bluuebunny/crossref_metadata_2025_split huggingface dataset:
LOCL-07 LOCO-REGIONAL INFUSION OF GB-13 (IL13.E13K-PE4E) AS A POTENTIALLY PROMISING TREATMENT FOR RECURRENT HIGH-GRADE GLIOMA
Authors: Rechberger Julian , Khatua Soumen , Campian Jian , Sarkaria Jann , Schwartz Jonathan , Daniels David , Schrecengost Randy 
Published: August 2022

Abstract

INTRODUCTION
High grade gliomas (HGG) are devastating diseases with largely unchanged survival outcomes despite decades of research. Recent studies suggest the interleukin 13 receptor subunit alpha 2 (IL-13Rα2) is selectively upregulated in up to 80% of HGG, including glioblastoma (GBM) and diffuse midline gliomas (DMG) harboring H3K27 alterations. Immunotoxins targeting IL-13Rα2 have been demonstrated as safe and have shown some benefit for patients with HGG in previous phase I/II and III clinical trials. We hypothesized that by using GB-13 (IL13.E13K-PE4E), a novel peptide-toxin that binds IL-13Rα2 with high specificity and possesses a Pseudomonas exotoxin moiety, we would enhance the anti-tumor effects of this immunotherapy for HGG in vitro and in vivo while decreasing off-target toxicity.

METHODS
We examined the pharmacological effects of GB-13 in multiple patient-derived cell lines and rodent models of HGG. GBM and DMG lines were used to confirm IL-13Rα2 expression and sensitivity towards GB-13. Tumor naïve rats were evaluated for toxicity, and orthotopic PDX mice were used to monitor tumor size and survival following loco-regional infusion of GB-13.

RESULTS
GB-13 induced a potent cytotoxic response strongly predicated on IL-13Rα2 expression in vitro. No treatment-related adverse effects were noted after 7-day continuous intracranial infusion of GB-13 in tumor naïve rats. Further, in IL-13Rα2-upregulated orthotopic PDX mice, direct intratumoral administration of GB-13 via convection-enhanced delivery abrogated tumor growth and prolonged survival.

CONCLUSIONS
Given these promising results as well as the critical need for novel therapies in CNS malignancies, we are progressing to human trials using GB-13 targeting recurrent HGG. Ongoing safety studies in tumor-bearing animals will be able to define dose levels for the initial adult study-arm and the following pediatric study-arm. In this Phase 1 clinical trial, we hypothesize that loco-regional infusion of GB-13 will safely enhance tumor clearance by causing selective killing of IL-13Rα2-upregulated HGG cells.
MMAP-02 A POPULATION - BASED STUDY ON RADIATION THERAPY FOR BRAIN METASTASIS FROM MALIGNANT MELANOMA IN BRITISH COLUMBIA: EVALUATING THE IMPACT OF IMMUNOTHERAPY AND STEREOTACTIC TECHNIQUES
Authors: Bahl Gaurav , Nguyen Thao 
Published: August 2022

Abstract

BACKGROUND
To evaluate population-based outcomes for patients with brain metastasis from malignant melanoma, treated using radiation therapy, and to assess the impact of immunotherapy (IMT) and stereotactic radiation techniques (SRT).

METHODS
Data was obtained from the BC Cancer Registry for all patients diagnosed with Melanoma in British Columbia, between 1st Jan 2005 and 31st Dec 2018. A total of 5133 patients were identified. These patients had received 2244 courses of RT, of which 461 were directed to the Brain, in 419 unique individuals. The median age was 62 years and majority, 89.5% (n=375), had cutaneous melanomas while 44 had mucosal or choroidal primary sites of disease. A total of 106 (25.3%) patients received IMT, and pembrolizumab was most commonly used (n=48). Over 85% of patients (n=358) received Whole Brain Radiation Therapy (WBRT) alone, with 20 Gy/5 being the most common dose fractionation. Stereotactic Radio-Surgery (SRS) or SRT alone was used in 31 patients, while 30 patients received a combination of SRS/SRT and WBRT. The most used fractionation for SRS was 30Gy/1 (n=9), and for SRT was 35 Gy/5 (n=25). Overall Survival (OS) was calculated from the date of starting radiation therapy.

