tbuckley/cabot-search huggingface dataset:
P17.13.B NANO-LM: AN UPDATED SCORECARD FOR THE CLINICAL ASSESSMENT OF PATIENTS WITH LEPTOMENINGEAL METASTASES
Authors: E Le Rhun, L Nayak, M Lim-Fat, R Rudà, E Pentsova, P Forsyth, B J O’Brien, M Preusser, P Kumthekar, D Brandsma, M Weller
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND There are no validated tools for the clinical neurological assessment of patients with leptomeningeal metastases. However, clinical examination during the course of the disease guides medical management and is part of response assessment in clinical trials. Standardization of clinical neurological assessment in LM is therefore essential, also because MRI may not always be obtained owing to rapid clinical deterioration and itself subject to rater disagreement. MATERIAL AND METHODS The RANO-LM group launched a 2-steps process, aiming at improving and homogenizing the clinical assessment in patients with leptomeningeal metastasis. We report here on the first step: the establishment of a consensus scorecard. The RANO-LM group had 9 virtual meetings to define general recommendations on neurological assessment and selected domains of interest that should be tested. Domains of interest were selected from the Neurological Assessment in Neuro-Oncology (NANO) scale and from the first RANO-LM proposal. RESULTS Fourteen domains in neurological assessment were selected: level of consciousness, cognition, nausea and vomiting, vision, eye movement, facial strength, hearing, swallowing, dysarthria, limb strength, ataxia, walking, cauda equina symptoms-bowels and cauda equina symptoms-bladder). For each item, a clear instruction on how to perform the assessment is provided with scoring criteria between 0 and 2. The general status of the patient and use of steroids, pain medications, and anti-emetics should be considered when assessing the patient. Neurological sequelae from previous brain metastases or treatment (neuropathy, post-radiotherapy toxicities) should be rated at the baseline evaluation; it should be specified in the comments when symptoms or signs may be related to a condition other than leptomeningeal metastasis. The evaluation should be declared as non-evaluable when neurological symptoms or signs that develop during the follow-up are related or suspected to be related to comorbidities or any other medical event. In these situations, specific details should be included in the comments. If these signs and symptoms are retrospectively interpreted as related to leptomeningeal metastasis and not to any comorbidity, the date of symptoms or signs appearance should be retrospectively back-dated to assess the response. CONCLUSION A NANO-LM consensus scorecard has been established. A prospective validation of the proposal is currently ongoing at various medical centers.
JS06.5.A MERTK ON TUMOUR CELLS AND MACROPHAGES: A THERAPEUTIC OPTION FOR NF2-RELATED AND SPORADIC MENINGIOMA
Authors: C Hanemann, F Dave, K Herrera, L L van de Weijer, S Henderson, J Dunn, L Singh, C L Adams, E Ercolano, D A Hilton, K M Kurian, E A Maze, S Ammoun, L Laraba, D B Parkinson
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Meningioma are common tumours of the nervous system. They occur sporadically or as part of the hereditary NF2-related schwannomatosis syndrome. There is an unmet need for new effective drug treatment. MATERIAL AND METHODS We analysed tumour tissue and used cell culture including 3D cultures and also PDX models applying different functional read outs after pharmacological inhibition and knock down. This was complemented by Western blots, co-IP, RNA seq and proteomic analysis. RESULTS We demonstrate overexpression/activation of TAM (TYRO3/AXL/MERTK) receptors and overexpression/release of ligand GAS6 in patient-derived meningioma tumour cells and tissue. For the first time, we reveal formation of MERTK/TYRO3 heterocomplexes in meningioma. We demonstrate interdependency of TAM receptor expression. We show that MERTK and AXL contribute to increased proliferation and survival of meningioma cells, which we inhibited in vitro using the MERTK/FLT3 inhibitors and the AXL inhibitors. MERTK inhibition was more effective and we show an effect also in 3D tumour models as well as PDX models. Further we found that TAM receptors are expressed by tumour-associated macrophages in meningioma and that MERTK inhibition strongly depleted macrophages in meningioma. CONCLUSION Inhibiting MERTK is a new therapeutic option for meningioma
JS02.5.A A PHASE 0/1B STUDY OF AZD1390 PLUS RADIOTHERAPY IN RECURRENT GLIOBLASTOMA PATIENTS
Authors: N Sanai, Y Umemura, S Desai, T Margaryan, J Molloy, C Lo Cascio, M Elliott, J Harmon, A Hong, E Luna Melendez, J Wanebo, K Braun, W Kennedy, M Garcia, W Yoo, A Tovmasyan, A Tien, S Mehta
