bluuebunny/crossref_metadata_2025_split huggingface dataset:
CELL-INTRINSIC METABOLIC PHENOTYPES IDENTIﬁED IN GLIOBLASTOMA PATIENTS USING MASS SPECTROMETRY IMAGING OF 13C-LABELED GLUCOSE METABOLISM
Authors: Tsyben Dr Anastasia , Dannhorn Dr Andreas , Hamm Dr Gregory , Couturier Dr Dominique Laurent , Briggs Dr Mayen , Mair Mr Richard , Brindle Prof Kevin 
Published: October 2024

Abstract

AIMS
Glioblastoma (GB) is an inherently heterogenous and invasive primary brain tumour. Genetic and transcriptomic studies have attempted to classify GB into subtypes that can identify therapeutic vulnerabilities and predict survival. An outstanding question and technical challenge is to visualise the metabolism of a tumour within its native microenvironment and understand to what extent its metabolism is driven by the microenvironment.

METHOD
Patients with GB tumours were infused with [U-13C]glucose and intra-operative multi-regional tumour samples were rapidly snap frozen for metabolic tracing analysis using mass spectrometry imaging (MSI). Tissue microenvironment was assessed using multiplexing of antibodies on immunocytochemistry (IMC) of parallel sections. Isotope tracing in human derived neurospheres and patient derived xenografts were used to conﬁrm the presence of metabolic phenotypes detected in the human samples and to test susceptibility of each phenotype to a panel of drugs targeting cellular metabolism.

RESULTS
Three metabolic signatures were identiﬁed in patient GB tumours: glycolytic, oxidative and a mixed glycolytic/oxidative phenotype. The phenotypes did not correlate with microenvironmental features, including proliferation rate, immune cell inﬁltration, and vascularisation. The phenotypes were retained when patient derived cells were grown in vitro, or as orthotopically implanted xenografts, and were robust to changes in oxygen concentration, demonstrating their cell intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes are large enough to be detected using clinically applicable metabolic imaging techniques. The phenotypes also demonstrate differential drug sensitivities.

CONCLUSION
This is the ﬁrst report to demonstrate high resolution imaging of metabolic ﬂuxes in a human tumour in vivo. In conjunction with studies on patient-derived neurospheres and orthotopically implanted xenografts we have demonstrated the presence of different metabolic phenotypes within GB that are tumour cell intrinsic and largely independent of the tumour microenvironment. These can be imaged clinically and used to stratify patients for personalised therapy.
MANAGEMENT OF THE OLDER PATIENT WITH GLIOBLASTOMA IN THE UK: AN INITIAL REPORT FROM THE HISTO-MOL GBM COLLABORATIVE
Authors: Robinson Dr Stephen , Ryan Dr Katherine , Black Dr Louisa , Forner Dr Sam , Hatton Dr Nathaniel Luke , Hatton Dr Rebecca , Aktar Dr Nurjahan , Lathangue Mr Haydn , Conkey Dr David , Durage Dr Praveen , de Luna Mr Paolo , Christodoulou Dr Pavlos , Hill Dr Timothy , MacArthur Ms Rachel , Teoh Dr May , Williams Dr Adenike , Golten Dr Jennifer , Aghadiuno Dr Tasia , Yogalingam Dr Kohgulakuhan , Kahan Dr Jennifer , Dixit Dr Sanjay , Guglani Dr Samir , Lewis Dr Rachel , Moleron Dr Rafael , Iqbal Dr Najmus , Wadd Dr Nick , Bhat Dr Prashanth , Giamas Prof Georgios , Mazarakis Dr Nektarios , Lorimer Dr Cressida , Chandy Dr Edward , Critchley Prof Giles 
Published: October 2024

Abstract

AIMS
The management of older (&gt;70 years old) patients with glioblastoma is challenging with signiﬁcant variation in practice. Using the Histo-Mol GBM database we analysed the variation in practice across 11 UK centres.