RESULTS
After a median follow-up of 43 months (95% CI: 18.2 - 67.7), a total of 377 patients had died, with a Median Survival of 2 months (95% CI: 1.46 - 2.53 months) and a 2 year OS of 11.7%. On univariate analysis, age over 65, use of IMT, and SRS/SRT had a significant impact on 2-year OS (14.5% vs 7.4%, p&lt;0.0001; 27.6% vs 6.7%, p&lt;0.0001; and, 38.7% vs. 7.1% p &lt;0.0001, respectively). These factors retained statistical significance on multi-variable analysis. The 2 year OS for patients who received IMT and SRS/SRT alone (n=22) was 54.7%.

CONCLUSION
Selected patients treated aggressively with SRS/SRT and IMT have a median survival of &gt;25 months and a 2-year OS &gt; 50%.
NEIM-07 DIFFERENTIAL DIAGNOSIS OF TUMOR RECURRENCE AND RADIATION NECROSIS AFTER STEREOTACTIC RADIOTHERAPY FOR BRAIN METASTASES WITH 320-ROW ADCT PERFUSION IMAGE AND T1/T2 MATCH: RADIOLOGICAL AND PATHOLOGICAL ANALYSIS
Authors: Mitsuya Koichi , Deguchi Shoichi , Ito Shohei , Asakura Koiku , Nakashima Kazuaki , Oishi Takuma , Sugino Takashi , Hayashi Nakamasa 
Published: August 2022

Abstract

BACKGROUND AND PURPOSE
Radiation necrosis occurs from 6 months to several years following stereotactic irradiation (STI) for brain metastases when tumor recurrences are also most likely. Conventional MR imaging does not provide sufficient information to differentiate between radiation necrosis and tumor recurrence. Methionine-PET, FDG-PET and MR spectroscopy sometimes lead to false positive findings. We applied 320-row area detector CT perfusion imaging for the differentiation because it shows vascularity of lesions in the whole brain. MR T1/T2 match sign also evaluate because it is convenient diagnostic method.

METHOD
Between October 2006 and September 2021, 48 lesions enlarged in 46 patients 3 to 122 months (median: 11 months) after STI. Differential diagnosis was performed with CT perfusion imaging and MR T1/T2 match sign. To calculate the regional cerebral blood volume (rCBV), the regions of interest (ROIs) were located in the enhanced areas. The lesions progressively increased in size or became symptomatic were resected and diagnosed by pathological examination.

RESULTS
Mean age was 63 years, and 60% were male. Primary were lung 31, breast 9, kidney 3, colon 2, melanoma 2, and uterus 1. Mean time to progression from STI was 11 months (range; 3-122). Pathological diagnosis revealed 38 lesions (79%) had tumor recurrence, and 10 (21%) had radiation necrosis. A cut off value rCBV of greater than 3.0 analyzed by ROC curve provided the best sensitivity and specificity for identifying recurrent metastatic tumors, at 89% and 100%, respectively. T1/T2 match sign was provided sensitivity and specificity for identifying recurrent tumors, at 84% and 90%, respectively. To estimate intralesional pathological heterogeneity, contradistinction of CBV map and T1/T2 match sign is useful for the choice of intraoperative maneuver.

CONCLUSION
Perfusion CT imaging and T1/T2 match sign demonstrated reliable methods for differentiating tumor recurrence from radiation necrosis after STI.
SPCR-04 EFFECTS OF BRAIN METASTASES ON NEUROCOGNITIVE FUNCTION: BASELINE RESULTS OF A LONGITUDINAL TRIAL
Authors: Higazy Randa , Ramotar Matthew , Liu Zhihui Amy , Santiago Anna T , Kosyak Natalya , Liu Geoffrey , Simpson Rebecca , Shultz David B , Edelstein Kim 
Published: August 2022

Abstract

PURPOSE
Neurocognitive dysfunction is common in patients with advanced metastatic cancer. The contribution of brain metastases (BrMets) to neurocognitive outcomes is uncertain. We examined the impact of BrMets on cognitive outcomes before CNS-directed treatment and compared findings to patients with advanced metastatic cancer without BrMets. Here we present results from an ongoing prospective, longitudinal study.