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND ATM inhibition is hypothesized to potentiate the effects of radiation by preventing acute phase DNA damage repair, and a Phase 1 trial of this combination in patients with GBM is ongoing (NCT03423628). This Phase 0/1b study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of AZD1390, a first-in-class ATM inhibitor, in combination with radiation in newly-diagnosed and recurrent GBM patients (NCT05182905). METHODS All patients received 3 days of AZD1390 prior to planned resection at 2-4, 4-6 or 23-25 hrs following the final dose (120/300mg for nGBM and 400mg for rGBM). Tumor tissue, cerebrospinal fluid (CSF), and plasma were collected. Total and unbound drug concentrations were measured using validated LC-MS/MS methods. ATM inhibition was assessed via ex vivo tissue radiation, quantifying pRAD50 levels compared to non-radiated control. A PK ‘trigger’ determined eligibility for Phase 1b and patients exceeding the PK threshold (2 nM unbound drug levels in Gd-non-enhancing tumor region) were eligible for therapeutic dosing of AZD1390 plus radiotherapy. RESULTS Thirty nGBM patients and twenty-nine rGBM patients were enrolled. Forty-eight out of the forty-nine evaluable patients exceeded the PK threshold and qualified for therapeutic dosing. The mean unbound concentrations of AZD1390 in Gd-nonenhancing tumors of nGBM patients were 13.2 pmol/g (4-6 hrs) and 4.4 pmol/g (23-25-hrs) at 120 mg dose and 17.9 pmol/g (4-6 hrs) and 4.5 pmol/g (23-25-hrs) at 300 mg dose. The mean unbound concentrations of AZD1390 were 75.6, 106.8, and 25.5 pmol/g in Gd-nonenhancing tumors of rGBM patients enrolled in 2-4, 4-6-, and 23-25-hrs cohorts, respectively. Following 5Gy ex vivo radiation of surgical specimens, pRAD50 expression was significantly suppressed in AZD1390-treated patients compared to untreated controls (median 0.2% (4-6 hrs 120mg), 1.9% (23-25 hrs 120mg), 0.3% (4-6 hrs 300mg), 1.1% (23-25 hrs 300mg), 1.2% (2-6 hrs 400mg) and 2.3% (23-25 hrs 400mg) vs 32.3% for control cohort, respectively. To date, six MGMT-unmethylated nGBM patients and 15 rGBM patients were enrolled in the Phase 1b component of the study, with median clinical follow-up of 7.0 months. Median progression-free and overall survival have not been reached in the nGBM population. Median OS was 15.4 months in the rGBM population. CONCLUSION AZD1390 is well-tolerated in both newly-diagnosed and recurrent GBM patients, achieving pharmacologically relevant concentrations in Gd-nonenhancing tumor tissue, and suppressing radiation-induced increase in pRAD50 levels. These data are the first to demonstrate AZD1390-mediated pharmacodynamic and pharmacokinetic response in GBM patients. Clinical efficacy data is maturing, but early results are encouraging.
The meaning and measure of concordance factors in phylogenomics
Authors: Robert Lanfear, Matthew W Hahn
Journal: Molecular Biology and Evolution (2024)

Abstract As phylogenomic datasets have grown in size, researchers have developed new ways to measure biological variation and to assess statistical support for specific branches. Larger datasets have more sites and loci and therefore less sampling variance. While we can more accurately measure the mean signal in these datasets, lower sampling variance is often reflected in uniformly high measures of branch support—such as the bootstrap and posterior probability—limiting their utility. Larger datasets have also revealed substantial biological variation in the topologies found across individual loci, such that the single species tree inferred by most phylogenetic methods represents a limited summary of the data for many purposes. In contrast to measures of statistical support, the degree of underlying topological variation among loci should be approximately constant regardless of the size of the dataset. “Concordance factors” (CFs) and similar statistics have therefore become increasingly important tools in phylogenetics. In this review, we explain why CFs should be thought of as descriptors of topological variation rather than as measures of statistical support, and argue that they provide important information about the predictive power of the species tree not contained in measures of support. We review a growing suite of statistics for measuring concordance, compare them in a common framework that reveals their interrelationships, and demonstrate how to calculate them using an example from birds. We also discuss how measures of topological variation might change in the future as we move beyond estimating a single “tree of life” toward estimating the myriad evolutionary histories underlying genomic variation.