METHOD
Biopsy conﬁrmed glioblastoma patients diagnosed between 01/01-31/12/2021 were identiﬁed. Descriptive statistics were used to compare demographic, tumour and treatment characteristics, and the Kaplan-Meier method was used to analyse survival, assessed from surgery date. Differences in treatment between centres were assessed using one way ANOVA.

RESULTS
In 2021, 81/330 (24.5%) patients with glioblastoma were &gt;70. Compared to younger patients, the older cohort had a greater proportion of males (79.0% vs 59.0%, p&lt;0.001), a worse performance status (66.7% vs 79.5% ECOG PS 0-1, p&lt;0.001), and more likely to have MGMT promoter methylation (30.9% vs 22.9%, p=0.027). Most patients received biopsy only (31/81, 38.3%), followed by subtotal resection (85-94% tumour resection) (26/81, 32.1%), whilst 8/81 (9.9%) underwent debulking, 8/81 near-total resection (95-99% tumour resection), and 8/81 gross total resection, with statistically signiﬁcant variation in resection extent between centres (p=0.031). Adjuvant radiotherapy was used in 56/81 patients (69.1%) with no difference between centres (p=0.220). However, there was a statistically signiﬁcant difference in radiotherapy regime between centres (p=0.041). 6/81 (7.4%) received conventional chemoradiotherapy, 28/81 (34.6%) hypofractionated chemoradiotherapy, 16/81 (19.8%) hypofractionated radiotherapy alone, 2/81 (2.5%) temozolomide alone both with MGMT promoter methylation, and 21/81 (25.9%) received no oncological treatment. Median progression free survival was 5.9 months and median overall survival (OS) was 7.1 months with no difference between centres (p=0.199 and p=0.083 respectively). Median OS was 8.4 months with conventional fractionation chemoradiotherapy, 11.2 months with hypofractionated chemoradiotherapy, 7.3 months with hypofractionated radiotherapy alone, 1.8 months with temozolomide alone, and 2.5 months with no oncological treatment.

CONCLUSION
We identify variations in the treatment of elderly glioblastoma patients across the UK, although these do not signiﬁcantly impact survival.
PCV ALONE IN GRADE 2 AND GRADE 3 OLIGODENDROGLIOMA – LONG-TERM RESULTS FROM A UK TERTIARY CARE CENTRE
Authors: Kalra Dr Babusha , Creak Dr Antonia , Lee Dr Ernest , Welsh Dr Liam , Solda Dr Francesca , Rosenfelder Dr Nicola , Klobukowski Dr Lukasz 
Published: October 2024

Abstract

AIMS
Oligodendroglioma is a subgroup of gliomas which affects young adults and has a favourable overall survival (OS) ranging between 31.5 to 56.6.% at 10 years. Standard management of these tumours is maximal safe resection followed by adjuvant radiotherapy and systemic chemotherapy with Procarbazine, Lomustine and Vincristine (PCV), or surveillance where appropriate. PCV alone is an option that helps defer or avoid radiotherapy and its neurocognitive side effects in a selected group of patients. Our retrospective study analyses outcomes with PCV alone in Oligodendroglioma.

METHOD
We screened patient records between 1999 to 2021 and identiﬁed 31 patients who had a histological diagnosis of grade 2/3 oligodendroglioma (with conﬁrmation of 1p19qcodeletion on molecular testing) and received PCV alone after surgery (biopsy/ tumour resection).

RESULTS
Out of 31 patients, twenty-six patients were grade 2 and ﬁve patients were grade 3 oligodendroglioma. Median age was 44 years and male: female was 15:16. Median follow up was 9.5 years. Twenty-ﬁve patients (80%) presented with seizures. 80% of patients had tumour resection & twenty four patients received 5 or more cycles of PCV alone as ﬁrst-line oncological treatment. There was no signiﬁcant difference in outcomes for grade2/3 tumours. Eighteen patients (58%) had local tumour relapse. Fourteen patients (45%) underwent salvage radiotherapy. Median time to radiotherapy was 7 years. Median OS was 19.4 years and median progression free survival (PFS) was 13.3 years. 9 deaths were reported.