METHODS
English-speaking adults followed at the brain metastases and lung cancer clinics underwent neurocognitive testing using a standardized battery (prior to cranial radiotherapy, if applicable), with follow-up assessments 3, 6, 9, 12, 18, and 24 months later. We calculated z-scores and impairment rates for composite neurocognitive function and memory, attention/working memory, processing speed and executive function domains. Impairment was defined according to International Cancer and Cognition Task Force criteria.

RESULTS
78 patients with BrMets (50% female; mean age (SD):61(11) years) and 28 patients with metastatic non-small cell lung cancer (mNSCLC) with no known BrMets (71% female; age 67(9) years) were included. Baseline neurocognitive composite scores were impaired in both groups (BrMets: 61.5%; nonBrMets: 60.7%). Impairment rates varied between groups and across domains (BrMets vs nonBrMets: memory: 35.9%vs25.0%; attention/working memory: 35.8%vs21.4%; processing speed: 10.3%vs7.1%; executive function: 44.0%vs35.7%). Subgroup comparisons between BrMets patients with mNSCLC (N=29) and mNSCLC patients without BrMets, none of whom had targetable mutations, revealed no differences in impairment rates, but BrMets patients had slower processing speed than nonBrMets patients (mean(SD): -0.6(1.4) vs -0.1(1.9); Wilcoxon signed-rank test, p = 0.043).

CONCLUSION
Neurocognitive impairment in patients with advanced cancers is common. Our preliminary findings demonstrate no clear difference in cognitive outcomes between patients with BrMets and those with advanced metastatic disease not involving the brain. Our work examining how neurocognitive outcomes evolve over time in patients with and without BrMets, and demographic, disease, and treatment variables associated with those outcomes, is ongoing.
SYST-04 PRELIMINARY REPORT OF A CLINICAL TRIAL EVALUATING THE SAFETY AND EFFICIENCY OF NEOADJUVANT CAMRELIZUMAB AND APATINIB IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS: A PROSPECTIVE, PHASE II, SINGLE-ARM STUDY
Authors: Lin Fuhua , Guo Chengcheng , Yang Qunying , Chen Yinsheng , Ke Chao , Sai Ke , Zhang Ji , Jiang Xiaobing , Hu Wanming , Xi Shaoyan , Zhou Jian , Li Depei , Zhou Zhihuan , Zhao Qinqin , Cao Xi , Chen Zhongping 
Published: August 2022

Abstract
High-grade glioma is the most common malignant primary brain tumor in the central nervous system. Multiple strategies such as surgery, radiotherapy, and chemotherapy have been used, but the prognosis of patients with high-grade glioma remains poor. No standard treatment exists for recurrent gliomas; however, combination therapies of programmed cell death protein 1 blockades with antiangiogenic agents have demonstrated promising effects in different solid tumors. We have initiated a clinical trial designed to evaluate the safety and efficiency of neoadjuvant therapy using camrelizumab and apatinib in patients with recurrent highgrade gliomas. In this prospective, Phase II, singlearm study, patients with recurrent highgrade gliomas will receive singledose intravenous injection of camrelizumab (200 mg) and daily oral administration of apatinib (250 mg/day for 7 days) 14 days before surgery for recurrent tumor. Sequential therapy will begin 2 weeks after surgery with the biweekly injection of camrelizumab and 4 weeks after surgery with the daily administration of apatinib. Treatment of camrelizumab and apatinib will be continued until disease progression or unacceptable toxicity or death. The trial is planned to enroll 30 patients. Up-to date (March 31, 2022), 12 patients had been enrolled, in which, 9 were GBM. Three patients died, while 4 cases on trial more than 6 months, the longest already 1 year. Although an evaluation is still impossible to be conducted yet, some patients have shown a promising outcome. We will present updated results on the meeting. These preliminary data suggest that this study would be worthwhile. This study was approved by the Ethics Committee of Sun Yatsen University Cancer Center (Guangzhou, China; approval No. SLB202014901). This study was registered with ClinicalTrials.gov under identifier NCT04588987.
Eudicot primary cell wall glucomannan is related in synthesis, structure, and function to xyloglucan
Authors: Yu Li , Yoshimi Yoshihisa , Cresswell Rosalie , Wightman Raymond , Lyczakowski Jan J , Wilson Louis F L , Ishida Konan , Stott Katherine , Yu Xiaolan , Charalambous Stephan , Wurman-Rodrich Joel , Terrett Oliver M , Brown Steven P , Dupree Ray , Temple Henry , Krogh Kristian B R M , Dupree Paul 
Published: August 2022