<i>Notes from the Field:</i> Enhanced Surveillance for Raccoon Rabies Virus Variant and Vaccination of Wildlife for Management — Omaha, Nebraska, October 2023–July 2024
Authors: Sydney R. Stein, Andrew J. Beron, Kathleen M. Nelson, Emma Price, Sergio E. Rodriguez, Victoria Shelus, Ann Carpenter, Amy R. Hess, Cassandra Boutelle, Clint N. Morgan, Crystal M. Gigante, Christina L. Hutson, John D. Loy, Duan S. Loy, Chad Wetzel, Justin Frederick, Lindsay Huse, Lillian Orciari, Richard B. Chipman, Ryan M. Wallace, Matthew Donahue, Bryan F. Buss
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

On September 28, 2023, a kitten aged approximately 6 weeks found in Omaha, Nebraska, had test results positive for rabies at the Nebraska Veterinary Diagnostic Center (NVDC) after dying with neurologic signs and having bitten and scratched its caretakers. Preliminary investigation identified 10 exposed persons for whom postexposure prophylaxis (PEP)
Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten — United States, 2023–24 School Year
Authors: Ranee Seither, Oyindamola Bidemi Yusuf, Devon Dramann, Kayla Calhoun, Agnes Mugerwa-Kasujja, Cynthia L. Knighton, Jennifer L. Kriss, Rebecca Miller, Georgina Peacock
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

In the United States, states and local jurisdictions set vaccination requirements for school attendance, conditions and procedures for exemptions from these requirements, grace periods for submitting documentation, and provisional enrollment for students who need more time to be vaccinated. States annually report data to CDC on the number of children in kindergarten who meet, are exempt from, or are in the process of meeting requirements. Data reported by 49 states and the District of Columbia (DC) for the 2023-24 school year were used for national- and state-level estimates of the following measures: complete vaccination with required doses of measles, mumps, and rubella vaccine (MMR), diphtheria, tetanus, and acellular pertussis vaccine (DTaP), poliovirus vaccine (polio), and varicella vaccine (VAR); exemptions from vaccination; and school attendance while meeting requirements. The 2023-24 kindergarten class became age-eligible to complete most state-required vaccinations during the COVID-19 pandemic, after schools had returned to routine in-person learning. Compared with approximated national coverage levels across all reported vaccines for the 2019-20 (95%) and 2022-23 (93%) school years, coverage dropped below 93% for the 2023-24 school year, ranging from 92.3% for DTaP to 92.7% for MMR. Exemptions increased to 3.3%, compared with those during the 2022-23 (3.0%) and 2021-22 school years (2.6%). Coverage with MMR, DTaP, polio, and VAR decreased in 35, 32, 33, and 36 jurisdictions, respectively, compared with the 2022-23 school year. Exemptions increased in 41 jurisdictions, with 14 reporting that >5% of kindergartners had an exemption from one or more vaccine. Efforts by health departments, schools, and providers are needed to ensure that students begin school fully vaccinated.
Study of Rates and Factors Associated to Psychosomatic Syndromes Assessed Using the Diagnostic Criteria for Psychosomatic Research across Different Clinical Settings
Authors: Wei Xu, Wenhao Jiang, Rongjing Ding, Hong Tao, Yanyong Wang, Yanping Tang, Dongfeng Liang, Yuping Wang, Mingwei Wang, Bingwei Chen, Youyong Kong, Lei Liu, Yingying Yue, Liangliang Tan, Lu Yu, Fiammetta Cosci, Yonggui Yuan
Journal: Psychotherapy and Psychosomatics (2024)

Diagnostic Criteria for Psychosomatic Research (DCPR) serve as an instrument for identifying and classifying specific psychosomatic syndromes that are not adequately encompassed in standard nosography. The present study aimed at measuring the prevalence of DCPR syndromes in different clinical settings and exploring factors associated to such diagnoses.
Update on Vaccine-Derived Poliovirus Outbreaks — Worldwide, January 2023–June 2024
Authors: Apophia Namageyo-Funa, Sharon A. Greene, Elizabeth Henderson, Mohamed A. Traoré, Shahzad Shaukat, John Paul Bigouette, Jaume Jorba, Eric Wiesen, Omotayo Bolu, Ousmane M. Diop, Cara C. Burns, Steven G.F. Wassilak
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Circulating vaccine-derived polioviruses (cVDPVs) can emerge and lead to outbreaks of paralytic polio as well as asymptomatic transmission in communities with a high percentage of undervaccinated children. Using data from the World Health Organization Polio Information System and Global Polio Laboratory Network, this report describes global polio outbreaks due to cVDPVs during January 2023-June 2024 and updates previous reports. During the reporting period, 74 cVDPV outbreaks were detected in 39 countries or areas (countries), predominantly in Africa. Among these 74 cVDPV outbreaks, 47 (64%) were new outbreaks, detected in 30 (77%) of the 39 countries. Three countries reported cVDPV type 1 (cVDPV1) outbreaks and 38 countries reported cVDPV type 2 (cVDPV2) outbreaks; two of these countries reported cocirculating cVDPV1 and cVDPV2. In the 38 countries with cVDPV2 transmission, 70 distinct outbreaks were reported. In 15 countries, cVDPV transmission has lasted >1 year into 2024. In Nigeria and Somalia, both countries with security-compromised areas, persistent cVDPV2 transmission has spread to neighboring countries. Delayed implementation of outbreak response campaigns and low-quality campaigns have resulted in further international spread. Countries can control cVDPV outbreaks with timely allocation of resources to implement prompt, high-quality responses after outbreak confirmation. Stopping all cVDPV transmission requires effectively increasing population immunity by overcoming barriers to reaching children.
