumper Shawn L. 
Published: June 2024

2048 Background: Molecularly-defined cellular subpopulations of glioblastoma secrete high levels of the synaptogenic protein thrombospondin-1 (TSP-1) which promotes functional integration of tumor into neural circuity. A greater extent of glioma-neuronal crosstalk portends worse survival for patients. In preclinical studies, gabapentin was shown to inhibit TSP-1, in turn disrupting neuronal synaptogenesis and neuronal activity-dependent glioblastoma proliferation; however, clinical survival data is lacking. We aim to determine whether treatment with gabapentin is associated with improved survival and reduced serum TSP-1 in a retrospective cohort of patients with IDH-wildtype glioblastoma. Methods: Newly-diagnosed, IDH-wildtype glioblastoma patients who received care at the UCSF Brain Tumor Center between 1997-2017 were included in this study. Kaplan-Meier curves and multivariate Cox proportional-hazards models, controlled for age, MGMT promoter methylation status, preoperative tumor volume, and extent of resection, were used for survival analyses. Differences in serum TSP-1 measured by ELISA for gabapentin treated patients and matched non-gabapentin treated controls were assessed using unpaired two-tailed student’s t-test. Control samples were matched 2:1 by age, tumor volume, and extent of resection. After 2005, patients were treated with chemoradiation with concurrent and adjuvant temodar. Results: Among 379 adult patients with glioblastoma, 36 (9.5%) were treated with gabapentin. The median daily dose of gabapentin was 600 mg (IQR: 300-900 mg). There were no significant differences between gabapentin treated and non-gabapentin treated patients by age (0.06), sex (p=0.14), or race (p=0.52). Median overall survival for gabapentin treated and non-gabapentin treated patients was 20.8 months (IQR: 11.7 - 32.1) and 14.7 months (IQR: 8.9-23.5), respectively (p= 0.02). On Kaplan-Meier survival analysis, overall survival was longer for gabapentin treated patients compared with non-gabapentin treated patients (p=0.005). In the multivariate Cox proportional-hazards model, gabapentin use was associated with decreased hazard of death (HR 0.67, p=0.030). Mean serum TSP-1 in gabapentin-treated patients was significantly lower than in the matched control group (10181 ng/ml vs 17015 ng/ml, p=0.017). Conclusions: Gabapentin use is associated with a survival benefit for patients with glioblastoma, possibly mediated through a reduction in TSP-1. This promising result lays the foundation for future prospective studies to further evaluate TSP-1 as a circulating prognostic biomarker as well as to explore the therapeutic benefits of gabapentin as a life-prolonging treatment for patients with newly diagnosed glioblastoma.
Improved Survival With Adjuvant Cyclooxygenase 2 Inhibition in PIK3CA-Activated Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance)
Authors: Nowak Jonathan A. , Twombly Tyler , Ma Chao , Shi Qian , Haruki Koichiro , Fujiyoshi Kenji , Väyrynen Juha , Zhao Melissa , Knight James , Mane Shrikant , Shergill Ardaman , Kumar Pankaj , Couture Felix , Kuebler Philip , Krishnamurthi Smitha , Tan Benjamin , Philip Philip , O'Reilly Eileen M. , Shields Anthony F. , Ogino Shuji , Fuchs Charles S. , Meyerhardt Jeffrey A. 
Published: June 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that PIK3CA mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045 ) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by PIK3CA mutational status was a preplanned study. PIK3CA gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant ( Pinteraction = .13). Overall survival was similarly improved for patients with PIK3CA gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with PIK3CA wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; Pinteraction = .04). Although the test for heterogeneity in DFS did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.
Magnitude and Temporal Variations of Socioeconomic Inequalities in the Quality of Life After Early Breast Cancer: Results From the Multicentric French CANTO Cohort
Authors: Sandoval José Luis , Franzoi Maria Alice , di Meglio Antonio , Ferreira Arlindo R. , Viansone Alessandro , André Fabrice , Martin Anne-Laure , Everhard Sibille , Jouannaud Christelle , Fournier Marion , Rouanet Philippe , Vanlemmens Laurence , Dhaini-Merimeche Asma , Sauterey Baptiste , Cottu Paul , Levy Christelle , Stringhini Silvia , Guessous Idris , Vaz-Luis Ines , Menvielle Gwenn 
Published: June 2024

PURPOSE Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends. PATIENTS AND METHODS We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498 ), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment. RESULTS Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SIIfinancial difficulties = –7.6 [–8.9; –6.2], SIIincome = –4.0 [–5.2; –2.8]), SIIeducation = –1.9 [–3.1; –0.7]). These inequalities significantly increased (interaction P < .05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment. CONCLUSION The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.
Health-related Quality of Life and Problem Behavior After GH Cessation in Adults Born Small for Gestational Age: A 12-Year Follow-up Study
Authors: Dorrepaal Demi Justine , van der Steen Manouk , de Ridder Maria , Goedegebuure Wesley Jim , Hokken-Koelega Anita Charlotte Suzanne 
Published: June 2024

Abstract

Context
Long-term data regarding health-related quality of life (HRQoL) and problem behavior in adults born small for gestational age (SGA) who were treated with GH during childhood are lacking.