Abstract
Hemicellulose polysaccharides influence assembly and properties of the plant primary cell wall (PCW), perhaps by interacting with cellulose to affect the deposition and bundling of cellulose fibrils. However, the functional differences between plant cell wall hemicelluloses such as glucomannan, xylan, and xyloglucan (XyG) remain unclear. As the most abundant hemicellulose, XyG is considered important in eudicot PCWs, but plants devoid of XyG show relatively mild phenotypes. We report here that a patterned β-galactoglucomannan (β-GGM) is widespread in eudicot PCWs and shows remarkable similarities to XyG. The sugar linkages forming the backbone and side chains of β-GGM are analogous to those that make up XyG, and moreover, these linkages are formed by glycosyltransferases from the same CAZy families. Solid-state nuclear magnetic resonance indicated that β-GGM shows low mobility in the cell wall, consistent with interaction with cellulose. Although Arabidopsis β-GGM synthesis mutants show no obvious growth defects, genetic crosses between β-GGM and XyG mutants produce exacerbated phenotypes compared with XyG mutants. These findings demonstrate a related role of these two similar but distinct classes of hemicelluloses in PCWs. This work opens avenues to study the roles of β-GGM and XyG in PCWs.
Frozen bean curd-inspired xenogeneic acellular dermal matrix with triple pretreatment approach of freeze–thaw, laser drilling and ADSCs pre-culture for promoting early vascularization and integration
Authors: Huang Xing , Zhu Zhu , Lu Lin , Jin Rui , Sun Di , Luo Xusong 
Published: August 2022

Abstract
Xenogeneic acellular dermal matrix (ADM) is widely used in clinical practice given its good biocompatibility and biomechanical properties. Yet, its dense structure remains a hindrance. Incorporation of laser drilling and pre-culture with Adipose-derived stem cells (ADSCs) have been attempted to promote early vascularization and integration, but the results were not ideal. Inspired by the manufacturing procedure of frozen bean curd, we proposed a freeze–thaw treatment to enhance the porosity of ADM. We found that the ADM treated with −80°C 3R+−30°C 3R had the largest disorder of stratified plane arrangement (deviation angle 28.6%) and the largest porosity (96%), making it an optimal approach. Human umbilical vein endothelial cells on freeze–thaw treated ADM demonstrated increased expression in Tie-2 and CD105 genes, proliferation, and tube formation in vitro compared with those on ADM. Combining freeze–thaw with laser drilling and pre-culture with ADSCs, such tri-treatment improved the gene expression of pro-angiogenic factors including IGF-1, EGF and vascular endothelial growth factor, promoted tube formation, increased cell infiltration and accelerated vascularization soon after implantation. Overall, freeze–thaw is an effective method for optimizing the internal structure of ADM, and tri-treatments may yield clinical significance by promoting early cell infiltration, vascularization and integration with surrounding tissues.
MAML2 Gene Rearrangement Occurs in Nearly All Hidradenomas: A Reappraisal in a Series of 20 Cases
Authors: Russell-Goldman Eleanor , Hanna John 
Published: August 2022