Real-World Evaluation of the Effectiveness and Safety of Dupilumab in Bullous Pemphigoid: An Ambispective Multicenter Case Series
Authors: Nidia Planella-Fontanillas, Xavier Bosch-Amate, Alicia Jiménez Antón, Carlos Moreno-Vílchez, María Gamo Guerrero, María del Mar Blanes Martínez, María Asunción Ballester Martínez, Patricia Bassas-Freixas, Juan Luis Castaño Fernández, Andrea Estébanez Corrales, Ricardo Suarez Fernández, Sergio Santos Alarcón, Ana Bauzá Alonso, Marina Torrent, Adrian Ballano Ruiz, Cristina Collantes Rodríguez, Agustín España, Eduardo Fonseca Capdevila, Inmaculada Gil Faure, Carlos Pelayo Hernández Fernández, Francisco Javier Melgosa Ramos, Jorge Spertino, Violeta Zaragoza Ninet, Lucia Armillas, Isabel Bielsa, Cristina Carrera, Mireia Esquius Rafat, Jon Fulgencio Barbarin, Javier Fernandez Vela, Miguel Lova Navarro, Clara Martín Callizo, Sara Martín-Sala, Rosa Ojeda, Maria Elisabet Parera Amer, Anna Sánchez Puigdollers, Ramon M Pujol, Sebastian Podlipnik, José Manuel Mascaró, Laia Curto-Barredo
Journal: British Journal of Dermatology (2024)

Bullous pemphigoid affects elderly individuals with multiple comorbidities, making conventional treatments unsuitable.
Tobacco Product Use Among Middle and High School Students — National Youth Tobacco Survey, United States, 2024
Authors: Ahmed Jamal, Eunice Park-Lee, Jan Birdsey, Andrenita West, Monica Cornelius, Maria R. Cooper, Hannah Cowan, Jia Wang, Michael D. Sawdey, Karen A. Cullen, Livia Navon
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Use of tobacco products in any form is unsafe, and nearly all tobacco product use begins during adolescence. CDC and the Food and Drug Administration (FDA) analyzed data from the 2024 National Youth Tobacco Survey to determine tobacco product use among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2024, current (previous 30-day) use of any tobacco product was reported by 10.1% of high school students (representing 1.58 million students) and 5.4% of middle school students (representing 640,000 students). Among all students, e-cigarettes were the most commonly reported tobacco product currently used (5.9%), followed by nicotine pouches (1.8%), cigarettes (1.4%), cigars (1.2%), smokeless tobacco (1.2%), other oral nicotine products (1.2%), heated tobacco products (0.8%), hookahs (0.7%), and pipe tobacco (0.5%). During 2023-2024, among all students, the estimated number who reported current use of any tobacco product decreased from 2.80 to 2.25 million students; e-cigarette use decreased (from 2.13 to 1.63 million students); and hookah use decreased (from 290,000 to 190,000 students). Among high school students, current use of any tobacco product decreased from 12.6% to 10.1% of students, and e-cigarette use decreased from 10.0% to 7.8%. Among middle school students, no statistically significant changes occurred. Evidence-based strategies can help prevent initiation and promote cessation of tobacco product use among U.S. youths.
The <scp>IL</scp>‐4–<scp>IL</scp>‐<scp>4Rα</scp> axis modulates olfactory neuroimmune signaling to induce loss of smell
Authors: Yannis Hara, Mithilesh Kumar Jha, Jeremy Y. Huang, Yingnan Han, Ingeborg M. Langohr, Giorgio Gaglia, Cheng Zhu, Peter Piepenhagen, Kaitlyn Gayvert, Wei Keat Lim, Seblewongel Asrat, Scott Nash, Juby A. Jacob‐Nara, Jamie M. Orengo, Dinesh S. Bangari, Emanuele de Rinaldis, Hamid Mattoo, Alexandra Hicks
Journal: Allergy (2024)

IL-4 and IL-13 have non-redundant effects in olfaction, with loss of smell in mice evoked only by intranasal administration of IL-4, but not IL-13. IL-4-evoked pathophysiological effects on olfaction is independent of compromised structural integrity of the olfactory neuroepithelium. IL-4-IL-4Rα signaling modulates neuronal crosstalk with immune cells, suggesting a functional link between olfactory impairment and neuroinflammation. Abbreviations: IL, interleukin; KO, knock-out; wk, week; WT, wild-type.