Objective
To investigate longitudinal changes in HRQoL and problem behavior in adults born SGA during 12 years after cessation of childhood GH treatment (SGA-GH) and compare these with 3 control groups at age around 30 years.

Participants
One hundred seventy-six SGA-GH adults and 3 untreated age-matched control groups: 50 born SGA with short stature (SGA-S), 77 born SGA with spontaneous catch-up growth to normal height (SGA-CU), and 99 born appropriate-for-gestational-age with normal height (AGA).

Main Outcome Measures
HRQoL and problem behavior were assessed using the TNO-AZL Adults Quality of Life questionnaire and Adolescent Behavior Check List at 6 months and 2, 5, and 12 years after GH cessation. Data at 12 years after GH cessation were compared with 3 control groups.

Results
During 12 years after GH cessation, HRQoL remained similar on 9 subscales in SGA-GH adults but decreased on 3 subscales (gross motor functioning, pain, sleep). Externalizing problem behavior decreased significantly, and internalizing problem behavior tended to decrease. SGA-GH and SGA-S adults had similar HRQoL and problem behavior. SGA-GH adults had, compared to AGA adults, similar HRQoL on 7 subscales, lower HRQoL on 5 subscales, and more internalizing and externalizing problem behavior. All SGA adults had lower HRQoL and more internalizing problem behavior than AGA adults. Adult height associated negatively with externalizing problem behavior, but the influence was small.

Conclusion
During 12 years after GH cessation, HRQoL remained mostly similar and problem behavior decreased in SGA-GH adults. SGA-GH and SGA-S adults had similar HRQoL and problem behavior. All SGA adults had lower HRQoL and more internalizing problem behavior than AGA adults.
Microelectrode Recording During Deep Brain Stimulation Does Not Consistently Represent Lead Trajectory
Authors: Hines Kevin , Sharan Isha , Schaefer Joseph , Fayed Islam , Atik Ahmet , Matias Caio M. , Wu Chengyuan 
Published: June 2024

BACKGROUND AND OBJECTIVES:
Long-term outcomes in deep brain stimulation (DBS) depend on accuracy of lead placement. Microelectrode recording (MER) is a long-used adjunct to leverage neurophysiological information to confirm satisfactory trajectory of implanted electrodes. The goal of this study was to evaluate the consistency in which electrodes are placed in sampled microelectrode trajectories.

METHODS:
This is a retrospective study using intraoperative computed tomography to measure final electrode deviation from MER probe placement during the DBS insertion targeting subthalamic nucleus. Fifteen patients had 29 DBS leads placed using MER assistance. Radial distance between the probe and the lead were measured for each patient using intraoperative imaging. In addition, the preoperative target to final lead error was measured in 14 patients undergoing subthalamic nucleus implants without the use of MER and compared with the 15 patients in which MER was used as an adjunct.

RESULTS:
There was no significant difference in the mean radial target error (1.2 vs 1.0 mm, P = .156) when comparing the leads placed with or without MER assistance, respectively. The mean difference in final position of microelectrode compared with DBS lead was 0.9 ± 0.1 (range 0.4-2.0 mm). Of all MER-assisted electrodes placed, 44.8% (13) of electrode final positions radially deviated 1.0 mm or more from the MER probe.

CONCLUSION:
Electrode placement may deviate significantly from MER trajectories. Given the concern that physiological data may not be representative of the final electrode trajectory, surgeons should consider using intraoperative imaging or other adjunctive techniques during DBS to confirm accuracy and satisfactory trajectory of DBS leads.
Microvascular Decompression Using the Gelatin Sponge Insertion Technique for Trigeminal Neuralgia: A Retrospective Cohort Study
Authors: Zhang Zhongding , Zhao Hua , Tang Yinda , Wang Baimiao , Yuan Qing , Wang Haopeng , Cai Xiaomin , Zhu Wanchun , Li Shiting 
Published: June 2024

BACKGROUND AND OBJECTIVES:
Microvascular decompression (MVD) is the primary surgical intervention for trigeminal neuralgia (TN), with Teflon being the most conventional decompressing material. However, Teflon has been associated with adhesion and granulomas after MVD, which closely correlated with the recurrence of TN. Therefore, we developed a new technique to prevent direct contact between Teflon and nerve. The purpose of this study is to compare the efficacy of MVD using the gelatin sponge (GS) insertion technique with that of Teflon inserted alone in treating primary TN.

METHODS:
We retrospectively analyzed the medical records and the follow-up data of 734 patients with unilateral primary TN who underwent MVD at our center from January 2014 to December 2019. After exclusions, we identified 313 cases of GS-inserted MVD and 347 cases of traditional MVD. The follow-up exceeded 3 years.