Abstract:
Hidradenoma is a benign cutaneous adnexal neoplasm that occurs across a wide age range and at a variety of anatomic sites. Its most characteristic morphologic feature is the presence of diverse cell types including squamoid, clear, plasmacytoid, and mucinous cells. Hidradenoma is morphologically and molecularly similar to mucoepidermoid carcinoma, and both tumors are characterized by recurrent CRTC1-MAML2 cytogenetic translocations. Previous studies have suggested that approximately half of hidradenomas possess this translocation. This finding raised the question of whether translocation-negative hidradenomas might have an alternate molecular basis. Here, we sought to reevaluate the frequency of MAML2 translocation in hidradenoma in a series of 20 cases. We find that 90% show evidence of MAML2 translocation, suggesting that this genetic event is a nearly invariant feature of hidradenoma. These results inform our molecular understanding of this tumor and may be useful in challenging cases to distinguish hidradenoma from its histologic mimics.
Mental health considerations in patients undergoing complex head and neck reconstruction
Authors: Philteos Justine , Noel Christopher W. , Hallet Jullie , Eskander Antoine 
Published: August 2022

Purpose of review
To summarize recent advances in the psycho-oncology literature, with a focus on findings relevant to the head and neck cancer patient.

Recent findings
Patients with cancer are at an increased risk of suicide and self-harm. Head and neck cancer patients are among the highest risk compared with other cancer patients. Unique challenges pertaining to disfigurement and voicelessness may, in part, explain these observations. Patient-reported outcome measures can be used to help identify high-risk patients.

Summary
Psychosocial support needs are highest for head and neck cancer patients. Patient-reported outcome measures should be integrated within clinical workflows to identify high-risk patients.
18F-Fluciclovine PET/CT
Authors: Marcus Charles , Schuster David M. , Tajmir Shahein Holmes 
Published: August 2022

Abstract
Incidental concomitant second primary malignancy may be detected on PET/CT imaging. We present an 18F-fluciclovine PET/CT of a patient undergoing evaluation of biochemically recurrent prostate cancer with incidental radiotracer uptake within lytic osseous lesions confirmed to be multiple myeloma. We present the 18F-fluciclovine PET/CT images of an 83-year-old man with prostate cancer treated in 2005 who presented with back pain and a CT scan revealing multiple lytic osseous lesions concerning for metastases versus a plasma cell neoplasm. Prostate-specific antigen at the time of evaluation was 0.1 ng/mL.
Using the Endsley Model to Evaluate Simulation-Based Situation Awareness Training for Medical and Nursing Students in India
Authors: Bhatia Manini R. , Malhotra Atul , Bansal Utkarsh , Singh Jai Vir , Kumar Arunaz 
Published: August 2022

Introduction
Situation awareness (SA) training is a vital part of healthcare training, and opportunities to provide SA training to healthcare workers are limited in low- and middle-income countries. We aimed to analyze undergraduate medical and nursing students' perception of their understanding of SA through an interprofessional obstetric neonatal emergency simulation workshop (ONE-Sim) and subsequently evaluate their perceived changes in SA understanding using the Endsley model (Hum Factors 1995;37(1):32–64).

Methods
Feedback on SA before and after the workshop was collected through questionnaire-based surveys. Thematic analysis was performed, with themes emerging from an inductive analysis followed by a deductive analysis using the Endsley model.

Results
The themes emerging from the inductive analysis included environmental awareness, evolving knowledge, skill development, and applicability to practice. These aligned with the 3 levels of SA in the Endsley model in the deductive analysis suggesting that participants transformed their perception, comprehension, and projection of SA after the workshop.