CONCLUSION
PCV chemotherapy alone is an effective adjuvant treatment option for selected patients with oligodendroglioma, with a favourable PFS and OS shown in our series. Its use may allow deferral of radiotherapy and avoidance of associated neurocognitive side effects which can have a detrimental effect of quality of life for these young patients.
EPIGENETIC MODULATION OF STEMNESS AND DIFFERENTIATION BY VALPROIC ACID IN MEDULLOBLASTOMA
Authors: Roesler Prof Rafael , Freire Ms Natalia Hogetop , de Farias Dr Caroline Brunetto , Brunetto Dr André , Jaeger Dr Mariane , Brunetto Dr Algemir , Herlinger Dr Alice Laschuk , Gregianin Dr Lauro 
Published: October 2024

Abstract

AIMS
Changes in epigenetic processes, including histone acetylation, are proposed as key events affecting tumor cell function and the initiation and progression of pediatric brain cancers. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we report VPA-induced alterations in features related to stemness and differentiation in medulloblastoma (MB) cells.

METHOD
Human MB cells were treated with different concentrations of VPA and cell viability was measured with a trypan exclusion assay. Cell cycle was evaluated with ﬂow cytometry. Expansion of MB cancer stem cells (CSCs) was evaluated by a neurosphere formation assay. Reverse transcriptase polymerase chain reaction (RT-qPCR) was used to analyze mRNA expression and Western Blot to analyze protein levels. H3K9 histone acetylation (H3K9ac) was measured with immunoﬂuorescence, and chromatin Immunoprecipitation (ChIP) was used to evaluate the occupancy of gene promoter regions by H3K9ac.

RESULTS
VPA reduced MB cell viability and expansion of MB CSCs, induced morphological changes consistent with neuronal differentiation, and increased expression of differentiation markers tubulin beta 3 class III (TUBB3) and enolase 2 (ENO2). Expression of stemness markers SOX2 and Nestin was differentially affected by VPA in cells representative of SHH or Group 3/4 MB molecular subgroups. VPA increased H3K9ac and its occupancy of promoter regions of TP53 and CDKN1A genes.

CONCLUSION
Our results indicate that VPA may exert antitumor effects in MB by inﬂuencing histone acetylation, which may result in modulation of stemness and stimulation of neuronal differentiation.
AUDIT TO EVALUATE CURRENT RADIOTHERAPY (RT) PLANNING PATHWAY: COULD CURRENT PRACTICE BE IMPROVED BY THE TIMING OF MAGNETIC RESONANCE IMAGING (MRI)?
Authors: Thurgood Ms Carol 
Published: October 2024

Abstract

AIMS
To evaluate the current guidance for glioblastoma (GBM) and primary brain radiotherapy (RT) planning. Current practice in this centre utilises pre and post-surgical MRI for RT target delineation. This study aims to explore the practicality and impact of scheduling an RT planning-speciﬁc MRI no more than 2 weeks before RT treatment start date (TSD). Time from surgery to RT TSD will also be explored.

METHOD
Fifty GBM patients, treated between August 2022 and October 2023, were audited retrospectively. Included patients were treated with radical intent and must have had surgery or biopsy. Age, gender or performance status (PS) were excluded from audit criteria. Age of MRI used for RT planning and surgery to TSD was noted.

RESULTS
Early results showed that the average age of MRI used for RT planning was 7 weeks old and Surgery to TSD was 7 weeks. A new pathway was introduced after 37 patients as these results were considered unacceptable. The new pathway included 1 reserved MRI appointment and one reserved RT Mask/CT appointment per week. 13 patients’ pathways were audited after introduction of the new pathway. The results showed that the average age of MRI used for RT planning was 2 weeks old and surgery to TSD was 6 weeks.