RESULTS:
The operating time of the GS-inserted group was longer than that of the Teflon group (109.38 ± 14.77 vs 103.53 ± 16.02 minutes, P < .001). There was no difference between 2 groups in immediate surgical outcomes and postoperative complications. The yearly recurrence rate for GS-inserted MVD was lower at first (1.0%), second (1.2%), and third (1.2%) years after surgery, compared with its counterpart of Teflon group (3.7%, 2.9%, and 1.7% respectively). The first-year recurrence rate (P = .031) and total recurrence rate in 3 years (P = .013) was significantly lower in the GS-inserted group than Teflon group. Kaplan–Meier survival analysis demonstrated better outcomes in GS-inserted MVD groups (P = .020).

CONCLUSION:
The application of the GS insertion technique in MVD reduced first-year postoperative recurrence of TN, with similar complications rates compared with traditional MVD.
Learning to Persuade on the Fly: Robustness Against Ignorance
Authors: Zu You , Iyer Krishnamurthy , Xu Haifeng 
Published: June 2024

How Can Platforms Learn to Make Persuasive Recommendations? Many online platforms make recommendations to users on content from creators or products from sellers. The motivation underlying such recommendations is to persuade users into taking actions that also serve system-wide goals. To do this effectively, a platform needs to know the underlying distribution of payoff-relevant variables (such as content or product quality). However, this distributional information is often lacking—for example, when new content creators or sellers join a platform. In “Learning to Persuade on the Fly: Robustness Against Ignorance,” Zu, Iyer, and Xu study how a platform can make persuasive recommendations over time in the absence of distributional knowledge using a learning-based approach. They first propose and motivate a robust-persuasiveness criterion for settings with incomplete information. They then design an efficient recommendation algorithm that satisfies this criterion and achieves low regret compared with the benchmark of complete distributional knowledge. Overall, by relaxing the strong assumption of complete distributional knowledge, this research extends the applicability of information design to more practical settings.
Operation room nursing based on humanized nursing mode combined with nitric oxide on rehabilitation effect after lung surgery
Authors: Wang Qiao-Li , Wang Zhi-Bo , Zhu Jin-Fu 
Published: June 2024

BACKGROUND
With advancements in the diagnosis and treatment of lung diseases, lung segment surgery has become increasingly common. Postoperative rehabilitation is critical for patient recovery, yet challenges such as complications and adverse outcomes persist. Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.
AIM
To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery, focusing on pulmonary function, recovery speed, and overall treatment costs.
METHODS
A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group (n = 39) receiving a routine nursing program and an experimental group (n = 40) receiving additional humanized nursing interventions and atomized inhalation of nitric oxide. Key indicators were compared between the two groups alongside an analysis of treatment costs.
RESULTS
The experimental group demonstrated significant improvements in pulmonary function, reduced average recovery time, and lower total treatment costs compared to the control group. Moreover, the quality of life in the experimental group was significantly better in the 3 months post-surgery, indicating a more effective rehabilitation process.
CONCLUSION
The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes, accelerates recovery, and reduces economic burden. This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.
Comparative effects of insulin pump and injection on gestational diabetes mellitus pregnancy outcomes and serum biomarkers
Authors: Wang Yan , Gao Wan , Wang Xiao-Juan 
Published: June 2024

BACKGROUND
Insulin injection is the basic daily drug treatment for diabetic patients.
AIM
To evaluate the comparative impacts of continuous subcutaneous insulin infusion (CSII).
METHODS
Based on the treatment modality received, the patients were allocated into two cohorts: The CSII group and the multiple daily injections (MDI) group, with each cohort comprising 210 patients. Comparative assessments were made regarding serum levels of serum-secreted frizzled-related protein 5, homocysteine, and C1q/TNF-related protein 9. Furthermore, outcomes such as fasting plasma glucose, 2-hour postprandial glucose levels, pain assessment scores, and the incidence of complications were evaluated post-treatment.
RESULTS
The CSII group displayed notably lower fasting plasma glucose and 2-h postprandial glucose levels in comparison to the MDI group (P < 0.05). Subsequent analysis post-treatment unveiled a significantly higher percentage of patients reporting no pain in the CSII group (60.00%) in contrast to the MDI group (36.19%) (P < 0.05). Additionally, the CSII group exhibited a markedly reduced occurrence of fetal distress and premature rupture of membranes compared to the MDI group (P < 0.05). However, there were no significant variances observed in other pregnancy outcomes between the two groups (P > 0.05). A statistical analysis revealed a significant difference in the incidence of complications between the groups (χ 2 = 11.631, P = 0.001).
CONCLUSION
The utilization of CSII via an insulin pump, as opposed to MDI, can significantly enhance the management of insulin administration in patients with GDM by diversifying the sites of insulin delivery. This approach not only promotes optimal glycemic control but also regulates metabolic factors linked to blood sugar, reducing the likelihood of adverse pregnancy outcomes and complications. The clinical relevance and importance of CSII in GDM management highlight its wide-ranging clinical usefulness.