Conclusion
Simulation-based education enhanced SA perception in obstetric and neonatal emergencies for medical and nursing students in a low- and middle-income country, and the Endsley model is a feasible framework to measure learner perceived changes in SA understanding through simulation-based education.
“Failure to Rescue” following Colorectal Cancer Resection
Authors: Wells Cameron I. , Varghese Chris , Boyle Luke J. , McGuinness Matthew J. , Keane Celia , O’Grady Greg , Gurney Jason , Koea Jonathan , Harmston Chris , Bissett Ian P. 
Published: August 2022

Objective:
To examine variation in “failure to rescue” (FTR) as a driver of differences in mortality between centres and over time for patients undergoing colorectal cancer surgery.

Background:
Wide variation exists in postoperative mortality following colorectal cancer surgery. FTR has been identified as an important determinant of variation in postoperative outcomes. We hypothesized that differences in mortality both between hospitals and over time are driven by variation in FTR.

Methods:
A national population-based study of patients undergoing colorectal cancer resection from 2010 to 2019 in Aotearoa New Zealand was conducted. Rates of 90-day FTR, mortality, and complications were calculated overall, and for surgical and nonoperative complications. Twenty District Health Boards (DHBs) were ranked into quartiles using risk- and reliability-adjusted 90-day mortality rates. Variation between DHBs and trends over the 10-year period were examined.

Results:
Overall, 15,686 patients undergoing resection for colorectal adenocarcinoma were included. Increased postoperative mortality at high-mortality centers (OR 2.4, 95% CI 1.8–3.3) was driven by higher rates of FTR (OR 2.0, 95% CI 1.5–2.8), and postoperative complications (OR 1.4, 95% CI 1.3–1.6). These trends were consistent across operative and nonoperative complications. Over the 2010 to 2019 period, postoperative mortality halved (OR 0.5, 95% CI 0.4–0.6), associated with a greater improvement in FTR (OR 0.5, 95% CI 0.4–0.7) than complications (OR 0.8, 95% CI 0.8–0.9). Differences between centers and over time remained when only analyzing patients undergoing elective surgery.

Conclusion:
Mortality following colorectal cancer resection has halved over the past decade, predominantly driven by improvements in “rescue” from complications. Differences in FTR also drive hospital-level variation in mortality, highlighting the central importance of “rescue” as a target for surgical quality improvement.
Trends in Surgical Technique and Outcomes of Ventral Hernia Repair in The United States
Authors: Howard Ryan , Thumma Jyothi , Ehlers Anne , Englesbe Michael , Dimick Justin , Telem Dana 
Published: August 2022

Objective:
To describe national trends in surgical technique and rates of reoperation for recurrence for patients undergoing ventral hernia repair (VHR) in the United States.

Background:
Surgical options for VHR, including minimally invasive approaches, mesh implantation, and myofascial release, have expanded considerably over the past 2 decades. Their dissemination and impact on population-level outcomes is not well characterized.

Methods:
We conducted a retrospective cohort study of Medicare beneficiaries undergoing elective, inpatient umbilical, ventral, or incisional hernia repair between 2007 and 2015. Cox proportional hazards models were used to estimate the adjusted proportion of patients who remained free from reoperation for hernia recurrence up to 5 years after surgery.

Results:
One hundred fort-one thousand two hundred sixty-one patients underwent VHR during the study period. Between 2007 and 2018, the use of minimally invasive surgery increased from 2.1% to 22.2%, mesh use increased from 63.2% to 72.5%, and myofascial release increased from 1.8% to 16.3%. Overall, the 5-year incidence of reoperation for recurrence was 14.1% [95% confidence interval (CI) 14.0%–14.1%]. Over time, patients were more likely to remain free from reoperation for hernia recurrence 5 years after surgery [2007–2009 reoperation-free survival: 84.9% (95% CI 84.8%–84.9%); 2010–2012 reoperation-free survival: 85.7% (95% CI 85.6%–85.7%); 2013–2015 reoperation-free survival: 87.8% (95% CI 87.7%–87.9%)].

Conclusions:
The surgical treatment of ventral and incisional hernias has evolved in recent decades, with more patients undergoing minimally invasive repair, receiving mesh, and undergoing myofascial release. Although our analysis does not address causality, rates of reoperation for hernia recurrence improved slightly contemporaneous with changes in surgical technique.