CONCLUSION
Limitations of the audit included disparity between number of patients before and after introduction of the new pathway. This was because of the time limitation for completion of the study. Improvement was seen in timing of MRI to TSD. However, the small improvement in timing of surgery to TSD was impacted by human factors rather than organisational inﬂuence, for example, surgical deconditioning, delays for wound healing and patient choice. This study has shown that the ideal timing of MRI can be achieved.
Managing Cancer and Living Meaningfully in adults with brain metastases: A NIH ORBIT model phase II feasibility and proof-of-concept trial
Authors: Loughan Ashlee R , Lanoye Autumn , Willis Kelcie , Braun Sarah Ellen , Davies Alexandria , Rodin Gary , Thacker Leroy , Fox Amber , Kleva Christopher , Zarrella Giuliana , Mazzeo Suzanne , Svikis Dace , Swartz Leigh 
Published: October 2024

Abstract

Background
Managing Cancer and Living Meaningfully (CALM) is a brief, evidence-based psychotherapy designed to help patients with advanced cancer cope with the practical and profound challenges of their illness. However, no study has systematically examined CALM in adults with brain metastases, despite the well-documented incidence of distress in this growing population. The primary aim of this trial was to assess the feasibility and acceptability of CALM in adults with brain metastases.

Methods
Patients with brain metastases (N = 13) and elevated symptoms of depression and/or death anxiety enrolled in this single-arm trial. CALM was administered in 6 biweekly sessions, with outcomes assessed at baseline and post-intervention. Feasibility was assessed based on established metrics including enrollment and retention rates. Acceptability was measured by post-session surveys and post-intervention interviews. Preliminary signal change on measures of psychological distress was explored.

Results
Of the 13 enrolled participants, 11 completed baseline assessments and initiated treatment: 73% female, Mage = 58 years (SD = 12.9; range = 37–75). Nine completed the study (81% retention rate). Overall, participants reported high perceived benefits and would recommend the program to others. Baseline to post-intervention assessments indicated improvements in depression, death anxiety, generalized anxiety, post-traumatic stress, suicidal ideation, and spiritual well-being. Life quality, substance use, and fear of cancer recurrence remained relatively stable.

Conclusions
CALM is feasible and acceptable and may improve psychological distress in adults with brain metastases. The findings of this study align with our previous trial of patients with malignant glioma and support a future National Institute of Health Obesity Related Behavioral Intervention Trials phase II randomized pilot trial of CALM in neuro-oncology.

Trial Registration Number
NCT05087095 registered on March 23, 2022.
Integrated detrital rutile and detrital zircon ages: a new perspective on the tectonic evolution of South China
Authors: Zou Hao , Li Hongkui , Li Zhongquan , Wang Danlin , Safonova Inna , Cao Huawen , Jin Xin , Chen Haifeng , Huang Changcheng 
Published: October 2024

ABSTRACT
Paleogeographic reconstructions are of key importance for understanding the history of continental breakups and amalgamations during Earth’s history. A special case is the history of the Asian continent, which, compared to other continents, consists of several large cratons and numerous smaller continental blocks. The history of the assembly of South China remains controversial in terms of the timing, Late Neoproterozoic or Early Paleozoic, and the participating continental blocks, e.g. Yangtze, Cathaysia, India and Australia. Detrital rutile U-Pb dating has significant potential with regard to deciphering tectonic settings as rutile frequently crystallizes during orogenic events associated with the processes of collision and subduction. Detrital zircon U-Pb dating is a perfect instrument for identifying the provenance characteristics and age characteristics of sedimentary sources. An integration of these two methods of dating offers better opportunities for reconstructing tectonic settings. This paper presents a first attempt to reconstruct the Neoproterozoic to Early Paleozoic tectonic history and paleogeography of the whole South China based on U-Pb geochronology of rutile and zircon and Hf-in-zircon isotopes from Lower Jurassic Baitianba Formation sedimentary rocks of the western margin of the Yangtze Block, a major part of South China. Our obtained integrated U-Pb rutile and zircon age data show three main age populations of 960–940 Ma, 630–610 Ma and 530–520 Ma. The new U-Pb detrital rutile and zircon ages, compared with former data from Gondwana and Australia, suggest that Yangtze amalgamated with Cathaysia to form South China during the Sibao orogeny at 960–940 Ma. The detrital rutile and zircons of the new 630–610 Ma age group could have been delivered from western Australia during the Late Neoproterozoic to Cambrian Paterson-Petermann orogeny. The abundant 530–520 Ma detrital rutile and zircon ages fit well with the coeval zircon age populations recorded in Gondwana-derived terranes, like India and Indochina.
Prize-Based Incentives for Smoking Cessation Among People With HIV: A Sequential Multiple Assignment Randomized Trial
Authors: Ledgerwood David M , Lundahl Leslie H , Greenwald Mark K , Cohn Jonathan , Arfken Cynthia L 
Published: October 2024