P21.02.A GERMAN TRANSLATION AND CROSS-CULTURAL ADAPTATION OF THE VESTIBULAR SCHWANNOMA QUALITY OF LIFE INDEX (VSQOL)
Authors: M Rutenkröger, S Wandke, J Gempt, L Dührsen, M Scheer, C Strauss, H Führes
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Vestibular schwannomas (VSs) are benign tumors of the vestibulocochlear nerve that often cause significant neurological and functional impairment. Patient-reported outcomes, including quality of life (QoL), are essential for understanding the overall impact of VS and its treatment. This study aimed to translate and culturally adapt the Vestibular Schwannoma Quality of Life (VSQOL) Index into German to expand its relevance to German-speaking populations. MATERIAL AND METHODS We used a qualitative approach including translation and cognitive interviews with 10 patients who underwent VS surgery. The translation process followed the TRAPD protocol to ensure linguistic and conceptual accuracy. Cognitive interviews assessed the comprehensibility and relevance of the translated questionnaire. RESULTS The translation showed remarkable consistency between translators, with minor discrepancies resolved by consensus. Cognitive interviews provided valuable insights that led to refinements in item wording and order. Participants emphasized the importance of an additional item on physician referrals, reflecting differences in health care systems between the United States and Germany. CONCLUSION The German VSQOL provides a comprehensive tool for assessing QoL in patients with VS that integrates patient-centered dimensions. A Validation study is underway to establish its reliability and validity.
P18.14.A DOES WHERE YOU LIVE INFLUENCE GBM SURVIVAL? - A SINGLE CENTRE EXPERIENCE
Authors: I Silva, M Choudhury, A Baig, A Stone, B Vaqas
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive form of primary brain tumour in adults. The treatment of these tumours involves biopsy or surgical resection, oncological treatment and/or best supportive care. Patients who undergo maximum resection followed by chemotherapy and radiotherapy still have a dismal survival of only 15.4 months. It is known that deprivation can influence access to cancer services and treatment, but it remains unclear if socio-economic factors influence survival in GBM when compared with other factors in a National Health Service. Aim was to investigate the influence of socio-economic factors, on the survival of patients diagnosed with GBM in a major neurosurgical centre in the UK serving a population of 2.5 million in a mix of urban and rural areas. MATERIAL AND METHODS A retrospective analysis was performed of all patients operated between January 2021 and December 2021 with a diagnosis of GBM. Data collected included post code, age, extent of resection, oncological treatment, survival, ethnic background, referral pathway and social connections. In addition, social information from the UK Census was accessed including the Index of Multiple Deprivation (IMD) which are a series of datasets consisting of multiple components of deprivation used to classify relative deprivation. Survival analysis was performed using Kaplan-Meier plots, Cox proportional hazards models and stratified Cox models. RESULTS The median overall survival (OS) was 7 months. Age was a significant predictor of survival, with each additional year increasing the hazard of death by 3.38% (HR = 1.0338, 95% CI: 1.016 to 1.052, p &amp;lt; 0.001). The extent of surgical resection was significantly associated with survival. Patients who underwent GTR had a median OS of 11 months, compared to 7 months for STR and 5 months for biopsy (HR = 0.5943, 95% CI: 0.4563 to 0.7739, p = 0.000113). Receipt of further treatment was associated with a 76.1% reduction in mortality risk (HR = 0.239, 95% CI: 0.1549 to 0.3687, p &amp;lt; 0.00001). Extent of surgical resection was associated with increased likelihood to receive treatment post-operatively. No significant association was found between IMD decile and OS when stratified by the type of resection (HR = 0.9796, 95% CI: 0.9116 to 1.053, p = 0.575) CONCLUSION Our data confirms that age, extent of surgical resection and further treatment are significant predictors of survival in GBM patients. More extensive surgical resection was also associated with a higher likelihood of further treatment, particularly CRT. Socio-economic status, as measured by IMD, did not significantly impact survival outcomes in this cohort. This study did not measure the impact of socioeconomic status on the quality of patient experience. A further qualitative study is being designed to ascertain this. Further studies are needed to see if socioeconomic factors influence outcomes in low grade gliomas.