Abstract

Introduction
Contingency management (CM) is an incentive-based approach that has demonstrated efficacy for smoking cessation in various populations. There is an unmet need for feasible and effective smoking cessation interventions in people with HIV (PWH). The purpose of this study was to assess the efficacy of prize-based CM for smoking cessation in PWH using a Sequential Multiple Assignment Randomization Trial (SMART) design selected to tailor intervention intensity based on early treatment response.

Methods
During phase I, 129 participants were randomly assigned to high-magnitude prize CM (HM-CM) or standard of care (SoC) for 4 weeks. Participants who did not reduce smoking were randomized in phase II to continued counseling with HM-CM plus monitoring support or only continued monitoring support for 8 weeks. Participants who reduced smoking were randomized to booster monitoring with low-magnitude CM or no additional care. Outcomes were biochemically verified smoking reduction and 7-day abstinence prevalence at posttreatment, 6-month, and 12-month follow-up.

Results
Phase I responders (based on biochemical indicators of smoking reduction) were significantly less likely to return to smoking (during treatment and at 6 and 12 months) if they received low-magnitude incentives. Notably, initial exposure to CM versus SoC did not increase the rate of phase I response, and high-magnitude incentives later in treatment did not lead to greater smoking cessation for early-treatment nonresponders.

Conclusions
Weekly CM sessions in the first 4 weeks of smoking cessation intervention did not perform significantly better than SoC. However, brief booster CM sessions aimed at maintaining early smoking cessation hold clinical promise and warrant further investigation.

Implications
This represents the first trial to examine the use of CM for smoking cessation among PWH within the context of a SMART design.
Clinical Trial Registration: NCT01965405 (https://clinicaltrials.gov/study/NCT01965405)
Community Mobilization to Guide the Public Health Response During the 2022 Ontario Mpox Outbreak: A Brief Report
Authors: Tan Darrell H S , Awad Adam , Zygmunt Austin , Murray James , Warshafsky Daniel , Mishra Sharmistha , Griffiths Dane 
Published: October 2024

Abstract
The 2022 mpox epidemic predominantly affected gay, bisexual, and other men who have sex with men (GBM). Led by a provincial community program and co-galvanized by clinician-researchers, GBM community leaders in Ontario coordinated a robust response, representing a reproducible strategy for community engagement and mobilization during future epidemics.
Virus Load Kinetics in Lassa Fever Patients Treated With Ribavirin: A Retrospective Cohort Study From Southern Nigeria
Authors: Ogbaini-Emovon Ephraim , Akpede George , Okogbenin Sylvanus , Osagiede Emmanuel , Tobin Ekaete , Asogun Danny , Okokhere Peter , Okonofua Martha , Akpede Nosa , Akhideno Peter , Erameh Cyril , Rafiu Mojeed , Azubuike Chukwuemeka , Iraoya Kelly , Iruolagbe Chris , Erohubie Christian , Ahmed Dazumi , Ediawe Osahogie , Okoguale Joseph , Eifediyi Reuben , Odia Ikponmwonsa , Agbukor Jacqueline , Adomeh Donatus , Odike Maxy A C , Ovienria Wilson , Elkanem Anieno , Muoebenam Ekene B , Ojide Kingsley C , Pallasch Elisa , Müller Jonas , Hinzmann Julia , Günther Stephan , Pahlmann Meike , Thielebein Anke , Duraffour Sophie , Oestereich Lisa , Krumkamp Ralf 
Published: October 2024

Abstract

Background
The standard of care for Lassa fever is the use of ribavirin with supportive therapy. There is little information on the course of viremia and its relationship with clinical outcomes in patients treated with ribavirin.

Methods
We conducted a retrospective analysis of virologic and clinical parameters of 152 reverse transcription polymerase chain reaction–confirmed Lassa fever cases admitted and treated with ribavirin therapy. We describe the Lassa virus RNA kinetics in blood in relation to the clinical course of the patients.

Results
The overall mortality was 9%. The median duration (interquartile range [IQR]) of illness before admission was 8 (5–12) days. Median (IQR) Ct values on admission (t0) were lower among patients who died (21 [20–27]) than in those who survived (34 [30–37]; P &lt; .01). The receiver operating characteristics curve of the association between outcome and Ct value at t0 had a high classification performance, with an AUC of 0.92 (95% CI, 0.86–0.98). The median time to viral clearance (IQR) was 10 (5–15) days. The viral load decreased steadily with the duration of treatment, and all survivors achieved viral clearance within 25 days of hospitalization.

Conclusions
Our study demonstrates that the Ct value on admission has prognostic value and Lassa fever patients treated with ribavirin typically clear the virus within 3–4 weeks of hospitalization. This kinetics has implications for the design of clinical case management and future clinical trial protocols.
Clinical and economic impact of pharmacist interventions to identify drug-related problems in multidisciplinary cancer care: a prospective trial
Authors: Giraud Jean-Stéphane , Korb-Savoldelli Virginie , Perrin Germain , Jouinot Anne , Sabatier Brigitte , Batista Rui , Ribault Matthieu , De Percin Sixtine , Villeminey Clémentine , Videau Margaux , Blanchet Benoit , Goldwasser Francois , Degrassat-Theas Albane , Thomas-Schoemann Audrey 
Published: October 2024

Abstract

Background
The prescription of antitumor drugs has often been associated with drug-related problems. Pretherapeutic multidisciplinary risk assessment programs including pharmaceutical care have been established to secure the initiation of injectable and oral antitumor therapies. This prospective cross-sectional double-center study evaluated the clinical and economic impact of the pharmacist in detecting drug-related problems in patients initiating antitumor therapies.

Materials and Methods
Following pharmaceutical consultations, pharmaceutical interventions were validated by a multidisciplinary team. A committee of independent clinical experts assessed the potential clinical impact of drug-drug interactions. The association of clinical variables with pharmaceutical interventions was tested using a multivariate logistic regression model. Pharmacist cost of the program was assessed by valuing pharmacists’ time at their salaries and compared with potentially avoided costs.

Results
Four hundred thirty-eight patients with solid tumors were included: 62% males, mean age of 65 ± 13 years, and average of 6 medications. Half of the patients required at least one pharmaceutical intervention and independent factors associated with pharmaceutical interventions were the number of medications (5-9 vs &lt;5: OR = 2.91 [95% CI 1.82-4.65], P &lt; .001) and the type of antitumor treatment (immunotherapy vs intravenous chemotherapy: OR = 0.35 [95% CI 0.18-0.68], P = .002). One hundred seventy-four out of 266 pharmaceutical interventions (130 patients) involved clinically significant drug-drug interactions. Pharmacist costs were estimated to range between €4899 and €6125. Average costs were estimated at €11.4-14.3 per patient. Avoided hospitalization costs were estimated to be €180 633.

Conclusion
Clinical pharmacists contribute to the cost-effective reduction of drug-related problems in pre-therapeutic assessment programs for patients with cancer.